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EO 12866_Antimicrobial Data Requirements_RIN 2070-AD30_FRM_RtC_2011-08-18.draft for OMB.docx 

Draft Comment Response 

Document for the 

Data Requirements for 

Antimicrobial Pesticides 

(Categorized Public Comments) 
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Table of Contents

1. INTRODUCTION AND OVERVIEW ............................................................................................ 1

Background .................................................................................................................................................. 1

EPA’s Categorization of Public Comments and Document Organization ........................................ 1

2. MASTER RESPONSES BY TOPIC AREA ...................................................................................... 5

Most Common Comments ........................................................................................................................ 5

General Comments on the Rule (10) ..................................................................................................... 36

Administrative Comments on the Rule (20) ......................................................................................... 38

Legal Issues (30) ........................................................................................................................................ 42

Economic Analysis (40) ........................................................................................................................... 57

Antimicrobial Use Patterns (50) .............................................................................................................. 66

Product Chemistry (60) ............................................................................................................................ 74

Product Performance (70) ....................................................................................................................... 76

Toxicology (80) .......................................................................................................................................... 82

Applicator/Handler (Human Exposure) (90) .................................................................................... 123

Post-application (Human Exposure) (100) ........................................................................................ 132

Residue Chemistry (110) ....................................................................................................................... 141

Environmental Risk Assessment (120) ............................................................................................... 166

Letter from Environmental Working Group (125)........................................................................... 171

Down-the-Drain (130) .......................................................................................................................... 175

Environmental Fate (140) ..................................................................................................................... 194

Non-Target Plant Protection (150) ..................................................................................................... 214

Non-Target Organism Exposure (160) ............................................................................................... 221

White Paper on the Use of SAR and QSAR (170) ............................................................................ 245

Endangered Species (180) ..................................................................................................................... 249

Guidelines (190) ..................................................................................................................................... 252

3. VERBATIM COMMENTS AND RESPONSE REFERENCES BY TOPIC AREA .............................. 270

General Comments on the Rule (10) .................................................................................................. 270

Administrative Comments on the Rule (20) ...................................................................................... 316

Legal Issues (30) ..................................................................................................................................... 327

Economic Analysis (40) ........................................................................................................................ 364

Antimicrobial Use Patterns (50) ........................................................................................................... 427

Product Chemistry (60) ......................................................................................................................... 460

Product Performance (70) .................................................................................................................... 466

Toxicology (80) ....................................................................................................................................... 498

Applicator/Handler (Human Exposure) (90) .................................................................................... 678

Post-application (Human Exposure) (100) ........................................................................................ 702
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Residue Chemistry (110) ....................................................................................................................... 724

Environmental Risk Assessment (120) ............................................................................................... 785

Letter from Environmental Working Group (125)........................................................................... 794

Down-the-Drain (130) .......................................................................................................................... 804

Environmental Fate (140) ..................................................................................................................... 842

Non-Target Plant Protection (150) ..................................................................................................... 906

Non-Target Organism Exposure (160) ............................................................................................... 914

White Paper on the Use of SAR and QSAR (170) ............................................................................ 973

Endangered Species (180) ..................................................................................................................... 991

Guidelines (190) ................................................................................................................................... 1002

Commenter Background; Introductions and Salutations (200) .................................................... 1028

APPENDIX 1 – LIST OF RELEVANT EPA COMMENT CODES .................................................... A-1

List of Exhibits

Exhibit 1: Public Submissions Received in Response to Data Requirements for Antimicrobial 

Pesticides; Proposed Rule (73 FR 59382) ................................................................................................ 3
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Introduction Page 1 

1. Introduction and Overview 

Background

On October 8, 2008, EPA published in the Federal Register (73 FR 59382, docket number EPA–HQ–

OPP–2008–0110) a proposed rule to revise and update the existing data requirements for pesticides 

designed as treatments for microbial pathogens (i.e., antimicrobial pesticides), titled: “Data 

Requirements for Antimicrobial Pesticides; Proposed Rule.” The comment period for the rule 

closed on April 6, 2009. 

This document presents public comments and EPA responses related to the proposed rule. EPA 

received 30 public submissions in the form of letters, e-mails, and/or postings to 

www.regulations.gov. All original public submissions can be found in the docket location, at 

www.regulations.gov, under Docket ID EPA–HQ–OPP–2008–0110. 

EPA’s Categorization of Public Comments and Document Organization

To address and respond to the public comments that were received, EPA developed a list of 

numerically ordered topics (referred to as “Comment Codes”) that were be likely to be addressed by 

commenters. The list of relevant EPA Comment Codes is provided in Appendix 1. 

To organize and track public submissions, EPA assigned Letter IDs to give each public submission a 

unique identifier, a four digit Letter ID. This Letter ID corresponds directly with the four digit 

Document ID numbers assigned under the proposed rule docket (Docket ID EPA–HQ–OPP–

2008–0110). For instance, Letter ID 0067, corresponds to the Document ID EPA–HQ–OPP–

2008–0110–0067, that was submitted by the organization “Beyond Pesticides”. Each public 

submission was subdivided into “comment sections,” or distinct issue areas, based on topical breaks 

within the submission. Each comment section (hereinafter referred to as “comments”) was assigned 

a five digit “Comment ID” by the tracking database. Comments that were similar in topic were 

assigned the EPA Comment Code corresponding to that topic (as listed in Appendix 1). 

Public Comments and EPA Responses – Document Organization 

Section 2 of this document presents master responses and final EPA testnotes for each major topic 

area. Section 3 contains the corresponding verbatim comments and response references for the 

relevant comment codes. 

Both sections are organized by major topic areas (e.g., Economic Analysis (40); Antimicrobial Use 

Patterns (50); Product Chemistry (60); etc.). EPA’s master responses, located in Section 2, are 

numbered for the purposes of cross referencing with the verbatim comments. To present the 

Agency’s master responses, EPA summarized a significant commenter point or theme, which is then 

followed by EPA’s corresponding response. For certain major topic areas, master responses are 

followed by testnotes, including EPA’s proposed and final language for each of the testnotes (also 

numbered for the purposes of cross referencing with the verbatim comments). 

Section 3 provides verbatim public comments with corresponding response and testnote cross 

referencing. These are first organized, as noted above, by major topic area, directly corresponding to 
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Introduction Page 2 

the organization of Section 2. Within each major topic area, the comments and response references 

are the organized by EPA Comment Code, (i.e., the topical subsections that are listed in Appendix 

1). Verbatim comments are organized numerically by Comment ID. Commenter name, 

Organization, and Letter ID are given for each comment. Any comment can be read as it appears 

within the commenter’s original letter, e-mail, or posting by searching on the associated Document 

ID on www.regulations.gov, under Docket ID EPA–HQ–OPP–2008–0110. The Document ID can also 

be used to find additional information, such as tables or figures, which may be included within the 

context of comments or attachments in the commenter’s original submission. 

Response and Testnote Cross Referencing 

For each verbatim comment, EPA has provided one or more cross references to relevant master 

response(s) or testnote(s). To find the cross referenced master response or testnote, readers can use 

the document Table of Contents to go to the referenced major topic area. For instance, all master 

responses and testnotes for the major topic area of “Toxicology” are located in Section 2 and are 

numerically ordered with the number 80 (e.g., 80.1, 80.2, etc.), as indicated by its title in the table of 

contents: “Toxicology (80)”. EPA notes that the master responses “appear” to have missing 

responses. For example there is not a 70.12, although there is a 70.11 and 70.13. As EPA processed 

the comments and began to formulate master responses, in some cases similar comments were 

combined. However, the responses were not renumbered. 

In addition, Appendix 1 provides a crosswalk between specific EPA comment codes (i.e., how 

comments were categorized and sorted) and the major topic area numbering (i.e., how EPA’s master 

responses are organized). Using this same example, in Appendix 1, readers will see that the major 

topic area of “Toxicology (80)” corresponds to all comments coded in the 80000 series, including 

“80000 Toxicology” through “89200 Commenter's Concept of Toxicology Data Requirements 

Table Revisions”. Software search functions can also be used to find the referenced response or 

testnote. Verbatim comments may have multiple cross references to responses and testnotes, 

depending on the complexity of the comment. In addition, the cross references may often be to 

major topic areas other than the one in which the comment has been binned. 

Who Submitted Comments 

EPA received approximately 30 public submissions from a variety of stakeholders, including: 

industry and industry associations; municipalities and regulators; and non-governmental 

organizations and consumer groups. Exhibit 1, below, lists commenters by organization name and 

Letter ID. 
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Introduction Page 3 

Exhibit 1: Public Submissions Received in Response to Data Requirements for 

Antimicrobial Pesticides; Proposed Rule (73 FR 59382)

Organization: 

Letter ID 

(Document ID under Docket 

EPA–HQ–OPP–2008–0110):

S.C. Johnson & Son, Inc. 0063 

Lanxess Corporation 0064 

Hampton Roads Sanitation District (HRSD) 0065 

Scientific & Regulatory Consultants, Inc. (SRC) 0066 

Beyond Pesticides 0067 

Consumer Specialty Products Association (CSPA), Product Ingredient Review 

Program (PIRP) 0068 

California Association of Sanitation Agencies (CASA) 0069 

National Association of Clean Water Agencies (NACWA) 0070 

SF Environment 0071 

ECOLAB 0072 (duplicate 0083) 

Sanitation Districts of Los Angeles County 0073 

ISSA 0074 

Clorox 0075 

Reckitt Benckiser, Inc. 0076 

Environmental Working Group 0077 

Mason Chemical Company 0078 

CropLife America 0079 

Innovation and Reform Group (IRG) 0080 

Proctor & Gamble 0081 

Dow Chemical Company 0082 

JohnsonDiversey, Inc. 0084 

Health Canada: Pest Management Regulatory Agency 0085 

Consumer Specialty Products Association (CSPA) 0086 

Tri-TAC 0087 

American Chemistry Council Biocides Panel 0088 

California Stormwater Quality Association (CASQA) 0089 

Humane Society 0090 
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Introduction Page 4 

Organization: 

Letter ID 

(Document ID under Docket 

EPA–HQ–OPP–2008–0110):

Troy Corporation 0091 

Alternative Testing Working Group (ATWG) 0092 

Physicians Committee for Responsible Medicine; Humane Society 

International; People for the Ethical Treatment of Animals 0104 
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Master Responses: Most Common Comments Page 5 

2. Master Responses by Topic Area 

Most Common Comments 

Master Responses for the Most Common Comments Section 

The following summary comments represent four of the most common comment themes that were submitted by 

stakeholders. EPA's responses are presented here, and cross referenced in the sections that follow. 

Comment 1: Commenters stated that antimicrobials are subject to FIFRA section 3(h)(3)(A)(ii) 

which specifies that EPA must differentiate the review of an antimicrobial from that of other 

pesticides. 

Response 1: FIFRA section 3(h)(3)(A)(ii) specifies, among other things, that, in proposed regulations 

to accelerate and improve the review of antimicrobial pesticide products, EPA shall define the 

various classes of antimicrobial use patterns, differentiate the types of review undertaken for 

antimicrobial pesticides, conform the degree and type of review to the risks and benefits presented 

by antimicrobial pesticides, and ensure that the registration process is sufficient to maintain 

antimicrobial product efficacy. While those elements apply to a proposed rulemaking that the 

Agency published on September 17, 1999 (64 FR 50671), the Agency has been mindful of those 

same elements in its development of part 158, subpart W. As applied to antimicrobial product 

registration actions, differentiation refers to the tailoring of data requirements so that they are 

responsive to considerations about the antimicrobial products to which they relate. In practice, 

differentiation means that the data requirements applied to antimicrobials are designed to respond to 

the special or unique needs of antimicrobials such as the nature of the products, their ingredients, 

their uses, etc. Differentiation or tailoring does not mean that the resulting data requirements for 

antimicrobials will necessarily be comprised of more, less, or the same number and type of data 

requirements as required for other types of pesticides such as conventional pesticides. 

 

For example, the residue chemistry data requirements for conventional pesticides focus on the 

application of agricultural pesticides to crops growing in the fields. However, the residue chemistry 

data requirements for antimicrobials, codified today, have been tiered to account for applications 

that focus not on crops growing in the fields (where antimicrobials are rarely used), but instead 

account for antimicrobial uses, including those that result in residues on food more indirectly, such 

as from use as sanitizers in food processing plants. The overall impact is to require fewer studies 

since the tiering used for the antimicrobial residue chemistry data requirements table is structured 

differently, and there are fewer “R” studies and most studies are “CR.” However, there are two 

residue chemistry data requirements (migration and nature of the residue on surfaces) for 

antimicrobials that are not included in the conventional residue chemistry data requirements table 

because they reflect the unique use sites for antimicrobials.; see Unit XVI for additional discussion. 

Ecotoxicity and environmental fate data requirements provide another example of the 

differentiation of data requirements between antimicrobials and conventional pesticides. While 

conventional or biochemical/microbial pesticides are often used outdoors, and are deliberately 

placed/spread in the environment, most antimicrobials are used indoors. As discussed in the 

preamble (73 FR 59406), previously EPA had assumed that many of the indoor uses went downthe-drain to a waste water treatment plant (WWTP), where the WWTP processes would mitigate 

environmental concerns. Therefore, in 1984, EPA required basic ecotoxicity and environmental fate 
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Master Responses: Most Common Comments Page 6 

data for conventional pesticides but made these types of data conditional for indoor uses such as 

antimicrobials based on whether antimicrobial-specific data indicated that environmental exposure 

may occur. However, as discussed in the proposed rule (73 FR 59407), in recent years there have 

been detections of antimicrobial chemicals (with indoor uses) in waterbodies. These antimicrobials 

are moving into the environment via treated effluent. Therefore, EPA is requiring for antimicrobials 

a specific tiered-set of data to evaluate the likelihood of environmental exposure to antimicrobials 

that may reach a WWTP, as a result of being washed down the drain via leachates, rinsates, and 

flushes. These data evaluate whether antimicrobials are likely to survive the treatment processes at a 

typical WWTP, and thus would be present in the WWTP effluent. Antimicrobials that do survive 

the treatment processes have the potential to end-up in the terrestrial or aquatic environments and 

higher-tiered ecotoxicity and environmental fate data are only triggered for these antimicrobials. 

 

Thus, differences in data requirements stem directly from the inherent differences in the nature of 

the particular type of pesticide's use. Even with such differentiation or tailoring, there is a general 

core of data requirements which may be expected to be applicable to any kind of pesticide product, 

such as product chemistry data requirements. EPA’s ultimate goal with its antimicrobial data 

requirements is to create a body of data requirements which produce sufficient information for 

Agency to consider and use in making its statutorily-required determinations regarding the risks and 

benefits, where applicable, of antimicrobial pesticides. The differentiation or tailoring of the 

antimicrobial data requirements is instrumental in accomplishing that goal. 

Comment 2: Several commenters requested that EPA rewrite and then repropose this rule. 

Response 2: EPA reviewed all submitted comments, and then analyzed those comments to identify 

the issues needing to be responded to within those comments. EPA considered those issues and 

then based on its analysis determined the changes to be made from the proposed rule to the final 

rule. One data requirement that was proposed is not being codified in today’s final rule and based 

on comments received two new data requirements are being added. All of the changes made in this 

final rule are discussed in the Response to Comments Document which contains the rationales for 

the changes. Thus, the changes made from the proposed rule to the final rule are a logical 

outgrowth of the proposal and the comments received on the proposal. 

The Commenters raised three arguments as to why EPA should repropose: 

 First, several commenters focused on the testnotes to the data requirements tables, and 

claimed that the proposed rule “leaves too many standards and decisions to the sole 

discretion of EPA, creating uncertainty and, inevitability, inconsistency in regulatory decision 

making.” Too many determinations, the commenter asserted, are at “EPA’s discretion” 

because the proposal is vague without clear-cut criteria. Additionally, they argued that there 

are too many places in the test notes where consultation with the Agency is required or the 

phrase “as determined by the Agency” is used. (One commenter listed 37 instances in which 

the proposal allegedly substituted a mandatory consultation process for regulatory criteria.) 

According to the commenters, EPA should eliminate most of the consultation requirements 

and instead, repropose the rule providing a clear set of requirements. 

 Second, commenters also argued that reproposal was necessary because they could not 

meaningfully comment on the proposal without understanding how the data would be used 

by EPA. Specifically, one commenter wrote: “It is not plausible for [the commenter] or 
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Master Responses: Most Common Comments Page 7 

others to meaningfully comment on the Proposal without the benefit of understanding the 

risk assessment approaches EPA plans to use, (e.g., human and ecological), the ways in 

which the data requirements will provide information to conduct those assessments and the 

ways EPA will use those risk assessments in making regulatory decisions. 

 Third, commenters argued that reproposal was needed because affected parties cannot 

properly evaluate the data requirements without final guidelines on how such studies should 

be conducted. 

For the first argument, see response to comment 3 below. 

For the second argument: EPA disagrees with this comment for several reasons. First, how EPA 

conducts risk assessments and how it uses toxicological, ecological, and exposure data in those risk 

assessments is well known. Risk assessment is not unique to OPP. The principles used by OPP and, 

in fact, by EPA are those used by the scientific community in general. OPP follows the processes 

and procedures in the many risk assessment guidance documents that have been issued by EPA (see 

http://www.epa.gov/riskassessment/guidance.htm). The Agency’s exposure and risk assessment 

procedures have been presented in numerous exposure and risk assessments for antimicrobial 

pesticides. EPA’s assessments reflect the best available data, and the state of the science of exposure 

and risk assessment models, methods, and procedures. 

Moreover, OPP’s risk assessment procedures are well-documented. EPA has recently concluded the 

process of completing Reregistration Eligibility Decision Documents for all pesticides under FIFRA 

and reassessing all FFDCA pesticide tolerances. This was a very open process involving multiple 

public comment opportunities as to each pesticide. Further, all regulatory decision documents as 

well as the underlying risk assessments have been made available to the public. EPA has now begun 

new pesticide reviews under the Registration Review program, and that process is equally open and 

transparent. 

A second reason why EPA believes this comment to be misdirected is that the proposed rule does 

not represent a change to EPA’s existing and transparent risk assessment procedures. Rather, the 

proposal is merely designed to tailor the existing data requirements that apply to all pesticides in a 

way that is more specific to antimicrobial pesticides, as well as including some new requirements 

applicable to antimicrobials. 

Finally, the comment is without foundation because EPA has explained the need for each study and 

provided background information on the purpose for which each study would be required. Part 

158, subpart B contains an extensive description of the need for and use of submitted studies (40 

CFR 158.130). Additionally, as explained in the preamble to the antimicrobials proposed rule, EPA 

relied on the proposed and final rules for establishing data requirements for conventional pesticides. 

As stated in the proposed rule for antimicrobials, the rationales for requiring and/or revising 

particular data requirements were in those rules. 

With few exceptions, these rationales are also applicable to antimicrobial pesticide chemicals, 

and as such have not been repeated in today’s proposed rule. Today’s proposal discusses in 

detail only those revisions that are singularly applicable to antimicrobial pesticides, including 

antifoulants and wood preservatives.” (73 FR 59384) 
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Master Responses: Most Common Comments Page 8 

Examples of studies applicable to antimicrobial pesticides and which a description of the need for 

the requirement was included in the preamble to the proposed rule for antimicrobials include the 

need for: 

 the 90-day dermal and 90-day inhalation studies for a heating, ventilation, air conditioning, 

and refrigeration uses ( 73 FR 59395) 

 a food migration study (73 FR 59404), and 

 environmental fate studies to support a down-the-drain assessment (73 FR59408). 

One commenter presented numerous examples of what the commenter labeled EPA’s “ad hoc risk 

assessment processes.” An examination of those examples shows that the commenter is concerned 

with what it labels as “inconsistency in EPA’s current practice” as to when a dietary risk assessment 

is needed for antimicrobial pesticides. The commenter argued that this alleged inconsistent practice 

shows the “need for stable, transparent guidance on risk assessment to support data requirements 

regulation.” EPA does not believe that it has been inconsistent in its risk assessments. 

Furthermore, EPA does not believe that such “inconsistencies,” if they exist, would mean that 

affected parties could not comment meaningfully on the proposed data requirements. Ultimately, 

the issue with the data requirements rule is whether EPA has asked for data needed for determining 

whether pesticides meet the relevant statutory safety standards. The fact that EPA might have been 

inconsistent in the past in its determinations with regard to the safety standard or how it went about 

assessing whether a pesticide met the safety standards (e.g., did EPA need to do a dietary risk 

assessment), does not handicap an affected party in determining whether a proposed data 

requirement is consistent with the statutory safety standards. To reiterate, the relevant question is 

not whether EPA has guidance on when dietary risk assessment is needed but whether the proposed 

data requirements pertaining to dietary risk would require information that are appropriate to EPA’s 

determination under the applicable statutory safety standards. To the extent, the commenter is 

concerned with any particular Agency decision regarding when a dietary risk assessment is needed 

for antimicrobials, EPA encourages the commenter to raise that concern directly with the Agency in 

the context of the specific matter causing the commenter concern. 

This commenter later filed additional comments that further developed the argument that 

reproposal is necessary because EPA allegedly has not clearly defined when a dietary risk assessment 

is needed. The commenter wrote: “[T]he Proposal does not clearly articulate any standards for 

determining what uses triggers a food analysis. It has become apparent since the Proposal was 

issued that the Agency will interpret this regulation to vastly increase the number of antimicrobials 

regulated as food use.” (ACC/CSPA letter in the docket at http://www.regulations.gov; document 

EPA-HQ-OPP.2008-0110-0107, p. 2). Further, the commenter then asserts that “EPA’s economic 

analysis does not even attempt to address the increase in the burden on registrants and applicants 

that this [alleged] expansion of the need for ‘food contact’ approvals will cause.” (Id.) These 

additional comments suggest that this commenter is concerned with EPA decisions issued prior to 

today’s final rule (and, in most cases, prior to issuance of the proposed rule) and fears how the final 

rule may be interpreted in the future. However, it is difficult to determine from these comments 

whether the commenter is claiming that this alleged “expansion” of food use antimicrobials is 

effected by any particular language in the proposed rule. To the extent the commenter is arguing 

that the expansion is caused by EPA’s application of the FFDCA section 408 standard to all 

antimicrobial food uses under FIFRA section 2(bb) (whether the use requires clearance under 

FFDCA section 408 or 409), the commenter, as explained in Unit XVI.A, misunderstands EPA’s 

authority under FIFRA and EPA’s practice as to antimicrobials since the passage of ARTCA. In 
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Master Responses: Most Common Comments Page 9 

another place in its recently-filed comments, the commenter argues that the use of the categories of 

“direct food use” and “indirect food use” “create the potential for almost all antimicrobials to be 

considered as possibly leaving residues on food.” (ACC attachment 1 in the docket at 

http://www.regulations.gov; document EPA-HQ-OPP.2008-0110-0108, p. 4) However, EPA 

adopted the categories of direct and indirect food use as a way to tier data requirements for residue 

chemistry and toxicology, not to expand the category of food uses. For a use to qualify as an 

indirect food use it must result in residues in food and EPA clearly has the authority under FIFRA 

and the FFDCA to request data on and assess the risk of pesticide residues in food. Despite the 

commenter’s claims to the contrary, it is not EPA’s intent to use this data requirements rule as a 

basis for expanding what antimicrobial uses qualify as direct or indirect food uses. Accordingly, 

EPA’s economic analysis has accurately captured the costs imposed by this rule. 

For the third argument: EPA disagrees with this comment: EPA can require submission of a 

particular study even if no guideline has been provided. The types of data needed for EPA to make a 

registration decision are clearly identified in its proposed rule. Testing laboratories routinely conduct 

these studies, as evidenced by the test cost data which was available for use in both EPA’s and the 

commenter’s economic analyses. Final guidelines are available for the majority of tests required, and 

draft guidelines provide information for the applicant to consider. Since there was an understanding 

of the types of data EPA proposed to require, the commenter had sufficient information to 

comment on whether EPA had asked for the data needed for determining whether pesticides meet 

the relevant statutory safety standards. 

It is important to keep in mind that, as noted in the proposed rule, new part 158, subpart W is 

“retaining most current data requirements for antimicrobials. . . and revises other existing data 

requirements.” (73 FR 59383) The guidelines that the commenter asserts as not providing 

sufficient information to permit meaningful comment pertain, for the most part, to these existing 

data requirements that are not being modified by this rulemaking. As to the “new” data 

requirements that are imposed by this rule, the commenter has not specifically explained why 

interested parties cannot meaningfully comment on these requirements or why a final guideline is 

needed to provide meaningful comments on these studies. In fact, as to these “new” studies, 

OPPTS guidelines are available for all except the nature of the residue on surfaces study. For that 

study, due to the many site- and chemical specific variations, a protocol review is required. 

This commenter later filed additional comments stating that “FIFRA requires EPA to issue test 

guidelines.” (ACC/CSPA letter in the docket at http://www.regulations.gov; document EPA-HQOPP.2008-0110-0107, p. 4). In accordance with FIFRA section 3(c)(2)(A), EPA has promulgated 

data requirement rules “specifying the kinds of information which will be required to support the 

registration of a pesticide.” EPA is not required to issue guidance explaining how studies that are 

addressing the data required under the regulations should be performed. 

Comment 3: Several commenters focused on the testnotes to the data requirements tables, and 

claimed that the proposed rule “leaves too many standards and decisions to the sole discretion of 
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Master Responses: Most Common Comments Page 10 

EPA, creating uncertainty and, inevitability, inconsistency in regulatory decision making.” Too many 

determinations, the commenter asserted, are at “EPA’s discretion” because the proposal is vague 

without clear-cut criteria. Additionally, they argued that there are too many places in the testnotes 

where consultation with the Agency is required or the phrase “as determined by the Agency” is used. 

Too many determinations are at “EPA’s discretion” because the proposal is vague without clear-cut 

criteria. (One commenter listed 37 instances in which the proposal allegedly substituted a mandatory 

consultation process for regulatory criteria; comment in the docket at http://www.regulations.gov; 

document EPA-HQ-OPP-2008-0110-0088.12.) According to the commenters, EPA should eliminate 

most of the consultation requirements and instead, repropose the rule providing a clear set of 

requirements. 

Response 3: EPA disagrees with this comment. Test notes often contain qualitative or quantitative 

measures for use in determining whether a study is triggered or not, most frequently this occurs 

when there is an initial study that relates to whether subsequent testing would be needed or not. 

Not all triggers are easily reduceable to quantitative measures and EPA believes that qualitative 

descriptors such as “expected to enter the environment in significant concentrations,” “if repeated 

dermal exposure is likely to occur under conditions of use,” and “the use of the pesticide is likely to 

result in repeated human exposure over a limited portion of the human lifespan” provide 

meaningful criteria for determining when a study is triggered. 

EPA has carefully reviewed the criteria for decision-making in the 37 examples from the testnotes 

cited by the commenter. EPA believes that the testnotes contain adequate criteria for decisionmaking and has only identified a few minor clarifying changes that are needed (see below). In no 

instance are decisions on data requirements left to the “sole discretion” of EPA: Decisions are 

based on the criteria specified in the regulations. The commenters have fundamentally 

misunderstood the purpose and effect of EPA’s inclusion of recommendations for consultation in 

the testnotes. Recommendations for consultation are just that, recommendations, and they do not 

give EPA sole discretion in decision-making on the data requirements. As discussed below, such 

consultations are not mandatory, but are optional for the registrant or applicant. 

In numerous places the test notes contain language stating that the criteria would be applied “as 

determined by the Agency.” Commenters have misinterpreted this as giving EPA the authority to 

make decisions on factors other than the regulatory criteria included or in its “sole discretion.” This 

was not EPA’s intent and, accordingly, EPA has removed all “as determined by the Agency” from 

all testnotes for the antimicrobials final rule so there can be no chance of a misunderstanding of how 

the criteria are to be applied. 

Commenters also asserted that EPA’s alleged mandatory consultation requirements rendered the 

testnotes meaningless as EPA would determine whether studies were required in private based on 

unspecified factors. EPA disagrees. The commenters have misread the proposed rule language and 

misunderstood the purpose for consultation. The consultation references were not intended to 

impose a mandatory consultation requirement. To the contrary, the references to consultation were 

an attempt by EPA to signal its willingness to meet with applicants to adapt studies, if necessary, to 

the specifics of individual antimicrobials. 
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Consultation is a longstanding, commonly used and valuable process in EPA’s Pesticide Program. 

Applicants often meet with OPP staff on a pre-submission basis to review and discuss the adequacy 

of the available data. OPP believes that such meetings are beneficial to both EPA and the 

applicants. In practice, such meetings are very often sought by registrants and applicants. EPA 

recognizes that these studies are complex and costly, and EPA has found prior discussions between 

EPA and an applicant to be beneficial, resulting in data that better meets EPA’s needs and saves 

resources for both EPA and the applicant. Depending upon what is intended to be addressed, such 

meetings do not necessarily need to be held in person, but can be frequently accomplished via teleconferencing. 

EPA did not intend its references to consultations in the test notes to impose mandatory 

consultation requirements; neither did EPA intend the consultation references as a means of 

establishing a different standard for determining if a study is triggered. EPA has carefully reviewed 

all test notes in the antimicrobials final rule and removed all references to consultation from all 

testnotes for the antimicrobials rule so there can be no chance of misunderstanding the voluntary 

nature of consultation. 

This also applies to protocol review. In the proposed rule, for certain studies, the following 

language was included in the testnote, “Protocols must be approved by the Agency prior to the 

initiation of the study. Details for developing protocols are available from the Agency.” During 

complex protocol development, discussions between EPA and an applicant to share details of how 

to generate data that meets EPA’s needs have often provided a valuable exchange of information 

before a protocol is submitted. Similarly, such consultation is not required, and the applicant may 

submit a protocol for review without discussing with EPA. EPA has removed “Details for 

developing protocols are available from the Agency.” from all testnotes for the final rule. 

EPA has carefully reviewed each of the 37 testnotes cited by one commenter and has identified 

several which included information that was intended as factors to be considered rather than as a 

regulatory standard. Similarly, the language was reviewed to identify consultations. EPA’s analysis of 

these 37 testnotes and resultant changes are in the table below. 

Appendix K (Document 88.12 Docket EPA-HQ-OPP-2008-0110) EPA’s Response 

Proposed Rule 

Section 

Text of the Proposed 

Regulation (emphasis 

added by ACC)

The Proposed 

Regulations Are 

Vague for the 

Following Reasons 

158.2200(c) Antimicrobial use 

patterns. “An applicant 

unsure of the correct use 

pattern(s) for his 

product should consult 

the Agency.” 

The Agency has not 

adequately stated what 

the correct use 

patterns for each 

product is, and also 

requires private 

consultation with the 

Agency. 

158.2201(a) contains the 

listing of the 

antimicrobial use 

patterns. 

Additionally, EPA is 

providing information on 

a new webpage “The 

Antimicrobial Pesticide 

Use Site Index” 
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Master Responses: Most Common Comments Page 12 

Consultation is voluntary, 

so this language has been 

removed. 

158.2220(a)(1) Product performance: 

Product performance 

requirement for all 

antimicrobial 

pesticides. “Each 

applicant must ensure 

through testing that his 

product is efficacious 

when used in 

accordance with label 

directions and 

commonly accepted pest 

control practices. The 

Agency may require, on 

a case-by-case basis, 

submission of product 

performance data for 

any pesticide product 

registered or proposed 

for registration.” 

The Agency has not 

adequately stated the 

criteria for 

determining whether 

product performance 

data for pesticide 

products registered or 

proposed for 

registration must be 

submitted. Such 

information requires 

private consultation 

with the Agency. 

Under 40 CFR 158.75 

EPA has the authority to 

require submission of 

data for any pesticide 

product registered or 

proposed for registration. 

This regulatory text 

merely clarifies that 

authority, by saying that 

EPA may require product 

performance data. 

158.2230(b) Toxicology data: Uses. 

“The applicant for 

registration must first 

determine whether the 

use is a high human 

exposure use or a low 

human exposure use. If 

an applicant is not sure 

if a specific use is a high 

human exposure or a 

low human exposure 

use, the applicant 

should consult the 

Agency.” 

The Agency has not 

adequately stated the 

criteria to determine 

whether a specific use 

is a high human 

exposure or a low 

human exposure, and 

requires private 

consultation with the 

Agency. 

As a result of comments 

received and for the 

reasons discussed in the 

preamble, EPA is no 

longer using the terms 

“high human exposure” 

and “low human 

exposure” as table 

headers as proposed for 

the Antimicrobial 

Toxicology Data 

Requirements Table 

[59433]. The regulatory 

text now reads: The 

applicant for registration 

must first determine 

whether the use is likely 

to result in pesticide 

residues in food or water 

and therefore should 

consult the “Food Use” 

columns of the table in 

paragraph (g) of this 
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Master Responses: Most Common Comments Page 13 

section. Generally, if the 

residues result from an 

application to a surface or 

incorporated into a 

material that may contact 

food or feed, and residues 

may be expected to 

transfer to such food or 

feed, then the “Indirect 

Food Uses” columns 

should be consulted. 

158.2230(e)(9) Toxicology data: Test 

notes. “The 90-day 

study is required in the 

rodent for hazard 

characterization 

(possibly endpoint 

selection) and dosesetting for the 

chronic/carcinogenicity 

study. . . . The applicant 

is also encouraged to 

consult with the Agency 

on the results of the 90-

day mouse study prior to 

conducting the 

carcinogenicity study.” 

The Agency has not 

adequately stated the 

criteria to determine 

whether the 

carcinogenicity study 

is necessary, and 

requires private 

consultation with the 

Agency. 

The commenter has 

misread the testnote. It 

does not set criteria for 

when a cancer study is 

required. Rather, it 

merely describes the 

purposes for the 90-day 

rodent study and advises 

consultation with EPA on 

the results of the 90-day 

study because it may 

impact design of the 

chronic/carcinogenicity 

study. EPA believes that 

a discussion on the dosesetting for the 

chronic/carcinogenicity 

study would provide 

value to both EPA and 

the applicant to assure 

that this complex and 

expensive study provides 

the needed information 

for a registration 

decision. However, the 

applicant may conduct 

and then submit the 

chronic/carcinogenicity 

study without 

consultation. Since 

consultation is voluntary, 

the consultation language 

has been removed. 

158.2230(e)(10) Toxicology data: Test 

notes. “A 1-year nonThe Agency has not adequately stated the 

Since the 1-year nonrodent (the dog) chronic 
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Master Responses: Most Common Comments Page 14 

rodent study (i.e., 1-year 

dog study) may be 

required if the Agency 

finds that a pesticide 

chemical is highly 

bioaccumulating and is 

eliminated slowly. Thus 

it does not achieve 

steady state or sufficient 

tissue concentrations to 

elicit an effect during a 

90-day study.” 

criteria to determine if 

a pesticide chemical is 

highly 

bioaccumulating and 

eliminated slowly. 

Any guidelines 

published on this 

matter would 

effectively surpass the 

notice and comment 

rulemaking 

procedures. 

study was not proposed 

(the study is no longer 

required), testnote 10 is 

attached to the 90-day 

non-rodent study as a 

reminder that where 

submitted data indicate 

that a pesticide may be 

retained in the body for 

longer than 90 days, 

metabolism and 

pharmacokinetic studies 

may be required to 

determine if a longer dog 

study will be required. 

The rationale for not 

requiring the 1-year dog 

study is described in the 

preamble to the 

conventional final rule 

and the same 

circumstances are 

described in testnote 36 

to the conventionals 

toxicology table. 

Under 40 CFR 158.75 

EPA has the authority to 

require submission of 

data for any pesticide 

product registered or 

proposed for registration. 

This regulatory text 

merely clarifies that 

authority, by saying that 

EPA may require a 1-

year non-rodent study 

based on consideration of 

bioaccumulation and 

slow elimination. The 

first sentence of testnote 

10 now reads: “A 1-year 

non-rodent study (i.e., 1-

year dog study) may be 

required if the Agency 

finds that a pesticide 
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Master Responses: Most Common Comments Page 15 

chemical is highly 

bioaccumulative and 

slowly eliminated.” 

158.2230(e)(10) Toxicology data: Test 

notes. “EPA may 

require the appropriate 

tier II metabolism and 

pharmacokinetic studies

to evaluate more 

precisely bioavailability, 

half life, and steady state 

to determine if a longer 

duration dog toxicity 

study is needed.” 

The Agency has not 

adequately stated the 

criteria to determine if 

the Agency will 

require tier II 

metabolism and 

pharmacokinetic 

studies. 

Since the 1-year nonrodent (the dog) chronic 

study was not proposed 

(the study is no longer 

required), testnote 10 is 

attached to the 90-day 

non-rodent study as a 

reminder that where 

submitted data indicate 

that a pesticide may be 

retained in the body for 

longer than 90 days, 

metabolism and 

pharmacokinetic studies 

may be required to 

determine if a longer dog 

study will be required. 

The rationale for not 

requiring the 1-year dog 

study is described in the 

preamble to the 

conventional final rule 

and the same 

circumstances are 

described in testnote 36 

to the conventionals 

toxicology table. 

Under 40 CFR 158.75 

EPA has the authority to 

require submission of 

data for any pesticide 

product registered or 

proposed for registration. 

This regulatory text 

merely clarifies that 

authority, by saying that 

EPA may require the 

appropriate metabolism 

and pharmacokinetic 

studies if there are 

additional questions to be 

answered. Thus, the 
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Master Responses: Most Common Comments Page 16 

second sentence of 

testnote 10 now reads: 

“EPA may also require 

the appropriate 

metabolism and 

pharmacokinetic studies 

to evaluate more 

precisely bioavailability, 

half life, and steady state 

to determine if a longer 

duration dog toxicity 

study is needed.” 

158.2230(e)(11) Toxicology data: Test 

notes. “For low human 

exposure uses, data are 

required if any of the 

following criteria are 

met: (i) the use of the 

pesticide is likely to 

result in repeated human 

exposure over a limited 

portion of the human 

lifespan, as determined 

by the Agency . . .” 

The Agency has not 

adequately stated the 

criteria used to 

determine if the use of 

the pesticide is likely 

to result in repeated 

human exposure over 

a limited portion of the 

human lifespan. 

As a result of comments 

received, EPA removed 

proposed testnote 11. 

158.2230(e)(12) Toxicology data: Test 

notes. “Data are 

required if the intended 

use of the antimicrobial 

pesticide product is 

expected to result in 

human exposure to the 

product, and the 

following three 

conditions are met . . . 

(ii) Expected human 

exposure is not 

purposeful, and is over a 

limited portion of the 

human lifespan;

however, as determined 

by EPA, the exposure is 

significant in terms of 

the frequency of 

exposure, magnitude of 

exposure, or the 

duration of exposure.” 

The Agency has not 

adequately stated the 

criteria used to 

determine if the 

exposure is significant 

in terms of the 

frequency of exposure, 

magnitude of 

exposure, or the 

duration of the 

exposure. 

As a result of comments 

received, EPA has 

revised testnote 12. The 

portion of testnote 12 

applicable to proposed 

12(ii) now reads as 

follows: Data are 

required if the intended 

use of the antimicrobial 

pesticide product is 

expected to result in 

repeated, dermal human 

exposure to the 

product..... EPA 

believes that “repeated, 

dermal human exposure 

to the product” is an 

adequate criterion for 

determining if the data 

are required. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Master Responses: Most Common Comments Page 17 

158.2230(e)(17) Toxicology data: Test 

notes. “Based on 

estimates of the 

magnitude and duration 

of human exposure, 

studies of shorter 

duration, e.g., 21- or 28-

days, may be sufficient 

to satisfy this 

requirement. Applicants 

for registration may 

consult with the Agency 

to determine whether 

studies of shorter 

duration would meet this 

requirement.”

The Agency has not 

adequately stated the 

criteria used to 

determine whether 

studies of shorter 

duration would meet 

the requirement. The 

Agency also requires 

private consultation 

with the Agency. 

Testnote 17 to the 

requirement for a 90-day 

inhalation study in the rat 

is meant as a cost-saving 

measure to applicants 

who wish to present the 

particulars of their 

product’s inhalation 

exposure to EPA, as part 

of a rationale for 

conducting a shorter 

study. Since inhalation 

studies are complex and 

expensive, EPA believes 

that a discussion on the 

appropriate length of 

study offers the 

applicants an opportunity 

for cost-saving. For 

example, a paint product 

that is labeled for a 

residential scenario 

would have a 

shorter/different exposure 

duration from that of a 

paint product that is 

labeled for commercial 

uses. 

To clarify the following 

language has been added 

to the testnote: “The 

prime consideration in 

determining the 

appropriateness of a 

shorter duration study is 

the likely period of time 

for which humans will be 

exposed.” In addition, 

since consultation is 

voluntary, the 

consultation language has 

been removed. 

158.2230(e)(20) Toxicology data: Test 

notes. “For low 

exposure, data are 

required if either of the 

The Agency has not 

adequately stated the 

criteria used to 

determine if the use of 

The phrase “as 

determined by the 

Agency” has been 

removed from the 
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Master Responses: Most Common Comments Page 18 

following criteria are 

met . . . (i) The use of 

the pesticide is likely to 

result in repeated human 

exposure over a limited 

portion of the human 

lifespan, as determined 

by the Agency.”

the pesticide is likely 

to result in repeated 

human exposure over 

a limited portion of the 

human lifespan. 

testnote. EPA believes 

that “likely to result in 

repeated human exposure 

over a limited portion of 

the human lifespan” is an 

adequate criterion for 

determining if the data 

are required. 

158.2230(e)(21) Toxicology data: Test 

notes. “For low 

exposure, data are 

required if any of the 

following criteria, as 

determined by the 

Agency are met . . .” 

The Agency has not 

adequately stated how 

it will assess the 

criteria set out in this 

subsection. 

The phrase “as 

determined by the 

Agency” has been 

removed from the 

testnote. The criteria 

speak for themselves. 

158.2230(e)(22) Toxicology data: Test 

notes. “If the 

requirements for 

carcinogenicity study in 

any species is modified 

or waived for any 

reason, then a 

subchronic 90-day oral 

study in the same 

species may be 

required.” 

The Agency has not 

adequately stated the 

criteria used to 

determine whether a 

subchronic 90-day oral 

study in the same 

species may be 

required. 

Under 40 CFR 158.75 

EPA has the authority to 

require submission of 

data for any pesticide 

product registered or 

proposed for registration. 

This regulatory text 

merely clarifies that 

authority, by saying that 

EPA may require a 

subchronic 90-day oral 

study dependent on the 

carcinogenicity study, if 

there are additional 

questions to be answered. 

158.2230(e)(25) Toxicology data: Test 

notes. “Additional 

testing by other routes 

of exposure may be 

required if the pesticide 

is determined to be a 

prenatal developmental 

toxicant after oral 

dosing.” 

The Agency has not 

adequately stated 

which other routes of 

exposure may be 

required or what 

criteria is used to 

determine if the routes 

of exposure are 

required, apart from 

the fact that the 

pesticide is determined 

to be a prenatal 

developmental 

toxicant after oral 

dosing. 

Under 40 CFR 158.75 

EPA has the authority to 

require submission of 

data for any pesticide 

product registered or 

proposed for registration. 

This regulatory text 

merely clarifies that 

authority, by saying that 

EPA may require 

additional prenatal 

developmental testing by 

a different route of 

exposure dependent on 

the results of the oral 

prenatal developmental 
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Master Responses: Most Common Comments Page 19 

study. 

158.2230(e)(26) Toxicology data: Test 

notes. “The 

developmental toxicity 

study in rodents may be 

combined with the twogeneration reproduction 

study in rodents by 

using a second mating 

of the parental animals 

in either generation. 

Protocols must be 

approved by the Agency 

prior to the initiation of 

the study. Details for 

developing protocols 

are available from the 

Agency.”

The Agency has not 

adequately stated the 

requirements of the 

protocol, and the 

“details for developing 

the protocol” should 

be published as notice 

and comment 

rulemaking. These 

required private 

negotiations are a 

procedure for the 

development of later 

tests. 

EPA believes that the 

concept of a protocol as a 

basic description of a 

standard of conduct for 

the study is wellunderstood. EPA has 

removed the reference to 

the availability of 

guidance from EPA on 

protocol development 

because commenters 

have misunderstood this 

reference as imposing a 

requirement. 

Consultation with EPA 

prior to protocol review 

is not required. 

158.2230(e)(28) Toxicology data: Test 

notes. “[Alternative 

proposed testing 

protocols] must be 

approved by the Agency 

prior to the initiation of 

the study. Details for 

developing protocols 

are available from the 

Agency.”

The Agency has not 

adequately stated the 

criteria for developing 

alternative proposed 

testing protocols. 

These required private 

negotiations are a 

procedure for the 

development of later 

tests. 

EPA believes that the 

concept of a protocol as a 

basic description of a 

standard of conduct for 

the study is wellunderstood. EPA has 

removed the reference to 

the availability of 

guidance from EPA on 

protocol development 

because commenters 

have misunderstood this 

reference as imposing a 

requirement. 

Consultation with EPA 

prior to protocol review 

is not required. 

158.2230(e)(32) Toxicology data: Test 

notes. “Testing in 

Salmonella and E. coli

may be acceptable, if the 

testing can be conducted 

at high enough levels, as 

determined by the 

Agency. If the testing 

cannot be conducted at 

high enough levels, then 

the applicant must 

The Agency has not 

adequately stated the 

criteria used to 

determine if 

Salmonella and E. coli 

are acceptable. These 

required private 

negotiations are a 

procedure for the 

development of later 

tests. 

This testnote has been 

revised. Due to the 

nature of antimicrobials, 

use of bacterial strains in 

mutagenicity testing can 

be problematic because 

the antimicrobial may kill 

the bacterial strain and 

thus defeat the purpose of 

the test. For this reason, 

for antimicrobials, EPA 
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Master Responses: Most Common Comments Page 20 

consult with the Agency 

to determine other 

needed mutagenicity 

testing.” 

prefers that mutagencity 

testing be done with a 

mammalian cell assay. 

Nonetheless, to the extent 

that mutagenicity testing 

has already been 

successfully completed 

using bacterial strains, 

EPA does not want to 

require needless retesting. 

The testnote is intended 

to convey this message. 

EPA has revised it to 

clarify this, as follows: If 

testing with bacterial 

strains has not been 

conducted, then testing 

using a mammalian cell 

assay such as the mouse 

lymphoma TK +/- assay 

is preferred. If reverse 

mutation assay testing 

with bacterial strains has 

already been conducted, 

and the testing was 

conducted at levels that 

did not cause toxicity to 

the bacterial strains 

tested, then the applicant 

may submit the study to 

fulfill this data 

requirement. 

158.2230(e)(35) Toxicology data: Test 

notes. “For low 

exposure, these data are 

required when chronic 

or carcinogenicity 

studies are also required. 

These data may be 

required if significant 

adverse effects are seen 

in available toxicology 

studies and these effects 

can be further elucidated 

by metabolism studies.” 

The Agency has not 

adequately stated 

when the data is 

required or not. 

As a result of comments 

received, EPA is no 

longer using the term 

“low human exposure” as 

table headers as proposed 

for the Antimicrobial 

Toxicology Data 

Requirements Table 

[59433]. This testnote 

has been revised to read 

as follows: Data are 

required when chronic or 

carcinogenicity studies 

are also required. 
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Master Responses: Most Common Comments Page 21 

158.2230(e)(36) Toxicology data: Test 

notes. “These data may 

be required if the 

product’s use will result 

in exposure to domestic 

animals through, but not 

limited to, direct 

application.” 

The Agency has not 

adequately stated the 

criteria used to 

determine when the 

data is required or not. 

This regulatory text 

speaks for itself : If a 

product is labeled for 

external use on domestic 

animals such as cats, 

dogs, cattle, pigs, and 

horses, then EPA may 

require a companion 

animal study if there are 

additional questions to be 

answered. For clarity the 

testnote now reads: “Data 

is required if the product 

label directs that it be 

applied to domestic 

animals, such as cats, 

dogs, cattle, pigs, and 

horses.” 

158.2240(a)(3) Nontarget organisms: 

General. “If the Agency 

determines that the 

transformation products 

of the parent compound 

are more toxic, 

persistent, 

bioaccumulative, or 

have been shown to 

cause adverse effects in 

mammalian or aquatic 

reproductive studies, 

then data on those 

transformation products 

are required to support 

registration.” 

The Agency has not 

adequately stated how 

the Agency will 

determine if the 

transformation 

products of the parent 

compound are more 

toxic, persistent, 

bioaccumulative, or 

have been shown to 

cause adverse effects 

in mammalian or 

aquatic reproductive 

studies. 

In response to comments, 

and as part of reevaluating these criteria, 

EPA determined to 

clarify and revise the 

criteria for testing of 

transformation products 

by providing a single set 

criteria for all 

antimicrobials, instead of 

breaking down the 

criteria by use patterns. 

The criteria now read as 

follows: 

“Data on 

transformation/degradatio

n products or leachate 

residues of the parent 

compound are also 

required to support 

registration, if the 

transformation/degradatio

n/leachate products meet 

one of the following 

criteria: 

(i) is more toxic, 

persistent, or 
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Master Responses: Most Common Comments Page 22 

bioaccumulative than the 

parent, 

(ii) have been shown to 

cause adverse effects in 

mammalian or aquatic 

reproductive studies, or 

(iii) the moiety of 

concern (i.e., functional 

group in the parent 

chemical molecule that 

imparts adverse effects) 

remains intact.” 

The proposed criteria 

speak for themselves. 

158.2240(a)(4) Nontarget organisms: 

General. “For wood 

preservatives, the 

Agency may require 

data on both the parent 

compound, which is 

incorporated into wood, 

and on 

transformation/degradati

on products which occur 

as dislodgeable residues 

(such as hand contact 

with treated wood) or 

leachate residues (such 

as from soil or water 

contact with treated 

wood). 

The Agency has not 

adequately stated on 

what grounds the 

Agency will require 

data on the both the 

parent compound and 

the on 

transformation/degrad

ation products for 

wood preservatives. 

Proposed 158.2240(a)(4) 

was combined with 

proposed 158.2240(a)(3) 

to derive final 

158.2240(a)(3). 

158.2240(f)(10) Nontarget organisms: 

Test notes. “For low 

environmental 

exposures, data are 

required if pesticide 

residues from the parent 

compound or 

transformation products 

are likely to enter 

freshwater or 

estuarine/marine 

environments, as 

determined by the 

Agency.”

The Agency has not 

adequately stated the 

factors it will use to 

determine whether for 

low environmental 

exposures, pesticide 

residues from the 

parent compound or 

transformation 

products are likely to 

enter freshwater or 

estuarine/marine 

environments. In 

addition, the Agency 

not adequately stated 

Proposed testnote 10 

contained two triggers: 

One for low 

environmental exposures, 

and one for wood 

preservatives. Based on 

comments received, the 

table designators for 

these studies have been 

revised from “CR” to 

“R”. Since the studies 

are now “R”, the triggers 

are no longer needed. 

Therefore the triggers, 

the first two sentences of 
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Master Responses: Most Common Comments Page 23 

the factors it will use 

to determine whether, 

for food preservatives, 

pesticide residues 

from the parent 

compound, 

transformation 

products, and/or 

leachates from 

preservative treated 

wood are likely to 

enter freshwater or 

estuarine/marine 

environments. 

the testnote have been 

removed from testnote 

10. 

158.2240(f)(15) Nontarget organisms: 

Test notes. “Protocols 

must be approved by the 

Agency prior to the 

initiation of the study. 

Details for developing 

protocols are available 

from the Agency.” 

Although the Agency 

states that the details 

for developing 

protocols are available 

from the Agency, the 

Agency has not 

adequately explained 

what the protocols 

entail. These required 

private negotiations 

are a procedure for the 

development of later 

tests. 

EPA believes that the 

concept of a protocol as a 

basic description of a 

standard of conduct for 

the study is wellunderstood. EPA has 

removed the reference to 

the availability of 

guidance from EPA on 

protocol development 

because commenters 

have misunderstood this 

reference as imposing a 

requirement. 

Consultation with EPA 

prior to protocol review 

is not required. 

158.2240(f)(21) Nontarget organisms: 

Test notes. “If beehives 

are constructed of 

treated wood a study 

similar to “Honey Bee 

Toxicity of Residues on 

Foliage” is required 

using treated wood 

instead of the foliage. 

Protocols must be 

approved by the Agency 

prior to the initiation of 

the study. Details for 

developing protocols 

are available from the 

Although the Agency 

states that the details 

for developing 

protocols are available 

from the Agency, the 

Agency has not 

adequately explained 

what the protocols 

entail. These required 

private negotiations 

are a procedure for the 

development of later 

tests. 

EPA believes that the 

concept of a protocol as a 

basic description of a 

standard of conduct for 

the study is wellunderstood. EPA has 

removed the reference to 

the availability of 

guidance from EPA on 

protocol development 

because commenters 

have misunderstood this 

reference as imposing a 

requirement. 

Consultation with EPA 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Master Responses: Most Common Comments Page 24 

Agency.” prior to protocol review 

is not required. 

158.2260(a)(1) Applicator exposure: 

General. “If EPA 

determines that 

industrial standards, 

such as the workplace 

standards set by the 

Occupational safety and 

Health Administration, 

provide adequate 

protection for a 

particular pesticide or a 

particular use pattern, 

applicator exposure data 

may not be required for 

that pesticide or the use 

pattern. Applicants 

should consult with the 

Agency on appropriate 

testing before the 

initiation of the studies.” 

The Agency has not 

adequately stated what 

the “appropriate 

testing” entails, and 

instead advises the 

applicant to consult 

with the Agency. 

These required private 

negotiations are a 

procedure for the 

development of later 

tests. 

Consultation is voluntary, 

so the consultation 

language has been 

removed. 

In addressing comment 

90.4, EPA realized that 

the proposed language is 

misplaced and also needs 

some textual 

modification. An OSHA 

PEL or ACGIH standard 

is part of hazard 

evaluation, not exposure. 

If the PEL or TLV is 

determined to be 

adequate to fulfill EPA’s 

selection of a toxicity 

endpoint, then the types 

and number of toxicity 

studies that may be 

required is impacted, not 

the need for exposure 

data. Therefore, EPA 

removed the language 

originally proposed for 

158.2260(a)(1) and 

158.2270(a)(1) 

concerning use of OSHA 

standards. With 

modifications, the 

language will appear in 

the Toxicity Table, 

§158.2230(e), as follows: 

“If industrial standards, 

such as the workplace 

standards set by the 

Occupational Safety and 

Health Administration, 

provide adequate 

protection for a particular 

pesticide or a particular 

use pattern, additional 

toxicity data may not be 

required for that pesticide 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Master Responses: Most Common Comments Page 25 

or the use pattern. 

Applicants should consult 

with the Agency on 

appropriate testing before 

the initiation of studies.” 

158.2260(a)(2) Applicator exposure: 

General. “The Agency 

may accept surrogate 

exposure data 

estimations from other 

sources to satisfy 

applicator exposure data 

requirements . . . The 

Agency will consider 

using such surrogate 

data for evaluating 

human exposure on a 

case-by-case basis.”

The Agency has not 

adequately explained 

the criteria used to 

determine if such 

surrogate data will be 

used or not. These 

required private 

negotiations are a 

procedure for the 

development of later 

tests. 

This regulatory text has 

been amended to provide 

the following clarifying 

information: The Agency 

may accept surrogate 

exposure data estimations 

and/or modeling 

estimations from other 

sources to satisfy 

exposure data 

requirements if the data 

meet the basic quality 

assurance, quality 

control, good laboratory 

practice, and other 

scientific requirements 

set by this rule. In order 

to be acceptable, the 

Agency must find that the 

surrogate exposure data 

estimations have 

adequate information to 

address the applicable 

exposure data 

requirements and contain 

enough adequate 

monitoring events of 

acceptable quality to 

reflect the specific use 

prescribed on the label 

and the activity of 

concern, including 

formulation type, 

application methods and 

rates, type of activity, and 

other pertinent 

information. 

158.2260(e)(4) Applicator exposure: 

Test notes. “The 

following test notes 

apply to the data 

The Agency has not 

adequately stated the 

data requirements for 

metal working fluids, 

This testnote was 

intended to indicate that 

these data may not be 

needed for antimicrobials 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Master Responses: Most Common Comments Page 26 

requirements [for 

applicator exposure] . . . 

For metal working fluids 

(MWFs), the Agency 

can provide written 

guidance concerning 

exposure, toxicity, and 

other data requirements 

for “open” and “closed” 

MWF systems.” 

and instead says that it 

will publish guidelines 

outside of the notice 

and comment 

rulemaking 

procedures. 

applied via a closed 

system. Based on 

comments requesting 

greater clarity in this 

testnote, testnote 4 now 

reads as follows: 

EPA will consider 

waiving this data 

requirement for 

antimicrobials applied via 

closed loading systems if 

the antimicrobial has a 

low vapor pressure. 

158.2270(a)(2) Post-application 

exposure: General. “If 

EPA determines that 

industrial standards, 

such as the workplace 

standards set by the 

Occupational Safety and 

Health Administration, 

provide adequate 

protection for a 

particular pesticide or a 

particular use pattern, 

post-application 

exposure data may not 

be required for that 

pesticide or the use 

pattern. Applicants 

should consult with the 

Agency on appropriate 

testing before the 

initiation of the studies.” 

The Agency has not 

adequately stated the 

criteria used to 

determine whether 

post-application 

exposure data is 

required or not. These 

required private 

negotiations are a 

procedure for the 

development of later 

tests. 

Consultation is voluntary, 

so the consultation 

language has been 

removed. 

In addressing comment 

90.4, EPA realized that 

the proposed language is 

misplaced and also needs 

some textual 

modification. An OSHA 

PEL or ACGIH standard 

is part of hazard 

evaluation, not exposure. 

If the PEL or TLV is 

determined to be 

adequate to fulfill EPA’s 

selection of a toxicity 

endpoint, then the types 

and number of toxicity 

studies that may be 

required is impacted, not 

the need for exposure 

data. Therefore, EPA 

removed the language 

originally proposed for 

158.2260(a)(1) and 

158.2270(a)(1) 

concerning use of OSHA 

standards. With 

modifications, the 

language will appear in 

the Toxicity Table, 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Master Responses: Most Common Comments Page 27 

§158.2230(e), as follows: 

“If industrial standards, 

such as the workplace 

standards set by the 

Occupational Safety and 

Health Administration, 

provide adequate 

protection for a particular 

pesticide or a particular 

use pattern, additional 

toxicity data may not be 

required for that pesticide 

or the use pattern..” 

158.2270(a)(3) Post-application 

exposure: General.

“The Agency may 

accept surrogate 

exposure data 

estimations from other 

sources to satisfy 

applicator exposure data 

requirements if the data 

meet the basic quality 

assurance, quality 

control, and other 

scientific requirements 

set by EPA . . . The 

Agency will consider 

using such surrogate 

data for evaluating 

human exposure on a 

case-by-case basis.” 

The Agency has not 

adequately stated the 

criteria used to 

determine whether it 

will accept surrogate 

exposure data. These 

required private 

negotiations are a 

procedure for the 

development of later 

tests. 

This regulatory text has 

been amended to provide 

the following clarifying 

information : The Agency 

may accept surrogate 

exposure data estimations 

and/or modeling 

estimations from other 

sources to satisfy 

exposure data 

requirements if the data 

meet the basic quality 

assurance, quality 

control, good laboratory 

practice, and other 

scientific requirements 

set by this rule. In order 

to be acceptable, the 

Agency must find that the 

surrogate exposure data 

estimations have 

adequate information to 

address the applicable 

exposure data 

requirements and contain 

enough adequate 

monitoring events of 

acceptable quality to 

reflect the specific use 

prescribed on the label 

and the activity of 

concern, including 
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Master Responses: Most Common Comments Page 28 

formulation type, 

application methods and 

rates, type of activity, and 

other pertinent 

information. 

158.2270(b) Post-application 

exposure: Criteria for 

testing. “Postapplication exposure 

data . . . are required 

based on toxicity and 

exposure criteria. Data 

are required if a product 

meets, as determined by 

the Agency, at least one 

of the toxicity criteria in 

paragraph (b)(1) of this 

section, and at least one 

of the exposure criteria 

in paragraph (b) (2) of 

this section.” 

The Agency has not 

adequately stated the 

criteria used to 

determine whether the 

data meets one of the 

toxicity criteria and 

one of the exposure 

criteria. 

The phrase “as 

determined by the 

Agency” has been 

removed from the 

testnote. 

158.2270(e)(1) Post-application 

exposure: Test notes. 

“Protocols must be 

approved by the Agency 

prior to the initiation of 

the study. Details for 

developing protocols are 

available from the 

Agency.” 

The Agency has not 

adequately stated the 

criteria used to 

determine whether the 

protocol will be 

approved. These 

required private 

negotiations are a 

procedure for the 

development of later 

tests. 

EPA believes that the 

concept of a protocol as a 

basic description of a 

standard of conduct for 

the study is wellunderstood. EPA has 

removed the reference to 

the availability of 

guidance from EPA on 

protocol development 

because commenters 

have misunderstood this 

reference as imposing a 

requirement. 

Consultation with EPA 

prior to protocol review 

is not required. 

158.2280(a)(2) Environmental fate: 

General. “If the Agency 

believes that the 

transformation products 

of the parent compound 

are more toxic, 

persistent, or 

bioaccumulative than 

The Agency has not 

adequately stated the 

criteria used to 

determine whether the 

“transformation 

products of the parent 

compound are more 

toxic, persistent, or 

In response to comments, 

and as part of reevaluating these criteria, 

EPA determined to 

clarify and revise the 

criteria for testing of 

transformation products 

by providing a single set 
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Master Responses: Most Common Comments Page 29 

the parent compound, or 

have been shown to 

cause adverse effects in 

mammalian or aquatic 

reproductive studies, 

then data on those 

transformation products 

are also required to 

support registration.” 

bioaccumulative than 

the parent compound, 

or have been shown to 

cause adverse effects 

in mammalian or 

aquatic reproductive 

studies.” 

of criteria for all 

antimicrobials, instead of 

breaking down the 

criteria by use patterns. 

The criteria now read as 

follows: 

“Data on 

transformation/degradatio

n products or leachate 

residues of the parent 

compound are also 

required to support 

registration, if the 

transformation/degradatio

n/leachate products meet 

one of the following 

criteria: 

(i) more toxic, persistent, 

or bioaccumulative than 

the parent, 

(ii) have been shown to 

cause adverse effects in 

mammalian or aquatic 

reproductive studies, or 

(iii) the moiety of 

concern (i.e., functional 

group in the parent 

chemical molecule that 

imparts adverse effects) 

remains intact.” 

158.2280(a)(3) Environmental fate: 

General. “For wood 

preservatives, the 

Agency may require 

data on both the parent 

compound that is 

incorporated into the 

wood, and on 

transformation/degradati

on products that occur in 

wood post-treatment or 

occur as dislodgeable 

residues(such as hand 

contact with treated 

wood)or leachate 

The Agency has not 

adequately stated the 

criteria used to 

determine whether the 

Agency will require 

data or not.

Proposed 158.2280(a)(3) 

was combined with 

proposed 158.2280(a)(2) 

to derive final 

158.2280(a)(2) 
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Master Responses: Most Common Comments Page 30 

residues (such as from 

soil or water contact 

with treated wood). 

158.2280(f)(12) Environmental fate: 

Testnotes. “Protocols 

must be approved by the 

Agency prior to the 

initiation of the study. 

Details for developing 

protocols are available 

from the Agency.”

The Agency has not 

adequately stated the 

criteria used to 

determine whether the 

protocol will be 

approved. These 

required private 

negotiations are a 

procedure for the 

development of later 

tests.

EPA believes that the 

concept of a protocol as a 

basic description of a 

standard of conduct for 

the study is wellunderstood. EPA has 

removed the reference to 

the availability of 

guidance from EPA on 

protocol development 

because commenters 

have misunderstood this 

reference as imposing a 

requirement. 

Consultation with EPA 

prior to protocol review 

is not required. 

158.2280(f)(15) Environmental fate: 

Testnotes. “For wood 

preservatives, an aquatic 

leaching study is 

required. A soil leaching 

study is required if 

human or environmental 

exposures are likely to 

occur from leachates 

that contain the active 

ingredient or principal 

transformation products 

from wood treated with 

a preservative product. 

For those studies, the 

Agency accepts the 

following methods or 

their equivalents: 

America Wood 

Preservers’ Association 

(AWPA) Method E11-

97 (aquatic leaching), 

and AWPA Method 

E20-04 (soil leaching). 

Prior approval of studies 

conducted according to 

The Agency has not 

adequately stated the 

criteria used to 

determine whether the 

protocol will be 

approved. These 

required private 

negotiations are a 

procedure for the 

development of later 

tests. 

The commenter provided 

information that the 

AWPA Methods were “of 

limited or no relevance to 

estimating environmental 

exposures” but did not 

provide alternative 

methods. Therefore EPA 

determined to remove the 

methods from the 

testnote. Testnote 15 now 

reads as follows: For 

wood preservatives, an 

aquatic leaching study is 

required. A soil leaching 

study is required if 

human or environmental 

exposures are likely to 

occur from leachates that 

contain the active 

ingredient or principal 

transformation products 

from wood treated with a 

preservative product. 

Protocols must be 

approved by the Agency 
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Master Responses: Most Common Comments Page 31 

E11-97 is not required. prior to the initiation of 

the study. EPA believes 

that the concept of a 

protocol as a basic 

description of a standard 

of conduct for the study 

is well-understood. 

158.2280(f)(16) Environmental fate: 

Test notes. “For 

antifoulant paints and 

coatings, a leaching 

study is required. The 

Agency accepts the 

following method or its 

equivalent: American 

Society for Testing and 

Materials (ASTM) 

Method D5108-90. Prior 

approval of studies 

conducted according to 

D5108-90 is not 

required. All other 

protocols must be 

approved by the Agency 

prior to the initiation of 

the study. Details for 

developing protocols 

are available from the 

Agency.” 

The Agency has not 

adequately stated the 

criteria used to 

determine whether the 

protocol will be 

approved. These 

required private 

negotiations are a 

procedure for the 

development of later 

tests. 

The commenter provided 

information that the 

ASTM method was not 

suitable for “estimating 

release rate limits for 

regulation purpose” but 

did not provide 

alternative methods. 

Therefore EPA 

determined to remove the 

methods from the 

testnote. Testnote 16 

now reads as follows: 

For antifoulant paints and 

coatings, a leaching study 

is required. Protocols 

must be approved by the 

Agency prior to the 

initiation of the study. 

EPA believes that the 

concept of a protocol as a 

basic description of a 

standard of conduct for 

the study is wellunderstood. 

158.2290(f)(10) Residue chemistry: 

Test notes. “A residue 

analytical method 

suitable for collecting 

data to establish 

tolerances must 

quantitate all residues of 

concern, as determined 

by the Agency.” 

The Agency has not 

adequately stated the 

criteria used to 

determine whether or 

how a method should 

quantitate residues of 

concern. 

The phrase “as 

determined by the 

Agency” has been 

removed from the 

testnote. 

158.2290(f)(23) Residue chemistry: 

Test notes. “Migration 

of residue data are 

required for 

antimicrobial pesticides 

The Agency has not 

adequately stated the 

criteria used to 

determine whether the 

protocol will be 

EPA believes that the 

concept of a protocol as a 

basic description of a 

standard of conduct for 

the study is well-
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Master Responses: Most Common Comments Page 32 

applied to hard food 

surfaces or incorporated 

into substrates (wood, 

plastic, paper, cloth, 

rubber or similar 

products) intended for 

contact with food or 

feed when theoretical 

(modeled) estimates of 

the amount of 

antimicrobial residue 

transferred to the food 

or feed may result in a 

risk of concern. 

Protocols must be 

approved by the Agency 

prior to the initiation of 

the study. Details for 

developing protocols 

are available from the 

Agency.” 

approved. These 

required private 

negotiations are a 

procedure for the 

development of later 

tests. 

understood. EPA has 

removed the reference to 

the availability of 

guidance from EPA on 

protocol development 

because commenters 

have misunderstood this 

reference as imposing a 

requirement. 

Consultation with EPA 

prior to protocol review 

is not required. 

One commenter also asked that EPA “propose new 158W standards that enable registrants 

to determine default data requirements from reading the regulation, without having to consult the 

Agency for many registration applications.” As stated in the preamble [59386], testnote triggers 

describe the “circumstances under which the Agency has learned through experience that 

information is needed.” EPA is unsure of the commenter’s use of the term “default”. If the 

commenter means data requirements that are predetermined, and involving no though process on 

the applicant’s part, then EPA could have set-up data tables that are all “NR” and “R” and with no 

testnotes. The applicant would be responsible for generating every “R” study, unless the applicant 

applied for and was given a waiver for that study. EPA believes that the use of “R”, “CR”, and 

“NR,” and the use of testnotes describing the circumstances that information is needed provides 

significantly more information to the applicant. 

 However, EPA emphasizes that applicants have a responsibility to provide information to 

EPA of suitable quality and completeness. EPA then determines “whether the data submitted or 

cited to fulfill the data requirements...are acceptable.” (§ 158.70(a)) Incomplete applications or 

studies that do not provide the appropriate information can cause rejection of an application 

package with partial loss of the PRIA fee, or time delays during review of the studies. Therefore, 

applicants have some initial decisions to make in instances where data requirements are 

accompanied by testnotes with such qualitative triggers. In such circumstances, the applicant using 

knowledge of the antimicrobial, and its use pattern and application rates may decide (with or without 

consultation with EPA) to generate the data or may decide to pose questions to the Agency 

concerning the need for such a study. In the latter case, the applicant may decide to submit a 

rationale with supporting information and discussion as to why the study should not be triggered 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Master Responses: Most Common Comments Page 33 

and should therefore not be required. Based on the information provided by the applicant as well as 

other information available to the Agency, EPA will review the matter and let the applicant know 

whether it agrees or disagrees with the request regarding the data requirement and the accompanying 

rationale. 

Comment 4: A commenter asked how OPP plans to implement the National Academy of Sciences 

(NAS)/EPA Vision of Toxicity Testing in the 21st Century or the Strategic Plan for Evaluating the 

Toxicity of Chemicals. The commenter noted that the rule should be specific in identifying 

alternative approaches that EPA will consider. 

Response 4: 

In the proposed rule, in section XVIII, entitled “Alternative Testing Paradigms,” EPA discussed 

its commitment to moving towards a more efficient and refined testing/risk assessment paradigm 

for antimicrobial pesticide chemicals. That discussion included the following: 

 OPP’s current thinking on how SAR and QSAR modeling could be used as part of an 

integrated approach to hazard and risk assessment to support a regulatory decision-making 

process for antimicrobial pesticides. 

 The evolution of the current paradigm of animal (in vivo) toxicity testing toward a more 

integrated tiered testing approach for antimicrobial pesticides. 

 Development of computational tools for interpreting data from computational chemistry, 

high-throughput screening (HTS) and genomic technologies. 

 The EPA-funded reports by the National Academy of Sciences entitled “Toxicity Testing for 

Assessment of Environmental Agents” (2006) and “Toxicity Testing in the 21st Century: A 

Vision and a Strategy” (2007). 

The NAS recommendations are truly visionary and involve a transformative paradigm shift in 

toxicology based largely on the increased use of in vitro molecular and cellular assays, and 

computational modeling that make testing faster and less costly, and reduces animal testing 

significantly. The new technologies are expected to help EPA better understand how chemicals 

perturb normal biological function(s), and thus identify toxicity pathways. Potential toxic effects of 

chemicals could then be predicted based on in vitro bioactivity profiles derived from a chemical’s 

effects on cellular molecules and processes. Thus, the scientific foundation for this new paradigm is 

based on linking in vitro effects with adverse outcomes in vivo, and on computer modeling that 

extrapolates to predicted responses in whole tissues, organisms and populations based on realistic 

human or environmental exposures. 

EPA is working to develop and evaluate new technologies in molecular, cellular, and computational 

sciences to supplement or replace the more traditional methods of toxicity testing and risk 

assessment. (see http://www.epa.gov/pesticides/science/testing-assessment.html.) Such an 

approach begins with consideration of exposure information along with hazard-based hypotheses 

about the plausible toxicological potential of a chemical or group of chemicals based on their 

physical-chemical properties and their effects on biological targets in vitro. This information is then 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Master Responses: Most Common Comments Page 34 

combined with computer modeling to target animal testing to the specific data needed for human 

health and ecological risk assessments. 

No single new technology will be able to address all situations. However, by using a suite of tools 

and approaches in combination, EPA believes it is possible to improve the hazard and exposure 

assessments that form the basis for understanding pesticide chemical risks. It will take time and 

substantial research to build this new approach. OPP will incorporate the new technologies into our 

hazard and risk assessment processes as the technologies are sufficiently developed and peer 

reviewed. Development and vetting of this new approach to chemical management must be 

accomplished while continuing to make pesticide registration decisions. Eventually, the new 

technologies should: 

 Create a broader suite of computer-aided methods to better predict potential hazards and 

exposures, and to focus testing on likely risks of concern. 

 Improve the approaches to more traditional toxicity tests to minimize the number of animals 

used while expanding the amount of information obtained. 

 Improve our understanding of toxicity pathways to allow development of non-animal tests 

that better predict how exposures relate to adverse effects. 

 Improve the diagnostic biomonitoring and surveillance methods to detect chemical 

exposures and identify causes of toxic effects. 

Since the publication of the proposed rule in October 2008, OPP announced its strategic direction 

to move toward an improved testing and assessment paradigm where in vivo (animal) testing would 

be targeted to the most likely hazards of concern. OPP envisions an enhanced testing/assessment 

paradigm that is a progressive, tiered-testing approach. This paradigm shift should accrue the 

following benefits to OPP: 

 Ability to evaluate more chemicals across a broader range of potential effects in a shorter 

time frame. 

 Potential to increase the feasibility of assessing the risks posed by mixtures. 

 Enhanced predictive ability to determine whether animal testing is needed to refine a risk 

assessment and to inform management decisions. 

 Refine and reduce animal testing by maximizing information obtained from animal studies, 

and focusing on effects of concern. 

 Opportunities for improved diagnostic biomonitoring and surveillance methods to detect 

chemical exposures and identify causes of toxic effects. 

 Enhance the quality and efficiency of risk assessment and risk management decisions. 

Over the next several years, OPP intends to improve and transform our approach to pesticide risk 

management by enhancing our ability to use integrated approaches to testing and assessment. Our 

work on an integrated approach means the development of increasingly effective laboratory animal 

tests that are designed to maximize the information generated about the nature of the effects being 

studied. OPP intends to expand our toolbox of predictive models. The new toxicity and exposure 

approaches will enhance priority-setting and screening approaches and therefore focus Agency and 

societal resources on those chemicals with the greatest risk potential. 
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Master Responses: Most Common Comments Page 35 

These advances will be incorporated within a risk assessment framework of problem formulation, 

hazard, dose response, exposure assessment, and risk characterization to support pesticide 

registration decisions. As this framework evolves, EPA will create pilot programs and guidance 

documents to inform applicants and others of the alternative approaches being used. 

It will require many years to realize the NAS vision of a new toxicity paradigm based on evaluating 

perturbations in cellular pathways by reliance on an array of computational and in vitro methods. 

However, the development and expansion of certain tools used to guide more intelligent in vivo

testing is anticipated to become available in the nearer term (≤5 years) which includes (Quantitative) 

Structure-Activity-Relationship -- (Q)SAR/expert systems, Toxicological Thresholds of Concern 

(TTC), and in vitro technologies As EPA transitions to the use of these components of intelligent 

testing or alternative methods, communication will be essential. Through its Pesticide Program 

Dialog Committee, OPP has created a 21st Century Toxicology/New Integrated Testing Strategies 

Workgroup. For additional information, see 

http://www.epa.gov/pesticides/ppdc/testing/index.html.

Additionally, OPP has and will continue to publicly vet this new approach. On May 24 – 26, 2011, 

OPP requested that the FIFRA Scientific Advisory Panel (SAP) consider and revise a set of 

scientific issues related to Integrated Approaches to Testing and Assessment (IATA) Strategies: Use 

of new computational and molecular tools. OPP plans to build on an established foundation of 

using a variety of tools in a tiered testing and assessment framework by systematically adding new 

tools and methodologies, as well as an advancing understanding of key events in toxicity pathways. 

OPP requested the SAP's input on EPA’s plans to maximize use of existing data from similar 

compounds, including information from new toxicity hazard computational and in vitro predictive 

models, and exposure modeling to target in vivo toxicity testing that is necessary to assess and 

manage chemical risks, appropriately. Two case studies illustrated the use of these approaches. The 

SAP Report, once completed, will be available at 

http://www.epa.gov/scipoly/sap/meetings/2011/052411meeting.html#frn.
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Master Responses: 

General Comments on the Rule (10) Page 36 

General Comments on the Rule (10) 

Master Responses for the General Comments on the Rule Section 

Please note that EPA responses are presented in numerical order. However, in the course of response development, 

some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are missing. 

Comment 10.1: A commenter requested that EPA clarify the manner in which the responsibilities 

among the registering divisions within OPP are distributed and the impact of these distributions on 

the data required for various uses of pesticide active ingredients. 

 

Response 10.1: Three divisions in the Office of Pesticide Programs have the responsibility for 

handling registration applications for pesticide products: Antimicrobials Division (AD), 

Biopesticides and Pollution Prevention Division (BPPD), and Registration Division (RD). These 

three divisions represent three categories of pesticides: antimicrobial, biopesticides and 

conventionals, respectively. 

 A large number of antimicrobial pesticides disinfect, and are therefore considered public 

health pesticides, since they target disease-causing microbes that pose a risk to human 

health. There are also non-public health antimicrobial pesticides, which target, for example, 

microbes that create smells. Also included within AD’s antimicrobial product work are 

antifoulant paints and coatings, and wood preservatives. 

 Biopesticides are naturally-occurring substances that control pests (biochemical pesticides), 

microorganisms that control pests (microbial pesticides), and pesticidal substances produced 

by plants containing added genetic material (plant-incorporated protectants) or PIPs. 

 Conventional pesticides are generally man-made chemicals. Their target pests are, among 

other things, insects, mice and other animals, unwanted plants (weeds) and fungi. They 

comprise the largest category of pesticides and include “everything else.” This means that if 

a pesticide is not assigned to BPPD or AD, that it is considered a conventional pesticide 

and assigned to RD. 

Before submitting an application to register a particular active ingredient for the first time, in all 

likelihood, the applicant has met and/or consulted with EPA staff before sending the application 

package to EPA. Therefore, the appropriate division is stated on the application package. From 

then on, all applications and correspondence for that active ingredient would be sent to the assigned 

division, unless a new use for that same active ingredient is subsequently sought, and the use is 

determined by the assigned division not to be within the scope of the assigned division. 

That application would then be routed to a different division. For example, applications for uses for 

products containing an identical active ingredient, such as propiconazole, have been reviewed by 

both RD and AD. In that instance, RD reviewed the product applications for field application to 

food crops and turf, and AD reviewed the product applications for uses as a wood preservative and 

a material preservative. 

 

Comment 10.2: A commenter argued that the data quality objectives must be outlined in advance of 

study planning and data collection in order to ensure data of the necessary quality to inform the 

decision making process. 
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Master Responses: 

General Comments on the Rule (10) Page 37 

 

 

Response 10.2: The Agency agrees with the commenter. It is important to have data of sufficient 

quality and completeness for risk assessment purposes. As discussed in the preamble (73 FR 59387) 

the Harmonized Test Guidelines provide “recommended instructions and test methods” that 

represent “the recommended approach to developing high-quality data that should satisfy EPA’s 

data needs for risk assessment.” 

Comment 10.3: Why is product use information required only for human health exposure 

assessment? Isn't it also needed for environmental assessments? 

 

Response 10.3: The commenter is correct that the guidelines for applicator and post-application 

product use information are under the 875 series for Occupational and Residential Exposure Test 

Guidelines. There is also a Directions for Use guideline under the 860 series for Residue Chemistry. 

Once this information is available to the Agency, this information can also be used for 

environmental risk assessment purposes. Hence, even though product use information is not 

specifically included as a proposed requirement in the proposed rule for assessing the environmental 

risk of pesticides, the Agency, as appropriate, can use the same data for both analyses. 

According to the Agency’s environmental scientists, the information most useful to them is the 

product label, since the application rates and the percent of the active ingredient in the product are 

on the label. When combined with information on the frequency of the application (either on the 

label, or historically-based assumptions), and then used as inputs for modeling, EPA is able to 

estimate environmental concentrations. 

Another source of information is the applicant, who can supply information on product volumes 

and sales to EPA, as needed. Typically, such information is needed for a down-the drain 

analysis to determine the influent volume of antimicrobial-containing products in wastewater 

treatment plants. Even for a new application, the applicant may have marketing projections, or the 

information may be capable of being estimated by EPA using other sources. 

 
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Master Responses: 

Administrative Comments on the Rule Section (20) Page 38 

Administrative Comments on the Rule (20) 

Master Responses for the Administrative Comments on the Rule Section 

Please note that EPA responses are presented in numerical order. However, in the course of response development, 

some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are missing. 

Comment 20.1: A commenter noted that in the preamble to proposed 158W EPA cites multiple 

Scientific Advisory Panel (SAP) reports that did not specifically mention antimicrobial pesticides. 

Therefore, the commenter thought these SAP reviews were insufficient. Another commenter noted 

that it has been nine years since the last SAP review and that EPA should request another SAP 

review prior to implementation of proposed 158W. Still another commenter argued that EPA’s 

request that the SAP waive its review of proposed 158W based on the SAP’s 1997 was improper, 

and that the SAP cannot waive its statutory review obligation. 

Response 20.1: EPA disagrees with the commenter. On June 3, 1997, EPA presented an early 

version of the part 158W proposal in an open meeting to the Scientific Advisory Panel (SAP). At 

that time, the SAP provided extensive comments in five areas: toxicology, residue chemistry, 

ecological effects and environmental fate, human exposure, and efficacy. Since then, the SAP 

considered many specific studies and scientific issues included in proposed part 158W as part of 

their reviews of guidelines and of data requirements for conventional agricultural pesticides. In 1997, 

the SAP also noted its concern about the possible effects of antimicrobials on wastewater treatment 

plants. Partially in response to the SAP comments, EPA proposed a tiered set of environmental fate 

data requirements that will allow the Agency to better characterize potential incidences of 

antimicrobials in surface waters, as a result of down-the-drain uses of antimicrobials. 

When the Agency prepared to propose 40 CFR Part 158 Subpart W (also referred to as 158W), EPA 

requested that the SAP waive its review of the about-to-be-proposed 158W because there were no 

new scientific issues. The SAP waived its review of 158W on February 19, 2008. The Agency 

continues to believe that there are no new scientific issues that warrant additional review by the SAP, 

and will request another SAP waiver before publishing the final rule. FIFRA section 25 requires 

EPA to give the SAP at least 60 days to review proposed regulations and 30 days to review final 

regulations. However, the SAP can determine to waive its review during statutory time periods. 

 

Comment 20.2: A commenter asked EPA to specify criteria to determine whether a data 

requirement is “R” (Required) or “CR” (Conditionally Required) data. According to the commenter, 

the discussion of “R” and “CR” suggests that a data requirement labeled “CR” may not be required 

to be addressed by the applicant. A second commenter thought that it is unclear how and when 

conditionally required data are triggered. Another commenter argued that data requirements should 

be waived only under extraordinary circumstances, and that the use of waivers can effectively 

preclude appropriate regulation of the pesticide under FIFRA. 

Response 20.2: In its proposed data requirement tables, EPA specified whether a data requirement is 

“Required”, “Conditionally Required”, or “Not Required” based on how likely the study is needed 
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Master Responses: 

Administrative Comments on the Rule Section (20) Page 39 

to complete an assessment of an antimicrobial pesticide. As a rule of thumb, a “required” study is 

likely to be needed 50 percent of the time or more and a “conditionally required” study is likely to be 

needed less than 50 percent of the time. Typically, a “conditionally required” study is triggered based 

on the results of a study that has already been conducted. Triggers in the testnotes indicate the 

circumstances under which the Agency has learned through experience that the information is 

needed. In many instances, the applicant would be able to make the determination that the trigger 

has been met and should include the data in their original submission. In other cases, EPA will make 

the determination based on its review of submitted data and would then request additional data 

from the applicant. EPA encourages applicants to consult with the Agency to determine the actual 

need for the data. 

All data requirements must be addressed by the applicant by either conducting the study or 

submitting information that could fulfill the data requirement, such as citing open literature or other 

data sources, or by requesting and receiving a data waiver. EPA grants data waiver requests only on a 

case-by-case basis and only when the available evidence indicates a particular study is not needed or 

that there are particular reasons for not conducting the study. For example, if the physical/chemical 

properties of the chemical did not lend themselves to the testing procedure, such as performing an 

inhalation study with a chemical that is a solid and has an extremely low vapor pressure, then a 

waiver might be granted. EPA also grants waivers in exceptional circumstances, for instance, if a test 

substance is so corrosive that animal studies would cause undue pain and suffering. 

Comment 20.3: Commenter stated EPA has not considered the impacts of antimicrobial pesticides 

from homes and businesses that reach Waste Water Treatment Plants (WWTPs). The commenter 

also noted that that FIFRA requires EPA to ensure pesticide use does not require mitigation under 

the Clean Water Act (CWA). Another commenter suggested that EPA should harmonize proposed 

data requirements with the testing required under CWA. 

Response 20.3: EPA disagrees that the Agency has not considered the impacts of antimicrobial 

pesticides from homes and businesses that reach WWTPs. While EPA expects the environmental 

exposures from these use sites to be small, EPA recognizes that antimicrobials move from these use 

sites into the outdoor environment as leachates, flushes, or rinsates released down-the-drain and 

eventually reaching a WWTP. In its proposed data requirements for antimicrobials, EPA indicated 

its intention to use the Down-the-Drain model to provide screening-level estimates of exposure 

concentrations of antimicrobials in surface water that receives effluent from a WWTP. The Downthe-Drain model is based on a database of domestic WWTPs. Many of these WWTPs receive 

wastewaters from commercial and institutional sources, as well as residential sources. 

Within EPA, both the Office of Water (OW) and the Office of Pesticide Programs (OPP) have a 

statutory mandate to protect health and the environment, including addressing water impacts. The 

Agency is confident that the pesticide registration process, including its data requirements 

regulations for antimicrobial pesticides, adequately consider the endpoints that are protected under 

the CWA. 

Recently, OW and OPP have been engaged in efforts to harmonize methodologies to characterize 

ecological assessments of chemicals to meet the mandates of the CWA and FIFRA. The existing 

efforts by the two offices to create a common ecological effects assessment methodology include 
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Master Responses: 

Administrative Comments on the Rule Section (20) Page 40 

considerations of the use of common data acceptability requirements, predictive tools, collaborative 

work on risk assessment, (e.g. in the areas of species sensitivity distributions analysis), and shared 

review of ecological risk assessments and criteria documents. As noted in the response to comments 

on the proposed conventional pesticide data requirements rule, the purpose of a water quality 

criterion under the CWA is to determine the level at which a water body may be at risk for 

environmental damage. Ambient water quality criteria (AWQC) are levels of individual pollutants, 

water quality characteristics, or descriptions of conditions of a water body that, if met, should 

protect the designated use(s) of the water. Examples of designated uses of a water body include 

swimming, drinking water, fishing, fish spawning, and navigation. States and authorized tribes 

establish designated uses for their water bodies. AWQC are recommended guidance that states and 

tribes may use as part of their water quality standards to protect water bodies for their designated 

use(s) from chemical pollutants. The purpose of the data requirements for pesticide registration is to 

allow the Agency to determine ecological risk of using a pesticide. 

In addition, EPA has engaged both the scientific and regulated community in its efforts to develop a 

common framework for performing ecological effects assessments that would meet the mandates of 

both the CWA and FIFRA. At the April 2009 meeting of the Pesticide Program Dialogue 

Committee, a forum for a diverse group of stakeholders to provide feedback to OPP on various 

pesticide regulatory, policy and program implementation issues, the Agency discussed OW and OPP 

efforts to develop common effects assessment methodologies. A scoping document from that 

meeting is available at: http://www.epa.gov/oppefed1/cwa_fifra_effects_methodology/scope.html. 

In addition, six regional stakeholders meetings were held in January 2010. 

In the Federal Register of November 1, 2010, EPA announced a national stakeholders meeting for 

December 1, 2010, concerning CWA and FIFRA Common Aquatic Life Effects Assessment for 

Pesticides Using Available Data. At this meeting EPA solicited input on the methods currently being 

evaluated by OW and OPP. EPA intends to build on the substantial high quality science developed 

under both OPP’s toxicity benchmarks and OW’s AWQC to develop a consistent and common set 

of effects characterization methods that integrates these approaches for regulators to use in different 

programs at both the Federal and State level. At the December 1 meeting three draft white papers, 

which explore (1) use of various tools to estimate aquatic toxicity data; (2) approaches for deriving 

community level benchmarks; and (3) procedures for better integrating plant effects data into 

community level assessments, were discussed. 

It should be noted that the two statutes provide different authorities for requiring testing. The CWA 

does not give EPA’s Office of Water the authority to require testing on specific chemicals. When 

developing an AWQC, OW collects the readily available public information. OW also solicits data 

from the public through a Federal Register notice. This means that EPA/OW cannot require studies 

on pesticide active ingredients from pesticide registrants. Under FIFRA, OPP can require studies on 

pesticide active ingredient(s) from pesticide registrants when the data are needed for an OPP risk 

assessment and regulatory decisionmaking. 

The commenter also stated the belief that FIFRA requires EPA to ensure pesticide use does not 

require mitigation under the CWA. The Agency is not certain what the commenter had in mind 

when making this comment, but FIFRA does not include such a provision regarding mitigation 

under the Clean Water Act. 
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Master Responses: 

Administrative Comments on the Rule Section (20) Page 41 

Comment 20.4: A commenter stated that the proposed rule does not comply with 1) Executive 

Order (EO) 12866, 2) the Regulatory Flexibility Act (RFA), 3) the Paperwork Reduction Act (PRA), 

4) Executive Order 12988, and 5) the Information Quality Act. 

Response 20.4: EPA disagrees with this comment. The Agency has followed the appropriate 

procedures in proposing 158W. 

1) EO 12866 requires the Agency to submit to OMB for review significant regulatory actions. 

EPA complied with EO 12866 during 2008. The changes that were made to the proposed 

rule as the result of OMB’s review are included in the docket. 

2) Pursuant to section 605(b) of the RFA, EPA certified that the rule will not have a significant 

adverse economic impact on a substantial number of small entities. As discussed in section 

XXIII of the proposed rule [59428-9], EPA conducted an economic analysis of proposed 

158W, which is also included in the docket. 

3) The PRA requires that the Agency submit Information Collection Requests (ICRs) to OMB. 

In compliance with the PRA, EPA prepared and submitted to OMB for approval a new ICR 

to address the proposed changes to the data requirements that impact the information 

collection activities related to antimicrobial pesticides. Section XXIII of the proposed rule 

[59429] contains a discussion of all the OMB-approved ICRs that cover the procedures for 

submitting data under FIFRA and FFDCA. 

4) The Agency also believes that the proposed rule is in compliance with EO 12988, requiring 

that rules be written in plain language. In addition, in compliance with FIFRA and the 

Administrative Procedure Act, the Agency published the proposed rule in the Federal 

Register and provided for a public comment period. The Agency received and reviewed 

comments regarding the clarity of the proposed rule and has taken these comments under 

consideration. 

5) The Agency has complied with the Information Quality Act (IQA, also known as the Data 

Quality Act). EPA’s “Guidelines for Ensuring and Maximizing the Quality, Objectivity, 

Utility, and Integrity of Information Disseminated by the Environmental Protection 

Agency” were published in October 2002. This is a policy and procedural guidance for 

ensuring and maximizing the quality of the information disseminated by EPA. Proposed 

158W was developed using these processes and procedures. 
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Master Responses: Legal Issues Section (30) Page 42 

Legal Issues (30) 

Master Responses for the Legal Issues Section 

Please note that EPA responses are presented in numerical order. However, in the course of response development, 

some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are missing. 

Comment 30.1: According to multiple commenters, a serious concern with the proposed rule is that 

it leaves many decisions to a case-by-case determination based on consultation with the EPA. The 

commenters counted 37 examples in the regulatory text where consultations are required. 

Commenters believe that consultations are evidence that the Agency is engaged in procedures for 

the later development of tests and not proper rulemaking as required by the Administrative 

Procedures Act. Commenter compares the current process for the proposed 158 Part W with the 

Ethyl Corp. v. EPA, in which the Court held that EPA did not meet its statutory obligation to 

establish regulations when the Agency simply established a framework for "case- by-case" approvals 

after "private proceedings with each manufacturer." 

Response 30.1: EPA disagrees with this comment. In proposed and final Part 158 W, respectively, 

the Agency proposed and now sets forth regulatory requirements for the data that are needed to 

support antimicrobial product registration. In addition to establishing data requirements, the Agency 

recognizes that, in certain cases, requirements cannot be always set forth and applied uniformly but 

may require some tailoring or other change depending upon the particular product and factors such 

as ingredient(s) in the product and uses being sought for the product, among other things. 

Additionally, protocol development as relates to certain data requirements is a critical step at which 

point the Agency and the applicant can benefit from discussions. Consultation is mandatory, but can 

be considered as a tool for both the Agency and applicants to consider specific situations that may 

be involved in a product application. Consultation is a longstanding, commonly used and valuable 

tool in the pesticide area and, as such, has served and continues to serve well the interests of both 

the Agency and the applicants. Also see response to comment 3 for a discussion of the voluntary 

nature of consultation. 

Comment 30.2: Several comments raised concerns about whether EPA adequately takes into 

account the extent to which both human and environmental exposures from antimicrobial uses are 

regulated under other environmental statutes. EPA should clearly explain and justify why it needs to 

evaluate under FIFRA potential ecological effects resulting from environmental exposures and 

should not duplicate other efforts, such as regulation of the disposal of pesticides by EPA’s Office 

of Resource Conservation and Recovery, formerly the Office of Solid Waste, and of discharges, 

which are addressed by the Clean Water Act (CWA). Another commenter noted that coordination 

between EPA offices is essential for the implementation of the CWA and meeting FIFRA’s goals. 

Response 30.2: In promulgating data requirements for antimicrobial pesticides, the Agency considers 

the purposes and goals of the statutes that regulate the human and environmental exposures that 

result from the use of antimicrobial pesticides. To the extent that antimicrobial uses may result in 

human and environmental exposures, the FIFRA provides EPA with the statutory authority to 

regulate the sale, distribution and use of antimicrobial pesticides in the United States to prevent 

unreasonable adverse effects on humans and the environment. FIFRA also contains provisions for 
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Master Responses: Legal Issues Section (30) Page 43 

safe pesticide storage and disposal, and requires, among other things, that the product label contain 

requirements and procedures for the transportation, storage, and disposal of the pesticide, any 

container of the product, or any rinsate containing the pesticide. However, the disposal of pesticides 

in certain quantities or those classified as hazardous under the Resource Conservation and Recovery 

Act (RCRA) involves RCRA regulations, which include stringent requirements for storage, transport, 

and disposal of hazardous waste, and severe penalties for failure to comply with regulations. The 

objective of the CWA is to restore and maintain the integrity of the nation's waters by preventing 

point and nonpoint pollution sources, providing proper management of sewage sludge (biosolids), 

providing assistance to publicly owned treatment works for the improvement of wastewater 

treatment, and maintaining the integrity of wetlands. EPA requires municipal wastewater treatment 

plants to conduct both acute and chronic toxicity tests regularly as conditions of Clean Water Actregulated NPDES permits. 

Under FIFRA, EPA requires data to, among other things, understand the uses of antimicrobial 

pesticides and the distribution of residues in the environment and possible human and 

environmental exposures from pesticide use. An important distinction between FIFRA and other 

statutes is that FIFRA generally requires applicants to submit data about a product before the 

product is registered and able to be lawfully sold or distributed. The data requirements being 

codified will provide information about the potential adverse effects of uses of pesticides, and to 

define what is generally required from applicants for registration in support of their products. 

For a discussion of the efforts of OPP and OW to develop a common effects characterization 

methodology for use in ecological assessment of chemicals by EPA to meet the mandates of the 

CWA and FIFRA, see response to comments 20.3, 190.1, and 190.2. 

Comment 30.3: Commenter notes that there is a loophole in the regulatory framework that allows 

the same active ingredient as a registered pesticide to be marketed in the US without EPA review as 

long as no pesticidal claim appears on the product label. 

Response 30.3: FIFRA is one component of EPA’s regulatory framework for evaluating the health 

and environmental effects of a chemical substance used as an active ingredient in a product. If a 

product makes a pesticidal claim, it falls under FIFRA. If there are no explicit pesticidal claims on 

the product label, the product may still be subject to regulation under FIFRA. Claims do not have to 

be on the label to be unlawful and provide a basis for a product being in need of registration to be 

lawfully sold or distributed. Implicit claims made in connection with the sale or distribution of the 

product either in writing, orally, electronically, or by use of various media or communications means 

can also form the basis for a product being in need of registration to be lawfully sold or distributed. 

Products containing the same active ingredients as a registered pesticide but without an implicit or 

explicit pesticidal claim would not fall under FIFRA. 

Comment 30.6: A commenter disagrees with EPA’s articulation of the jurisdictional boundary 

separating EPA and FDA authority. The commenter argued that EPA is asserting authority under 

FIFRA to regulate some antimicrobial food uses that are under the exclusive jurisdiction of FDA. 

The commenter notes EPA does not have the authority under FIFRA or FFDCA to review or 

change the terms of an FDA approval for a food additive. 
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Master Responses: Legal Issues Section (30) Page 44 

Response 30.6: If an antimicrobial is both a FIFRA “pesticide” and excluded from the definition of 

a “pesticide chemical” under FFDCA section 408, then both EPA and FDA would have regulatory 

authority over that substance – EPA under FIFRA, and FDA under FFDCA section 409. EPA is 

unaware of any instance in which it has asserted FIFRA jurisdiction over an antimicrobial which is 

not a FIFRA “pesticide.” Neither is EPA aware of any situation in which it has asserted FFDCA 

jurisdiction over an antimicrobial excluded from EPA’s FFDCA jurisdiction under FFDCA section 

408. Given that the commenter has not provided any specifics, no more detailed response to the 

comments is possible. 

Comment 30.11: Several commenters request that EPA impose more stringent conditions on issuing 

waivers for aquatic toxicity testing in the data requirements rule. The commenters believe that EPA 

should withhold registration decisions until all required testing is submitted and evaluated, noting 

that EPA had reregistered pesticides without receiving aquatic toxicity testing data. 

Response 30.11: Additional information on how EPA handles data waiver requests appears in the 

response to comment 20.2. With regard to aquatic toxicity testing, EPA would consider on a caseby-case basis granting a waiver, if the Agency anticipates a lack of any significant exposure potential. 

For example, if the Agency anticipates no exposure to aquatic organisms in the estuarine/marine 

environment, then toxicity testing for those species (e.g., fish, aquatic invertebrates) could be waived. 

Chronic data could be waived, but only if the available environmental fate data indicate the chemical 

degrades rapidly enough that chronic exposure is highly unlikely. 

Also, EPA wishes to clarify the use of "confirmatory data" when issuing a Reregistration Eligibility 

Decision (RED). EPA must have sufficient information to make a reregistration eligibility decision. 

However, as part of the Agency's risk assessment process, the Agency may need to use certain 

assumptions, and to then draw conclusions based on these assumptions. EPA could determine that 

the pesticide is eligible for reregistration and that additional data are needed to confirm the findings 

of the Agency’s risk assessments, or conclusions about a pesticide. After the RED is issued, EPA 

would then issue a Data Call-In Notice (DCI), requiring the registrant to submit the data identified 

in the RED. EPA would then use these data to confirm or disprove the assumptions and therefore 

the conclusions of the RED process. 

Comment 30.12: A commenter noted that the proposed rule requires acute aquatic toxicity tests for 

the technical grade active ingredient; higher tiered tests may be triggered, and that EPA also requires 

Publicly Owned Treatment Works (POTWs) to regularly conduct acute and chronic aquatic toxicity 

tests as conditions in National Pollutant Discharge Elimination System (NPDES) permits. The 

commenter noted that it is reasonable for EPA to require adequate aquatic toxicity testing before 

registering antimicrobial pesticides with uses that discharge to POTWs, and that EPA should 

withhold registration decisions until required testing is submitted and evaluated. 

Response 30.12: The commenter is correct that EPA’s proposed non-target organism data 

requirements are required (“R”) for Tier One testing, which includes two acute aquatic studies. The 

higher-tiered aquatic organism testing was proposed as either “R”, conditionally required (“CR”), or 

not-required (“NR”). As a result of comments received, the final table for the higher-tiered tests is a 

mixture of “CR” and “R.” 
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Master Responses: Legal Issues Section (30) Page 45 

Through its pesticide registration process, EPA/OPP evaluates each pesticide to ensure that it will 

not have unreasonable adverse effects on humans, and the environment. After EPA completes its 

review of an application for registration of a pesticide, EPA determines if the standard for 

registration has been met based on the available reliable information. If so, then EPA registers the 

pesticide. 

EPA believes that the environmental exposures for antimicrobial pesticides from use sites into the 

outdoor environment are likely to be the result of the indirect movement of antimicrobials present 

in leachates, rinsates, and flushes released down-the-drain, and that eventually reach a municipal 

wastewater treatment plant (WWTP). The Agency has proposed a screening level assessment and 

tiered system of data requirements to ensure that discharges of antimicrobial pesticides will not 

cause toxicity as a result of their presence in WWTP effluent. 

As discussed in the preamble to the propose rule (73 FR 59408), the EPA/OPP has conducted four 

case studies to assess whether the proposed screening level assessment and tiered system of data 

requirements provides the data needed to assess exposure and risk of antimicrobial pesticides 

released to the environment via down-the-drain use patterns. As case studies A and B demonstrated, 

chronic toxicity tests could be required to register a pesticide. In such cases, EPA would request this 

information from the applicant in order to continue the registration process. 

As case study D demonstrates, however, not all antimicrobials pesticides released down-the-drain 

pose an ecological risk. The proposed screening level assessment and tiered system of data 

requirements for antimicrobial pesticides effectively distinguishes between those that require more 

in-depth review and therefore higher-tiered studies versus those that require only the lower tiered 

environmental fate and ecotoxicity studies. 

The commenter is correct that permitting authorities (i.e., EPA Regions and National Pollutant 

Discharge Elimination System (NPDES) authorized states) may require both analytical testing to 

determine the concentration of specific chemical substances in the effluent, and water quality-based 

(WQB) requirements in NPDES permits. One WQB permit requirement is the use of whole 

effluent toxicity (WET) testing provisions within a NPDES permit. The permit may contain WET 

limits (acute or chronic including for sublethal endpoints) on the permitted effluent discharge, 

and/or sampling/monitoring and reporting requirements. These permit monitoring and controls are 

placed in NPDES permits to ensure compliance with EPA or State water quality standards (WQS) 

for aquatic life protection (ALP). By protecting states ALP WQS, it may support the protection of 

other waterbody designated uses for human health. 

EPA WET test methods (40 CFR Part 136) are performed differently than chemical-specific 

analyses used for required aquatic toxicity studies for pesticide registration. WET tests are designed 

to detect aggregate toxic impacts from a pollutant or mixture of pollutants that can either cause, 

contribute to, or potentially cause an exceedance of a state ALP WQS due to the possible toxicity 

from permitted point source effluents discharges and non-point sources into waters of the United 

States. The sample may be taken either at the end of the discharge pipe or in the receiving 

waterbody. The WET assessment is used for determining whether reasonable potential (RP) to 

exceed a WQS exists (thus requiring a WET limit) and for compliance with a permit’s WET limit(s). 

WET tests use diluted and undiluted (100 percent effluent) samples of the permitted effluent in a 

minimum of five dilution (the effluent is diluted with the same water used as the control sample) 
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Master Responses: Legal Issues Section (30) Page 46 

series (each with multiple replicates according to the particular WET test) to assess at which 

concentration the acute (survival/death) or chronic (inhibition of growth, reproduction, etc.) effects 

are observed due to exposure to the effluent. This is different from the chemical-specific nontarget 

organism testing required for a pesticide registration in which the test species is placed into a diluted 

mixture of water (the same water used as the control sample, which meets the appropriate quality 

parameters to ensure species survival) and the candidate antimicrobial pesticide at one or more 

specific concentrations. 

All discharging permittees as part of their NPDES application must declare, to the best of their 

knowledge, any potential impairments known to exist due to their facility’s operation. New and 

existing POTWs must perform and submit a minimum of 4 quarterly tests completed within 1 year 

from the year preceding the permit application or at least annually within the 4 1⁄2 year period prior 

to NPDES application (40 CFR Part 122.21(j)(5)(iv)(A) and (B)). 

Comment 30.13: Commenter notes that that the proposed rule for antimicrobial pesticides 

represents a higher degree of harmonization than existed previously but that differences in data 

requirements remain. Another commenter notes that the proposed 158W will impede harmonization 

because there are many studies requested that only the EPA requires. 

Response 30.13: EPA has engaged in extensive consultations with regulatory authorities worldwide 

to promote shared scientific and technical expertise, lessen the resource burden on governments and 

the regulatory community, and maintain high standards for the protection of human health and the 

environment. Over the last several years, substantial progress has been made toward international 

cooperation on pesticide regulatory review. In addition, EPA has participated in efforts to 

harmonize data requirements across a range of pesticidal products. The Agency looks forward to 

working with stakeholders and other regulatory authorities to identify those differences that can be 

resolved. 

As discussed in the preamble to proposed 158W, national data requirements are tied to national use 

patterns and environmental and ecological conditions (73 FR 59420-1). Data requirements in areas 

such as ecotoxicology and environmental fate can vary depending on tiering approaches. Thus, 

policy, methodological differences, differing statutory or regulatory requirements, or different 

environmental concerns may result in the EPA requiring sometimes more or sometimes less data 

than other countries or international organizations may require in registering the same pesticide. 

Comment 30.15: Several commenters have expressed concern over when the proposed rule would 

take effect. One commenter stated that compliance with the Administrative Procedures Act requires 

EPA to apply any final rulemaking on data requirements for antimicrobials only to applications 

submitted after the effective date; otherwise, EPA would be promulgating the proposed rule 

retroactively. The commenter also believes that EPA should be consistent in its implementation of 

effective dates, noting that EPA did not impose new data requirements on pending conventional 

pesticide registrants when the conventional pesticide rules were revised. A second commenter 

suggested that registrations pending at the time of the final rule publication be given conditional 

registration under Section 3(c)(7) of FIFRA or under 3(c)(5) if the requirements of 161 have been 

met, and that implementation of the 158W data requirements occur at the time of Periodic 

Registration Review. Another commenter noted that EPA has provided reasonable notice to 
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Master Responses: Legal Issues Section (30) Page 47 

registrants and recommends that EPA implement the rule as soon as technically feasible. Another 

commenter asked whether additional Pesticide Registration Improvement Act (PRIA) registration 

fees would be required for pending applications if the registrant did not meet new data requirements 

and withdrew the application, or if the Agency issued a determination that it cannot grant the 

application. 

Response 30.15: EPA will follow an approach similar to that used for conventional pesticides 

following the promulgation of that portion of 40 CFR Part 158. 

The final rule for antimicrobials contains eleven “new” data requirements. “New” means that the 

data requirement has never been required, or has rarely been required on a case-by-case basis and 

has not been routinely considered during the Agency’s evaluation of the data needed for the purpose 

of risk assessment. The new data requirements being codified include eight that were proposed and 

three that have been added based on public comments received about the proposed rule. The eight 

data requirements that were proposed are: developmental neurotoxicity; immunotoxicity; 

photodegradation in soil; soil residue dissipation; ready biodegradability study; porous pot study; 

activated sludge sorption isotherm study; and modified activated sludge, respiration inhibition test. 

The three additional data requirements that resulted from public comments about the proposed rule 

are: simulation tests to assess the biodegradability of chemicals in discharged wastewater, simulation 

test – aerobic sewage treatment: activated sludge units, and nature of the residue on surfaces. 

EPA recognizes that during early implementation of 40 CFR Part 158W not all application packages 

may have all of the newly-required data. Therefore during early implementation of 40 CFR Part 

158W, EPA will accept for review and evaluation application packages that may not have all of the 

newly required data in appropriate cases supported by adequate justification. This early 

implementation period could extend up to two years post-promulgation for situations in which a 

more time-intensive new study is missing but could be less for other situations. The registrant 

should address the issue of timing (i.e., why the data are not yet submitted and when the data can be 

submitted) with respect to any missing newly-required data, in their justification. 

EPA is statutorily required to evaluate the proposed pesticide thoroughly to ensure that it will not 

harm human health or the environment. For pesticides with food uses, EPA is statutorily required to 

make a safety finding that the pesticide can be used with "reasonable certainty of no harm." In cases 

where the application may not have all the required data, EPA would try to make a registration 

determination or a safety finding based on the available data or on the results of other studies in the 

pesticide’s database. If there is insufficient information, and if the database does not provide 

information on the endpoints that would be tested, or data provided by the applicant or information 

in the database shows evidence of effects, EPA may not be able to make a registration decision or 

safety finding. In such cases, the application may be denied or held-up. In some cases, conditional 

registrations may be appropriate for consideration. As always, any decision whether or not to issue a 

conditional registration will be made by EPA on a case-by-case basis. Among other things, a 

determination that the proposed use will not significantly increase the risk of unreasonable adverse 

effects on the environment will need to be made. If EPA can make that determination and the other 

elements for a conditional registration are met, then a conditional registration may be appropriate 

and the new data required as a condition of registration. If there is a basis for a conditional 

registration, then the timeframe for conditioning the registration would be determined based on 
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Master Responses: Legal Issues Section (30) Page 48 

factors such as the required studies involved and the length of time required to conduct those 

studies. 

Importantly, it should be noted that acceptance of an application for processing during early 40 CFR 

Part 158W implementation that does not result in a conditional registration would not permanently 

relieve the applicant from providing the newly required data. Based on the particular case involved, 

the Agency will employ appropriate mechanisms, for example, through a Data Call-In (DCI) or 

through the registration review process, to ensure the generation and submission of any missing 

newly-required data. 

 

With respect to pending applications that are withdrawn, additional PRIA registration fees will 

generally only be required if the applicant seeks to pursue the action again by submitting a new 

application (and addressing the deficiencies in the original application). In withdrawal situations, the 

Agency provides a refund for any work that the Agency did not perform on the application 

following a withdrawal. Similarly, a determination that the application cannot be granted does not 

require additional PRIA registration fees. In that case, additional fees will only be incurred if the 

application is subsequently withdrawn or denied, and the applicant seeks to pursue the action again 

and submits a new application. 

Comment 30.19: Commenter notes that the proposed rule has not clearly identified circumstances 

under which an Experimental Use Permit (EUP) would be required for antimicrobials or what data 

requirements are applicable. 

Response 30.19: An EUP is usually requested in order to derive information needed for a FIFRA 

section 3 registration. Most antimicrobial studies can be conducted in a laboratory. In fact, for 

efficacy data, laboratory studies are preferred since the study can be repeated using the same test 

method, test requirements and subject to the same performance standard. However, there are a few 

exceptions, which would be evaluated on a case-by-case basis, where field studies are required in 

addition to or in place of laboratory studies. Examples include use patterns such as swimming pools, 

where the discharge would likely be down-the-drain to a waste water treatment plant, a storm drain 

that discharges to a stream, or directly to soil; and antifoulants and ballast water treatments, where 

there may be direct exposure in or a discharge to the marine environment. If a field study is required 

to support a public health claim, the Agency usually requires that a protocol be submitted and 

approved prior to conducting the study. 

Since most antimicrobial studies can be conducted in a laboratory, EPA receives few EUP 

applications for antimicrobial pesticides. Applicants who believe an EUP is required often meet with 

EPA to discuss the data required to support an EUP application. Upon an initial evaluation of the 

product, its potential uses, and data presented by the applicant, EPA could advise the applicant to 

move forward directly to registration or to proceed with the EUP application process. In general, 

the data needed to issue an EUP for an antimicrobial are the same data that may support a FIFRA 

section 3 registration. EPA's experience is that EUP applicants often rely on the existing data base 

for the active ingredient since the EUP requested is often for an unregistered use of an existing 

active ingredient. 

EPA receives few EUP applications for antimicrobial pesticides. Therefore, when one is requested, 

the EUP applicant often cites and relies on the existing data base for a registered active ingredient. 
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Accordingly, EPA does not believe that specific requirements for antimicrobial EUP's are needed 

and intends to continue its current case-by-case approach. 

The regulations for EUPs are specified in 40 CFR part 172 subpart A. Pesticide Registration 

Improvement Act (PRIA) service fees and timeframes for EPA’s review of the EUP application are 

available on-line at http://www.epa.gov/pesticides/fees. For antimicrobials see PRIA code A520. 

Comment 30.24: Commenter notes that terms “antimicrobial” and “antimicrobial pesticide” have 

multiple meaning impacting the scope of the proposed rule. As a result, the scope should be 

clarified. 

Response 30.24: As discussed in the preamble to proposed 158W (73 FR 59385-3), the scope of 

proposed 158W has been expanded beyond the term “antimicrobial pesticide” as defined in FIFRA 

section 2(mm) to ensure that all pesticides currently considered as antimicrobial products for the 

purpose of PRIA fees and review periods are covered. A complete discussion of the PRIA 

categories can be found on-line at http://www.epa.gov/pesticides/regulating/fees/tool/categorytable.html. 

Comment 30.25: Commenter notes that, unlike conventional pesticides, antimicrobials are not 

intended for being directly broadcast into the environment. Hence, the rigor and extensiveness of 

environmental fate and ecotoxicity data requirements applied to conventional pesticide uses are not 

relevant to once-through antimicrobial uses. As an example, the commenter notes that any release 

from a once-through water treatment system is a point-source discharge comprehensively regulated 

under the Clean Water Act, whereas conventional pesticides directly broadcast to the environment 

are treated as non-point source discharges for which there are no equivalent permit requirements or 

regulations. 

Response 30.25: While many antimicrobials are not directly dispersed into terrestrial or aquatic 

environments, there are many uses for which a high potential for exposure exists, especially outdoor 

uses such as wood preservatives, ballast water, antifoulant paints/coatings, industrial processes and 

water circulating systems, aquatic areas, and others. Water circulating systems have the potential for 

significant environmental exposure when the treated water is released to the environment. Large 

volumes of water may be released directly to a river, estuary, or marine environment within minutes 

or hours of adding the antimicrobial to the system. In addition to the potential for environmental 

exposure after release, there is the potential for high human exposure via drinking water if the intake 

pipe for a drinking water treatment plant is downstream. Also, the water could be used in crop 

and/or livestock production thus providing for additional human exposure. 

Under the Clean Water Act, EPA regulates point source pollution wastes discharged from discrete 

and identifiable sources, such as pipes and other conveyances. Any facility that discharges 

wastewater to a municipal sewer system or directly to surface water may require an NPDES permit. 

As discussed in the preamble to the proposed rule (73 FR 59406-07), based on comment received 

on the conventionals data requirements proposed rule, EPA developed a methodology to conduct a 

screening-level assessment of down-the-drain antimicrobial uses. Under FIFRA, the Agency is now 

requiring the data needed to assess the uses of antimicrobial pesticides and the distribution of 

residues in the environment as a result of antimicrobial down-the-drain use. Before registering a new 
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pesticide or a new use for a registered pesticide, EPA must first ensure that the pesticide, when used 

according to label directions, can be used without posing unreasonable risks to humans and the 

environment. Based on the Agency’s concern about the potential effects of antimicrobials on the 

biological treatment processes used in wastewater treatment plants, as well as its concerns about the 

persistence of antimicrobials in the effluent and their possible effects on nontarget species, EPA 

believes that the same rigor and extensiveness of environmental fate and ecotoxicity data 

requirements applied to conventional pesticide uses are relevant to antimicrobial uses. 

Comment 30.26: The American Chemistry Council (ACC) Biocides Panel and other commenters 

have claimed that the scope of the proposed rule exceeds the EPA’s statutory authority because it 

imposes data requirements on pesticide uses that do not require clearance under FFDCA section 

408 by EPA but rather require clearance from FDA under FFDCA section 409. The ACC Biocides 

Panel argues that EPA is wrong to rely on FIFRA section 2(bb)(2) to impose a FFDCA section 408 

analysis on pesticide uses falling under FDA’s FFDCA section 409 jurisdiction. Labeling the 

interpretation of FIFRA section 2(bb)(2) in the proposed rule as “new,” the ACC Biocides Panel 

claims that EPA has contradicted its “long-standing” interpretation of this provision. The ACC 

Biocides Panel further asserts that EPA’s alleged “new” interpretation causes a host of practical 

problems. 

Response 30.26: 

In the preamble to the final rule, EPA has explained in detail its authority to require data relevant to 

FIFRA’s “unreasonable adverse effects” standard for antimicrobial pesticides. This explanation 

specifically addressed EPA’s authority to require dietary risk information on antimicrobial pesticides 

which are governed under the FFDCA under section 409 and not section 408. In this Response to 

Comments document, EPA has provided a further explanation of how the ACC Biocides Panel has 

misconstrued the ARTCA and FIFRA section 2(bb)(2). 

Contrary to the ACC Biocide Panel’s claim, EPA’s interpretation of FIFRA section 2(bb)(2) is not 

“new” but rather the interpretation of section 2(bb)(2) that EPA has consistently taken since the 

passage of the Antimicrobial Regulation Technical Correction Act (ARTCA), Public Law 105-324, in 

1998. ARTCA divided FFDCA jurisdiction between EPA and FDA with respect to antimicrobials. 

Moreover, the American Chemistry Council (ACC) Biocides Panel is well aware that EPA’s 

interpretation of FIFRA section 2(bb)(2) is not new, having been a frequent critic of EPA’s 

interpretation over the last 10 years. As explained below, EPA’s interpretation is fully consistent 

with the law. On the other hand, the ACC Biocides Panel’s approach would involve amending the 

language of section 2(bb)(2) in a manner specifically rejected by the Congress when it passed 

ARTCA. 

Prior to 1996, section 408 of the FFDCA only applied to pesticides used in the production of raw 

agricultural commodities. Pesticide residues in food not falling within this provision were regulated 

under section 409 of the FFDCA as food additives. Many antimicrobial pesticides used in 

manufacturing and processing foods, at that time, were regulated as food additives. This division of 

legislative authority was changed by the Food Quality Protection Act (FQPA). The FQPA amended 

the definition of “pesticide chemical” in the FFDCA to make it co-terminous with the definition of 
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a “pesticide” in FIFRA by deleting the language restricting pesticide chemicals to those pesticides 

used in the production of raw agricultural commodities. [P.L 104-170 § 402, 110 Stat. 1489, 1513 

(1996)]. Not only did Congress consolidate regulation of all pesticide residues in FFDCA section 

408 but it amended FIFRA to insure that the new safety standard in FFDCA section 408 was part 

and parcel of the FIFRA registration standard for pesticides resulting in residues in food. [7 U.S.C. § 

136(bb)(2)]. 

In 1998 in the ARTCA, Congress modified slightly its FFDCA decision to consolidate all pesticide 

chemical residues in foods under FFDCA section 408. That law amended the definition to pesticide 

chemical in FFDCA section 201 to exclude certain antimicrobial substances from the coverage of 

the definition [See 21 U.S.C. 321(q)]. More specifically, with certain qualifications, the ARTCA 

excepted, from the definition of pesticide chemical, substances that are FIFRA pesticides and are 

“applied for [an antimicrobial] use on food, or the substance is included for such use in water that 

comes into contact with food, in the preparing, packing, or holding of the food for commercial 

purposes.” [21 U.S.C. 321(q)(1)(B)(i)]. In addition, ARTCA excepted substances from the 

definition of pesticide chemical that are food contact substances, as defined in section 409(h)(6) of 

the FFDCA, based on certain circumstances related to their use. These antimicrobial substances 

were now no longer considered “pesticide chemicals” under the FFDCA but fell under the 

definition of “food additives.” That had the effect of shifting jurisdiction over the residues resulting 

from these antimicrobial substances from FFDCA section 408 to FFDCA section 409. FDA 

administers the establishment of food additive regulations under FFDCA section 409. Importantly, 

Congress, in ARTCA, did not amend FIFRA to remove these uses of antimicrobial substances from 

the definition of “pesticide” under FIFRA and left unchanged FIFRA section 2(bb)(2) which 

mandates that the section 408 safety standard is part of FIFRA’s unreasonable adverse effects 

standard as to FIFRA “pesticide” residues on food. Thus, EPA retained FIFRA jurisdiction over 

these antimicrobial substances (because they remained FIFRA “pesticides”) while FDA re-acquired 

FFDCA jurisdiction over them under FFDCA section 409 (because they were removed from the 

definition of “pesticide chemical”). To make clear its intent on EPA’s FIFRA jurisdiction, Congress 

included the following express disavowal as part of ARTCA: “With respect to the definition of the 

term ‘pesticide’ that is applicable to the Federal Insecticide, Fungicide, and Rodenticide Act, this 

clause [excluding certain antimicrobial substances from the FFDCA definition of “pesticide 

chemical”] does not exclude any substance from such definition.” [21 U.S.C. § 321(q)(1)(B)]. 

Since its passage, EPA has interpreted the ARTCA according to its plain language, excluding the 

designated antimicrobial substances from the coverage of FFDCA section 408 but continuing to 

regulate those antimicrobial substances that qualify as FIFRA “pesticides” under FIFRA and 

requiring that, when those antimicrobial pesticides result in residues in food, the risks from such 

residues not be inconsistent with the safety standard in FFDCA section 408. After all, FIFRA 

section 2(bb)(2), on its face, applies to FIFRA “pesticides” and not FFDCA “pesticide chemicals.” 

Any other result would be directly contrary to Congress’ dictate that it was not excluding any 

substances from the FIFRA definition of “pesticide.” 

EPA’s interpretation is also clearly consistent with Congress’ expressed intent at the time of the 

passage of the ARTCA. Although Congress indicated that it thought it had been a mistake to give 

EPA jurisdiction under the FFDCA over the affected antimicrobial substances, at the same time, 

Congress made clear that it did not intend to weaken the new safeguards imposed by the FQPA. On 

the House floor, Representative Bliley (R-VA), stated that “[the ARTCA] is strictly a technical 
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Master Responses: Legal Issues Section (30) Page 52 

corrections measure; it does not represent a change in FQPA policy, and it does not weaken any 

environmental safeguards.” [144 Cong. Rec. 24282 (1998)]. At the close of his statement, 

Representative Bliley asked for, and received, unanimous consent, to revise and extend his remarks. 

(Id.). Representative Bliley was, at that time, Chairman of the House Energy and Commerce 

Committee ---the Committee having jurisdiction over the ARTCA---as well as the sponsor of the 

ARTCA, and one of two floor managers of the ARTCA. The bill’s other floor manager, 

Representative Brown (D-CA) also addressed the question of how the ARTCA affected the FQPA 

protections in FIFRA. Representative Brown stated that “[t]his legislation would not change the 

Federal Insecticide, Fungicide, and Rodenticide Act or remove any use of a substance from 

regulation as a pesticide under that Act.” (Id.). He further explained that “[t]he Environmental 

Working Group, the Natural Resources Defense Council, and many other public interest groups 

have agreed not to oppose the legislation. At their request, language has been included to recognize 

that FQPA protective provisions have not been eliminated.” [144 Cong. Rec. 24283 (1998)]. Shortly 

after passage of the bill by the House but prior to the President’s signing of the legislation, 

Representative Bliley inserted his extended remarks into the Congressional Record. [144 Cong. Rec. 

27678-27679 (1998)]. Representative Bliley emphasized that the ARTCA would “affect the 

regulation of antimicrobial pesticides only under the FFDCA.” (Id.). According to Representative 

Bliley, “EPA would continue to regulate antimicrobial pesticides under FIFRA, and EPA’s 

authorities under that statute would not be changed.” (Id.). To remove any doubt as to his meaning, 

Representative Bliley then stated that EPA would examine antimicrobial pesticides under the FIFRA 

regulatory standard, as defined by section 2(bb), and he quoted section 2(bb)(2) in full. He 

concluded that “it is Congress’ intent that EPA, in deciding under FIFRA whether to grant, amend, 

or cancel a registration for an antimicrobial pesticide that poses a human dietary risk, shall take such 

action only if EPA determines that the risks from such residues are not inconsistent with the safety 

standard in FFDCA sec. 408.” (Id.). In line with its interpretation of FIFRA section 2(bb)(2), EPA 

has consistently reviewed applications for registration of antimicrobial pesticides under FIFRA 

under the standard in FIFRA section 2(bb)(1) as well as the safety standard set out in FFDCA 

section 408 as specified in FIFRA section 2(bb)(2). [R2C Refs. 3 – 10, 19]. The ACC Biocides Panel 

has been a frequent critic of that approach. As ACC Biocides Panel admitted in a 2006 filing with 

EPA, “[t]he ACC Biocides Panel has been working since 1999 to solve a set of problems caused by 

EPA’s interpretation of FIFRA and FQPA following the enactment of ARTCA of 1998.” [R2C Ref. 

1]. For example, in an August, 2000, letter to EPA [R2C Ref. 2], the ACC Biocides Panel wrote: 

The Environmental Protection Agency (“EPA”) currently is following a policy that requires it to 

conduct risk assessments under section 408 of the Federal Food, Drug, and Cosmetic Act 

(“FFDCA”), 21 U.S.C. § 321 et seq., [sic] before approving direct and indirect food contact uses of 

antimicrobial products that already have been approved by the Food and Drug Administration 

(“FDA”) under section 409 of the same statute. . . . EPA has implemented this policy of duplicative 

regulation based upon its interpretation of section 2(bb) of the Federal Fungicide, Insecticide, and 

Rodenticide Act [sic], (“FIFRA”), 7 U.S.C. § 136(bb), as amended by the Food Quality Protection 

Act of 1996 (“FQPA”), Pub. L. 104-170 (1996) and sections 408 and 409 of the FFDCA, as 

amended by the Antimicrobial Regulation Technical Corrections Act (ARTCA) of 1998, Pub. L. 

105-324 (1998). . . . [T]his interpretation is inconsistent with the plain language and purpose of the 

statutory provisions, and results in an irrational application of the statute. 

[R2C Ref. 2 transmitted by Letter R2C Ref. 14; See R2C Ref. 15 (noting that “two Panel member 

companies report that EPA is following this interpretation [of FIFRA section 2(bb)(2)] in acting on 
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registration amendments to add uses covered by clearances issued by FDA under Section 409 of 

FFDCA”)]. 

Similar memoranda and issue papers have been submitted by ACC Biocides Panel to EPA since that 

time. [See, e.g., R2C Ref. 11 (“EPA maintains that, although ARTCA removed antimicrobial food 

additive uses from EPA under FFDCA 408 [sic] and returned them to FDA under FFDCA [sic] 

408, FIFRA section 2(bb) mandates that EPA regulate antimicrobial food additive uses using the 

same methods, policies and practices it uses with pesticides under FFDCA 408 [sic].”); R2C Refs. 

16, 17, 18]. 

The ACC Biocides Panel in its comments on this proposed rule makes an abrupt about face. 

Ignoring a decade of ACC Biocides Panel criticism of EPA’s consistent and contemporaneous (with 

ARTCA) interpretation of FIFRA section 2(bb)(2) as applying to FIFRA pesticides excluded from 

FFDCA section 408, the ACC Biocides Panel now asserts that this EPA interpretation is a “new” 

interpretation which reverses a “long-standing position” and EPA has failed to give an adequate 

explanation for its change in policy. As support for this claim, ACC Biocides Panel cites to the 

following statement from EPA’s Threshold of Regulation Policy [R2C Ref. 12]: “FIFRA section 

2(bb)(2) does not apply to a registration decision when a tolerance is not required because use of the 

pesticide does not result in residues in or on the food.”1

 This statement, however, does not aid the 

ACC Biocides Panel’s claim; it is taken out of context from a policy statement having nothing to do 

with the ARTCA. Importantly, the statement does not say that section 2(bb)(2) applies only where a 

tolerance is necessary or only where a “pesticide chemical” is involved. Rather, it merely states that 

section 2(bb)(2) does not apply in the situation where a tolerance is not required because use of the 

pesticide does not result in residues in or on food. What the quoted statement from the Threshold of 

Regulation Policy does not address is whether section 2(bb)(2) applies when a tolerance is not 

required because residues of a pesticide that are in food are excluded by FFDCA section 201(q) from the coverage of 

section 408’s tolerance requirements. It is logical that the policy did not address this question because it 

concerned the meaning of section 408’s reference to “pesticide chemical residues in or on food” not 

the provisions of the ARTCA or the definitions of “pesticide” or “pesticide chemical.” Any possible 

ambiguity concerning what EPA meant by the quoted statement is resolved later in the policy 

statement where EPA made clear that section 2(bb)(2) was not limited to circumstances where a 

section 408 tolerance was required. Specifically, EPA wrote: “FIFRA section 2(bb)(2) applies to a 

registration decision when a tolerance is required for the use under consideration or the use otherwise 

results in residues in or on food. (Threshold of Regulation Policy [R2C Ref 12] at p.33 (emphasis added)). 

ACC Biocides Panel criticizes EPA’s interpretation of section 2(bb)(2) because it allegedly “causes a 

host of practical problems” – mainly the costs of verifying that the heightened FQPA safety 

standard is met and the possibility of different regulatory judgments under the different regulatory 

 

1

 This is a longstanding interpretation of EPA in this sense: except for the differences between the FIFRA definition 

of “pesticide” and the FFDCA definition of “pesticide chemical,” EPA has consistently interpreted section 

2(bb)(2)’s reference to “residues that result from a use of a pesticide in or on any food” as essentially identical to 

section 408(a)’s threshold requirement pertaining to “any pesticide chemical residue in or on food . . . .” In other 

words, EPA has interpreted any pesticide chemical residue qualifying under FFDCA section 408(a)’s reference to 

any “residue in or on food” as a “residue[] that result[s] from a use of a pesticide in or on any food” under FIFRA 

section 2(bb)(2). With the passage of ARTCA, the scope of FIFRA section 2(bb)(2) becomes broader extending to 

residues in food of pesticides, whether or not the pesticide is a pesticide chemical under the FFDCA. However, both 

standards focus on whether use of the defined substance results dietary exposure from residues in or on food. 
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standards in FFDCA sections 408 and 409. These alleged practical problems, however, do not 

permit EPA to evade the plain language of section 2(bb)(2) and the ARTCA. Basically, ACC 

Biocides Panel is unhappy that Congress in the ARTCA only amended the definition of “pesticide 

chemical” in the FFDCA and did not amend section 2(bb)(2) by substituting a reference to the 

FFDCA’s definition of “pesticide chemical” for the reference to a FIFRA “pesticide.” As the 

congressional debate makes clear, however, such an amendment could not have been accomplished 

by technical amendment which requires unanimous consent from Congress. Both Representatives 

Bliley and Brown emphasized on the floor of the House how important it was that the ARTCA was 

not weakening the recently-approved FQPA safety provisions for any pesticide. 

The ACC Biocides Panel also argues that the ARTCA is meaningless unless it is interpreted as 

amending FIFRA section 2(bb)(2). But this is not true. The ARTCA accomplished the most that 

could be accomplished given the limitation of the technical amendment process that demands 

unanimous consent. One key accomplishment was reclassifying certain uses of antimicrobial 

pesticides under the FFDCA as food additives and not pesticide chemicals. This was a major goal of 

Albright & Wilson Americas, Inc., a biocide manufacturer which campaigned tirelessly for the 

ARTCA. Albright & Wilson Americas had developed an antimicrobial pesticide that had received 

the Presidential Green Chemistry Challenge Award from EPA in 1997. In fact, Albright & Wilson 

America’s product became a rallying point for the passage of ARTCA. [See 144 Cong. Rec. 24282 

(1998) (statement of Rep. Bliley) (“one of the products blocked from the market [by the transfer of 

antimicrobials from FDA to EPA] actually won the President’s Green Chemistry Award of its 

environmental benefits”)]. This company desperately wanted approval quickly under the FFDCA 

and wanted that approval from FDA and not EPA. At one point, EPA offered to speed approval of 

Albright & Wilson Americas’ under FFDCA section 408 but Albright & Wilson responded that: 

“This approach would be a disaster for A&W, as its potential papermill customers will not use the 

product if it is regulated as a pesticide chemical.” [R2C Ref. 13] The ARTCA made sure that 

Albright & Wilson Americas’ would get FFDCA clearance for its product as a food additive but did 

not remove the product from FIFRA coverage. 

References: 

R2C Ref. 1: ACC Biocides Panel, “Regulation of Antimicrobials that are Indirect or Secondary 

Direct Food Additives” (February 2, 2006). 

R2C Ref. 2: Memorandum from American Chemistry Biocides Panel to Frank Sanders, “EPA’s 

Current Interpretation of the Antimicrobial Reform Technical Corrections Act and Section 2(bb) of 

FIFRA is Inconsistent with the Statutes” (August 3, 2000). 

R2C Ref. 3: McMahon, T; (D273502) (October 15, 2002); Sodium chlorite: risk assessment for use 

in swimming pools. 

R2C Ref. 4: McMahon, T; (D272375 and D272376) (January 17, 2002); Zeomic Type AJ10D Silver 

Zeolite A: Risk assessment for addition of uses to an existing label. 

R2C Ref. 5: McMahon, T; (D274634) (February 25, 2002); Review of Threshold of Regulation 

request for use of Chorine Dioxide on stored potatoes 
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R2C Ref. 6: Reregistration Eligibility Decision for Polyhexamethylene biguanidine (PHMD). 

September 30, 2004. Case 3122. See regulations.gov, Docket EPA-HQ-OPP-2004-0305. Also 

available at http://www.epa.gov/oppsrrd1/REDs/phmb_red.pdf. 

R2C Ref. 7: Reregistration Eligibility Decision for 1,2-Benzisothiazolin-3-one (BIT). September 29, 

2005. Case 3026. See regulations.gov, docket. EPA-HQ-OPP-2005-0200. Also available at 

http://www.epa.gov/oppsrrd1/REDs/benzisothiazolin_red.pdf. 

R2C Ref. 8: Reregistration Eligibility Decision for Halohydantoins. September 2007. Case 3055. See 

regulations.gov, Docket EPA-HQ-OPP-2004-0303. Also available at 

http://www.epa.gov/oppsrrd1/REDs/halohydantoins-red.pdf. 

R2C Ref. 9: Reregistration Eligibility Decision for Aliphatic Alkyl Quaternaries (DDAC). August 

2006. Case 3003. See regulations.gov, docket EPA-HQ-OPP-2006-0338. Also available at 

http://www.epa.gov/oppsrrd1/REDs/ddac_red.pdf. 

R2C Ref. 10: Reregistration Eligibility Decision for Alkyl Dimethyl Benzyl Ammonium Chloride 

(ADBAC). August, 2006. Case 0350. See regulations.gov, docket EPA-HQ-OPP-2006-0339. Also 

available at http://www.epa.gov/oppsrrd1/REDs/adbac_red.pdf. 

R2C Ref. 11: American Chemistry Council, Biocides Panel, “EPA/FDA Jurisdiction for Food 

Contact Antimicrobials” Vol. 1 (July 17, 2003) 

R2C Ref. 12: Office of Pesticide Programs, U.S. EPA, Threshold of Regulation Policy – Deciding Whether 

A Pesticide With A Food Use Pattern Needs A Tolerance 12 (October 18, 1999) available at 

http://www.epa.gov/fedrgstr/EPA-PEST/1999/October/Day-27/6042.pdf). 

R2C Ref. 13: Letter from Charles L. Grizzle, representative of Albright & Wilson Americas, Inc., to 

Lynn R. Goldman, Assistant Administrator for Prevention, Pesticides and Toxic Substances, U.S. 

EPA (September 11, 1997). 

R2C Ref. 14: Transmittal Letter for R2C Ref. 2 from Hasmukh C. Shah, Manager, Biocides Panel, to 

Frank T. Sanders, Director, Antimicrobial Division, Office of Pesticide Programs, U.S. EPA, 

(August 3, 2000). 

R2C Ref. 15: Comments of Chemical Manufacturers Association’s Biocides Panel On EPA’s 

September 17, 1999 Proposed Rule on Registration Requirements for Antimicrobial Pesticide 

Products and Other Pesticide Regulatory Changes for Codification (January 18, 2000) 

R2C Ref. 16: American Chemistry Council, Biocides Panel, “EPA/FDA Jurisdiction for Food 

Contact Antimicrobials” Vol. 3 Tab 3 (July 17, 2003) Tiered Testing for Risk Assessment of 

Antimicrobial Pesticides; ChemReg International, L.L.C., (September 12, 2002). 

R2C Ref. 17: American Chemistry Council, Biocides Panel, “EPA/FDA Jurisdiction for Food 

Contact Antimicrobials” Vol. 2 Tab 7 (July 17, 2003) Presentation by Seth Goldberg on Section 

2(bb) of FIFRA; Dual Jurisdiction Over Food Contact Antimicrobials (April 27, 2001). 
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R2C Ref. 18: American Chemistry Council, Biocides Panel, “EPA/FDA Jurisdiction for Food 

Contact Antimicrobials” Vol. 2 Tab 7 (July 17, 2003) Biocides Panel Comments on The Preliminary 

Risk Assessment for 1,4-Bis(bromoacetoxy)-2-butene (BBAB), (August 6, 2001). 

R2C Ref. 19: McMahon, T; (D262970) (December 20, 2000); “Fit” Fruit and Vegetable Wash: 

Request for dietary risk assessment. 
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Master Responses: 

Economic Analysis Section (40) Page 57 

Economic Analysis (40) 

Master Responses for the Economic Analysis Section 

Please note that EPA responses are presented in numerical order. However, in the course of response development, 

some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are missing. 

Comment 40.1: A commenter performed an independent economic analysis for the proposed rule. 

According to the commenter’s analysis, the cost of proposed 158W is greater than that estimated by 

the EPA. In addition, unit test costs and frequency of tests are different than EPA’s estimates. 

Response 40.1: EPA reviewed the commenter’s analysis and based on that review revised the EA for 

the final rule. EPA’s evaluation of the commenter’s EA indicated there were the following 

differences between the two EAs:

 the cost estimates used for the studies 

 overhead costs were included by the commenter, but not by EPA 

 costs for Registration Review (see comment ). 

The differences between the cost of the proposed rule as estimated by the commenter and the cost 

as assessed by the Agency for new registrations are explained in the following subunits. 

How data requirement costs are calculated

The annual cost of a data requirement to the industry for a use and registration type (new active 

ingredient or major new use) is the product of three factors: unit test cost, test probability, and the 

number of registrations in the industry per year for the registration type and use. That is: 

Industry Cost of a data requirement = Unit test cost x test probability x number of registrations 

These costs are summed for all data requirements, uses, and registration types to get the total annual 

cost of the data requirements for the industry. The terms used here are explained as follows: 

Data requirement—specific information, typically the results of a specified test, that is required 

under specified conditions 

Unit test cost—the cost of performing a test to fulfill a data requirement. 

Test probability—the probability of the test being required for a registration. This probability 

varies by the type of registration and by the pesticide use. 

Use—the use to which an antimicrobial is applied, such as food, nonfood, industrial, 

antifoulant, and wood preservative. 

Registration type—new active ingredient, major new use registration or amendment. 

Number of registrations in the industry per year for the registration type and use. 

The method of cost calculation is explained more precisely as follows: 

CDur = TD × PDur

Rur = ∑CDur 

Industry Cost of the data requirements = ∑(Rur× Nur) 

where 
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CDur = the expected cost of data requirement D on use pattern u for registration type r. 

TD = the unit test cost of data requirement D. 

PDur = the test probability of data requirement D for use pattern u and registration type r. 

Rur = the expected cost of a registration action for use pattern u and registration type r. 

∑CDur = the sum of the expected costs of all data requirements for use pattern u and registration 

type r. 

Nur = the number of registrations for the industry on use pattern u for registration type r. 

∑(Rur× Nur) = the sum of the expected cost of all registration actions for all use patterns and 

registration types. 

Differences in unit test costs

EPA acknowledges that there are significant differences between the Agency’s analysis and the 

commenter’s analysis regarding the unit test costs. According to the commenter’s EA, their costs are 

based on quotes from laboratories, actual experience, and professional judgment. EPA obtained data 

used to estimate the unit test costs for each data requirement by contacting established contract 

research organizations (CROs) to assess what the labs would charge to conduct studies according to 

specific designs provided by EPA, or as specified in OPPTS guidelines. Upper and lower cost 

estimates were requested. For each test the upper cost estimates from each CRO were averaged to 

obtain a high average estimate. A similar calculation was done for the lower cost estimate. EPA’s 

estimate is the average of the high and low average estimates. 

Test costs and overhead costs

The commenter added 30 percent to their test cost estimates to account for the overhead of the 

registrants managing and overseeing the tests they contract to the labs. EPA acknowledges that there 

are costs other than test costs associated with registering and maintaining the registrations of 

pesticide products. However, these are not new costs, and EPA does not believe these overhead 

costs will change significantly as a result of the proposed rule. EPA does not include overhead costs 

in its economic analyses of data requirements rules because the Agency accounts for other 

registration costs in the Information Collection Request (ICR) for FIFRA Section 3 Registration 

under the Paperwork Reduction Act. 

Test probabilities

EPA’s test probabilities (the probabilities of tests being required for a registration actions) were 

based on a sample of 70 actual antimicrobial registration actions out of 90 relevant new registration 

actions during the six year period from 2000 through 2005, supplemented EPA’s scientific 

judgment. The time period (2000-2005) was chosen for EPA’s EA because the analysis in the EA 

was started in 2006. The commenter claims to have based the test probabilities used to make their 

estimates on a sample of 29 registration review cases (not new registrations) occurring between 2008 

and 2010. 

Factors which drive costs for new registrations

As discussed above, the cost of data requirements is the product of three factors: unit test costs, test 

probabilities, and number of registrations. In addition, the commenter included overhead costs in 

their economic analysis. To determine the influence of these factors on the difference between the 

commenter’s and EPA’s estimates, EPA performed the following analysis on the data requirements 
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Economic Analysis Section (40) Page 59 

costs and incremental costs using the same unit test costs and test probabilities used in the proposed 

rule: 

1. To account for the effect of the unit test costs on the data requirements costs and 

incremental costs, EPA substituted the commenter’s unit test costs without overhead into 

EPA’s analysis of the proposed rule using EPA’s test probabilites and number of 

registrations. If there were no changes, this would indicate that the test costs were not 

driving the differences in estimates. 

2. To account for the effect of test probabilities and number of registrations, EPA substituted 

the commenter’s unit test costs with overhead into EPA’s analysis. In this case, the 

difference between the EPA’s and the commenter’s analysis is contained in the test 

probabilities and number of registrations. If there were no changes, this would indicate the 

test probabilities and number of registrations were not driving the differences between the 

two analyses. Since the commenter includes overhead in their analysis, overhead was 

included in this comparison to make other things equal so that the differences in test 

probabilities and number of registrations could be isolated. 

Table 1. Comparison of Data Requirement Costs and Factors for New Registrations 

Column A B C D 

Unit Test Costs according to: 

EPA 

Proposed 

Rule 

Commenter 

wthout 

overhead 

Commenter 

with 30% 

overhead 

Commenter 

with 30% 

overhead 

Test Probabilities according to: EPA EPA EPA Commenter 

Number of Registrations 

according to: 

EPA EPA EPA Commenter 

Data Requirement Cost according to 

Proposed Rule ($ millions) 

$15.0 $19.9 $25.5 $25.9 

Cost of Proposed Rule 

(Incremental Costs) ($ millions) 

$3.9 $7.6 $9.8 $9.2 

 

Results

The results of the factor analysis are presented in Table 1. Column A exhibits the data requirements 

and incremental costs from EPA’s Economic Analysis of the proposed rule. In column B, the data 

requirements and incremental costs are calculated using the commenter’s unit test costs without 

overhead costs, but EPA’s test probabilities and number of registrations. Column C is the same as 

column B, but with overhead costs included. Finally, column D exhibits the data requirements and 

incremental costs with overhead as calculated by the commenter. 

The result of the first factor analysis is demonstrated by comparing column A to column B. In this 

case, the difference between the two columns is the unit test costs. Inserting the commenter’s unit 

test costs, without overhead, into the cost estimates with EPA’s test probabilities and number of 

registrations leads to over a 30 percent increase in data requirements cost and a nearly 100 percent 

increase in incremental costs. 

The result of the second factor analysis is demonstrated by comparing columns C and D. In this 

case, the difference between the two columns is in the test probabilities and number of registrations. 
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Economic Analysis Section (40) Page 60 

While individual test probabilities may be different in EPA’s and the commenter’s analyses, the 

overall effect of the products of test probabilities and number of registrations, when summed with 

the unit test costs, including overhead, are similar in both of these analyses. The resulting differences 

in data requirements cost and incremental costs are less than 2 percent and about 6 percent, 

respectively. Therefore, EPA concludes that any differences in test probabilities and number of 

registrations used as input parameters in the calculations do not have a significant effect on the total 

data requirement cost of new registrations. 

Comparisons across columns A, B, and C also provide information on the portion of the cost 

difference accounted for by overhead costs. Columns A, B, and C compare the cost of data 

requirements using the unit test cost estimates of EPA, and those of the commenter with and 

without overhead. The overhead costs account for more than one-half of the difference in the total 

cost of the data requirements, but less than 40 percent of the difference in incremental costs (the 

incremental cost is the increase costs between the baseline, CFR part 161, and proposed part 158W). 

From this comparison, EPA makes the following conclusions. First, differences in test probabilities 

and number of registrations do not have a significant impact on the cost of the rule. Second, even if 

EPA and the commenter used the same probabilities and test costs, inclusion of overhead costs by 

the commenter would result in a 30 percent difference in costs. Finally, when the overhead costs are 

removed from the commenter’s analysis, differences in unit test costs between EPA and the 

commenter account for most of the differences in the estimates of the cost of the rule for new 

registrations. 

Revised test costs

In light of the results of the comparison between EPA’s and the commenter’s EA, EPA sought to 

verify its unit test cost estimates. EPA obtained new estimates for 30 selected tests shown in Table 

2. The criteria for selecting which test’s cost to update included how the difference in estimates 

would impact on the cost of the rule, the magnitude of the differences in estimates, and the age and 

source of EPA’s estimates. Table 2 below compares EPA’s revised unit test cost estimates with the 

unit test cost estimates used in the proposed rule and the commenter’s unit cost estimates with the 

registrant overhead removed. The revised test costs will be used in the EA (economic analysis) of 

the final rule. EPA is using its cost estimates because it has revised its most relevant and oldest unit 

test cost estimates. In addition, the commenter did not provide a basis or sufficient explanation to 

justify EPA’s accepting the commenter’s costs. 
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Economic Analysis Section (40) Page 61 

Table 2. Comparison of Revised Unit Test Costs, with Commenter’s and Test Costs Used in the Proposed Rule. 

Test 

Guideline Test Name 

Average 

Test Cost 

Used in 

Proposed 

Rule

Average 

Test Cost 

Revised 

by EPA 

in 2010 

Commenter's 

Test Cost 

Estimates less 

Registrant 

Overhead Cost

835 Environmental Fate 

835.1110 Activated Sludge Sorption Isotherm $10,051 $19,733 $20,000

835.1230 Sediment and soil adsorption/desorption $23,750 $42,741 $25,000

835.2120 Hydrolysis $25,230 $41,938 $150,000

835.2410 Photodegradation on soil (soil photolysis) $42,350 $73,979 $80,000

835.3110 Ready Biodegradability $10,364 $8,667 $10,000

835.3220 Porous Pot Test $41,413 $33,000 $30,000

835.4200 Anaerobic soil metabolism $71,250 $150,167 $150,000

835.4300 Aerobic aquatic metabolism $44,475 $102,200 $140,000

835.4400 Anaerobic aquatic metabolism $80,900 $107,224 $140,000

850 Ecological Effects Tests 

850.1735 Whole sediment acute toxicity invertebrates (freshwater) $20,250 $21,903 $40,000

850.4250 Vegetative vigor, Tier II – dose response $24,500 $36,963 $50,000

850.4300 Terrestrial field $111,863 $44,000 $1,000,000

850.4450 Aquatic field $220,000 $28,500 $200,000

850.5400 Aquatic plant growth (algal) Tier II – dose response $35,155 $14,426 $60,000

850.6800 Modified Activated Sludge, Respiration Inhibition Test $5,126 $4,292 $6,000

None Whole sediment chronic invertebrates fresh and marine $51,350 $64,757 $100,000

860 Residue Chemistry 

860.1400 Irrigated crops $18,000 $87,500 $500,000

860.1500 Crop field trials $163,667 $83,650 $750,000

860.1520 Processed food/feed $35,000 $89,925 $500,000

870 Health Effects 

870.3250 90-day dermal toxicity 870.2500 in EA $137,094 $132,130 $250,000

870.3700 Prenatal developmental toxicity study - rat $76,844 $117,053 $175,000

870.3700 Prenatal developmental toxicity study - rabbit $76,844 $166,653 $200,000

870.3800 Reproduction and fertility effects $378,469 $393,307 $600,000

870.4100 Chronic tox - non-rodent $950,000 $757,910 $500,000

870.6200 Acute neurotoxicity - rat $89,596 $155,600 $200,000

870.6300 Developmental neurotoxicity $406,904 $702,500 $900,000

875 Occupational and Residential Exposure 

875.1300 Inhalation outdoor exposure $164,286 $450,000 $500,000

875.2200 Soil residue dissipation $83,125 $253,733 $350,000

875.2300 Indoor surface residue dissipation $35,000 $75,427 $250,000

875.2600 Biological monitoring $166,875 $375,000 $1,500,000
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Economic Analysis Section (40) Page 62 

Comment 40.2: A commenter noted that EPA’s economic analysis does not include the benefits that 

antimicrobials provide to individuals and industry, or the opportunity costs of undeveloped 

products. In addition, the commenter claimed that the cost of the rule represents a significant barrier 

to the development and registration of new and improved antimicrobials, and may result in the 

withdrawal of registered products. As a result, fewer product choices could increase the risk to the 

public from antimicrobial pests, and reduce the benefits from products that use antimicrobials in 

their production process. The commenter further suggested that EPA should "estimate the number 

of products likely to be withdrawn, the availability of efficient and effective substitutes, and 

consequences in the likely event that substitutes are not as effective as products they replace." 

Response 40.2: EPA recognizes that antimicrobials play an important role in public health and 

safety. In its economic analysis of proposed 158W [page 7], which is in the docket at 

http://www.regulations.gov for this rule and titled “Economic Analysis of the Proposed Data 

Requirements for Antimicrobial Pesticides,” EPA discussed the benefits associated with 

antimicrobial pesticide use. EPA agrees that increasing the cost of new registrations may result in 

fewer new registrations. Registrants may also choose to withdraw an existing registration when faced 

with the cost of maintaining a registration. However, EPA has a statutory mandate to ensure that 

use of pesticide products will not result in unreasonable adverse effects on human health or the 

environment. To make such findings, EPA must have data to conduct the appropriate risk 

assessments. 

EPA encourages registrants to consult with the Agency to make sure that registrants submit only the 

data necessary for EPA to make a registration determination. The proposed data requirements in 

many instances are tiered, with higher-tiered testing triggered on the results of lower-tiered testing. 

The data requirements are also tailored according to use pattern because different uses require 

different types and amounts of data. Sometimes, tests may be waived on a case-by-case basis. If 

available, open literature or the same tests on similar products, or alternative means to meet data 

requirements, such as Quantitative Structure Activity Relationship (QSAR), can be submitted for 

Agency consideration. These may present opportunities for cost savings by registrants, while 

allowing the Agency to fulfill its role of making pesticide regulatory decisions that protect the 

general population, sensitive sub-populations, and the environment. 

The Agency also agrees that fewer new registrations and increased registration withdrawals would 

reduce the number of antimicrobial products on the market. However, EPA does not have a 

practical way of estimating the number of products likely to be withdrawn. EPA’s past experience, 

however, is that decreases in the number of products are usually small and mostly transitional. Some 

products are withdrawn from registration, but eventually other products are then registered that may 

fill voids left by withdrawn registrations. 

Comment 40.4: The Commenter stated that EPA, in underestimating costs, is not fully complying 

with Regulatory Flexibility Act (RFA) and the Small Business Regulatory Enforcement Fairness Act 

(SBREFA), and must prepare an Initial Regulatory Flexibility Assessment (IFRA). In addition, the 

commenter noted that small businesses will be adversely affected, that there will be an "increased 

disparity between registrants and a more uneven playing field," and that a SBREFA analysis should 

have been conducted. 
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Economic Analysis Section (40) Page 63 

Response 40.4: EPA acknowledges that the cost of the data requirements would likely be a larger 

percentage of a small business’s revenues, but did not find that the rule would have a significant 

adverse economic impact on a substantial number of small firms. 

A regulatory flexibility analysis examines the type and number of small entities potentially subject to 

the rule, recordkeeping and compliance requirements, and significant regulatory alternatives, among 

other things. The RFA, as amended by SBREFA, requires EPA to consider the economic impact of 

proposed rules on small entities. The RFA requires EPA to prepare an IRFA for each proposed rule, 

when the rule will have a significant economic impact on a substantial number of small entities. 

To comply with the RFA, EPA did a retrospective analysis of what the additional costs would have 

been on actual new registrations if the proposed rule had been in effect during 2000-2005. This 

analysis did not indicate a significant impact on a substantial number of small entities; instead, the 

analysis indicated that 5 percent of small firms are likely to experience some impact and only 2.8 

percent of small firms are likely to experience an economic impact of 3 percent or more of gross 

sales. Based on this analysis, EPA certified that the proposed rule would not have a significant 

adverse economic impact on a substantial number of small firms. As a result, EPA did not have to 

conduct an IRFA nor convene a SBREFA Panel for the proposed 158W rule. An impact would not 

be considered significant if fewer than 100 small businesses are likely to experience an economic 

impact of 3 percent or more of gross sales, and less than 20 percent are likely to experience an 

economic impact of 1 percent or more of gross sales. In the EA for the final rule, EPA re-estimated 

the SBREFA analysis with revised unit test costs and changes in data requirements. 

 About 23 small firms (almost 5%) are likely to experience an economic impact of 3% or

more of gross sales, and

 About 26 small firms, (over 5%) are likely to experience an economic impact of 1% or

more of gross sales.

Hence, had these results been estimated at the proposal stage, EPA would still have concluded that 

there would not be a significant impact on a substantial number of small entities. 

Comment 40.6: A commenter stated that EPA has not accurately stated the potential costs and 

benefits, as required by Executive Order (EO) 12866. In particular, the commenter contended that 

EPA has not included the impact of incremental costs of new data requirements on registration 

review, or the cost of consultations. The commenter also claimed that under the Paperwork 

Reduction Act, EPA should include the paperwork burden costs of registration review for existing 

registrants. 

Response 40.6 EO 12866 requires the Agency to submit to OMB for review significant regulatory 

actions. EPA complied with EO 12866 during 2008 by submitting drafts of both the economic 

analysis and the proposed rule to OMB. The changes that were made to the proposed rule as the 

result of OMB’s review are included in the docket at http://www.regulations.gov. The Agency notes 

that one purpose of soliciting comments on the economic analysis at the proposal stage is to get 

input on where the Agency might improve the economic analysis. 
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Economic Analysis Section (40) Page 64 

The commenter is not correct in asserting that EPA did not include the impact of incremental costs. 

The Agency has captured the anticipated costs necessary for complying with the regulations. In 

addition, the incremental costs per registration action are presented in section 5.3 of the Agency’s 

economic analysis, and the average impact per firm is presented in section 5.5 of the economic 

analysis. See the Economic Analysis in the docket at http://www.regulations.gov for a more detailed 

discussion, particularly sections 5.3 and 5.5. 

The commenter is correct in that the costs of fulfilling data requirements during registration review 

were not considered in the Agency’s economic analysis of the proposed 158W data requirements. 

EPA agrees with the commenter that registrants of existing antimicrobial products will incur costs 

during registration review. When registration review was proposed, EPA prepared an economic 

analysis of that program, which estimated the cost of data requirements and paperwork burden 

according to what would likely be required in registration review for existing registrants. The 

registration review EA estimate of data requirement costs for existing antimicrobial pesticides was 

based on what would likely be required for a sample of antimicrobial active ingredients including all 

tests that have been required in current practice whether or not in 40 CFR 158. However, the 

proposed part 158W included new tests, which were not anticipated when the economic analysis of 

the registration review process was completed. In a final economic analysis for part 158W, EPA 

addresses the additional costs and paperwork burden associated with these new tests, as well as 

other changes from the proposed to final rule including changes made as a result of the comments 

received. 

The commenter is also correct that EPA did not include the cost of consultation in its economic 

analysis. Consultations are longstanding, commonly used, and valuable processes in EPA’s Pesticide 

Program and are beneficial to both EPA and the applicants. See Response 3 for further Agency 

responses on the use and purpose of consultations. 

Comment 40.8: A commenter suggested that EPA should make a better effort to determine the 

magnitude of the burden on EPA and that EPA must comply with PRA section 3506(c)(1)(vi) to 

create a plan for the "efficient and effective management and use of the information collection, 

including necessary resources." 

Response 40.8: EPA’s paperwork burden is estimated in Section 9 of the Agency’s economic 

analysis. The paperwork burden on the Agency is a minor cost of the rule. The burden estimate is 

based on relevant burden data from the current Section 3 Application for New or Amended 

Pesticide Registration Data ICR (OMB Control No. 2070-0060), which has been reviewed and 

cleared by OMB for compliance with the Paperwork Reduction Act. 

Comment 40.12: A commenter asserted that non-compliance with Clean Water Act requirements 

can be extremely costly for Publicly Owned Treatment Works (POTWs). In addition, the 

commenter also noted that POTWs do not have the authority to regulate pesticides and can be fined 

if a pesticide causes a NPDES violation. 

Response 40.12: EPA has established Effluent Guidelines and Limitations for discharges from 

Pesticide Chemical Manufacturing, Formulating, and Packaging and Repackaging under 40 CFR 455. 
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Control Authorities, (ie., POTWs with approved Pretreatment Programs, States with authorized 

pretreatment programs, and EPA Regional Offices) are required to impose controls on these 

pesticide operations and their associated discharges from and management practices at nondomestic 

discharges through the General Pretreatment Regulations for Existing and New Sources, 40 CFR 

403. In addition, POTWs are required to establish site-specific limitations or prohibitions on the 

discharges from in order to prevent Pass Through and Interference of the POTW in accordance 

with 40 CFR 403.5(c). 

For a POTW to have an NPDES exceedance for a particular pesticide, the EPA or state would have 

imposed a water quality based effluent limitation in the NPDES permit. If the POTW exceeded the 

permit level, they could be potentially fined. However, the duration of the fine is not dependent on 

the U.S. EPA, U.S. Food and Drug Administration, and/or the California Department of Pesticide 

Regulation regulating the pesticide. 
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Master Responses: 

Antimicrobial Use Patterns Section (50) Page 66 

Antimicrobial Use Patterns (50) 

Master Responses for the Antimicrobial Use Patterns Section 

Please note that EPA responses are presented in numerical order. However, in the course of response development, 

some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are missing. 

Comment 50.1: A commenter has proposed different use patterns for EPA to consider. The 

commenter argued that the use patterns proposed by EPA are not use patterns but descriptions of 

product types. The commenter suggested six general use patterns for EPA to consider. These 

include: 

 Indoor industrial (all nonfood) 

 Indoor residential/commercial/institutional nonfood 

 Indoor commercial/institutional food 

 Aquatic areas nonfood 

 Aquatic areas food 

 Material preservative for exempt treated article uses 

Response 50.1: The Agency disagrees that these suggested use patterns are adequate substitutes for 

the proposed use patterns. The use patterns that EPA proposed provide a reasonable approach for 

allowing the Agency to more clearly identify and tailor the data requirements for the different type 

of antimicrobial pesticides. In some cases, that is best accomplished by using the product type to 

define the use pattern. EPA has reviewed the commenters’ descriptions of their six suggested 

general use patterns and has determined that they do not acknowledge all potential exposure 

pathways of antimicrobial pesticides, particularly those discharged to wastewater as a result of 

processing and end-use. Although three of the proposed general use patterns include “indoor” in the 

name, the exposure potential for these use patterns is not limited to the indoor environment since 

these include processes and end-uses of antimicrobial pesticides that are discharged to wastewater 

thereby leading to the potential for microorganisms in wastewater treatment plants to be exposed to 

antimicrobial pesticides and for aquatic organisms to be exposed to antimicrobial pesticides in 

surface water downstream of wastewater treatment plants. Exposures of humans to antimicrobials 

may also be associated with antimicrobials discharged to wastewater that enters wastewater 

treatment plants and subsequently enters surface water via wastewater treatment plant effluents if 

the antimicrobial is not completely removed during treatment. Furthermore, there may also be the 

potential for terrestrial organisms and humans to be exposed to antimicrobial pesticides if the 

antimicrobial that is discharged to wastewater partitions to biosolids. 

Since the processing or end-use of an antimicrobial pesticide in an indoor setting does not preclude 

the potential for its release to ambient environmental media, particularly under circumstances in 

which there is potential for discharges of antimicrobial pesticides to wastewater, EPA believes that 

the designation of an antimicrobial use patterns as “indoor” is misleading. Based on the conclusion 

that processing or end-use of an antimicrobial pesticide in an indoor setting does not preclude its 

release to the ambient environment, EPA believes that a down-the-drain analysis is needed for all 

use patterns with the exception of aquatic areas. 
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The commenter’s suggested use patterns are also inconsistent with EPA’s reevaluation of the data 

required for wood preservatives. In response to comments, the Agency determined that all treated 

wood needs to be considered as having the potential to come into contact with surface water. 

Therefore, for wood preservatives, EPA has changed several data requirements in both the 

environmental fate table and the non-target organisms table from “CR” to “R.” However, under the 

commenter’s six suggested use patterns, wood preservatives would be considered to be the same as 

material preservatives: the commenter did not differentiate the data needed between the two use 

patterns. EPA believes that the data needed for a wood preservative is distinctly different from that 

needed for a materials preservative and acknowledges the differences in the data needed by having 

two distinctly different use patterns: wood preservatives and material preservatives. 

Given the inclusion of the term “indoor” as part of the title of three of the suggested use patterns, 

and the combining of wood preservatives and materials preservatives into a single use pattern, EPA 

believes that the six general use patterns suggested by the commenter (see above) would not 

adequately serve EPA’s or the public’s needs. Additionally, the 1997 Science Advisory Panel review 

of EPA’s 12 antimicrobial use patterns indicated the SAP’s agreement that the Agency’s proposed 

designation of 12 use patterns was a reasonable approach. 

Therefore, EPA is codifying the 12 use patterns that were proposed, to read as follows: 

§ 158.2201 Antimicrobial use patterns.

 (a) Antimicrobial use patterns. The 12 general use patterns used in the data tables in this 

subpart are: 

(1) Agricultural premises and equipment. 

(2) Food-handling/storage establishments, premises and equipment. 

(3) Commercial, institutional and industrial premises and equipment. 

(4) Residential and public access premises. 

(5) Medical premises and equipment. 

(6) Human drinking water systems. 

(7) Materials preservatives. 

(8) Industrial processes and water systems. 

(9) Antifoulant paints and coatings. 

(10) Wood preservatives. 

(11) Swimming pools. 

(12) Aquatic areas. 

Comment 50.2: A commenter thought that the 1997 document on use patterns posted in the docket 

is inadequate. 

 

Response 50.2: The Agency agrees with the commenter. The 1997 document, entitled Appendix B – 

Antimicrobial Product Use Sites and Categories Index, (document 43 in the docket) is outdated. As 

stated in the proposed rule [59390], the 1997 document is “similar” to the information that will be 

posted on the Agency’s website. The Agency is in the process of updating this information before 

posting on the website. 
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Antimicrobial Use Patterns Section (50) Page 68 

Comment 50.3: A commenter asked how does the Agency distinguish between a treated article and 

the chemical used to treat the article for the purposes of 158W. 

 

Response 50.3: The term “treated article” typically refers to articles or products that are treated with 

an antimicrobial pesticide to protect the articles or products themselves. As described in 40 CFR 

152.25(a), when intended for use, and used, only in the manner specified. “An article or substance 

treated with, or containing, a pesticide to protect the article or substance itself (for example, paint 

treated with a pesticide to protect the paint coating, or wood products treated to protect the wood 

against insect or fungus infestation), if the pesticide is registered for such use” is exempt from the 

requirements of FIFRA. The article that was treated must be registered as a pesticide product if it 

does not meet each of the conditions in the exemption provision. For additional information see 

http://www.epa.gov/pesticides/factsheets/treatart.htm. 

 

Comment 50.4: A commenter asked what exactly is meant by wood preservative? Another 

commenter argued that all wood preservatives should be considered as having contact with water. 

Another commenter maintained that the industrial, commercial and do-it-yourself uses of wood 

preservatives are different and should be assessed differently. 

Response 50.4: Wood preservatives are pesticides for incorporation into wood products to control 

wood degradation problems due to fungal rot or decay, sapstain, molds, or wood-destroying insects. 

As explained in the proposed rule [59405] EPA’s current practice of determining the data required 

for a wood preservative product is dependent on the usage (land-only versus land and aquatic). 

According to this practice, fewer environmental fate and ecological effects studies are required for 

products that limit their use patterns to land-only uses. This practice also assumes that diversion 

does not occur and that wood that is treated for land-only uses does not end up in the water and 

vice versa. Based on comment 50.4, EPA has re-evaluated that practice. EPA considered three 

possibilities: 

 All treated wood could have the potential to come into contact with surface water. 

 An approach similar to that of the American Wood Protection Association (AWPA) 

approach which differentiates between marine/freshwater and ground contact use/above 

ground contact use 

 Maintain status-quo 

Wood preservatives used to protect wood structures placed directly in or over water (e.g., marine 

pilings, docks) will leach active ingredient into the water, resulting in potential exposure of aquatic 

organisms. Wood preservatives used in the terrestrial environment for uses such as fences, siding, 

and decks will leach active ingredient into soil where it may be transported into the aquatic 

environment and expose aquatic organisms. 

The Organization for Economic Co-operation and Development (OECD) Series on Emissions 

Scenario Documents, Emission Scenario Document (ESD) for Wood Preservatives provides 

guidance on how to estimate emissions of chemical substances in wood preservative products to air, 

water, and soil as a result of product application and storage of treated wood prior to shipment and 

treated wood-in-service. This OECD ESD documents the occurrence of pathways of release of 
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Antimicrobial Use Patterns Section (50) Page 69 

chemical substances during wood preservative application to facility drains that subsequently convey 

wastewater to wastewater treatment plants; entry of chemical substances to adjacent surface water 

bodies by way of run-off water from unpaved storage of wood preservative-treated products 

following a rain event; and leaching of chemical substances from in-service uses of treated exterior 

wood out of ground (i.e., fences, noise barriers), wood in-ground (transmission poles, fence posts), 

and wood in direct contact with fresh and sea water (poles and planks of jetties and wharfs). A 

discussion of indirect releases to surface water of antimicrobial pesticides used as wood preservatives 

can be found in the response to comment 134.1. 

Given this information, the Agency determined that all treated wood should be considered as having 

the potential to come into contact with surface water. 

All wood preservative risk assessments will now be performed considering that the treated wood 

could end-up either on the land or in the aquatic environment. As previously discussed there are 

multiple pathways for wood preservative degradates and/or leachates to reach surface water. Given 

this decision, the wood preservative columns of the environmental fate and the non-target 

organisms table were revised. 

For the environmental fate table, for the wood preservatives column, the data requirements for 

anaerobic soil metabolism, aerobic aquatic metabolism, and anaerobic aquatic metabolism, data 

requirements were changed from “CR” to “R” because the Agency believes that treated wood 

products have the potential to come into contact with surface water as well as soils which can 

become flooded or waterlogged and then be released to surface water. 

For the nontarget organism table, for the wood preservatives column, the data requirements for 

chronic toxicity testing with fish (fish early-life stage) and aquatic invertebrate (aquatic invertebrate 

life-cycle) are being changed from “CR” to “R” to provide chronic data when chronic exposure is 

expected. 

The Agency agrees that the industrial, commercial and do-it-yourself uses of wood preservatives are 

different in terms of human exposure . Industrial wood preservative uses are assessed for those 

workers involved in the actual treatment of the wood with the preservative. This includes operations 

at a pressure treatment facility where workers add the preservative to treatment cylinders, remove 

treated wood charges from the cylinders, check the treated wood to verify retention rates, and move 

the freshly treated wood around the facility (from cylinder to drip pad to storage to shipping). 

Industrial sapstain wood preservatives are also assessed at the treatment facility for the application 

of the pesticide. Worker tasks for the non-pressure treatment are slightly different than those at 

pressure treatment facilities. Separate exposure measurements unique to each type of treatment (PT 

vs non-PT) are used in the assessments. 

Exposures to commercial and do-it-yourself uses of treated wood are assessed for those installing 

the treated wood and for those exposed to the treated structures (e.g., play sets and decks). 

 

Comment 50.6: A commenter would like to know if it is possible to define high vs. low exposures 

for each use pattern by levels of exposure using various factors/criteria. 

Response 50.6: The commenter is interested in defining the level of human exposure for each of the 

12 use patterns. It is not possible to define the level of human exposure for a use pattern because 
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Master Responses: 

Antimicrobial Use Patterns Section (50) Page 70 

within each of the use patterns there are multiple ways in which an antimicrobial pesticide chemical 

can be used. The exposures within each use pattern may range from minimal because of a lack of 

contact with treated surfaces or from very low application rates to high exposure based on duration 

and/or magnitude of exposure. 

Comment 50.7: In the descriptions for the aquatic use patterns, concern for human exposure 

downstream of treatment sites is noted, according to a commenter. The commenter suggests adding 

that there are also possible human exposure concerns downstream of industrial process and water 

system effluents. 

 

Response 50.7: The Agency agrees with the commenter. There is not only potential concern for 

human exposure downstream of aquatic areas, but there is also concern for human exposure 

downstream of effluents from another antimicrobial use pattern, industrial process and water 

systems. In addition, the Agency has also determined that there is potential concern for human 

exposure downstream of domestic and industrial wastewater treatment plants. As discussed in the 

preamble to the proposed rule (73 FR 59407), there is indirect movement of antimicrobials from 

indoor use sites to the outdoor environment through water. Discharges of antimicrobial pesticides 

to surface water can also result from the processing and end-use of antimicrobials that are 

discharged to domestic and industrial wastewater treatment plants. The resulting effluents, which 

can contain antimicrobial pesticides, are then released to the environment. Based on this comment 

and response to comments 134.1 and 134.21, the data requirements being codified in the final rule 

include certain environmental fate and non-target organism data requirements in addition to those in 

the proposed rule. 

The “Down-the-Drain” module of OPPT’s Exposure and Fate Assessment Screening Tool (EFAST) is used to evaluate potential exposures resulting from antimicrobial pesticides discharged to 

domestic wastewater treatment plants and the “General Population Exposure” module of E-FAST 

is used to evaluate potential exposures resulting from antimicrobial pesticides discharged to 

industrial wastewater treatment plants. These modules not only provide screening-level estimates of 

surface water concentrations downstream of wastewater treatment plants and estimates of the 

number of days of exceedance of surface water concentrations above concentrations of concern to 

aquatic organisms, but they also provide screening-level estimates of potential exposures to humans 

from ingestion of drinking water and fish. 

Comment 50.8: A commenter disagrees with how the term “aquatic area” is used in the proposal. 

The commenter maintained that the Agency needs to define “aquatic area” to be consistent with 

FIFRA 2(mm) and with Agency practice. 

 

Response 50.8: In its proposal EPA defined the aquatic area use pattern as those products “designed 

to control or kill slime-forming bacteria, fungi, or algae in lakes, ponds, streams, drainage ditches, 

and other bodies of water” [59390]. This definition is consistent with the exclusion in FIFRA 

2(mm)(2)(C) which specifies that an aquatic herbicide is not within the definition of an antimicrobial 

pesticide. 
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Comment 50.9: A commenter argued that EPA’s proposed aquatic exposures classification scheme 

misses a set of outdoor use patterns involving transport of pesticides by rain water or discharge 

from outdoor locations without any treatment to gutters, storms, drains and surface water. While the 

commenter noted that the use pattern classifications presented in the proposed rule are a great 

improvement, the commenter maintained that they do not fully reflect actual pathways by which 

antimicrobial pesticides are transported to surface waters. The commenter requests that the 

proposed use pattern classifications be adjusted to reflect the urban runoff pathway by which 

antimicrobial pesticides are transported to surface waters. The commenter requests that the 

proposed use pattern classifications be adjusted to reflect the urban runoff pathway, thus ensuring 

that USEPA receives data adequate to evaluate the inevitable direct transport of antimicrobials from 

outdoor surfaces to surface water when it rains. The commenter thought that several antimicrobial 

use patterns can be reasonably expected to cause antimicrobial pesticides to reach both municipal 

wastewater treatment plants and storm drains, where they can flow directly to surface waters without 

any form of treatment. According to the commenter, the simplest method for addressing these dual 

discharge pathways under the structure of the proposed rule would be to classify the use patterns in 

both the “low” and “high” environmental exposure areas (i.e. swimming pools, recirculating waters 

system discharges, human and drinking water systems, and all other outdoor uses of antimicrobials.) 

Response 50.9: The Agency agrees that virtually all of its 12 use patterns can lead to antimicrobials 

entering surface water indirectly through wastewater treatment facilities or directly by rain water or 

discharge from outdoor locations. The Agency has developed a methodology for assessing 

exposures to antimicrobial pesticides in surface water as a result of down-the-drain releases. See 

response to comment 134.4 for more details on estimating exposures to antimicrobial pesticides in 

surface water from down-the-drain releases to wastewater treatment plants. 

At this time, however, currently available exposure and risk assessment methodologies are 

insufficient to adequately assess exposure and risks from releases to surface water via urban runoff 

pathways. As discussed in the conventional response to comments document, EPA acknowledges 

that these issues relating to urban applications of pesticides will need to be evaluated, but these 

issues will be addressed, if warranted, in a future update of the data requirements in part 158. 

Each end use of an antimicrobial pesticide can be categorized into one of the 12 use patterns.listed 

in the final rule. An application to register a new chemical or new use(s) can include multiple end 

uses and hence multiple corresponding use patterns. The type of data required varies depending on 

the use pattern and chemical-specific characteristics of the antimicrobial. If additional data are 

needed to address uncertainty in the risk assessment, EPA will employ assumptions to account for 

the uncertainty or require the applicant to provide the data. 

The Agency is currently evaluating various exposure models that might be appropriate for evaluating 

urban pesticide uses and possible runoff scenarios as down storm drains, for example. As part of 

this initiative, OPP sponsored a workshop in June 2007 to bring together exposure modelers, fate 

scientists and risk assessors from state and Federal government agencies, private companies, and 

other interested parties for presentations and discussions of the challenges of developing appropriate 

exposure models to simulate urban runoff and entry in urban watersheds. Some of the topics 

discussed were currently available agricultural models and adaptability to urban scenarios; the 

variability of urban scenarios that include not only sites exposed by runoff across hard surfaces such 

as pavement, but also sites exposed through runoff from large systems such as turfgrass; and the use 
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Master Responses: 

Antimicrobial Use Patterns Section (50) Page 72 

of Geographic Information Systems (GIS) to refine exposure estimates. The workshop afforded 

OPP the opportunity to gather information on modeling techniques and available data that should 

advance the state of the science of the Program’s overall exposure assessment methods, data, and 

tools. 

Currently, for antimicrobials, the Agency uses two models, Pesticide Root Zone Model (PRZM) and 

Exposure Analysis Modeling System (EXAMS), to estimate concentrations of antimicrobials 

pesticides in run-off water from the use of wood preservatives on wood structures such as decks. 

Comment 50.10: A commenter maintained that EPA should clearly define the data needed to 

register ballast water treatments. 

 

Response 50.10: In its proposal EPA included ballast water treatments with the Antifoulant 

Coatings and Paints use pattern [59390]. EPA believes that the data needed to register an antifoulant 

coating would be the same as that needed for a ballast water treatment. 

 

Comment 50.11: How will EPA account for reactive species such as sodium hypochlorite in its data 

requirements for ballast water? 

 

Response 50.11: A reactive species such as sodium hypochlorite should be neutralized prior to 

disposal. Antimicrobials such as sodium hypochlorite that are reactive or unstable would quickly 

degrade and would generally be expected to be subject to fewer data requirements for aquatic 

toxicity and environmental fate. 

Comment 50.13: A commenter disagrees with the use pattern designations proposed for the 

toxicology data requirements table. 

 

Response 50.13: As a result of comments received, EPA is now using a food/non-food approach, 

which has some similarities to that of conventional pesticides, to distinguish the use patterns 

generally needing more toxicity data from those that would generally need less. Also, see response to 

comments 80.71 and 80.72. 

Comment 50.14: A commenter maintained that EPA has been arbitrary in determining some of the 

use patterns as “high human exposure.” 

 

Response 50.14: As a result of comments received, EPA is no longer using the terms “high human 

exposure” and “low human exposure” as table headers as proposed for the Antimicrobial 

Toxicology Data Requirements Table [59433]. Instead EPA in the final rule is now using a 

food/non-food approach with some similarities to that of conventionals to distinguish the use 

patterns with higher exposure that need more toxicity data from those that need less. Accordingly, 

the table headers for the Toxicology Data Requirements Table in the final rule are: Direct Food 

Uses; Indirect Food Uses (>200 ppb); Indirect Food Uses (<200 ppb); Swimmers, Aquatic Areas, 

Wood Preservatives, Metal Working Fluids; and All Other Nonfood Uses. 
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Antimicrobial Use Patterns Section (50) Page 73 

Comment 50.16: Several commenters believe that antimicrobial use patterns should be described in 

40 CFR 158.100, not in part 158W. 

Response 50.16: EPA disagrees with this comment. The use patterns codified in 40 CFR 158.100 are 

appropriate for conventional, biochemical, and microbial pesticides but not for antimicrobial 

pesticides. Conventional pesticides and antimicrobial pesticides have very different uses and 

associated exposure pathways. The use patterns for antimicrobial pesticides will be codified in 50 

CFR 158.2201. 

Comment 50.17: What do “industrial use only” and “commercial use only” mean? Do these terms 

mean that the product is not for household use, or do the terms mean the same thing as "Restricted 

Use" and thus can only be applied by certified applicators? 

Response 50.17: These terms do not mean the same thing as “restricted use,” which would appear 

on labels for agricultural pesticide products that may be applied only by certified/licensed pesticide 

applicators. According to the Label Review Manual 

(http://www.epa.gov/oppfead1/labeling/lrm/chap-11.pdf). “For Use Only by” statements should 

not be on a label unless it refers to a group that can be clearly defined by FIFRA, an applicable 

regulation or an EPA policy which has defined an identifiable group of users—such as persons 

licensed by the state for termite control (PR Notice 96-7) or employees of mosquito control agencies 

(PR Notice 2005-1). Statements such as “For professional use only” or “For commercial use only” do 

not have accepted definitions, and the apparent “limitation” is meaningless and unenforceable, and 

may be considered misleading. Such phrases should not appear on a product label. Such statements 

are often used by registrants solely for marketing purposes, however, neither FIFRA nor the 

applicable regulations provide for labeling statements such as for “professional use”, “commercial 

use”, “industrial use” or other such terms. EPA’s registration process does not involve a 

determination that a product should be used, for example, only by “service persons”. Such 

statements are vague and they can mislead customers into believing that a product with such a 

statement is somehow more efficacious than another product. Also see 40 CFR 156.10(a)(5) for the 

labeling regulations on false and misleading statements, particularly 156.10(a)(5) (ii), which provides 

that any “false or misleading statement[s] concerning the effectiveness of the product as a 

pesticide...” shall be misbranding. Sale or distribution of a misbranded pesticide is an unlawful act 

under Section 12(a)(1)(E) of FIFRA. 
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Master Responses: 

Product Chemistry Section (60) Page 74 

Product Chemistry (60) 

Master Responses for the Product Chemistry Section 

Please note that EPA responses are presented in numerical order. However, in the course of response development, 

some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are missing. 

Comment 60.1: A commenter requested that EPA provide adequate justification for applying the 

existing product chemistry data requirements for conventional pesticides to antimicrobials without 

consideration of the highly dissimilar chemistries and inapplicability of many of the requirements. 

Response 60.1: It has been EPA’s longstanding practice to require product chemistry data. Product 

chemistry data are required to identify the chemicals used to manufacture a product and to 

understand the physical and chemical properties of the ingredient or product. Such information is 

generally independent of the intended use pattern. Product chemistry data are used during label 

development to identify information to be included on the label, such as the flammability statement, 

and directions for disposal of the product. Hence, despite any differences between conventional and 

antimicrobial pesticides, the Agency believes it is appropriate to apply the same product chemistry 

data requirements to antimicrobials as required for conventional pesticides of a pesticide. The 

guidelines for conducting product chemistry studies offer flexibility to account for differences 

between chemical classes. 

Comment 60.2: A commenter contended that registrants of antimicrobial pesticides were not given 

the opportunity to review and comment on conventional pesticide data requirements that are now 

being proposed for antimicrobial pesticides. 

Response 60.2: EPA disagrees with this comment. In the preamble to proposed 158W, EPA 

proposed to apply the product chemistry data requirements for conventionals in 40 CFR Part 158 

Subpart D to antimicrobial pesticides. Therefore, during the public comment period for the 

proposed 158W, from October 8, 2008 to April 6, 2009, any interested party could comment on the 

data requirements in subpart D and their potential applicability to antimicrobials. 

Comment 60.3: The phrase “and possibly” in the table at 40 CFR 158.310 in rows “Discussion of 

formation of impurities” and “Preliminary Analysis” is too imprecise and the related test notes are 

not adequately descriptive. 

Response 60.3: EPA agrees that “and possibly” is unusual for regulatory text. However, the language 

serves the purpose of indicating that more than one product may need testing. The testnote clearly 

refers the reader to 40 CFR 158.345, entitled “Preliminary Analysis,” which contains more 

information on when testing is needed. This significant amount of information could not be 

accommodated in a testnote. 

Comment 60.4: EPA should remove the data requirement in the table at 40 CFR 158.310 for 

“Particle size, fiber length, and diameter distribution” until EPA explains how such data will be 

used. 
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Product Chemistry Section (60) Page 75 

Response 60.4: EPA disagrees with this comment. The requirement for “Particle size, fiber length, 

and diameter distribution” provides characteristics of a substance that is helpful for product 

identification and comparisons of different products and product test substances. Particle size, fiber 

length, and diameter distribution influence the behavior of a substance, and data on these 

characteristics is used by EPA to assess whether a particle is respirable, the rate of dermal 

penetration of a substance, and other properties, such as surface area. Particle size and surface area 

can also affect the physiochemical and biological properties of a substance in environmental media, 

such as air, water, and soil, and in terrestrial and aquatic organisms. This information is critical for 

exposure risk assessment, as well as environmental fate and ecological effects risk assessments. 

Comment 60.5: A commenter asserted that test note 23 to the table at 40 CFR 158.310 is unclear. 

The commenter thought that the “and” should be changed to “or.” The commenter noted that 

either of the criteria should trigger the study. 

Response 60.5: Testnote 23 to the table at 40 CFR 158.310 describes two triggers for requiring the 

“Particle size, fiber length, and diameter distribution” study. The testnote currently reads, “Required 

for water insoluble test substances (>10-6 g/l) and fibrous test substances with diameter of ≥ 0.1 

μm.” EPA agrees with the commenter that either of these should trigger the study. In a future 

rulemaking, EPA will revise Testnote 23 to clarify when the study is required. 

Q60.6: The data requirement for “Water Solubility” should be revised to include other solvents since 

EPA has historically been interested in data on solubility in organic solvents. 

R60.6: EPA agrees with the commenter. Test methods for water solubility are provided in 

Guidelines 830.7840 and 830.7860. The Agency has historically required data on solubility in organic 

solvents. Guideline 830.1000, titled “Background for Product Properties Test Guidelines,” suggests 

on page 17 that solubility testing is also to be performed with n-octanol and representative polar and 

non-polar solvents (e.g., methanol and hexane) commonly used to formulate pesticide products. 

Several commonly accepted test methods for organic solubility are available. Applicants should 

discuss the choice of methods with the Agency prior to conducting the tests. In a future rulemaking, 

EPA will consider how to best specify its need for testing with organic solvents. 
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Master Responses: 

Product Performance Section (70) Page 76 

Product Performance (70) 

Master Responses for the Product Performance Section 

Please note that EPA responses are presented in numerical order. However, in the course of response development, 

some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are missing. 

Comment: 70.1: There were several comments that the guidelines specified by EPA in the proposed 

product performance data table were outdated and unavailable. What has happened to the new 810 

guidelines? They were promised for publication in 2009. 

 

Response 70.1: Four of the 810 series guidelines (810.2000, 810.2100, 810.2200, and 810.2300 for 

sterilants, disinfectants and sanitizers) were published in the Federal Register for public comment on 

January 27, 2010 (75 FR 4308). The guidelines for air, water and textiles (810.2400, 810.2500, and 

810.2600) will be published for comment prior to the finalization of the new antimicrobials data 

requirements rule. [update] 

 

Comment 70.2: : Several commenters shared their belief that EPA was seeking “avoid comment on 

the product performance data requirements in the Proposal by stating that the Agency ‘is not 

proposing to revise product performance data requirements’ at this time. Another commenter asked 

how the product performance section of the proposed rule could be finalized without the 810 

guidelines? 

 

Response 70.2: The proposed product performance data requirements table contained the older 91 

series guidelines. As stated in the proposed rule the requirements being proposed were “nearly 

identical” to the existing data requirements in § 158.400 and 161.640, and the table was “transferred 

essentially unchanged” (73 FR 59391). Since the 2008 proposed rule, EPA published the draft 810 

guidelines for comment. Four of the 810 series guidelines (810.2000, 810.2100, 810.2200, and 

810.2300 for sterilants, disinfectants and sanitizers) were published in the Federal Register for 

public comment on January 27, 2010 (75 FR 4308). These guidelines represent the Agency’s current 

recommendations for conducting product performance studies to support antimicrobial pesticide 

label claims. That Notice of Availability announced that the 810 guidelines series would be 

incorporated into the final data requirements regulation: As announced, in this final rule EPA is 

replacing the 91 series designations proposed in the part 158, subpart W product performance table 

with the appropriate 810 Series Guideline numbers and names. Thus, commenters had an 

opportunity to comment on the inclusion of the 810 series in the final Product Performance Data 

Requirements table. Three additional product performance guidelines (810.2400, 810.2500, and 

810.2600) should be published for comment in a timeframe similar to that of publication of the final 

rule for Antimicrobial Data Requirements. 

See response to comment 191.1 for a discussion on guidelines. 

 

Comment 70.3: The 810 guideline development should be a high priority for EPA. 

 

Response 70.3: The Agency agrees and is working to complete the guidelines. 

 
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Product Performance Section (70) Page 77 

Comment 70.4: The lack of up-to-date guidelines creates a situation in which delays are unavoidable 

and consultations with EPA become required. The Agency's protocol review process is slow and 

uncertain. 

 

Response 70.4: The guidelines are being updated to provide further clarity for determining the data 

necessary to support antimicrobial label claims. EPA believes that the draft 810 guidelines provide 

useful refinements and information that was not previously available in 1982 when the 91 series 

guidelines were issued, and once finalized should reduce the number of consultations with EPA. 

 

The Agency recognizes that efficacy protocol review and approval is a critical step in the preregistration process for public health pesticides, particularly for products that involve new 

technologies and use sites, and for which standardized methods may not exist. The Agency 

recommends a pre-registration meeting to discuss protocols to ensure the proposed method will 

generate data to support the intended label claim. In some instances, due to the uniqueness of the 

proposed method/technology, the Agency will need to consult with external experts, in addition to 

utilizing EPA’s own evaluation process. This pre-registration meeting will also assist with 

determining whether the protocol will undergo an internal review or need to be submitted to an 

external panel of experts, and help reduce the perceived uncertainty with the protocol review 

process. 

 

Comment 70.5: Why is there no formal regulatory practice for registering products to address public 

health emergencies or emerging pathogens promptly and effectively? 

 

Response 70.5: EPA does not believe that data requirements are the appropriate place to address 

emerging pathogens. A major consideration in the Agency's process for addressing public health 

emergencies and emerging pathogens is to work closely with the Centers for Disease Control and 

Prevention (CDC), Department of Agriculture (USDA) and Food and Drug Administration (FDA), 

as appropriate, to provide a timely and accurate response to these situations. Under FIFRA Section 

18, the Agency also has authority to grant certain exemptions from the provisions of FIFRA and 

also to approve the use of unregistered pesticides when emergency conditions exist. Additionally, in 

April 2008, the Agency implemented a disinfection hierarchy policy for addressing emerging viral 

pathogens. Information on this policy is available on the EPA website at 

http://www.epa.gov/oppad001/disinfection_hier.htm. EPA believes that emerging pathogens can 

require flexibility and speed in disseminating information and seeks to address such situations in a 

prompt and effective manner. 

 

Comment 70.6: The proposed definitions do not reflect the work done by the regulated community 

in cooperation with EPA since 1999 on the definitions in the draft guidelines. In particular, 

commenters did not agree with the proposed definitions of sanitizer and disinfectant. 

 

Response 70.6: Since the publication of the proposed rule, proposed definitions, including those for 

sanitizer and disinfectant, were published in the Federal Register for public comment on January 

27, 2010, as part of requesting comment on draft guideline 810.2000. (see regulations.gov, docket 

EPA-HQ-OPP-2009-0681). After further review of the comments submitted on the proposed 

definition for disinfectant and sanitizer, the Agency has revised the definitions that had been 
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Master Responses: 

Product Performance Section (70) Page 78 

proposed for both part 158W and the 810 Guidelines. The definitions for sanitizer and disinfectant 

will be the same in both part 158W and in the 810 Guidelines. 

The definition for disinfectant will be revised from, “Disinfectant means a substance, or mixture of 

substances that destroys or eliminates a specific species of infectious or public health 

microorganism, but not necessarily bacterial spores, in the inanimate environment” to read, 

“Disinfectant means a substance, or mixture of substances, that destroys or irreversibly inactivates 

bacteria, fungi and viruses, but not necessarily bacterial spores, in the inanimate environment.” 

The definition for sanitizer will be revised from, “Sanitizer means a substance that reduces the 

bacterial population in the inanimate environment by significant numbers, but does not destroy or 

eliminate all bacteria or other microorganisms” to read, “Sanitizer means a substance, or mixture of 

substances that reduces the bacteria population in the inanimate environment by significant 

numbers, (e.g., 3 log10 reduction) or more, but does not destroy or eliminate all bacteria. Sanitizers 

meeting Public Health Ordinances are generally used on food contact surfaces and are termed 

sanitizing rinses.” 

The definitions for fungicide, sterilant, tuberculocide, or virucide are also being revised by inserting 

the phrase: “or a mixture of substances” to clarify that the antimicrobial can be composed of more 

than a single substance. Inclusion of this phrase in all of the definitions in § 158.2203 for types of 

products that bear public health claims (excepting microbiological water purifier) means consistency 

in the definitions and an acknowledgement that the destroying, reducing, or inactivating may be 

accomplished via more than a single substance. Also, this makes these definitions similar to the 

FIFRA section 2 (u) definition of pesticide which also contains the phrase “or mixture of 

substances.” 

Additionally, the definition for virucide is being revised to include the word irreversibly, as 

follows: “Virucide means a substance, or mixture of substances, that destroys or irreversibly 

inactivates viruses in the inanimate environment, thus reading similar to the definition for 

tuberculocide. Additionally, the definition for sterilant will be revised to remove the second 

sentence of the proposed definition: “For purposes of this subpart, “sporicide” and “sterilant” are 

synonymous.” EPA no longer requires that products that make sporicidal claims also make sterilant 

claims. 

Comment 70.7: The issue of when to generate non-public health data should be discussed since 

registrants are required to develop data to substantiate label claims. 

 

Response 70.7: The Agency believes this issue has been addressed in Section 158.2220 "Product 

Performance", which clearly states that "Each applicant must ensure through testing that his product 

is efficacious when used in accordance with label directions and commonly accepted pest control 

practices.” However, to clarify the issue further, the Agency will add a definition for non-public 

health claims that will appear as 40 CFR 158.2204(b): 

 

Non-public health claim. An antimicrobial pesticide is considered to make a non-public health 

claim if the pesticide product bears a claim to control microorganisms of economic or 

aesthetic significance, where the presence of the microorganism would not normally lead to 

infection or disease in humans. Examples of non-public health claims would include, but are 
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Product Performance Section (70) Page 79 

not limited to, algaecides, slimicides, preservatives and products for which a pesticidal claim 

with respect to odor sources is made. 

Additionally, EPA will revise 40 CFR 158.2220(c)(3) to include: 

(3) Product performance data for each product that bears a non-public health claim. Each product that 

bears a non-public health claim, as described in §158.2204(b), must be supported by product 

performance data. Each registrant must ensure through testing that his product is efficacious 

when used in accordance with label directions and commonly accepted practices. The 

Agency reserves the right to require, on a case-by-case basis, submission of product 

performance data for any pesticide product registered or proposed for registration or 

amendment. 

Also, EPA will post on the Antimicrobials Division website the parts of the 91 Guideline series that 

apply to testing of non-public health products. Although, these guidelines are from 1982, they are 

still relied on to develop data to support non-public health label claims, EPA acknowledges that 

some of the references in the 1982 guidelines are to the older 91 series, which is being replaced by 

the 810 series. To assist readers, EPA will also post a cross-walk table so readers can locate the 

applicable section of the 810 Guidelines. 

Comment 70.8: For efficacy, EPA does not allow the flexibility typically associated with fulfilling a 

data requirement. Applicant must use protocols or test methods as specified by EPA. Protocol 

review is often required. 

 

Response 70.8: EPA believes that in order to ensure consistency in evaluating the effectiveness of 

antimicrobial performance label claims, standardized methods must be used. For efficacy studies, 

protocol review is only utilized in those instances where a standard test method does not exist or 

when major modifications to a standard test method (e.g., use of surrogate organisms, simulated or 

in-use testing, changes in methods for growing organisms) are made that warrant an agency review 

to determine if the modified protocol will support the intended label claims. 

 

Comment 70.9: Some of the definitions are inconsistent with FIFRA 

 

Response 70.9: The commenter is correct that FIFRA section 4(i)(4)(C), which concerns the 

reduction of waiver of fees for minor uses contains descriptors of sanitizers and disinfectants. The 

terms sanitizer and disinfectant are used as part of the descriptor of an antimicrobial active 

ingredient. These descriptors are different from the definitions being finalized in part 158W; 

however, a reading of subparagraph (C) indicates that these descriptors are for the purposes of “this 

subparagraph” only. This means that they are not definitions that are applicable outside of (C).. The 

definitions that are being codified are for the purposes of the part 158W. 

 

Comment 70.10: A commenter asserted that there is no need for including the same definitions in 

both regulation and guidance. 

 
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Product Performance Section (70) Page 80 

Response 70.10: The commenter is correct: if the definition is in the regulation then it does not need 

to also be in a guidance document. However, EPA believes it helpful to have all the definitions 

(including those that have been codified in the regulation) in the guidance document also. 

Comment 70.11: A commenter asserted that sanitizers and disinfectants should be allowed for nonpublic health claims as well as public health claims. 

 

Response 70.11: The Agency agrees there are certain situations where the designation "sanitizer" and 

"disinfectant" would be appropriate for non-public health claims, particularly for products used on 

farm animal and veterinary premises when the intent is to kill pathogens that are only infectious to 

animals. However, these terms are not appropriate in other situations, such as claims against odorcausing bacteria (on surfaces or in the air). The Agency will continue to review the appropriateness 

of the use of the term sanitizer and disinfectant associated with non-public health claims on a caseby-case basis. 

Comment 70.13: A commenter asked how does the EPA define the terms "hygienic" and “sanitary?” 

The commenter contended that EPA should change its long-standing position that the use of such 

terms does not imply a pesticidal claim. The commenter further stated that the public equates such 

terms with “germ-killing.” 

 

Response 70.13: Hygienic refers to the promotion or preservation of health. Like sanitary, the term 

hygienic is associated with a state of cleanliness and is not considered a pesticide claim. 

 

Comment 70.14: A commenter asked what does "similar in composition" mean. 

 

Response 70.14: In general, a proposed pesticide product is considered to be “substantially similar” 

in composition to a registered product when the following conditions are met: 

 

(1) the active ingredient(s) of the proposed product is identical to the active ingredient(s) of the 

registered chemical. The concentrations of the active ingredient(s) in the products would need to be 

similar. 

 

(2) The inert ingredients and their concentrations would need to be similar between the proposed 

product and the registered chemical. The differences in the inert ingredients may not cause changes 

in the physical or chemical properties of the proposed product or in the precautionary language. 

 

(3) The impurity profile would need to be similar where a technical grade of an active ingredient(s) is 

concerned. The proposed product would need to contain no impurities of toxicological significance 

that are not present in the registered product. 

 

Comment 70.15: A commenter argued that “the widespread and indiscriminate use” of antimicrobial 

agents can lead to the development of resistant bacteria and that EPA has not focused sufficiently 

on this issue. 

 
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Master Responses: 

Product Performance Section (70) Page 81 

Response 70.15: EPA is a participant on the Interagency Task Force on Antimicrobial Resistance. 

While the focus of this group is on the use of antibiotics, the Antimicrobials Division (AD) has 

participated in the taskforce efforts by providing review and comment on documents related to 

antimicrobial resistance, specifically, the reports of the Codex Ad Hoc Intergovernmental Task Force 

on Antimicrobial Resistance, issued through the Codex Alimentarius Commission. AD has also 

conducted a literature search into the use of antimicrobial pesticides and the development of 

resistant bacteria. The results of the literature search did not support a finding that the use of 

antimicrobial pesticides leads to development of resistant bacteria. EPA will continue to work with 

the Taskforce on Antimicrobial Resistance. 

Comment 70.16: A commenter maintained that most antimicrobial substances are ineffective and 

unnecessary and that there is little or no efficacy data. Therefore, the commenter maintained that the 

risks far outweigh any perceived benefit. 

 

Response 70:16 The Agency disagrees with this comment. It is well known that antimicrobial 

substances, particularly disinfectants, are widely used by the healthcare community as a part of a 

comprehensive infection control program. The Agency requires efficacy data to be submitted in 

support of all public health label claims. Therefore, in order for an antimicrobial product to be 

marketed for use in hospitals as a disinfectant, tuberculocide, or virucide, efficacy data were 

submitted and determined by the Agency to be adequate and appropriate to support the product 

claims prior to registration of the product. 

Comment 70.17: One commenter asked that the “portion of [Testnote 1 from the conventional 

product performance data requirements table in 40 CFR 158.640] relevant to antimicrobial 

pesticides” be included as a testnote to the antimicrobials product performance table. 

Response 70.17: EPA has included the relevant information in §158.2220(a) (1) and (2). 
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Master Responses: Toxicology Section (80) Page 82 

Toxicology (80) 

Master Responses and Testnotes for the Toxicology Section 

Please note that EPA responses and testnotes are presented in numerical order. However, in the course of response 

development, some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are 

missing. 

Comment: 80.1: Several commenters stated their belief that the proposed toxicology approach 

differed dramatically from EPA’s current practices 

Response 80.1: EPA disagrees with this comment. The proposed toxicology approach would codify 

many of the current practices of EPA regarding toxicology data requirements for antimicrobials. As 

noted in the proposed rule (59383), since 1984 “...every disciplinary area and requirement has been 

reconsidered and many have been revised in practice.” Additionally, the use patterns specific to 

antimicrobial pesticides are not specified in 40 CFR part 161 (the current location of antimicrobial 

pesticide data requirements). Thus, the existing data requirements are in some cases out of date and 

non-specific. The proposed data requirements are intended to clarify the data needed by EPA to 

continue making sound regulatory decisions. 

Comment 80.3: There should be a TTC (threshold of toxicological concern) type of approach for 

antimicrobials. 

Response 80.3: The Antimicrobials Division is aware of the TTC concept, and in conjunction with 

the International Life Sciences Institute (ILSI), is currently pursuing the development of an 

application of the TTC concept to evaluate antimicrobial pesticides. At this time, EPA anticipates a 

timeframe of 2 to 3 years for development. Once a TTC-based approach has been developed and 

piloted, then EPA would consider when/if the approach should be included in 158W. 

Comment 80.4: How will EPA generate an assessment for an antimicrobial chemical that is 

corrosive or a severe irritant? 

Response 80.4: The Agency notes both in 40 CFR 158.500 (testnote 3 to the toxicity table for 

conventional pesticides), and 40 CFR 161.340 (testnote 2 to the toxicity table for the current data 

requirements for antimicrobial pesticides), that the Agency has in place regulations that state certain 

conditions for waiving acute toxicity studies for chemicals that are corrosive or severe irritants. 

These same waiver conditions were in the proposed antimicrobial pesticide data requirements rule 

(proposed testnote 3 to the toxicity table in 40 CFR 158.2230.) For acute testing, the Agency would 

waive the requirement for acute dermal, primary eye irritation, primary dermal irritation, and dermal 

sensitization when the test material is corrosive to skin or has a strongly acidic (pH less than 2) or 

strongly alkaline pH (greater than 11). Where repeated dermal exposure is expected to occur, the 

Agency would have an interest in determining the concentration where an irritant effect occurs to 

protect against these effects. For these scenarios, the Agency uses dose-response information from 

repeated dermal toxicity studies to calculate a safe level of dermal exposure. EPA will also consider 

data from a validated in vitro corrosivity assay as a screen to judge whether a chemical may be 
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Master Responses: Toxicology Section (80) Page 83 

corrosive to the eye or skin. It is not necessary to conduct acute studies for corrosive chemicals 

unless the applicant seeks to determine a concentration where the effect occurs. 

In other cases, dilution of the test substance may be necessary to test a chemical that is an irritant to 

determine the non-irritating concentration, or the concentration that can be tested in order to 

examine other effects besides irritation (such as in acute inhalation testing). While there is always a 

way to conduct a study with a diluted solution, other (non-acute) data requirements for such 

chemicals are usually determined through consultation with the Agency or through submission of 

waiver requests with supporting scientific rationale. 

Comment 80.5: A commenter thought that proposed testnotes 3 and 5 to the Toxicology Table are 

contradictory. 

Response 80.5: EPA does not believe that proposed testnotes 3 and 5 are contradictory. Testnote 3 

specifies two conditions (test material is corrosive to skin or pH is less than 2 or greater than 11) 

when the acute dermal, primary eye irritation, primary dermal irritation, and dermal sensitization 

studies would not be required, i.e. the study would be waived. If the test substance were to meet the 

conditions of testnote 3, then those four acute studies would be waived. Proposed testnote 5 

specifies that dermal sensitization testing is required if repeated dermal contact is likely to occur. 

However, the dermal sensitization study would not be required if the conditions of testnote 3 were 

met. When these studies cannot be conducted due to the fact that the pesticide is a corrosive or 

severe irritant, then as noted in the Agency’s Label Review Manual, specific language is included on 

the pesticide label, thus mitigating against dermal contact. 

Comment 80.6: A commenter thought that proposed testnote 6 to the proposed toxicology table 

triggering the neurotoxicity studies is contradictory and unclear. What if the 90-day oral rodent study 

does not include a neurotoxicity screen? How does that impact proposed Testnote 6? 

Response 80.6: Proposed testnote 6 specifies that if the neurotoxicity screen that occurs in the 90-

day oral rodent study or any other data demonstrate neurotoxic effects, then both the acute 

neurotoxicity study and the 90-day neurotoxicity study are triggered. For certain use patterns with 

the potential for larger exposures (most notably food exposures), all three of these studies are 

initially required. Thus, according to proposed testnote 8 to the proposed toxicology table, the 

applicant may combine the 90-day oral toxicity study and the 90-day neurotoxicity study by adding a 

separate group of test animals. 

However, for some use patterns, the 90-day oral study is required, and the other two studies are 

conditionally required and then triggered based on proposed testnote 6. EPA acknowledges that 

when only the 90-day oral study is required, an applicant is at a disadvantage in terms of any chance 

of for combining the 90-day neurotoxicity study with the oral study: Once the 90-day oral study with 

its neurotoxicity screen has been performed, and neurotoxic effects are identified, then it is not 

possible to add a separate group of test animals to the already conducted study. 

As a point of clarification, EPA is adding a new testnote to the final toxicology table in § 

158.2230(g) to clarify that the neurotoxicity screen that is part of the 90-day oral study is not 

equivalent to a 90-day neurotoxicity study. If the 90-day oral toxicity study does not have a 
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Master Responses: Toxicology Section (80) Page 84 

neurotoxicity screen, then the acute neurotoxicity study in the rat would be required. The new 

testnote will also include: “if the 90-day oral rodent study does not include a neurotoxicity screen, 

then the acute neurotoxicity study will be required.” As part of renumbering, this new testnote will 

become testnote 11 to the toxicology table in the final rule. 

Comment 80.8: EPA has not required testing of “other” or inert ingredients, and instead is using a 

default assumption that inert ingredients are benign. 

Response 80.8: In the Office of Pesticide Programs inert ingredients are operationally defined as 

intentionally-added components in pesticide product formulations, that do not act as an active 

ingredient against the targeted pest. Inert ingredients are regulated under both the Federal 

Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug, and Cosmetic 

Act (FFDCA), and, similar to pesticide active ingredients, must meet the statutory standard of 

"no unreasonable adverse effects" on man and the environment. Before being included in a 

pesticide product, an inert ingredient must be approved by EPA for non-food use 

(http://www.epa.gov/opprd001/inerts/lists.html) or must have the appropriate tolerances or 

tolerance exemptions as established in 40 CFR part 180. New inert ingredients are evaluated 

using a process that considers both hazard potential (i.e. toxicity) as well as exposure potential 

and are subjected to the same risk assessment paradigm as that of pesticide active ingredients, 

considering the hazard, endpoints of toxicological concern, dose-response, exposure, and risk 

assessment.

Comment 80.9: EPA did not include any studies to assess endocrine disruption effects. 

Response 80.9: The commenter is correct that EPA has not included within the proposed subpart 

W, studies whose sole purpose is to assess endocrine disruption effects in avian and aquatic species. . 

The Agency is also not including such studies in the final rule. 

As required by FIFRA and FFDCA, EPA reviews a toxicological database of numerous studies to 

assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include 

acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, 

developmental, reproductive, and general or systemic toxicity. These studies include endpoints 

which may be susceptible to endocrine influence, including effects on endocrine target organ 

histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, 

reproductive loss, and sex ratios in offspring. A particularly important study, in this regard, is the 

two-generation rat reproduction study. EPA reviews these data and selects the most sensitive 

endpoints for relevant risk assessment scenarios from the existing toxicological database. 

Through a separate effort, the Agency has also developed a screening battery to identify chemicals 

that may have effects on the hormone systems of people and animals. 

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor Screening 

Program (EDSP) to determine whether certain substances (including pesticide active and other 

ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally 
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Master Responses: Toxicology Section (80) Page 85 

occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP 

employs a two-tiered approach to making the statutorily required determinations. Tier 1 consists of a 

battery of 11 screening assays to identify the potential of a chemical substance to interact with the 

estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 

screening and are found to have the potential to interact with E, A, or T hormonal systems will 

proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests 

are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine 

related effects caused by the substance, and establish a dose-response relationship between the dose 

and the E, A, or T effect. The test selected for tier 2 testing to identify endocrine-related effects in 

mammals is the two-generation rat reproduction study. 

Between October 2009 and February 2010, EPA issued test orders/data call-ins for 58 pesticide 

active ingredients and nine inert ingredients. This list of chemicals was selected based on the 

potential for human exposure through pathways such as food and water, residential activity, and 

certain post-application agricultural scenarios. This list should not be construed as a list of known or 

likely endocrine disruptors. 

Under FFDCA section 408(p) the Agency must screen all pesticide chemicals, including 

antimicrobials. Accordingly, EPA anticipates issuing future EDSP test orders/data call-ins for all 

pesticide active ingredients. 

For further information on the EDSP including the status and test guidelines, please visit our 

website: http://www.epa.gov/endo/. 

Comment 80.11: One commenter stated their contention that acute end product use-dilution 

toxicity testing is optional and requested greater clarification on when to test a diluted product. The 

commenter wondered whether extrapolation from the active ingredient or as-sold acute toxicity 

testing is acceptable? Another commenter argued that requiring end-product six-pack testing of one 

or more dilutions is duplicative. 

Response 80.11: Proposed testnote 2 specifies how to conduct acute toxicity testing for end-use 

products (EP). EP testing is conducted on the product as formulated for sale and distribution. From 

the EP acute toxicity studies, EPA derives toxicity categories which are then used to determine the 

precautionary labeling statements on the product. However, it is common for some products to be 

diluted before being used. The use-dilution testing is in addition to the as-formulated-for-sale testing 

since there are exposures to both. Acute toxicity testing on the product that has been diluted-for-use 

supplies the information needed to derive precautionary statements for the user of the product. EPA 

has revised proposed testnote 2 to make this clearer. 

Comment 80.12: Does Testnote 2 to the Toxicity Table also apply to acute inhalation studies? 

Response 80.12: Yes, proposed testnote 2 specifically states “For the six acute toxicity studies...”, so 

the acute inhalation study is included in that grouping. EPA will add testnote 2 to the acute 

inhalation study requirement. 
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Master Responses: Toxicology Section (80) Page 86 

Comment 80.13: How does the requirement for use-dilution acute toxicity testing intersect with the 

need for dilution of the test substance to distinguish between irritation and allergic reaction? 

Response 80.13: Proposed testnote 2 specifies how testing is to be conducted with end-use products 

as well as products labeled for further dilution. As described in proposed testnote 2 sometimes 

testing with both concentrations is needed. With regard to irritation and allergic reactions, these two 

physiological responses are based on different biological mechanisms; thus, there are separate 

toxicity tests for these reactions. Dilution of the test substance may be necessary to determine the 

non-irritating concentration, or the concentration that can be tested in order to examine other 

effects besides irritation (such as in acute inhalation testing). Testing of a concentration that is nonirritating may also be helpful in determining how to be protective against causing allergic reactions, 

although sensitization testing is also required. 

Comment 80.15: A commenter does not believe that the acute neurotoxicity study should be 

required. 

Response 80.15: The acute and subchronic neurotoxicity studies represent different types of 

exposure (i.e. a single exposure to the pesticide versus repeated exposures). It is important to require 

both studies to more completely understand the neurotoxic potential of the pesticide and adequately 

characterize the potential risk to human health. The acute and subchronic neurotoxicity studies 

include specific neurotoxicity parameters such as motor activity assessment, functional observation 

battery and neuropathy examination that are not assessed in traditional subchronic toxicity studies. 

These parameters are needed for risk assessment purposes. 

Comment 80.16: Several commenters asked EPA to identify the criteria to determine “repeated 

human exposure over a limited portion of the human life span.” They asked for EPA to specifically 

describe what the phrase “human exposure is not purposeful” mean? 

Response 80.16: Proposed testnote 11 specifies the triggers that would require the performance of a 

90-day oral study in the non-rodent. EPA has re-evaluated this testnote and decided to remove 

testnote 11 from proposed 158W. Proposed testnote 11(i) contained the phrase “repeated human 

exposure over a limited portion of the human life span.” EPA agrees that this phrase is not useful. 

Proposed testnote 11(ii) contained a trigger for any indirect food use that would have been 

considered to be a “low exposure”. Given the restructuring of the toxicity data requirements table, 

i.e., the shift away from using high and low human exposure as the table headers to a food/nonfood approach, testnote (11ii) is no longer needed. In the final toxicity table, the data required for an 

indirect food-use is specified directly and a trigger is not needed. 

Proposed testnote 12 specifies three triggers that would require the performance of a 21/28-day 

dermal study. EPA has also re-evaluated testnote 12 and agrees that the phrases “repeated human 

exposure over a limited portion of the human life span” and “human exposure is not purposeful” 

are not useful. EPA has decided to remove the first two of the triggers. Therefore, the 21/28 day 

dermal study is now triggered if the intended use of the antimicrobial pesticide product is expected 

to result in dermal human exposure to the product, and data from a subchronic 90-day dermal 
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Master Responses: Toxicology Section (80) Page 87 

toxicity study are not available and the 90-day dermal toxicity study has not been triggered (the third 

proposed trigger). 

Comment 80.17: The antimicrobial data requirements for the 90-day oral rat and the 90-day nonrodent are not consistent with those of conventionals. A 90-day oral rat is required for ALL 

antimicrobials, while it is conditional for conventional pesticides - required only if oral exposure is 

expected to occur for conventional pesticides. 

Response 80.17: The commenter is correct: For conventional pesticide chemicals a 90-day oral study 

is required for non-food uses only if oral exposure could occur. (see testnote 8 to the toxicity table 

for conventional pesticide (40 CFR 158.500)). 

In its proposed rule for antimicrobial pesticides, EPA used a definitional approach described by the 

terms high and low human exposure in the table headers to distinguish the use patterns needing 

more toxicity testing from those needing less testing. EPA defined high human exposure in the 

proposed rule by listing use and exposure patterns that it considered to have high human exposures. 

EPA continues to believe that the exposures listed are higher and that it is appropriate to distinguish 

the use patterns with higher exposure that need more toxicity data from those that need less. 

However, as a result of comments received, EPA is now incorporating a food/non-food approach 

with some similarities to that of conventionals to distinguish the use patterns needing more toxicity 

data from those that need less. Implicit within the concept of a food-use product is oral exposure. 

Therefore those products that are food-use will require a 90-day oral study in the rodent. 

For those use patterns that are non-food uses, EPA is adding a new testnote 38 to clarify that an 

oral 90-day study is required if oral exposure could occur. EPA is also revising testnote 7 to clarify 

that if the dermal and/or inhalation exposures are the primary route of exposure(s) then the dermal 

and/or inhalation 90-day studies are required so route-to-route extrapolation is not needed. 

Comment 80.18: EPA should not require (R) any neurotoxicity studies, but should instead 

conditionally require (CR) and trigger all 90-day neurotoxicity studies based on the results of the 

neurotoxicity screening in the 90-day oral or other required studies. 

Response 80.18: The neurotoxicity screen in the 90-day oral study is not sufficient to identify 

neurotoxic effects for risk assessment purposes. The 90-day neurotoxicity studies include 

specific neurotoxicity parameters such as motor activity assessment, functional observation 

battery and neuropathy examination that are not included in the neurotoxic screen of an oral 90-

day toxicity studies but are needed for risk assessment. 

Comment 80.19: The commenter does not believe that the 90-day neurotoxicity study or the 90-day 

immunotoxicity study should be routinely required. Instead, the commenter wants the 90-day oral 

study enhanced with additional neurotoxicity and immunotoxicity parameters to minimize the need 

for additional testing. Thus, both the 90-day neurotoxicity study and/or the 90-day immunotoxicity 

study would be triggered based on the results of the enhanced 90-day oral study. 
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Master Responses: Toxicology Section (80) Page 88 

Response 80.19: As discussed in response to comments 80.18 and 80.6, the neurotoxicity screen in 

the 90-day oral toxicity study can be used to trigger the 90-day neurotoxicity study. However, the 

90-day oral toxicity studies not specifically conducted to assess immunotoxic endpoints are 

inadequate to characterize the potential immunotoxicity of a pesticide. Since the 90-day oral 

study is designed to examine general toxicity, endpoints normally measured in an 

immunotoxicity study are not measured in the 90-day oral study, even if tissues likely to suffer 

immunotoxic insult are examined.

The Agency acknowledges that there is not a guideline that specifically addresses the issue of 

combining the 90-day oral with the 90-day immunotoxicity or 90-day neurotoxicity studies. 

However, to reduce costs and the number of test animals, the studies can be combined by having 

designated groups of animals specifically for conducting a routine subchronic study and for 

immunotoxicity or for neurotoxicity testing, respectively. Endpoints normally measured in the 

immunotoxicity or neurotoxicity studies would be measured in those designated groups. To clarify, 

EPA is revising testnote 8 to add that the 90-day immunotoxicity study and/or the 90-day 

neurotoxicity study can be combined with the 90-day oral study. 

Comment 80.20: A commenter stated that a dermal penetration study and the 90-day subchronic 

oral toxicity study can adequately replace the 90-day dermal toxicity study. 

Response 80.20: While EPA has sometimes accepted a dermal penetration study combined with the 

90-day oral toxicity study instead of having a 90-day dermal study, EPA does not believe that a 

dermal penetration study and the 90-day oral toxicity study exactly replaces the 90-day dermal 

toxicity study. It is not an exact substitution: using an oral study for a dermal route of exposure is 

not as accurate since it involves using an endpoint (an extrapolation) that is not a route specific 

endpoint. 

If, the primary route of exposure is dermal, then, for most circumstances, the most appropriate 

study would be the 90-day dermal study. Conducting two studies (90-day oral and dermal 

penetration) to replace the 90-day dermal is not an efficient use of resources, if the hazard question 

being asked can be answered with a 90-day dermal toxicity study. Dermal absorption data and data 

from a 90-day oral toxicity study have been used for hazard characterization and can continue to be 

used; however, the 90-day dermal toxicity study can examine both dermal and systemic effects that 

may occur from repeated dermal exposure. 

Comment 80.21: One commenter asked for additional clarification regarding the mouse rangefinding study. Is the agency encouraging the applicant to submit the 90-day mouse range-finding 

study when it has been conducted? 

Response 80.21: In proposed testnote 9, the range-finding study in the mouse is “encouraged” but is 

not required. If the range-finding study in the mouse has been conducted, then this study should be 

submitted. 
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Comment 80.22: The requirements for toxicity testing are defined by two terms high exposure and 

low exposure, which are not well-defined. The proposal would conditionally require the chronic 

study for low exposure uses, including non-food, subject to the "repeated human exposure over a 

limited portion of the human lifespan" which is also not well-defined. Conventional test note (17.i.) 

requires the chronic study only if exposure is “likely to result in repeated human exposure over a 

considerable portion of the human lifespan.” 

Response 80.22: As a result of comments received, EPA is no longer using the terms “high human 

exposure” and “low human exposure” as table headers for the proposed Antimicrobial Toxicology 

Data Requirements Table. Instead EPA in the final rule is now using a food/non-food approach 

with some similarities to that of conventionals to distinguish the use patterns with higher exposure 

that need more toxicity data from those that need less. Accordingly, the table headers for the 

Toxicology Data Requirements Table in the final rule are: Direct Food Uses; Indirect Food Uses 

(>200 ppb); Indirect Food Uses (<200 ppb); Swimmers, Aquatic Areas, Wood Preservatives, Metal 

Working Fluids; and All Other Nonfood Uses. 

EPA also notes that the terms “high human exposure” and “low human exposure” can be 

appropriate when discussing a particular antimicrobial use. A statement that a particular use results 

in “high human exposure” provides information and alerts the reader that more data is likely to be 

needed, rather than less data. 

 

EPA is also revising testnote 20 to read “considerable portion” instead of “limited portion” to read 

similarly to the comparable testnotes for conventional pesticide chemicals. 

Comment 80.23: EPA should use a different approach for requiring chronic/carcinogenicity studies 

for antimicrobials than that of conventional pesticide chemicals. For antimicrobials, these should be 

conditionally required (CR) studies “based on characteristics, such as genotoxicity, based on a weight 

of evidence approach, cumulative neurotoxicity established in multiple dose studies, and other 

morphologic changes indicative of long-term toxicity, as well as exposure.” 

Response 80.23: EPA disagrees with this comment and believes that chronic/carcinogenicity studies 

are needed to understand toxicological effects from long-term exposures. EPA also notes that these 

studies are currently required in part 161, are routinely submitted to EPA, and the data are used in 

EPA’s risk assessments. If the applicant believes that there is a specific reason for not requiring 

chronic/carcinogenicity studies for antimicrobials, then the applicant can request a waiver by 

submitting a rationale for the Agency to consider. 

Comment 80.24: According to several commenters, the mouse carcinogenicity study does not 

provide useful information, and is, in fact, not suited to determining/extrapolating human 

carcinogenicity. EPA should no longer require the mouse carcinogenicity study. This would also 

mean that there is no need for the mouse range-finding study. 

Response 80.24: The issue regarding the usefulness of the mouse for carcinogenicity testing is one 

that is currently under debate by the Office of Pesticide Programs (OPP). OPP is currently 

conducting a comprehensive analysis of its rodent chronic bioassay database to document the utility 
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Master Responses: Toxicology Section (80) Page 90 

of the mouse bioassay for both cancer risk assessment and Reference Does (RfD) derivation for 

noncancer endpoints. When this analysis is completed, a recommendation will be made regarding 

the testing needed for cancer hazard identification. OPP anticipates completing this analysis during 

2012. Once OPP’s internal review process is complete, then it is likely that EPA would solicit 

review and comment by the FIFRA Scientific Advisory Panel (SAP). If at a later date, the 

determination is made to alter the carcinogenicity data requirements, then appropriate changes 

would be made to data requirements and regulations pertaining to conventionals, biochemicals and 

microbials, and antimicrobials through rulemaking. 

Comment 80.27: A commenter stated that the requirement for a carcinogenicity study could be 

fulfilled based on toxicity information of a related chemical or waived based on the magnitude of 

exposure. 

Response 80.27: The Agency would always consider the scientific merit of a request for fulfilling the 

requirement for carcinogenicity studies using alternative approaches or information on a structurally 

related chemical, as long as the characterization is adequate and scientifically supported. For 

additional information on alternative approaches, see response to comment 170.2. It is unlikely that 

a carcinogenicity study would be waived based on a presumed lack of exposure. However as 

explained in response to comment 80.79, under certain circumstances the carcinogenicity study is 

held in reserve pending the outcome of human exposure data. 

Comment 80.28: A commenter thought the chronic study should not be triggered merely because 

the chemical is a food-use requiring the establishment of a tolerance or tolerance exemption. 

Response 80.28: EPA disagrees with this comment. As EPA stated in the preamble [59392] 

“Exposure to food and water, which occurs throughout the human life span, is therefore a high 

human exposure.” Therefore, EPA will continue to require a chronic study for food-uses and certain 

nonfood uses involving significant exposure (such as wood preservative uses, swimmers, and 

metalworking fluid uses). Endpoints selected from chronic toxicity studies are often used to derive 

Reference Dose values that are used to conduct the dietary risk assessments needed to establish a 

tolerance or exemption from tolerance. 

Comment 80.29: A commenter asked what counts as significant exposure. 

Response 80.29: Significant exposure is defined in terms of the frequency, duration, or magnitude of 

the exposure. Use patterns such as those involving the use of antimicrobial pesticides which result 

in exposures via food, to swimmers in swimming pools, and via exposures to preserved wood 

products represent examples where significant exposure is expected to occur. 

Comment 80.30: A commenter does not believe that the developmental toxicity study and the 2-

generation reproductive study should be combined. 

Response 80.30: EPA disagrees with this comment and notes the recommendation for combining 

the developmental toxicity study with the reproductive toxicity requirement in proposed testnote 26 
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Master Responses: Toxicology Section (80) Page 91 

to the toxicity table. There can be valid concerns that various effects of some test substances in a 

reproduction study protocol may interfere with standard developmental observations if the 

reproduction study has an added developmental toxicity component. Applicants and their 

contracted or in-house laboratories are encouraged to consult with the Agency when developing 

a protocol for a combined study. It is additionally noted that combining these studies is an option 

available for applicants to consider and is not a requirement by the Agency. 

Comment 80.31: A commenter contended that EPA has misinterpreted the 1997 retrospective 

analysis on reproductive toxicity testing (see document 15 in the docket EPA-HQ-OPP-2008-0110), 

and did not consider the options presented in that analysis. These options would include: “One 

[option] was simply to apply an extra 10X safety factor to the NOAEL from the developmental 

toxicity study. Another was to require the 90-day study to be by the oral route and incorporate some 

additional parameters into the evaluation.” Additionally, the commenter asserted that EPA should 

encourage new approaches. 

Response 80.31: EPA’s internal analysis of the information presented in 1997(document 15), 

including the options, determined that requiring a reproductive toxicity study (as were as two 

developmental toxicity studies) would ensure that EPA did not miss potential reproductive risks of 

concern. EPA’s consideration was conducted in light of the 1996 Food Quality Protection Act 

(FQPA) amendments to FIFRA and FFDCA. EPA continues to believe that these studies provide 

the best available information to address infant’s and children’s susceptibilities. 

The Agency does encourage alternative approaches as shown by including proposed testnote 28 as a 

trigger for reproductive toxicity study. Proposed testnote 28 describes how an information-based 

approach to testing is preferred. 

Comment 80.32: A commenter thought EPA should provide more specific criteria on when a DNT 

is triggered and also additional guidance on how to interpret the criteria that trigger a DNT. 

Response 80.32: In 1998 the SAP issued a recommendation to the Agency that the DNT study be 

required for all food use pesticides. However, since then, EPA has reviewed and analyzed many 

DNT studies. Based on that experience , EPA believes that the DNT should be conditionally 

required (CR) for all food and nonfood use conventional pesticides based on a weight-ofevidence approach. EPA provided additional information on its weight-of-evidence approach, in 

general, and particularly for the DNT in the preamble to the final rule for conventional pesticides 

(72 FR 60937-38). As explained in the preamble to the proposed rule [59388], the rationale, or 

weight-of-evidence (WOE) evaluation, is the part of the submission that explains the applicant’s 

belief as to why and how the predictive data would fulfill the data requirement. The WOE approach 

requires a critical analysis of the entire body of available data for consistency and biological 

plausibility. In support of a request that predictive data be considered, the applicant would need to 

explain why it believes the surrogate data or the modeling are appropriate for the intended use and 

are of sufficient completeness and quality, and therefore would fulfill the data requirement. 

The general types of information that are considered appropriate for a WOE approach would 

include: 

• Sufficiency of data. Studies that completely characterize both the effects and exposure of the agent 

have more credibility and support than studies that contain data gaps. 
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• Quality of the data. Potentially relevant studies are judged for quality and studies of high quality are 

given more weight than those of lower quality. 

• Evidence of causality. The degree of correlation between the presence of an agent and some adverse 

effect is an important consideration 

EPA is now continuing with this same WOE approach by conditionally requiring a DNT for all 

antimicrobials using the same WOE approach.

Comment 80.33: A commenter maintained that the second developmental toxicity study should not 

be required but instead triggered based on the results of the first developmental toxicity study. 

Another commenter thought that only the rabbit developmental toxicity study and the rat 

reproductive toxicity study should be required and the rat developmental toxicity study would be 

triggered based on the results of these two studies. 

Response 80.33: As part of their comments, one commenter submitted: According to Hurtt et al. 

(2003), “no single species was capable of detecting more than 61 percent of developmental 

toxicants.” EPA believes that this clearly supports the use of two species to assess developmental 

toxicity. It is unclear that a developmental toxicity study in the rabbit will be adequate to identify 

developmental toxicants adequately. The Agency proposed requiring the prenatal developmental 

study in a second species because two species will provide some assurance that EPA is not 

basing an assessment on a single species (e.g., rodent) which might be highly sensitive (or the 

opposite) when compared to another (e.g., nonrodent). Therefore, to adequately characterize 

potential hazards to pregnant women and their fetuses, the prenatal developmental study is 

required in two species for all pesticides.

EPA also notes that the developmental toxicity and reproductive toxicity studies are designed for 

different purposes and, while they can be combined into a single protocol, developmental testing in 

a second species is needed. 

Comment 80.34: A commenter argued that EPA should require the first developmental toxicity 

study and the extended F1-one-generation reproductive study. The commenter maintained that a the 

second developmental toxicity study should not be required, but instead triggered based on the 

results of the two required studies. The commenter noted that the one-generation reproductive 

study could be extended to a two generation study based on information obtained during the 

conduct of that study. 

Another commenter maintained that EPA should require the extended 1-generation reproductive 

toxicity study instead of a 2-generation study. 

Response 80.34: The Agency notes both in 40 CFR 158.500 (testnote 25 to the toxicity table for 

conventional pesticides) and in the proposed antimicrobial pesticide data requirements rule 

(proposed testnote 26), that developmental toxicity testing can be combined with the 2-generation 

reproduction toxicity test to address developmental toxicity in the rodent. The Agency also 

acknowledges the extended F1-reproduction toxicity test can provide evidence in support of both 

reproductive and developmental toxicity hazard characterization. 
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The Agency notes that although developmental toxicity testing in two species and a 2-generation 

reproduction toxicity study are required for all uses of antimicrobial pesticides, the Agency allows 

flexibility in how these data requirements can be addressed. The developmental toxicity testing and 

reproductive toxicity testing can be combined, and alternative testing protocols are encouraged as 

well by the Agency to address these data requirements. 

At this time, EPA is evaluating if an extended 1-generation reproduction toxicity study would be 

considered a viable alternative to the 2-generation reproduction toxicity study. Once its evaluation is 

completed, EPA intends to present its analysis to the SAP. 

Comment 80.36: A commenter thought that for the “Low Human Exposure,” that the 2-generation 

reproductive toxicity study should be CR instead of R. 

Response 80.36: EPA disagrees with this comment. The reproductive toxicity testing is required for 

all use patterns. Magnitude of exposure alone is not a determinant of reproductive toxicity potential. 

Those scenarios that involve exposure of infants and children as well as pregnant females need to be 

assessed for reproductive toxicity potential in order to satisfy the FQPA statutory standard. 

Comment 80.37: How do the developmental and reproductive toxicity studies account for the 

exposure of the male parent? 

Response 80.37: The developmental toxicity study does not account for exposure to the male parent. 

It is designed to measure effects in the pregnant female and on the offspring. 

However, the reproductive toxicity test guideline (OPPTS 870.3800 available at 

http://www.epa.gov/oppts/pubs/frs/publications/Test_Guidelines/series870.htm) does include 

exposure of the male parent and measurement of male reproductive parameters. Therefore, there is 

dosing of both the male and female parental animals. Dosing of male and female parents is also 

continued in the 2nd (F1) generation as specified in the reproductive toxicity testing guideline. 

Comment 80.38: Several commenters felt that EPA should clarify proposed testnote 28, yet there 

were no specific suggestions as to how this testnote should be clarified. One commenter asked why 

is a waiver mentioned in proposed testnote 28? No other testnotes discuss waivers. 

Response 80.38: Proposed Testnote 28 describes an information-based approach for conducting 

two studies (reproductive toxicity and DNT). These are complex studies that can particularly benefit 

from considering all the available information before beginning testing. It is possible that a review of 

the existing information of the chemical’s hazard, pharmacokinetic, or mechanistic data could fulfill 

the data requirement, offer alternative approaches to fulfilling the data requirement, or indicate that 

a standard guideline study or enhanced guideline study should be conducted. 

EPA agrees that the language on the waiver in proposed testnote 28, can be removed. An applicant 

can always submit a request for a waiver with a supporting rationale. 
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Comment 80.39: A commenter ,contended that “if the compound is shown to be hormonally active 

in vivo” should be added to the triggers for a DNT study. 

Response 80.39: The need for a DNT study is triggered by a weight-of-evidence approach, which 

includes four considerations which are described in proposed testnote 30. The four triggers relate to 

“treatment-related effects” in adult animal studies, “treatment-related effects” in developing animal 

studies, “causative association”, or “mechanism that is associated with.” By itself a hormonal 

disturbance is not a sufficient trigger for a DNT. There would need to be a link to an adverse effect 

and evidence of treatment-related neurological effects in adult and/or developing animals. Once that 

link has been understood, then it is very possible that a DNT would be triggered based on the 

existing triggers. 

It is noted that the Agency has established, under a separate Agency effort 

(http://www.epa.gov/ocspp/pubs/frs/publications/Test_Guidelines/series890.htm) the Tier I 

testing strategy under the Endocrine Disruptor Screening Program to determine the potential for 

hormonal activity of pesticides. 

Comment 80.41: The Ames assay should not be required. Since 1997, it has been recognized as 

inappropriate for antimicrobials that kill bacteria. 

Response 80.41: It is recognized that the Ames assay may not be useful for assessment of mutagenic 

potential of antimicrobial pesticides, as this test uses strains of bacteria as the primary test material, 

and antimicrobials are designed to kill, among other things, bacteria. So, the bacteria may be killed 

before mutagic effects are demonstrated. However, for some antimicrobial pesticides, the Ames 

assay has already been conducted and if the Ames assay was conducted at levels that do not cause 

toxicity to the bacterial strains tested, then the study may be acceptable to fulfill the reverse mutation 

assay requirement. However, if an Ames assay has not yet been conducted for a particular 

antimicrobial, then, the Ames assay should not be conducted. Testnote 32, to the reverse mutation 

assay requirement, will be revised to indicate that assays such as an in vitro mammalian cell assay, (e.g. 

the mouse lymphoma TK +/- assay) can be performed. 

Comment 80.42: A commenter noted that there is an incorrect guideline number listed: 870.5380 

Response 80.42: The incorrect guideline number (875.5380) is noted and will be removed from the 

table for the entry for in vivo cytogenetics assay. 

Comment 80.43: A commenter noted that the mutagenicity data requirements are not harmonized 

with the Global EU guidance, which includes doing the Ames and/or the Mouse Lymphoma Assay 

without doing an in vivo test unless there is a positive or equivocal test in the in vitro tests. 

Response 80.43: The Agency is aware of the European Commission’s Scientific Committee on 

Consumer Products (SCCP) document entitled “Position Statement on Genotoxicity / Mutagenicity 

Testing of Cosmetic Ingredients Without Animal Experiments” ( January 2009.) (see 

http://ec.europa.eu/health/ph_risk/committees/04_sccp/docs/sccp_s_08.pdf) 
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Master Responses: Toxicology Section (80) Page 95 

This document “bans the testing on animals of ingredients or combination of ingredients of 

cosmetics as of 11 March 2009.” 

The Agency’s requirements for mutagenicity testing of pesticides differs from the approach in this 

document. The Agency has not adopted an approach of using only results from in vitro 

mutagenicity tests for assessment of mutagenic potential of pesticide chemicals. As noted within the 

SCCP document itself, “In vivo testing has a decisive role in current mutagenicity testing since it is 

not possible to predict the results in vivo based on the outcome of positive in vitro tests alone,” and 

“The use of an in vitro-only test battery with the currently established in vitro tests for mutagenicity 

testing might lead to a scientifically unjustified high attrition rate of substances which would have 

been considered [non-mutagenic] after in vivo testing.” 

Comment 80.44: A commenter thought EPA should explore the feasibility of combining the 

micronucleus assays into the subchronic toxicity studies, as is done in the pharmaceutical sector. 

Response 80.44: EPA would consider an alternative protocol proposal that was submitted for 

review, especially if the study outlined in the proposal could reduce the number of test animals while 

providing sufficient information for a regulatory decision. 

Comment 80.46: A commenter maintained that the DNT should be required for certain use patterns 

(homes, schools, parks and daycare centers), and dose and exposure should be considered as triggers 

for the DNT. Another commenter stated that “if effects ‘triggering’ the DNT occur only at very 

high does (such that they do not impact the NOAEL for risk assessment),” then the DNT is not 

needed.

Response 80.46: EPA notes that the triggers for conduct of the DNT study are based, in part, on 

results obtained from other toxicology studies conducted in support of the hazard characterization 

of a pesticide. The hazard characterization would note potential indicators of neurotoxicity both to 

the adult and to the developing organism. In addition to treatment-related effects, structure-ActivityRelationship analysis can reveal structural similarity to known neurotoxicants. 

The Agency considers all adverse effects in the evaluation of hazard and risk. If effects “triggering” 

the DNT were at dose levels or concentrations significantly above the expected exposures, this 

would be reflected in the Agency's calculation of the Margins of Exposure (MOEs). MOEs which 

are above the Agency's level of concern would be considered acceptable, i.e., with no expectation of 

significant risk. The Agency evaluates all available toxicological information in the evaluation of 

hazard and risk based on test results received in mammalian species and its risk determinations are 

health-protective for any adverse effect, including potential neurotoxicity to developing mammalian 

organisms. Although effects triggering the DNT may have been observed in other toxicity studies 

only at high doses, this does not mean that effects in the DNT will also only be observed at high 

doses, as the developing nervous system can be sensitive to chemical exposures in comparison to 

other systems. In the determination of risk to pesticide exposures, the most health-protective 

endpoint(s) are always used by the Agency. 
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Master Responses: Toxicology Section (80) Page 96 

Although the acute and 90-day neurotoxicity studies and the reproduction toxicity study may be 

primary sources for determining neurological effects, the Agency does not limit itself to only these 

studies in deciding the need for a DNT. The need for a DNT is based on a WOE approach, which 

is a hazard characterization and is not focused on a particular dose or exposure. 

Comment 80.47: The 21/28-day and 90-day dermal studies should not be required for EP (end-use 

product) testing. 

Response 80.47: The Agency recognizes that it would be cost prohibitive and highly impractical to 

test each formulated EP. Proposed testnote 13 describes the limited and very specific circumstances 

when testing of the EP is needed. The need for dermal EP testing is infrequent. 

Comment 80.49: A commenter thought that EPA only needs to require one subchronic study, that 

testing in two species is duplicative, and is not the recommendation of Health and Environmental 

Sciences Institute – Agricultural Chemical Safety Assessment (HESI-ACSA). 

Response 80.49: In the proposed rule, EPA proposed to require two 90-day oral (subchronic) 

studies for high human exposure uses, and one 90-day study for low human exposure use. EPA is 

no longer using these descriptors. In its final rule EPA intends to require two 90-day oral 

subchronic toxicity studies for the following use categories: direct food uses, indirect food uses, and 

certain non-food uses such as swimmers, wood preservatives, and metal working fluid uses. In each 

of these use categories, assessment of subchronic oral toxicity in two species is needed to conduct a 

more extensive hazard and risk assessment in comparison to the other nonfood uses that will be 

described in the final rule as “all other nonfood uses” 

For the “all other nonfood uses,” a single subchronic toxicity study is required. However, two 

subchronic toxicity studies are required for nonfood uses if oral exposure could occur. This is 

consistent with requiring two subchronic toxicity studies for food uses. 

Comment 80.50: A commenter noted that the extended 1-generation reproductive study should 

include an evaluation of neurodevelopmental endpoints rather than having to conduct a stand-alone 

study later. 

Response 80.50: One of the cohorts in the draft extended (F1) 1-gen study protocol does include an 

evaluation of neurodevelopmental endpoints. These endpoints are included as a screening tool to 

determine if a DNT would be required. EPA has received one study conducted under this protocol 

and is currently reviewing the study. 

Comment 80.51: A commenter asked how many/which species are to be tested in the 

immunotoxicity tests? 
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Master Responses: Toxicology Section (80) Page 97 

Response 80.51: As stated in the Office of Chemical Safety and Pollution Prevention (OCSPP) 

Harmonized Guideline for Immunotoxicity testing (870.7800), “These tests are intended for use in 

rats and/or mice. Commonly used laboratory strains should be employed.” 

Comment 80.52: A commenter asked whether the immunotoxicity testing be combined with the 

subchronic testing, or the enhanced 1-gen study? 

Response 80.52: The Agency agrees that the guidelines do not specifically address the issue of 

combining subchronic studies or reproductive studies with immunotoxicity studies. However, the 

studies can be combined as long as there are designated groups of animals specifically for 

conducting a routine subchronic study and immunotoxicity testing, respectively. A combined study 

could be considered acceptable as long as, among other things, sufficient information is available to 

fulfill both data requirements. 

EPA is adding to testnote 8 to the toxicology table to clarify that immunotoxicity testing can also be 

combined with the 90-day oral study, as was proposed for the neurotoxicity testing. 

 

Comment 80.53: Since sensitization is an immunological response, how will EPA conduct 

immunotoxicity testing with known sensitizers. 

Response 80.53: EPA agrees that dermal sensitization is an immunologically-based response. 

However, the Agency has developed guidelines for the separate study of dermal sensitization and 

immunotoxicity. Sensitization, while an immune response, is not the result of primary toxic insult to 

the immune system, but rather a normal immune-based response. By contrast, the immunotoxicity 

guideline seeks to examine whether there is toxic insult to the immune system from exposure to 

pesticides and measures different endpoints than a dermal sensitization study. 

Comment 80.54: A dermal study on the TGAI should only be conducted if there are indications that 

the dermal route of exposure is more hazardous. 

Response 80.54: The Agency disagrees with this comment. Dermal studies on the TGAI are 

conducted on the basis of exposure as well as hazard. If the primary route of exposure is dermal, 

then this is the route of exposure that should be tested for hazard characterization. 

Comment 80.55: A commenter thought that proposed testnotes 7, 14, and 16 are confusing and that 

EPA should clarify when a 90-day dermal or inhalation study may be substituted for the 90-day oral 

study. The commenter asked whether the dermal study is always required? 

Response 80.55: Proposed testnote 16 specifies the 90-day inhalation toxicity study is required if 

there is the likelihood of significant repeated inhalation exposure. Proposed testnote 7 specifies that 

if the primary route of exposure is dermal or inhalation, then the dermal or inhalation 90-day study 

is to be conducted. Proposed testnote 14 specifies that a 90-day dermal toxicity study is required if 

the dermal route is the primary route of exposure, or if the active ingredient is known to metabolize 
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Master Responses: Toxicology Section (80) Page 98 

differently via the dermal route of exposure and a metabolite of the active ingredient is the toxic 

moiety. 

EPA believes for 90-day studies that the appropriate route – the primary route of exposure - should 

be tested. This means that the submitted 90-day studies will reflect the primary routes of exposure, 

which depends on use pattern desired by the applicant. 

EPA agrees that the testnotes should be clearer, especially since they are inter-related, and therefore 

will revise: 

 Proposed testnote 14 to remove the phrase “ if the use pattern is such that the dermal route 

would be the major route of exposure” as this is duplicative of testnote 7. 

 Proposed testnote 7 is revised to clarify that a 90-day dermal and/or inhalation exposure 

study is required if those are the primary routes of exposure. 

A new testnote 38 will specify that a 90-day oral study is required if there is the potential for oral 

exposure. 

No changes are needed for proposed testnote 16. 

Comment 80.56: EPA should accept in vitro skin penetration data. This would harmonize with 

requirements in the EU and elsewhere. There are well-established OECD guidelines for these 

studies. Proposed testnote 37 should not apply to corrosive/irritant products. 

Response 80.56: The Agency has, on a case-by-case basis, used in vitro dermal absorption studies to 

determine the magnitude of dermal absorption of pesticide chemicals. However, the Agency has not 

adopted an official policy of using only in vitro data to support these decisions. The OECD guideline 

428, while describing an in vitro method for dermal absorption, does not rule out the use of in vivo

data along with in vitro data to determine dermal absorption. Further, the test guideline notes that 

formal validation studies of the in vitro method have not been performed. 

The Agency is working on developing a more formal policy that would use both in vivo and in vitro

dermal penetration data in a WOE determination in appropriate cases. The Agency would always 

consider QSAR or other models, submitted in support of the determination of dermal absorption. 

The decision to accept such information is the Agency’s., based on its review and evaluation of the 

submission. 

Proposed testnote 37 specifies that the trigger for requiring a dermal penetration study is a risk 

assessment “assuming that dermal absorption is equal to oral absorption.” If a subchronic dermal 

study and/or dermal absorption data are not available, then a risk assessment could be conducted 

using the default assumption of equivalent absorption by the dermal and oral routes of exposure. If 

unacceptable risks are found, then either the subchronic dermal study or a dermal absorption study 

would be required. EPA recognizes that the assumption of 100 percent dermal absorption is 

conservative; however, this assumption would only be used in the absence of an acceptable dermal 

subchronic study or dermal absorption data. EPA will revise testnote 37 to clarify this process. EPA 

also agrees that corrosive/irritant products should not be tested in dermal absorption studies. 

Therefore, testnote 3 which specifies that testing is not needed for corrosive materials is added as a 

trigger for not requiring the dermal absorption study. 
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Comment 80.57: A commenter thought EPA had not clearly explained in testnote 35 the triggers for 

metabolism and pharmacokinetic studies. Another commenter argued that ADME (absorption, 

distribution, metabolism, and excretion) data should be considered as key information that should 

be acquired early in the testing process, and therefore, it should be required for the low exposure 

grouping instead of conditionally required. 

Response 80.57: EPA agrees that proposed testnote 35 could be confusing since it includes two 

triggers for requiring metabolism and pharmacokinetic studies, and this is further complicated by 

one trigger that says “required” and another trigger that says “may be required.” 

The data requirements for chronic/carcinogenic studies and a metabolism/pharmacokinetics study 

are intertwined: if the chronic/carcinogenic studies are required, then the 

metabolism/pharmacokinetics study is also required. 

However, there may also be other circumstances, when the chronic/carcinogenic study is not 

required that may require a metabolism and pharmacokinetics study. It is also possible that the 

dermal route of exposure could be a consideration in requiring a metabolism and pharmacokinetics 

study if that route is considered a primary route of human exposure. However, it is unlikely that 

these data would be needed for all use patterns, and therefore will remain CR. 

To clarify, testnote 35 will be split into two testnotes. Testnote 35 will be revised to state “These 

data are required when chronic or carcinogenicity studies are required.” A new testnote 39 will be 

added to state: “These data may be required if significant adverse effects are seen in available 

toxicology studies and these effects can be further elucidated by metabolism studies.” 

Comment 80.59: A commenter maintained that EPA has not provided meaningful tiering for its 

toxicology requirements for antimicrobials. Another commenter argueg that exposure alone is not 

an appropriate criterion to use for a tiered testing scheme, but that both exposure and risk should be 

considered. A third commenter contended that the high and low human exposure categories for 

toxicity are not appropriate and suggested that a tiered scheme such as that used for environmental 

fate data requirements would be more appropriate. 

Response 80.59: EPA disagrees with these comments. In its proposed rule EPA proposed a tiered 

testing scheme for toxicology testing that was based on the amount of exposure as defined by use 

patterns. Based on its experience in conducting risk assessments, EPA understands which use 

patterns have higher exposures, and therefore could have greater risks. Use patterns with higher 

exposures would require more submission of data than use patterns with lower exposures. 

Comment 80.60: A commenter asked whether the 200 parts per billion (ppb) used as the dividing 

line between high and low human exposures is the concentration of a substance in an adult’s daily 

food consumption? 

R80.60: The derivation of the 200 ppb level was previously established by FDA for indirect food use 

biocides, and is described in the proposed rule (73 FR 59394, October 8, 2008). (Also, see document 

10 in the docket at http://www.regulations.gov. As discussed in the proposed rule, the 200 ppb is 

derived by dividing FDA’s cumulative exposure upper limit of 1000 ppb level by 5 to account for 
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the fact that antimicrobial pesticides (e.g. biocides) are a class of pesticide that are generally toxic by 

design. The 200 ppb level is the concentration of the antimicrobial residues in or on the food item. 

EPA is using 200 ppb as delineation consistent with the FDA’s toxicology recommendations for 

food contact substances. Therefore, those indirect food uses that have residues that are less than or 

equal to 200 ppb on or on the food item usually have fewer data requirements than those that have 

residues that are greater than 200 ppb in or on the food item. For clarity, the following information 

concerning the 200 ppb level and its derivations from FDA levels has benn added to §158.2239(d): 

 The 200 ppb was originally used by the Food and Drug Administration with respect 

to the concentration of residues in or on food for tiering of data requirements for 

indirect food use biocides. The Agency has also adopted this same residue level 

for determining toxicology data requirements for indirect food uses of antimicrobial 

pesticides. The 200 ppb is the concentration of antimicrobial residues in or on the 

food item. 

Comment 80.62: A commenter contended that all food uses, whether direct or indirect, should be 

considered high exposure. 

Response 80.62: EPA disagrees with this comment. The nature of the food use does make a 

difference and we use the use pattern as well as the exposure to determine the data needed. The 

Agency, in consultation with the Food and Drug Administration (FDA), has established the 200 ppb 

concentration level to determine the need for more or less data for indirect food use antimicrobial 

pesticides. The FDA has an extensive history of regulation for indirect food uses which also involves 

a tiered approach for testing requirements. The Agency intends to be consistent with this approach 

but will require additional studies, if needed, to adequately characterize the hazard for an 

antimicrobial food use. 

Comment 80.64: A commenter stated that the high/low human exposure categories proposed for 

antimicrobial pesticides is confusing, and prefers the food/non-food approach used for 

conventional pesticide chemicals. 

Response 80.64: EPA agrees with this comment and has revised the toxicity table accordingly. 

Comment 80.65: A commenter contended that EPA should accept bridging principles to fulfill acute 

toxicity data requirements. 

Response 80.65: With respect to bridging, the Agency will always consider documentation that 

supports such an approach. Generally, if the Agency finds the supporting documentation and 

rationale to be sufficiently complete and appropriate, then the bridging would be accepted. EPA is 

currently working on a project with industry to develop a document that will integrate all the current 

policies that address bridging principles for fulfilling acute toxicity data requirements. This project’s 

projected completion is 1 to 2 years. Also see response to comment 170. 7. 
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Comment 80.67: A commenter argued that EPA has not appropriately considered the 1997 FIFRA 

Scientific Advisory Panel review in developing the toxicology data requirements for antimicrobials, 

and maintained that EPA is proposing to require more and higher tier studies than specified in 1997, 

and has not considered the Panel’s recommendations. 

Response 80.67: EPA disagrees with this comment. As explained in the proposed rule [59417] EPA 

asked for specific comment on five scientific disciplines covered in 158W and has incorporated 

changes with regards to the SAP’s concerns . The proposed rule contains a section (XV) that 

specifically discusses the 1997 SAP review of an earlier version of the proposed 158W test rule, 

including the questions asked of the SAP and the course of action taken by EPA. EPA believes that 

the proposed rule published on October 8, 2008 addresses the SAP’s concerns. 

Comment 80.68: A commenter prefers the 3-category approach to toxicity testing in the 1987 DCI. 

Response 80.68: The 1987 DCI for antimicrobials specified three exposure categories (high, 

medium, and low) for addressing toxicology data requirements, and listed toxicology data required 

for each category. Each category was further tied to specific antimicrobial use sites, e.g. high 

exposure was associated with metalworking fluid uses, for example. As explained in the proposed 

rule, since 1987, in practice the low and medium exposure categories merged. Therefore the 3-

category approach is no longer used. 

Also, since the 1987 DCI, the use patterns for antimicrobial pesticides have been clarified. These 12 

use patterns were the ones presented to the SAP in 1997. Today, to specify the toxicity data 

requirements, EPA is using these 12 use patterns and relating them to food/nonfood uses while also 

acknowledging the differences in exposure that can occur. 

Comment 80.69: A comment wanted to know what the criteria are for when a 21/28-day study is 

required versus a 90-day study. The commenter asked whether there could be circumstances in 

which both the 21/28 day dermal study and the 90 day dermal study could be required. 

Response 80.69: . The Agency looks at the exposures of the use pattern to determine which study is 

needed. The 90-day dermal toxicity study would be required when the dermal route is known to be 

the primary route of exposure. The 21/28 day study would be required for exposures that are not 

intentional and which are of a shorter timeframe. However, the Agency would examine the results 

of any available dermal studies to determine the usefulness of the data in the context of the exposure 

scenario. Thus, it is possible that results of a 21/28 day study could be used in place of a 90-day 

study. Typically both studies are not required for the same antimicrobial pesticide. 

Proposed testnote 12 specifies the criteria for requiring the 21/28-day dermal toxicity study. The 

21/28 day study would be triggered if there is dermal exposure, and yet the 90-dermal study has not 

been triggered. Typically only one of these studies is required for the same antimicrobial pesticide. 

Comment 80.71: A commenter maintained that there are several use patterns that should also be 

designated as high exposure uses for determining the toxicity data required: children’s exposures to 

treated toys, fabrics, and play areas; workers who use the same cleaning products daily. 
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Master Responses: Toxicology Section (80) Page 102 

Response 80.71: EPA recognizes that there are nonfood use patterns with a greater potential for 

exposure that would require a more complete toxicology data set. In the revised toxicology data 

requirements table, EPA has distinguished between nonfood use patterns with higher exposures, 

and those with lower exposures. 

EPA always considers the type and duration of exposure in our risk assessments. Once we 

understand the nature of the exposure then we assure that we have the appropriate toxicity test data 

and the appropriate models for estimating exposure. Children’s exposures are not always considered 

to be high exposure. Their exposures can be intermittent. If the exposures did involve daily 

exposure then EPA would consider these to be long-term exposures, and would assess as such. The 

Agency has developed specific exposure methods to assess childrens’ exposures to treated toys, 

fabrics, and play areas. These are used in conjunction with the required toxicity data to develop risk 

characterizations for these scenarios. 

Comment 80.72 In the comments submitted to EPA, the commenters developed two alternative 

toxicity data requirement approaches for EPA to consider. Alternative approach 1 was organized in 

paragraphs and Alternative approach 2 was in a table format similar to that proposed by EPA. 

Response 80.72: As discussed in response to comments 80.22, as a result of comments received, 

EPA is no longer using the terms “high human exposure” and “low human exposure” as table 

headers for the proposed Antimicrobial Toxicology Data Requirements Table. Instead EPA in the 

final rule is now using a food/non-food approach with some similarities to that of conventionals to 

distinguish the use patterns with higher exposure that need more toxicity data from those that need 

less. Accordingly, the table headers for the Toxicology Data Requirements Table in the final rule are: 

“Direct Food Uses;” “Indirect Food Uses (>200 ppb);” “Indirect Food Uses (<200 ppb);” 

“Swimmers, Aquatic Areas, Wood Preservatives, Metal Working Fluids;” and “All Other Nonfood 

Uses.” 

Unlike conventional pesticide chemicals, a strict food/nonfood use “split” for delineating data 

requirements is not appropriate for antimicrobial chemicals. Such an approach does not fully address 

the unique use patterns for antimicrobials, most specifically those involving indirect food uses. As a 

result of comments received, EPA decided to employ a modification of the food/nonfood approach 

to delineate the specific data requirement needs for antimicrobial pesticides. 

The flowchart below explains the approach that EPA intends to use. EPA believes that this 

approach is clearer than the definitional approach used in the proposed rule, while maintaining the 

uniqueness needed for antimicrobials. The flowchart is read by first asking if the use is a “Food 

Use?” The “yes” or “no” answer then prescribes which path to follow. Additional questions lead in 

a similar fashion to a column number. (note that C3 stands for column 3 of the data requirements 

table published in the final rule, similarly for C4, etc) 
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As previously discussed, the commenters provided two alternative approaches for data requirements 

for antimicrobials. As stated by the commenter, Alternative Approach 1 is “a dramatic change from 

EPA’s proposal.” The commenter did not provide to EPA the same or similar table-type of format 

used for part 158 data requirements. There were no testnotes to define the triggers for moving from 

tier to tier. EPA does not believe that at this time, that this approach meets the needs of the Agency, 

or those members of the public that have become accustomed to data requirement tables such as in 

part 158. The paragraph format would result in a more complex decision tree, that would require a 

significantly greater amount of interpretation and consultation than for the existing table formats. 

The issues raised in the paragraphs were separated into the various disciplinary areas of the 

toxicology comments and are addressed in that manner. 

Food? Swimming Pools, 

Wood Preservative, 

Metal Working 

Fluid 

Aquatic Area? 

Direct 

FoodUse? 

Indirect 

Food-Use 

(> 200 ppb)? 

C3 

C4 

C5 

C7 

C6 

yes 

no 

yes 

no 

no 

no

yes 

yes 
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EPA has also evaluated Alternative Approach 2. While this alternative approach is in a table-type of 

format, the testnotes developed by the commenters are extremely detailed and contain information 

that EPA believes should be in guidance. However the commenters’ suggested testnote 32 to the in 

vivo cytogenetics study, offered the following language: “The micronucleus rodent bone marrow 

assay is preferred; however, rodent bone marrow assays using metaphase analysis (abberations) are 

acceptable.” EPA’s proposed testnote 34 to the in vivo cytogenetics study in the proposed toxicology 

table read as follows: “There is a choice of assays, but initial consideration should be given to the 

rodent bone marrow assay. The micronucleus rodent bone marrow assay is preferred; the rodent 

bone marrow assays using metaphase analysis (aberrations) are acceptable.” EPA believes that the 

language from the commenters’ suggested testnote is clearer and will modify the proposed testnote 

accordingly, to read: “There is a choice of assays, but the micronucleus rodent bone marrow assay is 

preferred; the rodent bone marrow assays using metaphase analysis (aberrations) are acceptable.” 

EPA has already responded to the issues raised by the testnotes since the same issues were raised in 

other parts of the commenter’s comments. For food-uses the commenter is suggesting that EPA 

require 14 studies, which does not include a 2-generation reproductive study or an immunotoxicity 

study. EPA intends to require 19 studies which will provide the information needed by the Agency 

to conduct the hazard and risk assessments needed to register an antimicrobial pesticide chemical 

with a food use. 

The commenter has also asked that EPA include within subpart W a new section 158.2235 which 

would be analogous to 40 CFR 158.510 for conventional chemicals (Tiered Testing Options for 

Nonfood Use Pesticides). EPA does not believe this is needed for antimicrobials. As seen in the 

flowchart, once it has been determined that the use is nonfood, then certain of the nonfood 

scenarios require the submission of more data, and certain require the submission of less data. Thus 

the tiering is already built into the approach used for antimicrobials. 

Comment 80.73: A commenter aksed why testing is needed for both the wood preservative active 

ingredient, and also the transformation/degradation products. 

Response 80.73: exposure can be to both the parent and transformation product. If the Agency does 

not have any information on the toxicity of the transformation products, then EPA would have to 

use the assumption that the transformation products have the same toxicity as that of the parent. 

Therefore the Agency evaluates the toxicity of the transformation products on a case-by-case basis, 

using several sources of information and the following type of procedure. First, the transformation 

products are identified from product chemistry data and environmental fate data. Once the 

transformation products are identified, then EPA reviews the available mammalian toxicology data 

(reproduction tests, developmental tests, non-rodent chronic studies) using a variety of sources 

which could include open literature to determine toxicity. EPA also looks at available information 

from closely related chemicals to determine if the data can be bridged and from monitoring and 

incident data. On occasion Structure Activity Relationships (SAR) and Quantitative SAR are used to 

predict the toxicity of the degradates. 

Testing of transformation/degradation products is required when such products are known or 

suspected to be more toxicologically significant than that of the parent, and if the substance may 

persist in any of the various environmental media and may result in possible exposure to humans. 
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EPA also notes that for requiring toxicity testing, a similar process would be used to determine the 

toxicity data needed for any antimicrobial whose use pattern indicated that exposure is to both the 

parent and the transformation/degradation product. Also see response to comments 140.5 and 

160.3 for an explanation of transformation/degradation products for fate and ecological effects, 

respectively. 

Comment 80.75: A commenter asker why a dermal and an inhalation 90-day study are needed for 

heating, ventilation, air conditioning, and refrigeration (HVAC&R) uses. 

Response 80.75: Both a 90-day dermal and 90-day inhalation study are needed for HVAC&R uses as 

these two routes of exposure are expected to be the major routes of exposure for this use pattern. 

An oral 90-day study is not needed for HVAC&R uses since oral exposures are not expected. (see 

proposed testnote 15) 

Comment 80.76: A commenter stated that proposed testnote 3 should apply to all in vivo data 

requirements 

Response 80.76: EPA disagrees with this comment. Proposed testnote 3 specifies two conditions 

(test material is corrosive to skin or pH is less than 2 or greater than 11) when the acute dermal, 

primary eye irritation, primary dermal irritation, and dermal sensitization studies would not be 

required, i.e. normally the study would be waived. In the case of the acute dermal toxicity test which 

is designed primarily to measure mortality by the dermal route of exposure, testnote 3 assures that 

large amounts of a corrosive material or highly acidic/basic material are not applied to the animal’s 

skin. A study conducted with a corrosive or highly acidic/basic material is unlikely to give a 

meaningful result and may result in unnecessary suffering of the animal. However, for repeat dose or 

longer term toxicity studies, mortality is not the endpoint being investigated. These studies are 

designed to yield a dose and endpoint for use in risk assessment. So, for repeat dose or longer term 

toxicity studies, test materials with corrosive properties or pH extremes are diluted to avoid these 

effects while still examining other potential systemic effects of the chemical. 

Comment 80.78: A commenter thought that antifoulant paints and coatings should be classified as 

“high human exposure uses.” 

Response 80.78: The Agency disagrees with this comment. In the proposed rule, antifoulant paints 

and coatings were not classified as “high human exposure uses” because the use pattern does not 

comprise a chronic exposure scenario. 

Comment 80.79: A commenter noted that EPA uses metal working fluids (MWFs) as an example of 

distinguishing between an “open” or “closed” system. The commenter wondered whether there is a 

definition for a closed system, and whether there are other examples that should be considered for 

requiring fewer toxicity studies. 

Response 80.79: Since 2005, for MWFs, EPA has required less data for a “closed” system than for 

an “open” system. EPA reduced the toxicology data requirements for a “closed” system provided 
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that certain human exposure data were developed to address worker exposures (applicator dermal 

and inhalation exposure, product use information, and description of human activity)for that 

“closed” system. Specifically, developmental toxicity in a second species, reproductive toxicity, 

chronic toxicity/carcinogenicity studies, and metabolism/pharmacokinetic studies would be held in 

reserve pending the outcome of the exposure data. Once the Agency has completed review of the 

exposure data, there are two possible outcomes: (1) If the calculated worker Margin of Exposures 

(MOEs) indicate minimal risk concerns, with the use of a “closed” system, then the reserved data 

would not be required, or (2) If the calculated worker MOEs indicate risks of concern, with the use 

of a “closed” system, then the reserved data would be required. 

Comment 80.80: A commenter asked why applicator exposures are classified as “high” for 

swimming pools, noting that “applicator exposure for swimming pool chemicals can be low or 

nonexistent depending upon the application method.” 

Response 80.80: EPA agrees that there can be a difference between the exposures of those who 

apply the chemicals to a pool and those who swim in a pool. As discussed in response to comment 

80.29, swimmers are considered to have significant exposure: there is substantial contact with the 

treated pool water and long-term exposure frequency for competitive swimmers. The applicator’s 

exposure would depend on the application method used to apply the product. EPA needs to 

perform two assessments for a swimming pool chemical: one assessment for the swimmer and one 

for the applicator. To have the data needed for these two assessments, the swimming pool use 

pattern requires more toxicity data than may be required for some other nonfood use patterns. 

Comment 80.81: A commenter asked that the term weight-of-evidence be better defined. 

Response 80.81: In its proposed rule [59388], EPA described a weight-of-evidence (WOE) approach 

and the considerations that are included in such an approach. A WOE approach is not simply 

tallying the number of positive or negative studies but instead refers to a decision logic that is 

determined not by the results of one single study or piece of data, but using scientific judgment in 

conjunction with several pieces of data on the effect being investigated to arrive at a scientifically 

sound decision. 

Comment 80.82: A commenter maintained that EPA should use existing high-quality data that has 

already been conducted, instead of requiring new studies and that EPA should accept in-vitro and 

non-animal studies that have been conducted according to validated protocols. 

Response 80.82: EPA always uses the highest quality data available. As discussed in the preamble 

[59387], an applicant is not required to use a particular protocol. EPA has launched a pilot program 

on the Antimicrobials Pesticides website to help the Agency determine if non-animal approaches for 

eye irritation testing can be used in place of in vivo animal testing. 

Comment 80.83: A commenter asserted that the final rule should not specify a guideline number. 

Instead, according to the commenter, the final rule should describe the endpoint in question, and 
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the information needed for EPA’s risk assessment. The commenter argued that OPP could develop 

guidance that could be placed on the web. 

Response 80.83: EPA agrees with this comment. The guideline number column could be removed 

from the table. Instead EPA could have an internet page that described multiple methods of 

fulfilling the data requirements. An internet table could be updated faster to reflect newer techniques 

than rulemaking to revise the regulation in the CFR. However, there is also value in having the 

guideline number in the CFR, which then shows the available guidelines relevant to the particular 

study that should be considered in addressing the requirement. EPA has made no decision on 

whether or not to initiate a rulemaking to remove all the guideline numbers from the data 

requirement tables in 40 CFR part 158. The tables in subpart W will include guideline numbers. 

Comment 80.86: A commenter asserted that EPA should also consider (Q)SAR approaches for 

assessing dermal absorption/penetration. 

Response 80.86: As discussed in the proposed rule, the Agency will always consider QSAR and 

other alternative approaches for hazard assessment, including dermal absorption. In fact, OPP/AD 

has received submissions which include such information. 

Comment 80.87: A commenter encouraged EPA to expand the eye irritation pilot project to other 

antimicrobial product classes, and to replace the OCSPP guideline for the Draize eye test with the 

newer validated methods being used in the pilot program. 

Response 80.87: EPA has encouraged submission of data under this pilot program and is beginning 

to receive studies conducted using this protocol for assessment of eye irritation potential. Once the 

studies are evaluated, then EPA will recommend whether the eye irritation pilot project should be 

extended to other classes of antimicrobial products. EPA cannot make a determination to “replace 

the OCSPP guideline” at this time because of the limited studies conducted so far under the pilot 

program , but will consider doing so in the future once enough data have been reviewed to 

determine if the in vitro approach produces results that accurately predict the results of the current in 

vivo test. 

Comment 80.88: A commenter asserted that EPA should specifically state in its regulations that 

non-animal methods are acceptable for fulfilling a data requirement. The Draize study in rabbits 

should be eliminated. 

Response 80.88: Non–animal test methods are continually being examined for use in fulfilling the 

toxicology data requirements that are used to assess the hazard of pesticide chemicals. However, in 

order for non-animal approaches to be used for fulfilling toxicology data requirements, these 

approaches must first be scientifically validated to ensure that they are as good as the existing test 

method for predicting hazard and also assessed to determine whether they meet the Agency’s “3 R” 

goals of reduce, refine, and replace the use of animals in testing. With respect to antimicrobial 

pesticides, the Agency has started to explore such approaches. One example of this is the voluntary 

pilot program for eye irritation testing of antimicrobial pesticides using non–animal test methods, 

found at http://www.epa.gov/oppad001/eye-irritation.pdf
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Comment 80.89: A commenter contended that the proposed data requirement for acute systemic 

toxicity provides limited information that is only useful for labeling. The commenter emphasized 

that acute toxicity testing has never been validated and is “not based on a documented good 

performance, but on the lack of better tests.” 

Response 80.89: EPA agrees that one of the major uses of acute toxicity testing for both the TGAI 

as well as the end use formulation is to develop the proper labeling of the pesticide product. These 

labeling statements are critically needed to protect and inform the users. 

Comment 80.91: A commenter maintained that the acute dermal irritation study can be replaced by 

models (such as EpiDerm, EpiSkin, and SkinEthic) that have been validated in the European Union 

(EU). A late comment indicated that the Organization for Economic Co-operation and 

Development (OECD) test guideline (TG) 439, “In Vitro Skin Irritation: Reconstructed Human 

Epidermis (RhE) Test Method” which allows the use of these three validated methods has been 

finalized. The commenter thought that EPA should replace the OCSPP guideline. 

Response 80.91: The Agency is aware that OECD TG 439 was adopted recently for use in 

determination of skin irritation testing under the Globally Harmonized System (GHS) labeling 

classification system. As noted by the commenter, OPP is in the process of exploring adoption of 

GHS labeling. While OECD TG 439 has not currently been used by OPP, as OPP moves in the 

direction of adopting the GHS labeling classification system, the in vitro skin irritation tests in 

OECD TG 439 would also be considered for determination of skin irritation potential. 

Comment 80.93: A commenter maintained that the Local Lymph Node Assay (LLNA) should 

replace the dermal sensitization study in guinea pigs. In late comments, the same commenter 

suggested that EPA consider the LLNA and “limit” LLNA protocols for skin sensitization testing as 

done by the OECD “reduced” LLNA (rLLNA) in OECD guideline 429 “Skin Sensitisation: Local 

Lymph Node Assay.” 

Response 80.93: The Agency acknowledges the usefulness of the Local Lymph Node Assay (LLNA) 

and notes in its guideline for dermal sensitization (OCSPP 870.2600) on page 2 that the “LLNA 

...is a preferred alternative method, where applicable, to the traditional guinea pig 

test...”(see http://www.epa.gov/oppts/pubs/frs/publications/Test_Guidelines/series870.htm) 

With respect to the ‘reduced’ LLNA the Interagency Coordination Committee on the 

Validation of Alternative Methods (ICCVAM) report “The Reduced Murine Local Lymph 

Node Assay: An Alternative Test Method Using Fewer Animals to Assess the Allergic Contact 

Dermatitis Potential of Chemicals and Products” notes that: 

“...the scientific validity of the rLLNA has been adequately evaluated 

and that the performance of the rLLNA, when conducted in accordance with the updated 

ICCVAM-recommended LLNA protocol, is sufficient to distinguish between skin sensitizers and 

non-sensitizers in cases that do not require dose-response information. ICCVAM also concludes 
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that, compared to the traditional LLNA, the rLLNA will reduce animal use by 40 percent for each 

test. Accordingly, ICCVAM recommends that the rLLNA test method should be used routinely to 

determine the ACD potential of chemicals and products before conducting the traditional LLNA. 

Negative substances can be classified as non-sensitizers, and positive substances can be classified as 

sensitizers. “ 

The Agency, as a participant in this report, agrees with the recommendation put forth by ICCVAM 

and would use the ‘reduced’ LLNA in a manner consistent with the ICCVAM recommendations. 

Comment 80.95: A commenter asserted that an in vitro dermal penetration study should be required 

before the in vivo dermal 21/28 or 90-day studies are required. Marginal or no dermal penetration in 

the in vitro study should be the basis of waiving the in vivo studies. 

Response 80.95: Although an in vitro study may indicate the extent or lack thereof of dermal 

penetration, an in vivo dermal study will allow determination of any dermal effects from repeated 

exposure and can also provide information on dermal penetration. These two studies do not 

measure the same thing. Even in the absence of systemic toxicity, EPA would use dermal effects to 

form the basis of our dermal risk assessments. 

Comment 80.96: A commenter asserted that Tier 1 ecotoxicity testing is not needed for indoor uses 

of antimicrobials. 

Response 80.96: EPA disagrees with this comment. Exposure from indoor industrial uses occurs 

primarily through water via point-source discharges directly to the environment or indirectly via 

passage through Waste Water Treatment Plants (WWTPs). Leachates, rinsates, or flushes are often 

released down-the-drain and eventually reach a WWTP. After treatment, effluents (water or 

biosolids) are released into the aquatic environment or in wastewater treatment plant sludge (aka 

biosolids) that may be land-applied, deposited in surface impoundments, or disposed of in landfills, 

thereby leading to potential for non-target organisms to be exposed. 

Comment 80.97: A commenter asked how an antimicrobial could be applied to an animal as part of 

a Companion Animal Study. The commenter thought such an application would would be an animal 

drug? 

Response 80.97: The commentor is correct. As stated in 40 CFR §152.6(d)(1), “Fungi, viruses, 

bacteria or other microorganisms on or in living animals are not “pests” under section 2(t) of 

FIFRA. Products intended for use against such organisms are “animal drugs” regulated by the FDA 

under the FFDCA.” Since few pesticide products are likely to have direct applications to animals, 

EPA is revising proposed testnote 36 to remove the phrase “through, but not limited to, direct 

application.” 

Comment 80.98: A commenter asked for the definition of domestic animals. 
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Response 80.98: Animals that are domesticated for human use as companions or for the production 

of food or other products. Examples (that will be added to testnote 36) would be cats, dogs, cattle, 

pigs, and horses. 

Comment 80.99: A commenter asserted that EPA should have a way to encourage the use of new 

tests without rulemaking. 

Response 80.99: EPA does encourage use of new and alternative tests without rulemaking. For 

example, the eye irritation pilot project within the Office of Pesticide Products was developed 

without rulemaking. In addition, EPA is an active member of the Interagency Coordination 

Committee on the Validation of Alternative Methods (ICCVAM). ICCVAM is an interagency 

committee with members representing 15 U.S. Federal regulatory and research agencies. Among its 

functions, ICCVAM coordinates interagency technical reviews of new and revised safety testing 

methods with regulatory applicability, including alternative test methods that may reduce, refine, or 

replace the use of animals in order to advance animal welfare while ensuring human health and 

safety. ICCVAM also coordinates cross-agency issues relating to development, validation, 

acceptance, and national and international harmonization of new, modified, and alternative 

toxicological test methods. These activities, in which EPA is an active participant, are accomplished 

without using the rulemaking process. 

Comment 80.100: A commenter asserted that EPA should require “full testing” of active ingredient 

mixtures that are co-formulated into products to determine cumulative risk. 

Response 80.100: The Agency’s Office of Pesticide Programs assesses testing of pesticide active 

ingredients through testing of the technical grade, or pure form of the active ingredient. It is 

recognized that pesticides can be formulated into active ingredient mixtures. The Agency’s approach 

to testing is to assess the hazard of each active ingredient including information on the potential 

mode of action by which toxicity is produced for each active ingredient. To assess cumulative risk, 

the Agency has developed guidance documents on assessment of pesticide chemicals that have a 

common mechanism of toxicity for purposes of assessing cumulative risk. These documents are 

available at http://www.epa.gov/oppfead1/trac/science/. The Agency has also developed 

supplementary guidance for assessment of chemical mixtures, available at 

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=20533

Comment 80.101: A commenter stated that there is “limited value of acute systemic toxicity testing 

via the dermal route for the purpose of classification and labeling.” 

Response 80.101: The Agency acknowledges the reference citations (6 – 10) provided by the 

commenter. These citations provide information regarding the comparison of results of acute oral 

and acute dermal toxicity testing that are available in the public literature. Together with an analysis 

of the Agency’s own internal database of acute oral and acute dermal toxicity test comparisons, this 

could form the basis for further investigation of the continued requirement for the acute dermal 

toxicity test. 
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With respect to in vitro dermal penetration assessments, OPP encourages submission of such data to 

evaluate the need for in vivo testing. 

Comment 80.102: A commenter asked EPA to consider incorporating the following OECD 

guidelines into the new part 158W to reduce the number of animals killed in LD50 tests: OECD 

guidelines 436: Acute Inhalation Toxicity - Acute Toxic Class Method, and revised 223: Avian Acute 

Oral Toxicity Test, and Short Guidance on the Threshold Approach for Acute Fish Toxicity. 

Response 80.102: OPP does not have a policy for use of OECD 436 for acute inhalation toxicity. If 

a study conducted according to OECD 436 were submitted for the purpose of assessing acute 

inhalation toxicity, we would review and accept the results if the study were conducted in an 

acceptable manner and provided sufficient information to fulfill the data requirement. Similarly, if a 

study conducted according to OECD 223 or the Threshold Approach, were submitted, then EPA 

would review the study and then make a determination on whether the study was conducted in an 

acceptable manner and provided sufficient information to fulfill the data requirement. 

Based on the comments received, the Testnotes to the Toxicology Table in the final rule 

will read as follows: 

T80.1 Testnote 1 to the Toxicology Table 

Proposed: 

Not required if test material is a gas or highly volatile liquid. 

 

Final: 

Not required if test material is a gas or highly volatile liquid. 

T80.2 Testnote 2 to the Toxicology Table 

Proposed: 

For the six acute toxicity studies conducted with the end-use product, the test must be conducted 

using the product as formulated for sale and distribution. However, if the end-use product is labeled 

that the product is to be diluted for use, the applicant may also conduct certain studies using the 

highest diluted concentration (i.e. the least diluted product) permitted by the labeling. The end-use 

dilution testing is in addition to the as- formulated-for-sale testing and used only for labeling 

purposes. Consultation with the Agency is highly suggested to assure that the appropriate product 

and any appropriate dilutions are tested. 

Final: 

The six end-use product (EP) acute toxicity studies are required using the product as formulated for 

sale and distribution. In addition, if the EP label has directions for diluting the product, then, the 

applicant may also need to conduct certain of the acute toxicity studies using the highest diluted 
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concentration (i.e. the least diluted product) permitted by the labeling. The end-use dilution testing is 

in addition to the testing conducted on the EP. 

T80.3 Testnote 3 to the Toxicology Table 

Proposed: 

Not required if the test material is corrosive to skin or has a Ph less than 2 or greater than 11.5. 

Final: 

Not required if test material is corrosive to skin or has pH less than 2 or greater than 11.5. 

 T80.4 Testnote 4 to the Toxicology Table 

Proposed: 

Data are required when the product consists of, or under conditions of use will result in, a respirable 

material (e.g., gas, vapor, aerosol or particulates). 

Final: 

Data are required when the product consists of, or under conditions of use will result in, a respirable 

material (e.g., gas, vapor, aerosol or particulates). 

T80.5 Testnote 5 to the Toxicology Table 

Proposed: 

Data are required if repeated dermal exposure is likely to occur under conditions of use. 

Final: 

Data are required if repeated dermal exposure is likely to occur under conditions of use. 

T80.6 Testnote 6 to the Toxicology Table 

Proposed: 

For low exposure uses, data are required if the neurotoxicity screen in the 90–day oral rodent study 

or other data indicate neurotoxicity 

Final: 

For Indirect Food Uses < 200 ppb, and All Other Nonfood Uses, data are required if the 

neurotoxicity screen in the 90-day oral rodent study or other data indicate neurotoxicity. 

T80.7 Testnote 7 to the Toxicology Table 

Proposed: 
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The 90–day dermal toxicity study or 90–day inhalation toxicity study may be substituted for the 90–

day oral toxicity study if the Agency determines that dermal or inhalation exposure is a major route 

of exposure. 

Final: 

The 90-day dermal toxicity study and/or 90-day inhalation toxicity study are required if the Agency 

determines that dermal and/or inhalation exposure is the primary route of exposure. 

 

T80.8 Testnote 8 to the Toxicology Table 

Proposed: 

All 90–day subchronic studies in the rodent can be designed to simultaneously fulfill the 

requirements of the 90–day neurotoxicity study by adding separate groups of animals for testing. 

Final: 

All 90-day subchronic studies in the rodent can be designed to simultaneously fulfill the 

requirements of the 90-day neurotoxicity and/or immunotoxicity studies by adding separate groups 

of animals for testing of neurotoxicity and/or immunotoxicity parameters. 

T80.9 Testnote 9 to the Toxicology Table 

Proposed: 

The 90–day study is required in the rodent for hazard characterization (possibly endpoint selection) 

and dose-setting for the chronic/carcinogenicity study. It is not required in the mouse, but the 

Agency would encourage the applicant to conduct a 90–day range finding study for the purposes of 

dose selection for the mouse carcinogenicity study to achieve adequate dosing and an acceptable 

study. The applicant is also encouraged to consult with the Agency on the results of the 90–day 

mouse study prior to conducting the carcinogenicity study. 

Final: 

The 90-day study is required in the rodent for hazard characterization (possibly endpoint selection) 

and dose-setting for the chronic/carcinogenicity study. It is not required in the mouse, but the 

Agency would encourage the applicant to conduct a 90-day range finding study for the purposes of 

dose selection for the mouse carcinogenicity study to achieve adequate dosing and an acceptable 

study. 

T80.10 Testnote 10 to the Toxicology Table 

Proposed: 

A 1–year non-rodent study (i.e., 1–year dog study) may be required if the Agency finds that a 

pesticide chemical is highly bioaccumulating and is eliminated slowly. Thus it does not achieve 

steady state or sufficient tissue concentrations to elicit an effect during a 90–day study. EPA may 

require the appropriate tier II metabolism and pharmacokinetic studies to evaluate more precisely 

bioavailability, half life, and steady state to determine if a longer duration dog toxicity study is 

needed. 
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Final: 

A 1-year non-rodent study (i.e., 1-year dog study) may be required if the Agency finds that a 

pesticide chemical is highly bioaccumulating and is eliminated slowly. This means that the pesticide 

chemical does not achieve steady state or sufficient tissue concentrations to elicit an effect during a 

90-day study. EPA may require the appropriate tier II metabolism and pharmacokinetic studies to 

evaluate more precisely bioavailability, half life, and steady state to determine if a longer duration 

dog toxicity study is needed. 

T80.11 Testnote 11 to the Toxicology Table 

Proposed: 

For low human exposure uses, data are required if any of the following criteria are met: 

 i. The use of the pesticide is likely to result in repeated human exposure over a limited 

portion of the human lifespan, as determined by the Agency. 

 ii. The use is an indirect food use (less than 200 ppb). 

Final: 

Although the subchronic toxicity testing guidelines include measurement of neurological endpoints, 

such screens do not meet the requirement of the 90-day neurotoxicity study. For Nonfood Uses, if 

the 90-day study does not include a neurotoxicity screen, then the acute neurotoxicity study will be 

required. 

T80.12 Testnote 12 to the Toxicology Table 

Proposed: 

Data are required if the intended use of the antimicrobial pesticide product is expected to result in 

human exposure to the product, and the three following conditions are met: 

 i. Human exposure is via skin contact. 

 ii. Expected human exposure is not purposeful, and is over a limited portion of the human 

lifespan; however, as determined by EPA, the exposure is significant in terms of the frequency of 

exposure, magnitude of exposure, or the duration of exposure. 

 iii. Data from a subchronic 90–day dermal toxicity study are not available and the 90–day 

dermal toxicity study has not been triggered. 

Final: 

Data are required if the intended use of the antimicrobial pesticide product is expected to result in 

repeated, dermal human exposure to the product, and data from a subchronic 90-day dermal toxicity 

study are not available and the 90-day dermal toxicity study has not been triggered 

T80.13 Testnote 13 to the Toxicology Table 

Proposed: 
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Master Responses: Toxicology Section (80) Page 115 

EP testing is required if the product or any component of the product may increase dermal 

absorption of the active ingredient(s) or increase toxic or pharmacologic effects, as determined by 

testing the TGAI or based on available information about the toxic effects of the product or its 

components. 

Final: 

EP testing is required if the product or any component of the product may increase dermal 

absorption of the active ingredient(s) or increases its toxic or pharmacologic effects, as determined 

by testing using the TGAI or based on available information about the toxic effects of the product 

or its components. 

T80.14 Testnote 14 to the Toxicology Table 

Proposed: 

Data are required if the use pattern is such that the dermal route would be the major route of 

exposure or if the active ingredient of the product is known or expected to be metabolized 

differently by the dermal route of exposure than by the oral route, and a metabolite of the active 

ingredient is the toxic moiety. 

Final: 

Data are required if the active ingredient in the product is known or expected to be metabolized 

differently by the dermal route of exposure than by the oral route, and a metabolite of the active 

ingredient is the toxic moiety. 

T80.15 Testnote 15 to the Toxicology Table 

Proposed: 

A 90–day oral toxicity test is not required for heating, ventilation, air conditioning, and refrigeration 

systems (collectively referred to as HVAC), and two 90–day toxicity tests, one by the dermal route 

and one by the inhalation route are required. 

Final: 

A 90-day oral toxicity test is not required for heating, ventilation, air conditioning, and refrigeration 

systems (collectively referred to as HVAC&R). Instead two 90-day toxicity tests, one by the dermal 

route and one by the inhalation route are required. 

T80.16 Testnote 16 to the Toxicology Table 

Proposed: 

Data are required if there is the likelihood of significant repeated inhalation exposure to the pesticide 

as a gas, vapor, or aerosol. 

Final: 
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Master Responses: Toxicology Section (80) Page 116 

Data are required if there is the likelihood of significant repeated inhalation exposure to the pesticide 

as a gas, vapor, or aerosol. 

T80.17 Testnote 17 to the Toxicology Table 

Proposed: 

Based on estimates of the magnitude and duration of human exposure, studies of shorter duration, 

e.g., 21– or 28–days, may be sufficient to satisfy this requirement. Applicants for registration may 

consult with the Agency to determine whether studies of shorter duration would meet this 

requirement. 

Final: Based on estimates of the magnitude and duration of human exposure, studies of shorter 

duration, e.g., 21- or 28-days, may be sufficient to satisfy this requirement. The prime consideration 

in determining the appropriateness of a shorter duration study is the likely period of time for which 

humans will be exposed. 

T80.18 Testnote 18 to the Toxicology Table 

Proposed: 

Based on the positive results of the acute and/or 90–day neurotoxicity studies, or on other data 

indicating neurotoxicity, a chronic neurotoxicity study (i.e. a chronic study with additional 

neurotoxicity evaluations) may be required to provide information about potential neurotoxic effects 

from long-term exposures. 

Final: 

Based on the positive results of the acute or 90-day neurotoxicity studies, or on other data indicating 

neurotoxicity, a chronic/neurotoxicity study (i.e. a chronic study with additional neurotoxicity 

evaluations) may be required to provide information about potential neurotoxic effects from longterm exposures. 

T80.19 Testnote 19 to the Toxicology Table 

Proposed: 

Studies which are designed to simultaneously fulfill the requirements of both the chronic oral and 

carcinogenicity studies (i.e., a combined study) may be conducted. 

Final: 

Studies which are designed to simultaneously fulfill the requirements of both the chronic oral and 

carcinogenicity studies (i.e., a combined study) may be conducted. 

T80.20 Testnote 20 to the Toxicology Table 

Proposed: 

For low exposure, data are required if either of the following criteria are met: 
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Master Responses: Toxicology Section (80) Page 117 

 i. The use of the pesticide is likely to result in repeated human exposure over a limited 

portion of the human lifespan, as determined by the Agency, or 

 ii. The use requires that a tolerance or a tolerance exemption be established. 

Final: 

For indirect food uses ≤ 200 ppb, and all other nonfood uses, data are required if either of the 

following criteria are met: 

i. The use of the pesticide is likely to result in repeated human exposure over a considerable 

portion of the human lifespan; or 

ii. The use requires that a tolerance or a tolerance exemption be established. 

T80.21 Testnote 21 to the Toxicology Table 

Proposed: 

For low exposure, data are required if any of the following criteria, as determined by the Agency, are 

met: 

 i. The use of the pesticide is likely to result in significant human exposure over a 

considerable portion of the human life span which is significant in terms of frequency time, 

duration, and/or magnitude of exposure. 

 ii. The use requires that a tolerance or a tolerance exemption be established. 

 iii. The active ingredient, metabolite, degradate, or impurity 

 A. is structurally related to a recognized carcinogen, 

 B. causes mutagenic effects as demonstrated by in vitro or in vivo testing, or 

 C. produces a morphologic effect in any organ (e.g., hyperplasia, metaplasia) in subchronic 

studies that may lead to a neoplastic change. 

Final: 

For indirect food uses < 200 ppb, and all other nonfood uses, data are required if any of the 

following criteria, are met: 

i. The use of the pesticide is likely to result in significant human exposure over a 

considerable portion of the human life span which is significant in terms of frequency time, 

duration, and/or magnitude of exposure. 

ii. The use requires that a tolerance or a tolerance exemption be established. 

iii. The active ingredient, metabolite, degradate, or impurity 

A. is structurally related to a recognized carcinogen, 

B. causes mutagenic effects as demonstrated by in vitro or in vivo testing, or 

 C. produces a morphologic effect in any organ (e.g., hyperplasia, metaplasia) in subchronic 

studies that may lead to a neoplastic change. 

T80.22 Testnote 22 to the Toxicology Table 

Proposed: 

If the requirement for a carcinogenicity study in any species is modified or waived for any reason, 

then a subchronic 90–day oral study in the same species may be required. 
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Master Responses: Toxicology Section (80) Page 118 

Final: 

If the requirement for a carcinogenicity study in any species is modified or waived for any reason, 

then a subchronic 90-day oral study in the same species may be required. 

T80.23 Testnote 23 to the Toxicology Table 

Proposed: 

Testing in two species is required for all uses. 

Final: 

Testing in two species is required for all uses. 

T80.24 Testnote 24 to the Toxicology Table 

Proposed: 

The oral route, by oral intubation, is preferred, unless the chemical or physical properties of the test 

substance, or the pattern of exposure, suggest a more appropriate route of exposure. 

Final: 

The oral route, by oral intubation, is preferred, unless the chemical or physical properties of the test 

substance, or the pattern of human exposure, suggest a more appropriate route of exposure. 

T80.25 Testnote 25 to the Toxicology Table 

Proposed: 

Additional testing by other routes of exposure may be required if the pesticide is determined to be a 

prenatal developmental toxicant after oral dosing. 

Final: 

Additional testing by other routes of exposure may be required if the pesticide is determined to be a 

prenatal developmental toxicant after oral dosing. 

T80.26 Testnote 26 to the Toxicology Table 

Proposed: 

The developmental toxicity study in rodents may be combined with the two-generation reproduction 

study in rodents by using a second mating of the parental animals in either generation. Protocols 

must be approved by the Agency prior to the initiation of the study. Details for developing 

protocols are available from the Agency. 

Final: 

The developmental toxicity study in rodents may be combined with the two-generation reproduction 

study in rodents by using a second mating of the parental animals in either generation. Protocols 

must be approved by the Agency prior to the initiation of the study. 
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Master Responses: Toxicology Section (80) Page 119 

T80.27 Testnote 27 to the Toxicology Table 

Proposed: 

A two-generation reproduction study is required. 

Final: 

A two-generation reproduction study is required. 

T80.28 Testnote 28 to the Toxicology Table 

Proposed: 

An information-based approach to testing is preferred, which utilizes the best available knowledge 

on the chemical (hazard, pharmacokinetic, or mechanistic data) to determine whether a standard 

guideline study, an enhanced guideline study, or an alternative study should be conducted to assess 

potential hazard to the developing animal, or in some cases to support a waiver for such testing. 

Applicants must submit any alternative proposed testing protocols and supporting scientific 

rationale to the Agency. Protocols must be approved by the Agency prior to the initiation of the 

study. Details for developing protocols are available from the Agency. 

Final: 

An information-based approach to testing is preferred, which utilizes the best available knowledge 

on the chemical (hazard, pharmacokinetic, or mechanistic data) to determine whether a standard 

guideline study, an enhanced guideline study, or an alternative study should be conducted to assess 

potential hazard to the developing animal. Applicants must submit any alternative proposed testing 

protocols and supporting scientific rationale to the Agency. Protocols must be approved by the 

Agency prior to the initiation of the study. 

T80.29 Testnote 29 to the Toxicology Table 

Proposed: 

The use of a combined two-generation reproduction/developmental neurotoxicity study that utilizes 

the two-generation reproduction study in rodents as a basic protocol for the addition of other 

endpoints or functional assessments in the immature animal is encouraged. 

Final: 

The use of a combined two-generation reproduction/developmental neurotoxicity study that utilizes 

the two-generation reproduction study in rodents as a basic protocol for the addition of other 

endpoints or functional assessments in the immature animal is encouraged. 

T80.30 Testnote 30 to the Toxicology Table 

Proposed: 

A DNT study is required using a weight-of-evidence approach when: 
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Master Responses: Toxicology Section (80) Page 120 

 i. The pesticide causes treatment-related neurological effects in adult animal studies 

(i.e, clinical signs of neurotoxicity, neuropathology, functional or behavioral effects). 

 ii. The pesticide causes treatment-related neurological effects in developing animals, 

following pre- or post-natal exposure (i.e., nervous system malformations or neuropathy, brain 

weight changes in offspring, functional or behavioral changes in the offspring). 

 iii. The pesticide elicits a causative association between exposures and adverse neurological 

effects in human epidemiological studies. 

 iv. The pesticide evokes a mechanism that is associated with adverse effects on the 

development of the nervous system (i.e., structure-activity-relationship (SAR) to known 

neurotoxicants, altered neuroreceptor or neurotransmitter responses). 

Final: 

A DNT study is required using a weight-of-evidence approach when: 

 i. The pesticide causes treatment-related neurological effects in adult animal studies (i.e, 

clinical signs of neurotoxicity, neuropathology, functional or behavioral effects). 

 ii. The pesticide causes treatment-related neurological effects in developing animals, 

following pre- or postnatal exposure (i.e., nervous system malformations or neuropathy, brain 

weight changes in offspring, functional or behavioral changes in the offspring). 

 iii. The pesticide elicits a causative association between exposures and adverse neurological 

effects in human epidemiological studies. 

 iv. The pesticide evokes a mechanism that is associated with adverse effects on the 

development of the nervous system (i.e., structure-activity-relationship (SAR) to known 

neurotoxicants, altered neuroreceptor or neurotransmitter responses). 

T80.31 Testnote 31 to the Toxicology Table 

Proposed: 

To enhance the weight-of-evidence determination for the pesticide’s mutagenicity, the Agency 

requires submission of other mutagenicity test results, besides those specifically listed in this table, 

that may have been performed for other endpoints that may be predictive of mutagenicity. A 

reference list of all studies and papers known to the applicant concerning the mutagenicity of the 

test chemical must be submitted with the required studies. 

Final: 

To facilitate the weight-of-evidence determination for the pesticide’s mutagenicity, the Agency 

requires submission of other mutagenicity test results, besides those specifically listed in this table, 

that may have been performed. A reference list of all studies and papers known to the applicant 

concerning the mutagenicity of the test chemical must be submitted with the required studies. 

T80.32 Testnote 32 to the Toxicology Table 

Proposed: 

Testing in Salmonella and E. coli may be acceptable, if the testing can be conducted at high enough 

levels, as determined by the Agency. If the testing cannot be conducted at high enough levels, then 

the applicant must consult with the Agency to determine other needed mutagenicity testing. 
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Master Responses: Toxicology Section (80) Page 121 

Final: 

Due to the nature of antimicrobials, if testing with bacterial strains has not been conducted, then 

testing using a mammalian cell assay such as the mouse lymphoma TK +/- assay is preferred. If 

reverse mutation assay testing with bacterial strains has already been conducted, and the testing was 

conducted at levels that did not cause toxicity to the bacterial strains tested, then the applicant may 

submit the study to fulfill this data requirement. 

T80.33 Testnote 33 to the Toxicology Table 

Proposed: 

For the in vitro mammalian gene mutation study, there is a choice of assays using either mouse 

lymphoma L5178Y cell thymidine kinase (tk) gene locus, maximizing assay conditions for small 

colony expression and detection; Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast 

(v79) cells, hypoxanthine-guanine phosphoribosyl transferase (hgprt) gene locus, accompanied by an 

appropriate in vitro test for clastogenicity; or CHO cells strains AS52, xanthine-guanine 

phosphoribosyl transferase(xprt) gene locus. 

Final: 

For the in vitro mammalian gene mutation study, there is a choice of assays using either mouse 

lymphoma L5178Y cell thymidine kinase (tk) gene locus, maximizing assay conditions for small 

colony expression and detection; Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast 

(v79) cells, hypoxanthine-guanine phosphoribosyl transferase (hgprt) gene locus, accompanied by an 

appropriate in vitro test for clastogenicity; or CHO cells strains AS52, xanthine-guanine 

phosphoribosyl transferase (xprt) gene locus. 

T80.34 Testnote 34 to the Toxicology Table 

Proposed: 

There is a choice of assays, but initial consideration should be given to the rodent bone marrow 

assay. The micronucleus rodent bone marrow assay is preferred; the rodent bone marrow assays 

using metaphase analysis (aberrations) are acceptable. 

Final: 

There is a choice of assays, but the micronucleus rodent bone marrow assay is preferred; the rodent 

bone marrow assays using metaphase analysis (aberrations) are acceptable. 

T80.35 Testnote 35 to the Toxicology Table 

Proposed: 

For low exposure, these data are required when chronic or carcinogenicity studies are also required. 

These data may be required if significant adverse effects are seen in available toxicology studies and 

these effects can be further elucidated by metabolism studies. 

Final: 

Data are required when chronic or carcinogenicity studies are also required. 
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Master Responses: Toxicology Section (80) Page 122 

T80.36 Testnote 36 to the Toxicology Table 

Proposed: 

These data may be required if the product’s use will result in exposure to domestic animals through, 

but not limited to, direct application. 

Final: 

Data may be required if the product label directs that it be applied to domestic animals, such as cats, 

dogs, cattle, pigs, and horses 

T80.37 Testnote 37 to the Toxicology Table 

Proposed: 

A risk assessment assuming that dermal absorption is equal to oral absorption must be performed to 

determine if the dermal penetration study is required, and to identify the doses and duration of 

exposure for which dermal absorption is to be quantified. 

Final: 

In the absence of dermal absorption data or a repeated does dermal toxicity study, the assumption 

of 100% dermal absorption would be used in a risk assessment to determine if a dermal penetration 

study is required, and to identify the doses and duration of exposure for which dermal absorption is 

to be quantified. 

T80.38 Testnote 38 to the Toxicology Table 

Proposed: 

N/A 

Final: 

Required for antimicrobial nonfood uses, if oral exposure could occur. 

T80.39 Testnote 39 to the Toxicology Table 

Proposed: 

N/A 

Final: 

Data may be required if significant adverse effects are seen in available toxicology studies and these 

effects can be further elucidated by metabolism studies. 
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Master Responses: 

Applicator/Handler (Human Exposure) Section (90) Page 123 

Applicator/Handler (Human Exposure) (90)

Master Responses and Testnotes for the Applicator/Handler (Human Exposure) 

Section 

Please note that EPA responses and testnotes are presented in numerical order. However, in the course of response 

development, some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are 

missing. 

Comment 90.1: A commenter stated that application of an additional 3X safety factor “based on the 

potential for residential exposure” is not consistent with FQPA or with any OPP guidance known to 

the commenter. The commenter cited as a specific example the Reregistration Eligibility Decision 

Document (RED) for trimethoxysilyl quaternary ammonium chloride compounds and stated that 

the RED was not publicly available via the Agency’s website. 

Response 90.1: EPA disagrees with this comment. The Food Quality Protection Act (FQPA) safety 

factor is inclusive of special sensitivity in infants and children and exposure to pesticides in food, 

drinking water, residential exposures, or to compensate for an incomplete database. Therefore, there 

may be instances where the FQPA safety factor would be appropriate for residential exposure if 

there is uncertainty in the exposure estimate. 

For the specific example cited by the commenter (i.e., the Reregistration Eligibility Decision 

Document (RED) for trimethoxysilyl quaternary ammonium chloride compounds), EPA determined 

that there were no toxicological endpoints of concern for repeated oral or dermal exposure. Since 

risk is a function of both hazard and exposure, when a specific scenario does not have an associated 

hazard (i.e., no tox endpoints), then neither a risk estimate nor the risk is calculated for that scenario. 

As a result, for this RED, residential exposures were not estimated. This means that the additional 

FQPA safety factor did not factor into the residential risk assessment. 

EPA also notes that the RED has been finalized and is publically available: 

http://www.epa.gov/oppsrrd1/REDs/trimethoxysilyl-quats-red.pdf. 

Comment 90.2: A commenter stated that applicator and post-application exposures for material 

preservatives are significantly different from exposures associated with the use of a preserved 

material. 

Response 90.2: EPA agrees with this comment and does consider the differences in the exposures as 

well as mitigation options when conducting a risk assessment for a material preservative. EPA 

considers the exposures of workers applying a pesticide product labeled as a material preservative 

into finished products (e.g., treated articles such as consumer goods like textiles and paints) 

differently than exposures to the treated articles themselves. Differences in exposures for material 

preservatives account for: (1) the population exposed (e.g., workers in manufacturing settings versus 

children wearing treated clothing), (2) the magnitude of exposure (e.g., concentrated pesticide 

products used in manufacturing settings versus the amount of a pesticide bound to clothing), (3) 

routes of exposure (e.g., workers are often limited to dermal and inhalation exposure while children 

may be exposed via dermal, inhalation, and/or incidental oral exposure resulting from mouthing 

activities), and (4) exposure mitigation options (e.g., personal protective equipment (PPE) and 
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Applicator/Handler (Human Exposure) Section (90) Page 124 

engineering controls can be required on pesticide product labels used by manufacturing workers, but 

are not required on treated articles such as in-can preservative uses of antimicrobials for paint). 

Additional information on treated articles is available at 

http://www.epa.gov/pesticides/factsheets/treatart.htm. 

Comment 90.3: A commenter sees no reason to distinguish between indoor and outdoor exposures 

for applicator data requirements and believes that proposed testnote 3 is sufficient to explain how 

one determines the venue for testing. 

Response 90.3: EPA agrees with the commenter that proposed testnote 3 sufficiently explains how 

an applicant can determine if the most appropriate exposure study to conduct is either indoors or 

outdoors based on the use patterns of the product. To clarify the presentation of indoor versus 

outdoor for dermal and inhalation exposure data requirements, EPA has revised the applicator 

exposure data requirement table. The revised table no longer has separate entries for indoor and 

outdoor data requirements. There is now a single row titled “dermal exposure” and another titled 

“inhalation exposure”. Both the indoor and outdoor specific guideline numbers are specified in the 

Guideline Number column. In almost all instances only one study, either indoor or outdoor, 

normally would be required. 

Comment 90.4: A commenter maintained that EPA should be consistent with OSHA and other 

standards with regard to exposure limits and handling practices, and incorporate the OSHA 

standards into risk assessment evaluations. The commenter also asked that when EPA stated that an 

OSHA or American Conference of Governmental and Industrial Hygienists (ACGIH) standard is 

not adequately protective for an antimicrobial, that the finding should be substantiated. 

Response 90.4: The OSHA workplace standard is the permissible exposure limit (PEL).When 

developing a PEL, OSHA considers the toxicity of the chemical, often using data from the open 

literature as well as the feasibility that exposures could be reduced to the PEL using process 

modifications, engineering controls and personal protective equipment (PPE). Approximately 500 

PELs have been established. 

The ACGIH establishes health–based Threshold Limit Values (TLVs), which are non-governmental 

guidelines used by professional industrial hygienists in making decisions about safe levels of 

exposure to a chemical substance in the workplace. The TLVs were established for some chemicals 

as early as 1946 and they are updated on a regular basis as new health effects information becomes 

available. Like the OSHA PELs, the TLVs are based on health effects data from the open literature, 

however, unlike the OSHA PELs, feasiblity issues are not considered in establishing TLVs. TLVs 

are not available for most pesticide chemicals. 

However for those pesticide chemicals with both TLVs and RfCs (Reference Concentrations are 

established by OPP based on studies submitted by the registrants), the RfCs are often lower than the 

TLVs. There could be several reasons for such differences. OPP’s data is submitted by the pesticide 

registrants and the toxicity database is composed of animal studies. Uncertainty factors are used to 

derive the RfCs (exposure limits). Instead of animal studies, ACGIH prefers to rely on epidemiology 
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Master Responses: 

Applicator/Handler (Human Exposure) Section (90) Page 125 

studies/case reports of human, particularly worker, exposures from the literature and on 

professional judgment. 

For example, ACGIH and OPP established different inhalation limits for formaldehyde based on 

slightly different interpretations of the same literature studies. The TLV for formaldehyde is 300 

ppb and the OPP “RfC” for occupational uses is 100 ppb. Although the TLV is greater than the 

“RfC,” ACGIH does acknowledge in their TLV documentation that irritation can occur in some 

workers at levels of 100 to 300 ppb. 

EPA believes that an existing OSHA or ACGIH standard should be considered as part of EPA’s 

hazard evaluation. However, before using an OSHA or ACGIH standard, EPA would review the 

standard and the health effects (toxicology) documents supporting the standard’s development to 

determine if EPA believes that the standard provides adequate protection. EPA agrees with the 

commenter that EPA’s evaluation of an existing OSHA or ACGIH standard should be part of its 

hazard evaluation documentation. 

In its proposed rule, EPA proposed in the Applicator Exposure Table (40 CFR 158.2260(a)(1)) and 

the Post-Application Exposure Table (40 CFR 158.2270(a)(1)) to use established workplace 

standards, such as OSHA’s. The proposed language was: 

If EPA determines that industrial standards, such as the workplace standards set by the 

Occupational Safety and Health Administration, provide adequate protection for a particular 

pesticide or a particular use pattern, applicator exposure data may not be required for that pesticide 

or the use pattern. Applicants should consult with the Agency on appropriate testing before the 

initiation of studies. 

 

In addressing this comment, EPA realized that this proposed language is misplaced and also needs 

some textual modification. As discussed above an OSHA PEL or ACGIH standard is part of hazard 

evaluation. If the PEL or TLV is determined to be adequate to fulfill EPA’s selection of a toxicity 

endpoint, then the types and number of toxicity studies that may be required is impacted, not the 

need for exposure data. Therefore, EPA will remove the language originally proposed for §

158.2260(a)(1) and 158.2270(a)(1) concerning use of OSHA standards. With modifications, the 

following language will appear in the final toxicity table: 

If EPA determines that industrial standards, such as the workplace standards set by the 

Occupational Safety and Health Administration, provide adequate protection for a particular 

pesticide or a particular use pattern, additional toxicity data may not be required for that pesticide or 

the use pattern. Applicants should consult with the Agency on appropriate testing before the 

initiation of studies. 

Comment 90.5: One commenter discussed his belief that “A toxicity study alone cannot be used to 

determine when a risk assessment is needed. It must be teamed with information on exposure to make a decision on the 

need for a risk assessment. Therefore, the regulation should be revised to state that the triggering mechanism for 

determining when a quantitative risk assessment by a particular route of exposure is necessary is based on a finding of 

“significant adverse effects” and sufficient data on exposure to determine that exposure by the relevant route leads to a 

concern.” 
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Applicator/Handler (Human Exposure) Section (90) Page 126 

Response 90.5: The EPA agrees with the commenter that both toxicity and exposure data are 

needed to prepare a risk assessment. EPA disagrees with the commenter that there must be a 

predetermined definition of significant adverse effects in order to conduct the risk assessment. EPA 

risk assessments are, in part, conducted to determine the magnitude of the risk and the need for 

mitigation. This can only occur once the toxicity and exposure data are identified and a risk 

assessment is developed. The Agency’s exposure and risk assessment procedures have been 

presented in numerous exposure and risk assessments for antimicrobial pesticides. These documents 

are publicly available. While EPA’s assessments reflect the best available data, and the state of the 

science of exposure and risk assessment models, methods, and procedures, we are continually 

striving to increase the exposure data base and improve exposure methodologies. 

Comment 90.6: A commenter asserted that “poisoning incident data” should not be incorporated 

into this regulation unless the EPA can provide criteria to trigger the need for exposure data based 

on poisoning incidents. The commenter contended that regulating based upon anecdotal reports of 

“poisoning” is not appropriate. 

Response 90.6: EPA agrees that anecdotal reports that cannot substantiate a clear dose response 

(cause-effect) relationship of “poisoning” are not appropriate for regulatory endpoints. In-depth 

information on the dose response is the critical information needed for regulatory endpoints, and 

poisoning incident data rarely include this information. Based on this comment, the text for the 

toxicity triggers in 40 CFR 158.2260 and 158.2270 has been modified to clarify that the poisoning 

incident data must have a clear dose response (cause-effect) relationship to indicate that adverse 

health effects may have resulted from exposure to the pesticide. 

Comment 90.7: Several commenters suggested that the Agency add information about the 

Antimicrobial Exposure Joint Venture (AEJV) data to the preamble discussion on the acceptability 

of surrogate data. One commenter encouraged EPA to incorporate survey tool recommendations 

(such as in-home observations) in their product use guidelines. 

Response 90.7: The AEJV is a consortium of 14 companies that is collecting information on 

consumer uses of antimicrobial pesticide products. The AEJV will provide this information to EPA. 

EPA agrees that such antimicrobial use information can provide valuable information from sources 

such as in-home observations, diary surveys detailing residential uses of antimicrobial products, an 

“amount used” survey, and pool/spa surveys. Such information, if found to be appropriate, could be 

used to fulfill the required product use information and required description of human activities data 

requirements, providing that the use site of the surrogate data matches the intended product uses. 

Additionally, the AEJV is in the process of collecting use information on industrial and institutional 

applications of antimicrobials. 

Comment 90.9: A commenter asked why EPA requires biomonitoring (biological monitoring) data 

in addition to or in lieu of dermal or inhalation exposure data. 
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Master Responses: 

Applicator/Handler (Human Exposure) Section (90) Page 127 

Response 90.9: EPA does not require submission of biomonitoring data in addition to dermal and 

inhalation (passive dosimetry) exposure data. The submission of biomonitoring data is a registrantbased decision. In some circumstances the applicant may want to address certain risk assessment 

issues (e.g., dermal absorption of a chemical in a matrix such as paint) by performing a 

biomonitoring study rather than a dermal passive dosimetry study. 

Comment 90.10: A commenter asked whether EPA usually requires both a dermal and an inhalation 

study, and whether both a dermal and an inhalation risk assessment are needed for all 

antimicrobials? 

Response 90.10: EPA assesses the need for dermal and inhalation risk assessments based on the 

potential for route-specific exposure and by the toxicological data base for dermal and inhalation 

routes. There could be times when both studies are required such as when there is exposure by both 

routes and the toxicology endpoints indicate the need for assessing the hazards of both routes. 

Comment 90.11: One commenter stated that EPA needed to realize that it is impossible to collect 

children’s exposure or biomonitoring data. 

Response 90.11: Research with human subjects is subject to the Common Rule. As explained in the 

proposed rule [59420-21] studies such as biomonitoring, mixer/loader or applicator, and postapplication studies are subject to the Common Rule. The work of the Human Studies Review Board 

(HSRB) assures that test subjects are treated in an ethical manner. Under the Common Rule, 

exposure studies cannot be conducted on children or on pregnant women, and therefore, as 

discussed in response to comment 100.13, EPA has removed the data requirement for non-dietary 

ingestion exposure (875.3000) from the post-application exposure data requirements table. Nondietary ingestion exposure estimates resulting from such activities as children’s hand-to-mouth and 

object-to-mouth behaviors (e.g., plastic toys, clothing) will be generated using modeling techniques. 

Comment 90.12: A commenter asserted that proposed testnote 10 to the post-application table 

should be re-evaluated since “any such study would raise significant ethical questions.” The 

commenter asked how an applicant would determine “what, if any, data are required when passive 

dosimetry is not an option.” 

Response 90.12: Proposed testnote 10 is one of the triggers for the biomonitoring study. EPA 

agrees that proposed testnote 10 does not provide appropriate information and is removing the 

testnote. (EPA notes that due to renumbering, there is a new testnote 10.) 

Comment 90.13: A commenter stated that Guidelines 875.1100 through 875.1700 do not provide 

sufficient or appropriate guidance for antimicrobial pesticide products, focusing on how 

observational studies are conducted versus investigational or intentional exposure studies. 

Response 90.13: EPA agrees that these guidelines are not up-to-date as they do not reflect the 

current state of the science of exposure assessment models, methods, and procedures. Significant 
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Applicator/Handler (Human Exposure) Section (90) Page 128 

changes have occurred in the last 10 years. The SAP meeting on worker exposure assessment 

methods in January 2007 (http://www.epa.gov/scipoly/sap/meetings/2007/010907_mtg.htm) as 

well as the recent HSRB meetings have discussed and reviewed exposure methodologies, as well as 

reviewing submitted protocols for human exposure monitoring. Revisions to the EPA guidelines will 

not be undertaken until after completed exposure studies have gone through HSRB final review. 

Any study limitations recommended by the HSRB will need to be considered in the design of 

exposure studies and in the revision of guidelines. Until then, EPA is planning to provide citations 

to the SAP and HSRB meeting presentations and minutes for the most up-to-date information on 

conducting human exposure monitoring. 

Additionally, the product information (875.1700 and 875.2700) and surface residue (875.2300) 

guidelines will be finalized before the final rule is published, and then provided on the EPA website 

at http://www.epa.gov/ocspp/pubs/frs/home/guidelin.htm. 

EPA agrees that for certain scientific disciplines or certain studies that antimicrobial-specific 

guidance may be needed. See response to comment 191.6 for a discussion on guidelines specific to 

antimicrobial pesticide products. 

Comment 90.14: A commenter stated that data reporting and calculations should not be required for 

applicator exposures, the data should only be required for post-application exposure. 

R 90.14: EPA disagrees. For any study that is conducted in the field collecting exposure data, the 

submitter must also fulfill the data reporting and calculations requirement. As discussed in the 

preamble to the proposed rule (73 FR 59398-9) this includes submitting information about the 

formulas and data used in the calculations as well as information concerning the ethical conduct of 

the study. This information is usually not a separate report, but included within (for example) the 

dermal or inhalation study. EPA will revise testnote 5 to the proposed Applicator Exposure Data 

Requirements Table and testnote 11 (now renumbered to 10) to the proposed Post-Application 

Exposure Data Requirements Table to clarify that the data reporting and calculations are only 

required when exposure data are required. 

Comment 90.15: A commenter submitted both an applicator exposure table and a post-application 

exposure table for EPA to consider. 

Response 90.15: The commenter’s suggested applicator exposure table was similar to EPA’s 

proposed table in structure and format. One of the differences was a lack of distinction between 

indoor and outdoor dermal and inhalation uses. As explained in response to comment 90.3, EPA 

revised its table so that there are no longer separate entries for indoor and outdoor uses. 

Another difference was the commenter’s suggestion that the dermal and inhalation studies be “CR” 

in the applicator exposure table. EPA disagrees with the “CR” approach suggested by the 

commenter and has retained the approach in its proposal for requiring the dermal and inhalation 

studies for applicator exposure. Without this information, EPA cannot perform an exposure and 

risk assessment. 
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Applicator/Handler (Human Exposure) Section (90) Page 129 

The commenter’s descriptions in their suggested testnote state that applications such as closed 

systems do not require data collections. EPA agrees that for some antimicrobial applications using 

closed systems (e.g., closed loading of liquid formulations with low vapor pressures) data normally 

will not be required. Proposed testnote 4 indicated that EPA would provide guidance on the toxicity 

and exposure data needed for closed systems. EPA has revised testnote 4 to provide greater clarity 

and to include the above example of a closed system . 

The commenter also suggested using “NR” (not required) for biomonitoring. Biomonitoring is 

seldom required by EPA, rather it is an option that some data submitters choose on their own, and 

therefore EPA will continue to specify as “CR”. 

Based on the commenter’s suggested testnote 1, to reflect the role of the HSRB, EPA is revising 

proposed testnote 1 to both the Applicator Exposure and the Post-Application Exposure Tables to 

acknowledge the role of HSRB review. Proposed testnote 1 will become a new testnote 3 to the 

Post-Application Data Requirements Table. It will be used to indicate the need for protocol review 

for those studies that do not require review by the HSRB. 

The commenter suggested a post-application exposure data requirements table that was also similar 

in structure and format, but there were fewer data requirements and mostly “CR”s. Based on public 

comments, modeling options, and likelihood of requiring the data, EPA changed most of the Rs to 

CRs. See response to comments 100.4, 100.7, 100.9, and 100.10. Additionally, the commenter 

suggested the deletion of both the soil residue and incidental ingestion data requirements. The EPA 

disagrees with removing the soil residue studies: For certain uses of wood preservatives in residential 

areas, soil could be an important exposure pathway. There may be circumstances where soil residue 

data may be needed to perform the risk assessment. Since it would be rarely required, EPA 

acknowledges the low frequency of needing this study in the testnote and “CR” classification. 

However, the incidental ingestion data requirement has been deleted from the post-application table 

as discussed in response to comment 100.13. 

Based on the comments received, the Testnotes to the Applicator Exposure Table in the 

final rule will read as follows: 

T90.1: Testnote 1 to the Applicator Exposure Table 

Proposed: 

Protocols must be approved by the Agency prior to the initiation of the study. Details for 

developing protocols are available from the Agency. 

Final: 

Prior to initiation of the study, protocols involving intentional exposure of human subjects must be 

submitted for review by EPA and then the Human Studies Review Board (HSRB) according to 40 

CFR 26.1125. Examples of proposed human study research can be found in various reviews 

provided by the Human Studies Review Board (http://www.epa.gov/osa/hsrb/index.htm). 
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Applicator/Handler (Human Exposure) Section (90) Page 130 

T90.2: Testnote 2 to the Applicator Exposure Table 

Proposed: 

Biological monitoring data may be submitted in addition to, or in lieu of, dermal and inhalation 

passive dosimetry exposure data, provided the human pharmacokinetics of the pesticide or 

metabolite/analog compounds (i.e., whichever method is selected as an indicator of body burden 

or internal dose) allow for the back calculation to the total internal dose. 

Final: 

Biological monitoring data may be submitted in addition to, or in lieu of, dermal and inhalation 

passive dosimetry exposure data, provided the human pharmacokinetics of the pesticide or 

metabolite/analog compounds (i.e., whichever method is selected as an indicator of body burden 

or internal dose) allow for the back calculation to the total internal dose. 

T90.3: Testnote 3 to the Applicator Exposure Table 

Proposed: 

For products with both indoor and outdoor uses, and similar conditions of use, data are generally 

required for the indoor applications only. However, data for outdoor uses are required if the 

Agency expects outdoor uses to result in greater exposure than indoor uses (e.g., higher use rates 

and application frequency, or longer exposure duration, or application methods/equipment create 

potential for increased dermal or inhalation exposure in outdoor versus indoor use sites). In 

certain cases, when a pesticide is used both indoors and outdoors under dissimilar conditions of 

use, the Agency may require submission of applicator exposure data for both use patterns.

Final: 

For products with both indoor and outdoor uses, and similar conditions of use, data are generally 

required for the indoor applications only. However, data for outdoor uses are required if the 

Agency expects outdoor uses to result in greater exposure than indoor uses (e.g., higher use rates 

and application frequency, or longer exposure duration, or application methods/equipment create 

potential for increased dermal or inhalation exposure in outdoor versus indoor use sites). In 

certain cases, when a pesticide may be used both indoors and outdoors under dissimilar 

conditions of use, the Agency may require submission of applicator exposure data for both use 

patterns.

T90.4: Testnote 4 to the Applicator Exposure Table 

Proposed: 

For metal working fluids (MWFs), the Agency can provide written guidance concerning exposure, 

toxicity, and other data requirements for ‘‘open’’ and ‘‘closed’’ MWF systems. 

Final: 

EPA will consider waiving this data requirement for antimicrobials applied via closed loading 

systems if the antimicrobial has a low vapor pressure. 
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Applicator/Handler (Human Exposure) Section (90) Page 131 

T90.5: Testnote 5 to the Applicator Exposure Table 

Proposed: 

Data reporting and calculations are required when handler exposure data are required. 

Final: 

Data reporting and calculations are required only if handler exposure data are required. 

 
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Post-application (Human Exposure) (100) Page 132 

Post-application (Human Exposure) (100) 

Master Responses and Testnotes for the Post-application (Human Exposure) 

Section 

Please note that EPA responses and testnotes are presented in numerical order. However, in the course of response 

development, some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are 

missing. 

Comment 100.1: A commenter maintained that there should be few circumstances when a soil 

residue dissipation study is needed. Another commenter stated that the soil residue dissipation study 

is inappropriate for wood preservatives. 

 

Response 100.1: The Agency agrees with the commenter that there are only a few circumstances for 

which a soil residue dissipation study would be required for antimicrobial pesticide uses. The soil 

residue dissipation data requirement is specified as “CR” in the proposed post-application exposure 

data requirements table for both occupational and residential uses to reflect this situation. However, 

the Agency disagrees that the study is inappropriate for all wood preservatives: there may be 

circumstances when incidental ingestion of soil may be an important exposure pathway. Proposed 

test note 2 will be revised to specify that a soil residue dissipation study may be required if the 

potential exposure to soil has the potential to be an important exposure pathway. 

 

Comment 100.3: A commenter argued that there is a significant amount of post-application 

exposure data available that should be considered/used before requiring data under FIFRA. 

 

Response 100.3: EPA acknowledges that there are existing exposure data either in the literature, or 

via other governmental organizations such as OSHA, or academia, etc. When available and 

appropriate, EPA uses such exposure data and/or information in its risk assessments. For example, 

the risk assessments for both chlorine dioxide and ethylene oxide relied heavily on the workplace air 

concentration monitoring data available in OSHA’s Chemical Exposure Health Database (CEHD), 

formerly known as, Integrated Management Information System (IMIS). To access CEHD, users 

navigate on the OSHA homepage (http://osha.gov/) to Chemical Exposure Health Data under the 

Data and Statistics section towards the bottom right of the page. Users can search CEHD by 

Establishment Name, State, Zip Code, Year Range, Standard Industrial Classification (SIC), North 

American Industrial Classification System Code (NAICS), Chemical Abstracts Service Number 

(CAS), Chemical Name, or Result Range. 

Applicants who are aware of existing data that could fulfill a data requirement should submit the 

data to EPA. EPA will consider the appropriateness and robustness of the data, and, if appropriate, 

will use the data in the Agency’s risk assessment. 

 

Comment 100.4: A commenter argued that all of the post-application data requirements should be 

CR, not R. Additionally, the commenter thought that there should be far greater clarity “with regard 

to the triggers that would create a need for post-application exposure data.” 
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Post-application (Human Exposure) (100) Page 133 

 

Response 100.4: As discussed in the preamble for the proposed rule (73 FR 59386), the R/CR 

terminology is a general presentation of the likelihood that a data requirement will apply. The use of 

R does not necessarily indicate that a study is always required, but that it is more likely to be required 

than not. The use of CR means a study is less likely to be required. However, both R and CR 

designations must be read in the context of the accompanying testnotes. An applicant may assume 

that a data requirement with R will typically be required all the time. The test notes accompanying 

that R designation may provide supplementary information or identify some condition(s) when the 

study may not be required. The testnotes indicate the circumstances under which the Agency has 

learned through experience that the information is needed. 

Based on comments received specifically discussing the feasibility and purpose of some of the R 

designations for post-application studies, EPA is revising three of the data requirements from R to 

CR. The post-application data requirements for the occupational use pattern for indoor surface 

residue dissipation, dermal exposure, and inhalation exposure; and the residential use pattern for 

dermal exposure, and inhalation exposure have been revised from R to CR. Under certain 

circumstances, for particular use patterns, these changes reflect the potential for fulfilling a postapplication data requirement via an alternate method. For example, dermal post-application 

exposure for antimicrobial pesticides in treated textiles is most often estimated based on residue 

leaching and the assumption of contact with the full surface area of clothing worn or a child 

mouthing a section of a blanket, shirt, etc. For this type of an application, a residue study is more 

appropriate (and feasible) than monitoring human skin. The need for an inhalation post-application 

(bystander) exposure study would be conditioned on factors such as the pesticide’s high vapor 

pressure or the use of a spray/mist-type of application, where there is greater potential for bystander 

exposure. Also see response to comments 100.7, 100.9, and 100.10. 

 

Comment 100.5: A commenter asked what the toxicity and exposure criteria are that will trigger the 

need for post-application exposure data? 

 

Response 100.5: EPA specified the toxicity and exposure criteria for triggering a post-application 

exposure study in proposed 40 CFR 158.2270. Both the exposure criteria and the toxicity criteria 

must be triggered for post-application exposure data to be required. This means that if EPA’s review 

and evaluation of the toxicity studies or incident data having a clear cause-effect relationship indicate 

adverse effects and if there is the potential for post-application exposures occurring such as workers 

coming in contact with treated articles or surfaces or breathing gases or mists, the post-application 

exposure data are required. If there are no significant adverse effects or if there is no exposure, then 

the combination of both criteria is not triggered, and post-application exposure data are not 

required. 

 

Comment 100.6: Given the huge variety of occupational settings for antimicrobial uses, a 

commenter maintained that EPA should consider engineering controls, process restrictions, and 

personal protective equipment required by OSHA, before requiring post-application occupational 

data under FIFRA. 
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Post-application (Human Exposure) (100) Page 134 

Response 100.6: EPA differs from OSHA in that we use pesticide label language to communicate 

the required PPE and engineering controls to users while OSHA sets standards for industries to 

meet. EPA relies on a risk-benefit assessment to determine the need for pesticide label required 

engineering controls and/or personal protective equipment such as respirators for occupational 

uses. When determining the potential for exposure and the need for data, EPA does consider factors 

such as the availability of engineering controls and the potential for process limitations, and is likely 

to require less data if such factors indicate that exposures would be minimal, e.g. closed loading 

systems. With respect to personal protective equipment, if EPA cannot reliably model the air 

concentration then EPA would require exposure data to determine the “original” concentration 

before risk-reduction measures are applied. Then EPA can consider how the application of PPE 

could change the concentration. Often this is done by using surrogate data and various factors to 

determine if the reduction in exposure provides an adequate level of protection. This is particularly 

the case for respiratory protection where inhalation exposure data would be needed before 

determining which type of respirator would be required. To determine if exposure data are needed 

the label uses need to be well defined. For this, exposure-related, informational data are required, to 

provide thorough descriptions of how, when, where, and why the exposures occur and this 

information is required under product use information and description of human activity. 

 

Comment 100.7: A commenter maintained that there is little justification for requiring (R) the soil 

residue dissipation and indoor surface residue dissipation studies. 

 

Response 100.7: In the proposed rule, EPA conditionally required the soil residue dissipation study 

for both occupational and residential scenarios. EPA agrees that the likelihood of requiring soil 

residue dissipation data is low for the majority of antimicrobial use patterns. The low likelihood is 

reflected in the “CR” designation in the proposed post-application exposure data requirements table 

for the soil residue dissipation study for both occupational and residential use patterns. No changes 

are needed. 

In the proposed rule, EPA required the indoor surface residue dissipation study for both 

occupational and residential scenarios. However, the likelihood of requiring indoor surface residue 

dissipation data is high for residential products such as antimicrobial-treated clothing and plastic 

consumer items/toys, as well as direct applications such as carpet shampoos, laundry detergents, and 

floor cleaners that are antimicrobial products. Therefore, the indoor surface residue dissipation study 

for the residential use sites will remain “R” as proposed. 

However, EPA has re-evaluated the “R” proposed for occupational use sites. When compared to 

residential use sites, occupational use sites are less likely to result in the need for indoor surface 

residue dissipation data. Therefore, the data requirement for indoor surface residue data is revised 

from “R” to “CR” for occupational uses. 

In most manufacturing settings, there is less contact with surfaces than in most residential scenarios. 

For example, under most circumstances workers do not crawl around the floors of manufacturing 

plants. The need for indoor surface residue dissipation data for workers is limited by the residue 

distribution where contact may occur. EPA now agrees that the occupational use sites are less likely 

to result in the need for indoor surface residue dissipation data, and therefore, the “R” has been 

revised to “CR”. 
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Post-application (Human Exposure) (100) Page 135 

Comment 100.9: A commenter argued that for the indoor surface residue dissipation data 

requirement, despite the use of guideline 875.2300, it is not clear exactly what data EPA is seeking. 

The commenter maintained that for an indoor surface residue dissipation study to be required, there 

needs to be a relationship between the surfaces where antimicrobial residues could be deposited and 

the human activities occurring around them that would lead to an expectation of significant dermal 

exposure. The commenter also maintained that proposed testnote 5 is overly broad and needs to 

contain an objective standard that would be used to determine when there is an expectation of 

significant dermal exposure. Another commenter stated that proposed testnote 6 is overly broad, 

and does not accurately reflect the use sites and circumstances when the test should be triggered. 

Response 100.9: Proposed testnote 5 triggers the indoor residue surface dissipation study for postapplication occupational use sites “...if the human activity data indicate that workers are likely to have postapplication dermal contact with treated indoor surfaces while participating in typical activities.” This means that a 

surface residue study is required if the pesticide is applied to surfaces that would then be typically 

contacted by workers. EPA believes that the significance of these dermal exposures, depends upon 

the pesticide use pattern, i.e., the nature of the use and the various post-application worker activities, 

as well as the toxicity of the antimicrobial pesticide. Therefore, developing an “objective standard” for 

the dermal route of exposure to indicate the need for a surface residue study is not feasible and none 

of the comments provided an alternative to refine this testnote. 

Testnote 6 also triggers the indoor residue surface dissipation study, but for residential use sites. It is 

essentially a listing of use patterns that have residential components. EPA disagrees that the listing is 

overly broad but does acknowledge the challenge of providing a definitive list that covers every 

circumstance. EPA has revised testnote 6 to provide greater clarity and has included some specific 

examples that routinely require surface residue data are provided in the testnote including clothing, 

plastic toys, and treated wood used in areas of frequent contact such as decks and play sets. 

 

 

Comment 100.10: A commenter stated that the indoor surface residue dissipation study could 

provide information that would obviate the need for dermal/inhalation exposure studies. 

 

Response 100.10: EPA agrees with the commenter that in most instances the indoor surface residue 

dissipation study can be used to estimate post-application dermal exposure. For example, in a 

screening-level assessment EPA uses the amount of residue leached from clothing that has been 

treated by a material preservative to estimate potential dermal exposure. Because the dermal 

exposure estimate for many use sites and/or patterns can be derived from surface residues, the 

dermal exposure requirement is revised from “R” to “CR” for both occupational and residential use 

patterns. To reflect the use of exposure estimates from the indoor surface residue dissipation study 

in antimicrobial risk assessments, proposed testnote 3 has been deleted. (It will be replaced by a 

different testnote.) 

EPA disagrees with the commenter that the indoor surface residue dissipation study would provide 

any relevant information for the inhalation route of exposure. However, the inhalation study has 

also been changed to “CR” for both the occupational and residential use sites. The likelihood of 

requiring the inhalation exposure study is dependant upon several factors: vapor pressure and/or 
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Post-application (Human Exposure) (100) Page 136 

generation of aerosols during application, the proximity of bystanders, and the availability of 

modeling the vapor and/or aerosol generation. The conditions of when the inhalation data 

requirement is triggered are specified in testnotes 7 and 9. 

 

Comment 100.12: A commenter stated that the testnotes for post-application dermal and inhalation 

data requirements should be written to be more specific about post-application exposures. The 

commenter noted that the testnotes should not be the same as those for applicator exposure. The 

commenter also maintained that proposed testnote 9 is drafted too broadly, and is not helpful “with 

regard to its condition that data are ‘required if aerosols are generated where bystanders may be 

exposed’.” The commenter contended that there “needs to be reliance on conditions such as 

chemical characteristics, ambient monitoring, human activities and other relevant factors to 

determine when these data would be needed.” 

 

Response 100.12: EPA examined the testnotes to the proposed applicator and post-application 

tables. The testnotes describing the need for protocols and description of biomonitoring studies are 

similar. However, the testnotes for dermal and inhalation studies are very different for postapplication exposure versus applicator exposure. There are also more testnotes for post-application 

exposures when compared to applicator exposures. EPA believes that the testnotes strike the correct 

balance of specificity while offering some flexibility. 

EPA disagrees with the commenter that parts of proposed testnote 9 are drafted too broadly. If 

there is a worker and/or bystander in the vicinity of pesticide use, and there is a substance in the air, 

in the form of a gas, vapor, and/or particulate that could be breathed by that worker and/or 

bystander, then there is the potential for inhalation exposure to occur. EPA would then require the 

data to conduct its exposure and risk assessment. 

EPA does agree with the commenter that different circumstances/conditions should be considered. 

There is an existing policy paper on granting waivers for the inhalation toxicity study. Some of the 

circumstances described in the existing policy paper relate to the potential for inhalation exposure 

(or lack thereof). The policy paper addresses low volatility and aerosol particle size. Testnote 9 is 

revised to read: “Data are required for occupational and residential uses if there is the potential for 

bystander exposure and the pesticide use could result in respirable and/or inhalable material (e.g., 

gas, vapor, aerosol, or particulates). 

 

Comment 100.13: A commenter argued that the proposed requirement for non-dietary ingestion is 

impractical and unnecessary, and maintained that it could be replaced by modeling. 

 

Response 100.13: EPA agrees that the non-dietary ingestion study is impractical. Non-dietary 

ingestion exposure (i.e., incidental oral ingestion by children) is of potential concern for treated 

articles or surfaces that may be accessed by children. For example, uses such as carpet shampoo, 

hardwood floor treatments, pressure-treated wood, and impregnated materials (including but not 

limited to plastic toys or treated clothing) are assessed for non-dietary exposures when toxicity 

criteria are triggered. In all of these instances, non-dietary ingestion exposures are estimated using 

residue data from the treated surface combined with activity factors for children’s behaviors (e.g., 
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Post-application (Human Exposure) (100) Page 137 

frequency of hand-to-mouth contact). Often, EPA models this route and pathway of exposure using 

inputs from the available, reliable published research. If EPA were to require data to estimate this 

exposure pathway, EPA would require surface residue data, rather than requiring the actual 

monitoring of children or having individual registrants collecting data on frequency of hand-tomouth activities as these are not chemical-specific. Given the unlikelihood of requiring non-dietary 

ingestion exposure studies, EPA will remove this data requirement from the final post-application 

exposure table as well as the accompanying proposed testnote 12. 

 

Based on the comments received, the Testnotes to the Post-Application Exposure Table in 

the final rule will read as follows: 

T100.1: Testnote 1 to the Post-Application Exposure Table 

Proposed: 

Protocols must be approved by the Agency prior to the initiation of the study. Details for 

developing protocols are available from the Agency.

Final: 

Prior to initiation of the study, protocols involving intentional exposure of human subjects must be 

submitted for review by EPA and then the Human Studies Review Board (HSRB) according to 40 

CFR 26.1125. Examples of proposed human study research can be found in various reviews 

provided by the Human Studies Review Board (HSRB) (http://www.epa.gov/osa/hsrb/index.htm). 

T100.2: Testnote 2 to the Post-Application Exposure Table 

Proposed: 

For residential wood preservative uses, data are required if there is likely to be soil in contact with or 

adjacent to treated wood, including but not limited to decks, play sets, and gazebos.

Final: 

For residential wood preservative uses, data may be required if soil is in contact with or adjacent to 

treated wood, including but not limited to decks, play sets, and gazebos, and if soil has the potential 

to be an important exposure pathway. 

T100.3: Testnote 3 to the Post-Application Exposure Table 

Proposed: 

The applicant must submit residue dissipation data in conjunction with dermal exposure data, to 

establish chemical transfer coefficients used to estimate transfer of residues to human skin. 

Final: 

Protocols must be approved by the Agency prior to the initiation of the study. 
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Post-application (Human Exposure) (100) Page 138 

T100.4: Testnote 4 to the Post-Application Exposure Table 

Proposed: 

For wood preservatives, data are required for treated wood surfaces where post-application contact 

with treated wood is anticipated. 

Final: 

For wood preservatives, data are required for treated wood surfaces where post-application contact 

with treated wood is anticipated. 

T100.5: Testnote 5 to the Post-Application Exposure Table 

Proposed: 

For occupational uses, data are required if the pesticide is applied to or around surfaces, and if the 

human activity data indicate that workers are likely to have postapplication dermal contact with 

treated indoor surfaces while participating in typical activities. 

Final: 

For occupational uses, data are required if the pesticide is applied to or around surfaces, and if the 

human activity data indicate that workers are likely to have post-application dermal contact with 

treated surfaces while participating in typical activities. 

T100.6: Testnote 6 to the Post-Application Exposure Table 

Proposed: 

Data are required for residential sites. This includes but is not limited to the following use patterns: 

commercial, institutional, and industrial premises and equipment (including residential school and 

daycare institutions); residential and public access premises; material preservatives (including those 

used in residential products including but not limited to paints and plastic toys) and wood 

preservatives (when contact with treated wood is likely to occur). 

Final: 

Data are required for residential sites. This includes but is not limited to the following: Residential 

schools and daycare institutions; residential and public access premises; material preservatives 

(including those used in residential products, including but not limited to clothing and plastic toys) 

and wood preservatives (when contact with treated wood is likely to occur). 

T100.7: Testnote 7 to the Post-Application Exposure Table 

Proposed: 

Data are required for occupational and residential use sites if the human activity data indicate the 

potential for postapplication dermal exposures while participating in typical activities. 

Final: 
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Post-application (Human Exposure) (100) Page 139 

Data are required for occupational and residential uses if the human activity data indicate the 

potential for post-application dermal and/or inhalation exposures while participating in typical 

activities and no acceptable modeling options are available. . 

T100.8: Testnote 8 to the Post-Application Exposure Table 

Proposed: 

Biological monitoring data may be submitted in addition to, or in lieu of, dermal and inhalation 

passive dosimetry exposure data provided the human pharmacokinetics of the pesticide or 

metabolite/analog compounds (i.e., whichever method is selected as an indicator of body burden or 

internal dose) allow for a back-calculation to the total internal dose. 

Final: 

Biological monitoring data may be submitted in addition to, or in lieu of, dermal and inhalation 

passive dosimetry exposure data provided the human pharmacokinetics of the pesticide or 

metabolite/analog compounds (i.e., whichever method is selected as an indicator of body burden or 

internal dose) allow for a back-calculation to the total internal dose. 

T100.9: Testnote 9 to the Post-Application Exposure Table 

Proposed: 

Data are required for occupational sites if the vapor pressure is greater than 1E–3 mmHg at 25° C 

and there is the potential for bystander exposure. Data are also required if aerosols are generated 

where bystanders may be exposed.

Final: 

Data are required for occupational and residential uses if there is the potential for bystander 

exposure and the pesticide use could result in respirable and/or inhalable material (e.g., gas, vapor, 

aerosol, or particulates). 

T100.10: Testnote 10 to the Post-Application Exposure Table 

Proposed: 

Biological monitoring data are required when passive dosimetry techniques are not applicable for a 

particular exposure scenario (such as a swimmer/spa exposure) and exposure estimates from 

modeling techniques used in conjunction with the toxicity data indicate a risk of concern. 

Final: 

Data reporting and calculations are required only if post-application exposure data are required.

T100.11: Testnote 11 to the Post-Application Exposure Table 

Proposed: 
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Post-application (Human Exposure) (100) Page 140 

Data reporting and calculations are required when any post-application exposure monitoring data 

are required.

Final: 

Proposed testnote 11 was renumbered and revised slightly; it is now testnote 10. 

T100.12: Testnote 12 to the Post-Application Exposure Table 

Proposed: 

Data are required for residential sites if post-application exposures, particularly those of children, are 

likely. The selection of a sampling method will depend on the nondietary pathway(s) of interest. 

Data must be generated to consider all potential pathways of non-dietary ingestion exposure that are 

applicable (e.g., soil ingestion, hand-to-mouth transfer, and object-to-mouth transfer of surface 

residues). 

Final: 

Proposed testnote 12 was removed. 
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Residue Chemistry (110) 

Master Responses and Testnotes for the Residue Chemistry Section 

Please note that EPA responses and testnotes are presented in numerical order. However, in the course of response 

development, some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are 

missing. 

Comment 110.1: Several commenters found the scope of coverage of the residue data requirements 

in section 158.2290(b) to be vague and confusing. Further, the ACC Biocides Panel asserted that this 

section required data for uses for which a FFDCA section 408 tolerance is not required and over 

which, therefore, EPA allegedly has no jurisdiction. Specifically, the Panel wrote: 

In general, the Panel encourages EPA to explain when residue chemistry data are required, refrain 

from regulating uses for which EPA does not have jurisdiction under FFDCA 408, and clarify 

the vague regulations. Because the proposed rule appears to be largely a reiteration of existing 

data requirements at 40 CFR Part 161 or those for conventional pesticides at 40 CFR 158.1410, 

the proposed rule contains numerous inapplicable requirements and inappropriate test notes for 

some antimicrobial applications. In a following section, the Panel offers an alternative proposal 

that is consistent with the statutory requirements and the intent for identification of potential 

residue chemistry data requirements for antimicrobial pesticides. 

First, contrary to assertions in the preamble and Section 158.2290(b), EPA’s residue chemistry data 

requirements can only legally apply when a tolerance or tolerance exemption under FFDCA 408 is 

required (ACC Biocides Panel Comments, Appendix I, p.2). 

Response 110.1: EPA agrees that the scope of the residue data requirements in section 158.2900(b) 

is unclear. Therefore, EPA is clarifying section 158.2290(b) which pertains to the scope of the 

residue data requirements. In the preamble to the proposed rule, that section can be read as limiting 

the residue chemistry data requirements to pesticide products requiring a tolerance or tolerance 

exemption. This apparent limitation is inconsistent with both the general description of the scope of 

this subpart and the description of the scope of the residue data requirements section in the 

preamble of the proposed rule, and is internally inconsistent with the terms of proposed section 

158.2290(b). Various commentators noted the lack of clarity in this portion of the proposed rule. 

However, EPA disagrees with the ACC Biocides Panel’s contention that EPA should not require 

residue data on antimicrobial pesticide uses that do not require a tolerance under FFDCA section 

408. In the preamble of the proposed rule, the general discussion of the scope of Subpart W made 

clear that this Subpart was not limited to “antimicrobial pesticides” as defined by FIFRA section 

2(mm) but extended to among other things, “[p]esticide products for antimicrobial use in/on food” 

(73 FR 59385). This discussion provides no suggestion that the Subpart is limited to antimicrobial 

uses requiring FFDCA section 408 tolerances or exemptions from tolerances. The proposed rule 

preamble’s discussion of toxicity data requirements expressly notes that data are needed under 

Subpart W to assess dietary risk whether or not a section 408 tolerance is required. The preamble to 

the proposed rule specifically notes that, although certain antimicrobial food uses are regulated 

under the FFDCA by FDA under section 409 and not section 408, EPA still needs data on these 

uses to assess dietary risk to fulfill its statutory obligations under FIFRA section 2(bb)(2) (see 73 FR 
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59394). The proposed rule preamble’s discussion of residue chemistry data requirements states that 

these data are needed for “direct and indirect food uses” including direct application to “food or 

water” both to assess risk and for tolerance-setting purposes (73 FR 59401). Finally, both the 

preamble’s discussion of residue chemistry data requirements and the relevant rule text in the 

proposed rule discuss antimicrobial uses that do not require section 408 tolerances as if they were 

covered by this provision. For example, both the preamble and rule text refer to “fruit and vegetable 

rinses,” antimicrobials “incorporated into a material that may contact food or feed,” and “[a]quatic 

uses that have the potential to result in residues in potable water” and all of these uses may not need 

section 408 tolerances (73 FR 59401 and 73 FR 59444). 

Accordingly, EPA has revised §158.2290(b) to specify unambiguously that the residue data 

requirements apply to antimicrobial uses that may result in residues in food or water. EPA also 

includes in subsection (b) a non-exclusive list of uses that provides guidance on which antimicrobial 

uses are covered by this section. This revision to §158.2290(b) makes clear that the residue data 

requirements apply to antimicrobial uses that may result in residues in food or water whether or not 

a FFDCA section 408 tolerance is needed. Section 158.2290(b) is revised by first replacing the 

opening sentence with the following: 

 “Residue chemistry data are required for: (1) Antimicrobial end-use products with uses that 

 may result in residues in food or water including, but not limited to: (i) Products that require 

 a tolerance or tolerance exemption.” 

Second, §158.2290(b) (i) through (iv) are renumbered as paragraphs (2) through (5). Finally, each of 

the subparagraphs are revised to refer to “products” rather than “uses” for consistency and clarity. 

Although the subparagraphs are overlapping (i.e., a product may fall in more than one paragraph), 

the revised paragraphs now clarify the overall scope of this section. These revisions make 

§158.2290(b) in the final rule consistent with the scope of the rule described in the proposed rule 

preamble and the scope of the toxicology data requirements discussed in the proposed rule. 

Also, see response to comment 30.26 for the supporting legal basis. 

Comment 110.4: A commenter asserted that the potable water data requirement should be required 

more often. 

Response 110.4: The potable water study determines the effects of an antimicrobial pesticide on 

water treatment facilities and whether residues of the antimicrobial are likely to be present in treated 

drinking water. Based on this comment, EPA re-evaluated the need for the potable water study. 

There are conditions under which treatment of agricultural premises and aquatic areas is not 

expected to result in contamination of drinking water and conditions under which indirect and direct 

food uses could result in residues of the antimicrobial in drinking water. EPA believes that there are 

conditions under which the potable water study either will be or will not be required for all the uses 

in the residue chemistry table. 

 The table descriptors “R” for the agricultural premises and the aquatic areas are revised to 

“CR”

 The table descriptors “NR” for the direct and indirect food uses are revised to “CR”
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Proposed testnote 18 (now renumbered to testnote 12) has been revised to include that a potable 

water study will be required if run-off or leachate could contaminate the drinking water supply. Also 

see response to comment 110.35. 

Comment 110.5: A commenter asserted that EPA should reference IDREAM (Incidental Dietary 

Residential Exposure Assessment Model) in part 158W. 

Response 110.5: EPA disagrees with this comment. The names of specific models are not codified 

as they are suggested methods. 

Comment 110.6: A commenter indicated that proposed §158.2290(b)(1)(i) and (iii) should be 

combined due to their similarities in describing “animal or poultry drinking water” and “potable 

water or in water used for livestock and poultry drinking water.” 

Response 110.6: EPA agrees that the assessments of potable water and livestock/poultry drinking 

water are similar. However, the reason §158.2290(b)(1)(i) and (iii) were separated was to make clear 

that §158.2290 applies to antimicrobials applied for the purpose of disinfecting animal or poultry 

drinking water as well as to antimicrobials applied to water for another purpose that have the 

“potential to result in residues” in animal or poultry drinking water. As noted in the response to 

comment 110.4, there are scenarios under each of the use patterns that could result in residues in 

potable water, livestock drinking water, or both. The final residue chemistry data requirement table 

reflects this as the potable water requirement is CR for all four use patterns. Also see responses to 

comments 110.1 and 30.26 for a description of and the statutory bases to the changes to 

§158.2290(b). 

Comment 110.7: A commenter maintained that the term “residue of concern” should be replaced 

with “residue definition” to reflect the NAFTA and OECD approved terminology. 

Response 110.7: EPA uses the term “residue of concern (ROC)” to refer to “the parent pesticidal 

compound and its metabolites, degradates, and impurities of toxicological concern.” These are the 

residues used to conduct a dietary risk assessment and hence, all of these residues are measured in 

the magnitude of the residue studies using one or more data collection methods. This definition of 

“residue of concern” has been added to §158.2290(f) and is the same as that codified for 

conventional pesticides in 40 CFR 158.1410(c). EPA uses the term “residue definition” to refer to 

the residues included in the tolerance expression. The residue definition is comprised of the residues 

listed in the tolerance regulations at 40 CFR part 180. The residue definition may be identical to the 

ROC, it may be a subset of the ROC (e.g., indicator compound), or it may be more inclusive than 

the ROC (e.g., certain pesticide tolerances enforced using a common moiety method). Residue 

definition and ROC are defined in OPPTS 860.1550, the Test Guideline for Proposed Tolerances. 

Comment 110.8: A commenter stated that additional clarification is needed concerning EPA’s 

statement: “in the absence of data [the Agency will] evaluate the need for a tolerance or tolerance 
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Residue Chemistry Section (110) Page 144 

exemption by assuming complete transference of the chemical into food over the lifetime of the 

treated product.” 

Response 110.8: Complete transference refers to an assumption that the Agency would initially make 

regarding the migration of antimicrobial residues from an impregnated food contact material to the 

food contacting that material over the typical use life of the antimicrobial-impregnated material. This 

worst-case assumption is that 100 percent of the antimicrobial residues resulting from use at the 

maximum registered rate transfers into the food, which is then used to estimate a conservative 

dietary exposure. If the aggregate risk calculated using this conservative assumption, from use of the 

antimicrobial in question, is less than EPA’s level of concern, then no measured data are needed. If 

the aggregate risk meets or exceeds EPA’s level of concern, then chemical-specific data quantifying 

residue migration to refine this dietary exposure component may be required. To refine the 

exposure, the applicant may choose to perform one or more of the FDA protocols to estimate 

migration rate into food simulants (FDA/CFSAN, 2007, Preparation of premarket submissions for 

food contact substances: chemistry recommendations (Ref. 11 to the proposed rule, in docket EPAHQ-OPP-2008-0110). Alternatively, or subsequently, the applicant may choose to conduct a 

chemical-specific nature of the residue on surfaces study and a migration study investigating actual 

impregnated materials using representative foods. 

Comment 110.9: A commenter argued that more attention to the indirect contamination of food 

from impregnated materials is needed. 

Response 110.9: EPA agrees that attention needs to be paid to human dietary exposure due to 

contamination of food by antimicrobials impregnated into food-contact materials/surfaces. 

Impregnated food-contact materials are becoming more common and are becoming increasingly 

available to homeowners and commercial establishments. To determine if migration of residues into 

food is likely, migration studies have been and will continue to be required. The nature of the 

residue on surfaces (a new study) now triggers the migration study. 

In its proposed rule, EPA proposed to conditionally require a migration study only for indirect food 

uses. Based on this comment, EPA has re-evaluated the need for migration studies and believes that 

these studies could be needed for other uses. Such situations may include, but are not limited to, 

migration of residues from treated surfaces to livestock in their premises; treated fruit wrappers into 

fruit; or impregnated netting into aquacultural water and fish. Based on this comment, the table 

descriptors for the agricultural premises, direct food uses, and aquatic uses will be revised from 

“NR” to “CR.” Proposed testnote 23 described anticipated instances when a migration study would 

be required. However, since the results of the new data requirement “nature of the residue on 

surfaces” are now used as the trigger for requiring the migration study, the anticipated instances 

have been removed. A new testnote 5, based partially on proposed testnote 23, describes the 

circumstances for triggering the migration study. 

Comment 110.10: A commenter asked EPA to explain the term “post-harvest storage of 

commodities.” 
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Response 110.10:“Postharvest storage of commodities” refers to storage of raw agricultural 

commodities (RACs) once they are harvested. The expression “Postharvest storage of commodities” 

was used in proposed testnote 3 because, under the Use Pattern “Agricultural Premises,” a Nature 

of the Residue in Plant study would only be applicable to stored RACs which are typically 

metabolically active. Testnotes provide information concerning the specific case or conditions that 

trigger the need for the data. Thus, under the use pattern “Agricultural Premises,” a plant 

metabolism study is required if an antimicrobial could be used in facilities storing RACs after 

harvest. Proposed testnote 3 is now part of new testnote 8 which includes postharvest treatments as 

a trigger. 

Comment 110.11: A commenter asked why there is a requirement for a Nature of Residue in Plant 

study even though antimicrobials are not applied to growing crops. 

Response 110.11: An antimicrobial could be applied to growing crops if the pesticidal claim involves 

control of a public health pest (such as E. coli or B. anthracis) as opposed to a plant pathogen. Such a 

use is uncommon but, if such a use were to occur, then the plant metabolism (nature of the residue) 

study is needed. Also, soil or irrigation water could be treated or contaminated with an antimicrobial 

which could inadvertently contact RACs via drift or be taken up by the roots of agricultural crops. 

Stored RACs, which are typically metabolically active, could also be directly or inadvertently 

treated/contaminated. 

Comment 110.12: A commenter did not understand proposed testnote 5, or when it would trigger a 

study. According to the commenter, irrigated water could be applied to growing crops. The 

commenter sought clarification on which crops would be tested if such a study were to be 

conducted for an antimicrobial chemical. 

Response 110.12: Proposed testnote 5 (now part of new testnote 8) was one of three triggers for the 

Nature of the Residue in Plant Study. The proposed testnote specified that data would be required 

to “support applications to water if any residues could occur in irrigated crops, or to crops treated 

directly in the field.” EPA agrees that additional clarification is needed and has revised the testnote 

(now renumbered to 8). The new testnote 8 combines proposed testnotes 3, 4, and 5 and provides 

additional examples. Proposed testnote 5 becomes 8(iii) and has been simplified to state “use of 

antimicrobial-treated water for irrigation.” Therefore, if antimicrobial-treated water could be used 

for irrigation, then a nature of the residue in plants study is required. 

 

If residues could be reasonably likely to transfer from irrigation water to food crops the crops to be 

subjected to Nature of the Residue in Plant Studies (plant metabolism studies) are very chemicaland use pattern-specific and would typically be three diverse, unrelated crops that are likely to be 

irrigated in the major geographic locations the antimicrobial could be used. Given this variability, the 

crops or commodities to be tested are not included in a testnote. 

Comment 110.13: A commenter noted that, according to Appendix A in part 161 antimicrobials are 

excluded from applications to crops treated directly in the field. 
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Response 110.13: Appendix A to part 161 is considered to be outdated. EPA is aware of several 

examples of an antimicrobial being used on food or feed crops in the field, greenhouse, or water to 

control the public health microbial pests E. coli or B. anthracis (not agricultural pests) in soil, irrigation 

water, or crops. Also, antimicrobials are used to control antifouling organisms on ropes, posts, 

fencing, nets, etc. used to retain fish and shellfish raised for food via aquaculture; thus, 

antimicrobials are used outdoors in aquatic settings which justifies requiring residue chemistry data 

for water, fish, and shellfish. When the Antimicrobial Data Requirements Rule becomes effective, 

part 161 and Appendix A to part 161 will be removed from the CFR. 

Comment 110.14: A commenter stated his belief that if a data requirement is CR for conventionals, 

then it should also be CR for antimicrobials, not R. The commenter cited the following examples: 

Nature of the Residue in Plants, Nature of the Residue in Livestock, Residue Analytical Methods for 

Tolerance Enforcement, Residue Analytical Method for Data Collection, and Multiresidue Method 

Testing. 

Response 110.14: EPA compared the five data requirements in the proposed data requirements for 

antimicrobials to the four data requirements in conventionals; note that data collection and tolerance 

enforcement methods for conventionals are combined into one requirement, Residue Analytical 

Methods (OPPTS 860.1340). The nature of the residue in plants, and the analytical methods and 

testing requirements are a mixture of “R” and “CR” in the conventional, as well as in the 

antimicrobial. For both conventionals and antimicrobials, the “R”s and “CR”s are determined based 

on the use patterns and the likelihood of EPA’s needing the data. EPA is not sure of the difference 

noted by the commenter. 

Based on the review of this comment as well as responses 110.12, 110.20, and 110.31, EPA has 

made changes to the proposed data requirements table so that all of the nature of the residue studies 

are now “CR.” 

 Nature of the residue in plants: 

o for indirect food uses: “NR becomes “CR” 

o for direct food uses: “R” becomes “CR” 

o for aquatic uses: “R” becomes “CR” 

 Nature of the residue in livestock: 

o for agricultural premises: “R” becomes “CR” 

o for indirect food uses: “NR” becomes “CR” 

EPA believes that these nature of the residue studies will be rarely required and the testnotes 

provide details of the triggers. “CR” is appropriate since the testnotes provide adequate descriptions 

to trigger these studies. Proposed testnotes 3, 4, and 5 were combined to create new testnote 8 for 

the nature of the residue in plants. Since all of the nature of the residue in plant studies are now 

“CR,” additional clarifying examples to explain when (under what conditions) an applicant needs to 

submit data have been included in new testnote 8. 

EPA believes that proposed testnotes 6, 7, and 8 are captured in new testnote 9. Even with the 

change in phrasing, EPA believes that the studies will be required at the same frequency as in the 

proposed rule. 
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See response to comment 110.32 for a discussion of the changes to the residue analytical method for 

data collection, residue analytical method for enforcement of tolerances, and multiresidue method 

testing. 

Comment 110.15: A commenter contended that residue analytical methods are often not 

appropriate for environmental monitoring. The commenter asserted that methods for monitoring 

residues in surface waters should also be required. 

Response 110.15: EPA assumes that, by use of the term “residue analytical methods,” the 

commenter is referring to a single-chemical method to analyze food or feed items. Such methods are 

typically not sensitive enough to detect and quantify ppb-levels in environmental water samples in 

the presence of potentially interfering compounds. A method useful for determining 

environmentally-relevant concentrations would generally be a different method than that required 

for residue chemistry. EPA does not routinely require the development of a water method for 

pesticides that may be present in surface waters. Rather, the development of a water analytical 

method would be required in the fairly uncommon event that EPA requires a field water monitoring 

study. 

Comment 110.16: A commenter asked why there is a data requirement for processed food and feed? 

The commenter argued that antimicrobials could have an FFDCA sec. 408 tolerance exemption for 

use on Raw Agricultural Commodities (RACs) in the field, during transportation, and in packing 

houses, and that the FFDCA section 409 approval would cover food processing facilities. 

Response 110.16: An antimicrobial could be applied to field, greenhouse, or aquatic food crops if 

there is a pesticidal claim that the product controls a public health pest or microbial fouling 

organisms as opposed to a plant pathogen. Soil or irrigation water could also be treated with an 

antimicrobial which could inadvertently contact RACs via drift or by being taken up by the roots of 

agricultural crops. RACs could also be dipped in an antimicrobial prior to shipping, storage, or 

transport to a processing facility. RACs from any of these situations could be processed such that 

residues may concentrate compared to those in the RAC; this residue level is needed for 

determination of dietary exposure and aggregate risk whether or not an FFDCA section 408 

tolerance/exemption is needed for the processed food due to concentration of residues. EPA agrees 

that use of an antimicrobial in a food processing facility would often fall under FFDCA section 409. 

It should be noted that there are some antimicrobial uses in food processing facilities, such as use of 

hard surface sanitizers, which need a section 408 tolerance/tolerance exemption. However, even for 

antimicrobials that fall under section 409, these residues would also need to be included in dietary 

exposure and aggregate risk. 

Comment 110.17: A commenter aked why EPA is trying to regulate drinking water pursuant to 

FFDCA sec. 408 in residue chemistry testnote 18. The commenter asked for clarification on “direct 

application to water” where there is “potential” that the use could be in human drinking water is 

needed. 
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Response 110.17: EPA/OPP does not establish tolerances for pesticide residues in drinking water. 

See responses to comments 110.1 and 30.26 for an explanation of how FIFRA section 2(bb)(2) 

requires that a safety finding be made under FFDCA sec. 408. 

As explained in response to comment 110.4 proposed testnote 18 (now renumbered to 12) triggers 

the potable water study. The new testnote 12 retains the phrase “directly applied to water” but also 

includes additional clarification of indirect or inadvertent sources of contamination. 

Comment 110.18: A commenter asked whether an antimicrobial becomes a convential pesticide if 

the antimicrobial pesticide is applied to irrigation water, and that water is applied to growing crops. 

The comment maintained that testnote 20 needs to be clarified. 

Response 110.18: Proposed testnote 20 (now renumbered to testnote 14) triggers the Irrigated 

Crops study. The proposed testnote 20 (now 14) has been revised to contain the phrase “...applied 

directly to water used for irrigation of food crops or such that contaminated water could run-off, 

leach, or be discharged from treated sites or materials to make its way into water used for irrigation 

of food crops.” It is the use pattern, especially the target pest, which determines whether a given use 

is an antimicrobial use or a conventional use not the fact that growing crops are exposed. Use 

patterns that could result in contamination of field crops with an antimicrobial include, but are not 

limited to: (i) control of microbes in pulp and paper process water that is discharged, runs off, and is 

eventually used for irrigation; (ii) control of slime-forming bacteria and fungi in irrigation systems to 

prevent clogging; or (iii) direct-spraying food crops in the field to prevent contamination with foodborne bacteria or viruses of public health concern. 

Based on the review of this comment, and given that residues from multiple sites could end-up in 

irrigation water, EPA has made changes to the proposed irrigated crops data requirement: 

o for agricultural premises: “NR” becomes “CR” 

o for indirect food uses: “NR” becomes “CR” 

o for direct food uses: “NR” becomes “CR” 

EPA believes that this study will be rarely required but that the conditions under which it will be 

required have been included in new testnote 14. 

Comment 110.19: A commenter argued testnote 21 needs to be revised to reflect the division of 

authority between EPA and FDA. Proposed residue chemistry testnote 21 addresses the conditions 

under which a food-handling establishment study is required. According to the commenter, EPA 

regulates use of an antimicrobial only on fresh fruits and vegetables (RACs) rinsed in the field, 

during transport, or in a facility where no further processing occurs whereas FDA regulates all other 

uses as secondary indirect food additives. 

Response 110.19: Proposed testnote 21 (renumbered to testnote 3 in the final rule) described the 

trigger for the food-handling study. EPA disagrees with the commenter and does not believe that 

significant changes are needed to the first sentence of proposed testnote 21. As discussed in 

responses to comments 110.1 and 30.26, there is a clear distinction between the division of authority 

of EPA and FDA regarding use of a food-use antimicrobial. EPA agrees that many uses of an 
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antimicrobial in a food processing facility would fall under FFDCA section 409 and therefore FDA’s 

jurisdiction. The precise division of authority between EPA and FDA under FFDCA is defined in 

the definition of “pesticide chemical” in FFDCA section 201(q). However, even where FFDCA 

jurisdiction over pesticide residues in food falls under FFDCA section 409, the pesticide would still 

need to be registered under FIFRA. FIFRA’s registration standard for pesticides that result in 

residues in food requires EPA to determine both that the pesticide does not pose an “unreasonable 

risk” and that the pesticide is consistent with the safety standard in FFDCA section 408. In making 

these determinations, EPA may need residue data under this subpart. 

With minor revisions, such as specifying the nature of the residue study as the “surfaces” study, the 

first sentence of proposed testnote 21 (renumbered to testnote 3 in the final rule) has been retained. 

Sentence two is removed, as it is no longer needed. 

Also, EPA has relocated the food-handling study based on the commenter’s suggested tables. As a 

result of commenter suggestions that Tier 3 residue chemistry testing focus on food-contact 

surfaces, EPA decided to group five studies under the category of “Food-contact surfaces or 

antimicrobial-impregnated materials” as these types of uses comprise the majority of registered food 

uses of antimicrobial pesticides. The five studies include the “Nature of the residue on surfaces” 

study which is a new study suggested by two commenters; EPA agrees this is a valuable study. These 

five studies also include the related “Migration studies,” “Analytical method for data collection,” and 

“Storage stability” study which the Agency had originally proposed. These four studies were 

grouped together because they relate to food-contact surfaces and materials. EPA believes that the 

food-handling study logically completes the suite of five studies since the food-handling study 

addresses magnitude of the residues in food where it is held, processed, prepared, and/or served. 

For more detailed discussion, refer to response to comment 110.36. 

EPA proposed that the Food-handling study be “R” for Direct Food Uses, “CR” for Indirect Food 

Uses, and “NR” for Agricultural Premise and Aquatic Uses. As there are many chemical-specific 

variables such as use patterns, physical/chemical characteristics, etc., three of these have been 

changed as listed below. The Food-handling study requirement remained “CR” for Indirect Food 

Uses. Based on EPA’s evaluation of this comment and also in response to comment 110.36, EPA 

has made changes to the proposed data requirements so that the food-handling study is now “CR” 

in the final residue chemistry table for all four uses: 

o For agricultural premises: “NR” becomes “CR”; 

o For direct food uses: “R” becomes “CR”; 

o For aquatic uses: “NR” becomes “CR”. 

Comment 110.20: A commenter asked how an antimicrobial could be applied to livestock. In that 

case, the commenter thought that the antimicronial would be considered an an animal drug. The 

commenter also asked how an antimicrobial could be added to livestock feed. The commenter 

maintained that direct application to livestock feed is not subject to FIFRA. 

Response 110.20: EPA agrees that intentional treatment of livestock would be an animal drug but 

only if the article is “...intended for use in the diagnosis, cure, mitigation, treatment, or prevention 

of disease in...animals.” [FFDCA Section 201(g)(1)(B)]. Intentional or inadvertent exposure of 

livestock or their raw agricultural commodities to an antimicrobial, for example, to control spoilage 
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organisms or to reduce contamination by microbes of public health concern would be pesticide uses 

subject to EPA registration under FIFRA and subject to EPA purview under FFDCA sec. 408. 

Direct antimicrobial treatment of processed feed would be under FDA’s FFDCA sec. 409 purview, 

but would not be subject to FIFRA registration. Refer to EPA responses to comments 110.1 and 

30.26 for further details of the responsibilities of FDA and EPA concerning antimicrobial pesticides. 

EPA has revised “applied directly to livestock” to “treatment or contamination of sites” that could 

result in exposure of livestock, including feed or water. There could also be either direct or 

inadvertent deposition of antimicrobial residues on surfaces resulting from treatment of livestock 

premises. 

Comment 110.21: A commenter contended that the meat/milk/poultry/egg (MMPE) data 

requirement is stricter for antimicrobials than for conventionals. 

Response 110.21: EPA disagrees with this comment. The table descriptors for the MMPE data 

requirement were proposed as “CR” for all uses for antimicrobials. The codified table descriptors 

for the same data requirement is “CR” for all use patterns for conventionals, except Outdoor 

Residential Uses (which is “NR”). 

Comment 110.22: A commenter contended that EPA does not have the authority to regulate egg 

washes. 

Response 110.22: EPA disagrees with this comment. This is a pesticidal use under FIFRA. 

Comment 110.23: A commenter argued that the proposed rule is inconsistent with these two longstanding EPA policy documents: DIS/TSS 19 on Label Requirements for Poultry House 

Disinfectants, and DIS/TSS 18 on Label Requirements for Farm Premise Treatment 

Response 110.23: The commenter was not entirely clear regarding the their contention that the 

proposed rule is inconsistent with DIS/TSS 18 and 19. DIS/TSS 18 and 19 provide the language 

that should appear on labels of disinfectant products to permit the nonfood classification of use in 

poultry houses or farm premises. Generally, if classified as a nonfood use, the residue chemistry data 

requirements would not apply. 

Comment 110.24: A commenter preferred to remove the text proposed at 40 CFR 158.2290(c) and 

instead have that text as a testnote. 

Response 110.24: The proposed text for 40 CFR 158.2290(c) was as follows: 

“Except as described in paragraph (b) of this section, residue chemistry data are not required to 

support a tolerance exemption if dietary exposure estimates are not needed due to low toxicity of the 

active ingredient or theoretical (modeled) estimates of exposure are adequate to assess dietary risk.”
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EPA believes that this text is appropriately placed. Having this text appear before the residue 

chemistry data requirement table has the overall effect of making it applicable to all of the residue 

chemistry data requirements in the table at §158.2290(h). 

40 CFR 158.2290(c) was reworded to more specifically define the hazard (“...adverse effects (no 

toxicity endpoints)...”) and to explain the interplay between hazard and exposure to estimate risk 

(“...theoretical (high-end) dietary exposure estimates combined with the applicable toxicity 

endpoint...”). Also, the text was revised by deleting “...to support a tolerance exemption...” to 

clarify that it was applicable to all potential food uses, not just those for which a tolerance 

exemption has been deemed appropriate. The clarification for the term “theoretical” came from the 

preamble to the proposed rule [59404]. These additional details render 40 CFR 158.2290(c) more 

useful as an overarching statement that is applicable to all residue chemistry data requirements. 

Revised text wording is as follows: 

“Residue chemistry data are not required under paragraph (b) of this section if no adverse effects 

(no toxicity endpoints) are associated with dietary exposure to the active ingredient or if theoretical 

(high-end) dietary exposure estimates combined with the applicable toxicity endpoint result in acute 

or chronic dietary risks that are below the Agency levels of concern.” 

Comment 110.25: Some commenters maintained that EPA should not describe in this rulemaking 

“how exposure assessments should be conducted or what procedures to follow in conducting any 

necessary studies.” The commenters cited 40 CFR 158.1(b)(3) which states: “This part does not 

include study protocols, methodology, or standards for conducting or reporting test results; nor does 

this part describe how this Agency uses or evaluates the data and information in its risk assessment 

and risk management decisions, or the regulatory determinations that may be based upon the data.” 

Response 110.25: EPA agrees with the commenter that the protocols/procedures to be used to 

conduct individual studies or exposure assessments should not be described in part 158W. Part 

158W is a regulation, not guidance. Care has been taken to avoid describing such detailed 

procedures in the Residue Chemistry data requirements section. 

Comment 110.26: A commenter had concerns about the many antimicrobials that are found in 

surface waters resulting in contamination of drinking water, fish, and other aquatic organisms 

consumed by humans. The commenter argued that, as per FFDCA, EPA must assure that there is a 

reasonable certainty that no harm will result from aggregate exposure to residues of these pesticides. 

Response 110.26: The Agency is also concerned about pesticide residues in surface water and the 

potential for these residues to persist, migrate, and be transferred into drinking water and aquatic 

food sources. New environmental fate studies have been added to Subpart W (40 CFR §158.2280) 

to determine the effects of antimicrobials on waste water treatment plants; these studies will help 

predict the potential for residues of antimicrobials to survive these treatment processes and to be 

released into surface water and then for potential use as drinking water. 

In evaluating the comment, EPA has considered, as suggested by the commenter, that surface water 

contamination by antimicrobial residues may occur followed by transfer to fish and shellfish 

consumed by humans, and also in light of EPA’s knowledge of such occurrences as an increasing 

incidence of aquatic contamination by antifoulants, developmental effects in wildlife possibly due to 
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pesticides, discharges of antimicrobials by industries, and survival of certain antimicrobials through 

drinking water treatment processes. Therefore, the “Fish” study data requirements for the following 

uses have been changed: 

o for agricultural premise uses: “NR” becomes “CR;” 

o for indirect food uses: “NR” becomes “CR;” and 

o for direct food uses: “NR” becomes “CR” 

To reflect conditions under which certain aquatic uses may not be expected to result in the 

transferrence of specific antimicrobials to fish and shellfish, the “Fish” study data requirement for 

the following use has been changed: 

o for the aquatic uses: “R” becomes “CR.” 

EPA believes that this study will be rarely required, and the proposed testnote 19 (now renumbered 

to 13) has been revised to account for the fact that the fish study is now conditionally required for 

all uses. These changes are consistent with the expressed intent in the proposed rule to require data 

necessary to conduct an aggregate dietary risk assessment. 

In response to the second half of comment 110.26, we note that residues of certain antimicrobials 

could also be taken up into crops from contaminated irrigation water or inhaled if the compound is 

volatile. EPA registers pesticide products for sale or distribution in the U.S. To register a pesticide 

under FIFRA, EPA must determine that it meets the safety standards for registration in FIFRA. If 

there is human exposure from a pesticide residue in food, FIFRA also requires that dietary risk from 

the pesticide be consistent with the safety standard of FFDCA section 408, i.e., that there is a 

“reasonable certainty of no harm” (see responses to comments 110.1 and 30.26). 

Comment 110.27: A commenter offered new language to substitute for proposed 158.2290(b). Their 

language basically states that EPA can only require residue data to support uses that are regulated 

under FFDCA sec. 408. 

Response 110.27: The commenter’s suggested text for 158.2290(b) describes their interpretation of 

the conditions under which residue chemistry data requirements would be applicable. The Agency 

disagrees that data can only be required if the use is “regulated” under FFDCA sec. 408. Under 

FIFRA, the Agency may require any data necessary to determine that a pesticide poses no 

“unreasonable risks to man or the environment” and, if a pesticide use results in residues in food, 

any data necessary to show that dietary risk from the pesticide is consistent with the safety standard 

in FFDCA section 408. Also see responses to comments 110.1 and 30.26. 

Additionally, the commenter’s suggested language uses the use patterns suggested by the same 

commenters. As explained in response to comment 50.1, EPA is not adopting these use patterns. 

Comment 110.28: According to a commenter, pre-FQPA there was a policy that a sec. 409 clearance 

was sufficient for a sec. 408 clearance for direct and indirect food additives. The commenter 

contended that this needs to be clarified in the rule text, not in a testnote. 

Response 110.28: Prior to the passage of the Food Quality Protection Act of 1996 (FQPA), EPA 

often relied upon a FDA clearance of a substance under FFDCA sec. 409 in assessing dietary risk 
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under FIFRA. Now, FIFRA, as amended by FQPA, requires that EPA evaluate whether pesticide 

uses resulting in dietary exposure are consistent with FFDCA sec. 408. 

Comment 110.29: The commenter stated that dietary exposures from products used indoors in 

residential settings can only be regulated under FIFRA. 

Response 110.29: EPA “regulates” residential uses of pesticides under FIFRA in that it decides 

whether or not a pesticide may be registered for that use. EPA does not approve a pesticide for 

residential uses under FFDCA section 408 but FFDCA section 408 does require EPA to consider 

pesticide exposures from residential uses in evaluating whether to approve a pesticide tolerance. 

FFDCA sec. 408 directs EPA to assess the safety of a pesticide tolerance based on “all anticipated 

dietary exposures and all other exposures for which there is reliable information. [21 U.S.C. § 

346a(b)(2)(A)(ii)]. Additionally, FFDCA sec. 408 requires EPA in assessing pesticide risk to consider 

“available information concerning the aggregate exposure levels of consumers (and major 

identifiable subgroups of consumers) to the pesticide chemical residue and to other related 

substances, including dietary exposure under the tolerance . . . and exposure from other nonoccupational sources.” [21 U.S.C. § 346a(b)(2)(D)(vi)]. EPA has consistently interpreted these 

provisions as requiring it to consider pesticide exposure occurring in residential settings. 

Comment 110.30: A commenter asked what the difference between “direct food uses” and “direct 

food contact uses” in proposed 158.229 is? 

Response 110.30: The two expressions were intended to be interchangeable. To avoid further 

confusion, EPA has removed the word “contact” from the several instances in which the term 

“direct food contact uses” was used. 

Comment 110.31: A commenter questioned why the requirement for Nature of the Residue in 

Livestock is NR for Indirect Food Uses when several of the triggers for requiring this study are 

indirect food uses. The commenter argued that this is not consistent with the CR for Direct Food 

Use and Aquatic Uses. 

Response 110.31: The Agency agrees with the commenter and has changed the “NR” to “CR.” 

Indirect Food Uses are treatments not directed at food for antimicrobial purposes but that , 

nevertheless, could inadvertently result in residues in food. Also see response to comment 110.14. 

Comment 110.32: A commenter questioned the “CR” for the Analytical Methods for the 

Agricultural Premises, Indirect Food Use, and Aquatic Use Patterns when a Proposed Tolerance is 

“R” for all Use Patterns. The commenter maintained that analytical Methods should only be 

required when a tolerance is proposed. 

Response 110.32: Based on this comment and also 110.1, EPA has made a number of changes to 

the residue chemistry data table. First, the title of the proposed data requirement “Proposed 

tolerance” is changed to “Proposed tolerance/tolerance exemption.” This is a clarification of this 
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data requirement as proposed. The testnote to this data requirement, as proposed, states that “a 

petition proposing a numerical tolerance or a tolerance exemption is required for any food or feed 

use subject to section 408 of the FFDCA if the use is not covered by an existing tolerance or 

tolerance exemption.” Expanding the title of this proposed data requirement is thus consistent with 

EPA’s proposal. Also, for the purpose of clarification, EPA would note that it is appropriate to use 

an “R” in all of the use columns as to this data requirement because all uses coming within section 

158.2290 will need either a section 408 tolerance or exemption or clearance from FDA under 

FFDCA section 409. To the extent a use under section 158.2290 is not subject to FFDCA section 

408, a petitioner/applicant can fulfill this requirement by referencing the relevant clearance under 

FFDCA section 409 or a petition to FDA seeking such clearance. 

Further, the title of the proposed data requirement “Residue analytical methods for enforcement of 

tolerances” is changed to “Residue analytical methods for tolerance/tolerance exemption 

enforcement” to clarify the requirement. EPA has determined that an analytical method for 

tolerance/tolerance exemption enforcement is only needed in circumstances where there is a 

numerical residue level to enforce. Numerical residue levels are generally only used with tolerances. 

For this reason, proposed testnote 9 only required a residue analytical method when a numeric 

tolerance is proposed. Thus, if an exemption from the requirement from tolerance is sought, and 

that exemption contains no numerical limitation as to residue levels, a method is not needed. With 

this clarification, it is apparent why EPA proposed to use CR in all of the use columns as to this data 

requirement – namely, a residue analytical method is only required where a numeric value is 

proposed in the petition. 

The discussion above is likewise applicable to the requirement for “Multiresidue method testing,” 

which is also needed only in circumstances where there is a numerical residue level to enforce. 

Similar to the enforcement method, it is appropriate to use CR in all use columns as to this data 

requirement. 

Finally, the table as revised retains the requirement for “Residue analytical methods for data 

collection.” This type of analytical method is only required in circumstances where a magnitude of 

residue is sought. Accordingly, it is appropriate to use “CR” in all of the use columns as to this data 

requirement. 

To summarize, based on the discussion above, the data requirements in the “Direct Food Uses” 

column were changed as follows: 

o For “Residue analytical methods for data collection:” “R” becomes “CR”; 

o For “Residue analytical methods for tolerance/tolerance exemption enforcement:” “R” 

becomes “CR”; 

o For “Multiresidue method testing:” “R” becomes “CR”. 

Comment 110.33: A commenter asked why the storage stability study is R when the studies that it 

validates (magnitude of the residue studies) are CR. 

Response 110.33: EPA agrees with the commenter that clarification is needed. “R” is correct for 

storage stability studies. If a magnitude of the residue study is required, then the storage stability 
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study is also required. EPA has revised proposed testnote 12 (now renumbered to 7) to clarify that 

the storage stability study is required only when a magnitude of the residue study is required. 

Comment 110.34: A commenter asked why the processed food/feed study for the Agricultural 

Premises use pattern is NR instead of CR. 

Response 110.34: EPA agrees with this comment: the requirement for Processed Food or Feed 

study should be changed from NR to CR for the Agricultural Premises use pattern. The reason for 

this change is that Agricultural Premises are commonly associated with production of livestock and 

their products, especially milk and eggs. Antimicrobials are used during milking and egg-laying 

(agricultural premise use) but their use is particularly critical to sanitize equipment during processing 

of milk and eggs (processed food or feed). A number of the processed products of milk and eggs are 

generated via concentration, fractionation, and/or extraction which are processes that can affect 

pesticide residue levels. Therefore, there are a number of opportunities for antimicrobial residue 

levels in certain processed products to be higher than they were in the raw agricultural commodity. 

EPA must be aware of these concentration differences so that they can be applied to our human 

health risk assessments and/or tolerance-setting process. These circumstances are exactly what 

Processed Food or Feed studies are intended to ascertain. Proposed testnote 15 has been 

renumbered to 17 with very minor changes. 

Comment 110.35: A commenter thought that proposed residue chemistry testnote 18 for the 

Potable Water data requirement conflicts with R for the Agricultural Premises use pattern. 

Response 110.35: The Agency agrees with the commenter because the Potable Water data 

requirement is applicable to any route that an antimicrobial pesticide might have taken to 

contaminate drinking water be it Direct or Indirect Food Use, Aquatic Use, or Agricultural Premise 

Use. Therefore, the Potable Water requirement has been changed to CR for all four uses. Also, see 

response to comment 110.4. In summary, the potable water data requirement has been changed for 

all uses as follows: 

o for agricultural premise uses: “R” becomes “CR” 

o for indirect food uses: “NR” becomes “CR” 

o for direct food uses: “NR” becomes “CR” 

o for aquatic uses: “R” becomes “CR.” 

Testnote 18 (renumbered to 12) has been revised to include the conditions under which the Potable 

Water study is required. 

Comment 110.36: Two different commenters suggested two different options as alternative 

approaches to the antimicrobial residue chemistry data requirement table proposed by EPA. One of 

the commenters separated the requirements into two tables, referred to as Part 1 and 2 [ACC 

Comment in the docket at http://regulations.gov; document EPA-HQ-OPP-2008-0110-0088.10]. 

The other commenter used a single table [CSPA Comment in the docket at http://regulations.gov; 

document EPA-HQ-OPP-2008-0110-0086.2 ]. 
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Response 110.36: All three of the commenter-suggested tables had the same five “Supporting 

Information” studies as the table proposed by EPA, but with various mixtures of “R,” “CR,” and 

“NR.” In the final rule EPA has retained the Supporting Information section of the residue 

chemistry table as proposed. 

EPA has adopted the commenter’s suggested tiered format. After review, EPA believes the 

suggested tiered approach is more suitable to antimicrobials than that proposed by EPA. All three 

commenter tables suggested that Tier 1 consist of a “Screening-level dietary exposure assessment.” 

Although an applicant may opt to conduct a dietary exposure assessment, EPA does not consider 

this to be a data requirement. Applicants often conduct a dietary exposure assessment to understand 

the dietary risks before submitting an application to EPA. If submitted, EPA would review the 

assumptions used by the applicant in their assessment and compare to the assumptions that EPA 

would have used. Based on the Agency’s acceptance of the applicant’s screening-level assessment, 

and indications that dietary risk is likely to meet or exceed the Agency’s level(s) of concern, the 

applicant may decide to continue on to Tier 2 or 3. Therefore, EPA has not added a requirement to 

conduct a dietary exposure assessment. 

Both the Part 1 Table and the single table suggested that Tier 2 consist of a “Refined dietary 

exposure assessment.” As is the case for the commenter’s suggested Tier 1 “Screening-level dietary 

exposure assessment,” this is optional for the applicant; therefore, EPA has not added a requirement 

to conduct a refined dietary exposure assessment. 

Both the Part 1 Table and the single table suggested that Tier 3 consist of “Nature of residue on 

surface,” “Bioaccumulation,” “Magnitude of residue,” “Residue analytical method,” and “Storage 

stability.” These are each addressed individually below: 

 Nature of residue on surface. The Agency agrees that this study is applicable and a valuable 

addition to the data set necessary to support registration and risk assessment of antimicrobial 

uses on/in food-contact surfaces and impregnated materials (treated articles). EPA has 

added this study into the Antimicrobial residue chemistry data requirements table in the 40 

CFR part 158W Final Rule. 

 Bioaccumulation. EPA believes that the commenters intended that this study apply only to 

fish and that the commenters intended that the fish bioaccumulation study required for 

ecological effects (OCSPP Guideline 850.1730) should substitute for the nature of the 

residue on surface study for aquatic uses or indoor/outdoor raw agricultural commodity 

uses. EPA has found that the fish bioaccumulation study is often not useful for residue 

chemistry purposes because characterization of fish residues is only required if the 

bioconcentration (of total residues) factor is >1000. The fish bioaccumulation study has not 

been adopted by EPA for residue chemistry. Of much more use to residue chemistry are the 

fish metabolism and magnitude of the residue studies in fish that are portions of OPPTS 

Guideline 860.1400, which has been retained in the final rule. 

 Magnitude of residue (MOR). Commenters proposed this study by the very general title 

“Magnitude of residue.” EPA considers MOR to be any study designed to determine “how 

much” of the residues of concern will result in food, on surfaces, in water, etc., following use 

of an antimicrobial according to label directions. The commenters stated in a footnote to 

this study that, in the case of food-contact sanitizers and treated articles, MOR would consist 

of a migration study. Because food-contact sanitizer and treated article uses comprise at least 

80 percent of all antimicrobial food uses, EPA has retained the Migration study and the 

Food-handling study by name but moved them to a different tier. All the remaining 
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proposed types of MOR studies are much more rarely required due to such characteristics as 

the use pattern and/or physicochemical properties of the antimicrobial in question. For that 

reason, the following have been grouped as “Higher tiered” studies in the final rule: Nature 

of the residue in plants, Nature of the residue in livestock, Residue analytical methods for 

tolerance/tolerance exemption enforcement, Multiresidue method testing, Potable water, 

Fish, Irrigated crops, Meat/milk/poultry/eggs, Crop field trials, Processed food or feed, and 

Anticipated residues. 

 Residue analytical method. EPA agrees with the commenters that an analytical method for 

data collection is required whenever magnitude of the residue studies are required. The 

Agency has retained this study in the final residue chemistry table. 

 Storage stability. EPA agrees with the commenters that storage stability data are required 

whenever magnitude of the residue studies are required. The Agency has retained this study 

in the antimicrobial residue chemistry data requirements table. 

The Part 2 Table did not recommend requiring a Refined Dietary Exposure Assessment. Rather, its 

Tier 2 consists of studies entitled “Nature of the residue in commodity,” “Nature of the residue in 

livestock,” “Residue analytical methods for enforcement of tolerances,” “Multiresidue analytical 

method,” “Magnitude of the residue: in commodities, in water, and in meat/milk/poultry/eggs,” 

“Storage stability,” and “Anticipated residues.” EPA agrees that all of these studies should be 

required and we have retained all of them in our highest tier in the final residue chemistry table. 

Note that two of the commenter-suggested studies (“Nature of the residue in commodity” and 

“Magnitude of the residue in commodities”) apply only to raw agricultural commodities (RACs) 

treated via a fruit and vegetable rinse whereas the analogous EPA data requirements apply to both 

crop plants and metabolically-active RACs. The Agency does not believe the commenter versions of 

these two plant studies are broad enough to encompass all use scenarios. The data requirements in 

the final rule easily subsume the studies proposed by a commenter in the Part 2 Table. The 

commenter feels that EPA only has authority to require residue data for RACs of plants treated by a 

fruit or vegetable rinse whereas EPA interprets FIFRA and FFDCA as amended by FQPA as 

meaning data may be required for any use if necessary to support registration of any use under 

FIFRA (see EPA responses to comments 110.1 and 30.26). 

As evidenced by their recommendation to divide EPA’s single proposed data requirement table into 

two tables (Parts 1 and 2 Tables), the commenters believe the data requirements are distinctly 

different depending on the use pattern of interest. While this is sometimes the case, the Agency has 

found that there is much overlap between which studies are necessary to characterize the dietary 

exposure potentially resulting from a given use. That is why the testnotes provide the conditions 

under which each study is required, likely to be required, or not required. EPA has historically and 

currently developed a single data requirement table for each scientific discipline; doing so permits 

the interrelationships between use pattern, tiering, and data needs to be more evident. 

The commenters did not account for data needed to estimate dietary exposure associated with uses 

requiring no FFDCA sec. 408 tolerance or exemption (see Responses to Comments 110.1 and 30.26 

for detailed discussion). The commenters also did not account for data needed to estimate dietary 

exposure from food residues inadvertently resulting from, but not limited to, discharges of 

antimicrobial-treated water from indoor industries, leaching from preserved lumber, treatment of 

food crops when a public health claim is made on the label, etc. 
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EPA also notes that the commenter’s Part 2 Table for the anticipated residues data requirement did 

not list a guideline number, instead specifying “none.” EPA agrees that there is not a guideline for 

an anticipated residue study, and will revise the final residue chemistry data requirements table to 

read none, and include in the testnote the need for a protocol review. Instead of a guideline, there 

are two policy papers: “Data for Refining Anticipated Residue Estimates Used in Acute Dietary 

Probabilistic Risk Assessments” (available on the Agency’s website at 

http://www.epa.gov/pesicides/trac/science/residues.pdf), and a draft, entitled “Use of Anticipated 

Residue of Pesticides in Foods for Use in Chronic Dietary Exposure Assessment.” EPA will work to 

make this draft document available to the public. 

Comment 110.37: A commenter submitted a document entitled “Background on the FDA 

Regulation of Food-Contact Sanitizing Solutions Under FFDCA and Estimation of Dietary 

Exposure” (dated 11/25/08). This document contained attachments consisting of one FDA e-mail 

dated 10/2/08 and 14 FDA memoranda. The FDA e-mail was a response from Mark Hepp to a 

9/30/08 e-mail inquiry from Elizabeth Brown of Steptoe & Johnson, LLP. The e-mail addresses 

whether FDA dietary exposure estimates “...for the use of a sanitizing solution in public eating 

places also anticipated the use of the same solution on food processing equipment and utensils.” 

The final answer was that the model FDA used to estimate exposure reflecting use in public eating 

places resulted in exposure estimates about 100 times those estimated using the model for use of a 

sanitizer on all food processing equipment and utensils. The latter model, in turn, resulted in 

exposures that greatly exceeded those reflecting use in food processing equipment excluding dairy 

equipment. Thus, addition of exposures from use of a sanitizer on all food processing equipment 

and utensils had no significant effect on the exposure estimate from use in public eating places. The 

FDA memoranda were evaluations of Food Additive Petitions on specific antimicrobial sanitizers 

conducted between 1982 and 1995. The commenter described the historical approaches and 

methodologies by which FDA conducted dietary exposure assessments for sanitizer products using 

the FDA memoranda as supporting documentation. The purpose of this commenter document was 

to provide evidence that EPA’s use of an industry-developed dietary exposure model for commercial 

establishments results in overly conservative dietary risk estimates. The claim is that the Agency has 

made assumption changes to the model in order to use it for commercial and institutional settings 

whereas the model was developed for use only in residential settings. 

Response 110.37. The commenter did not address the subject proposed regulation concerning data 

requirements for antimicrobials. Consequently, this comment is not applicable to finalization of this 

rule. However, the Agency acknowledges the importance of the commenter’s concerns and is 

currently working to resolve these concerns on a separate timeline. 

The testnotes to the residue chemistry table were significantly renumbered from the proposed to 

final rule. The following table crosswalks the changes: 

As proposed..... Was Renumbered to.... 

1 1 

2 2 

3 8 

4 8 

5 8 
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6 9 

7 9 

8 9 

9 10 

10 6 

11 11 

12 7 

13 16 

14 Removed 

15 17 

16 15 

17 15 

18 12 

19 13 

20 14 

21 3 

22 18 

23 5 

 There is a new 4 

Based on the comments received, the following changes are made to the Testnotes to the 

Residue Chemistry Table. 

Since, as indicated in the table above, the testnotes were rearranged and therefore renumbered from 

the proposed rule to the final rule, the proposed testnote is usually placed out of sequence and is 

numbered in parenthesis according to the proposal. 

T110.1: Testnote 1 to the Residue Chemistry Table: 

Proposed (1) 

A petition proposing a numerical tolerance or a tolerance exemption is required for any food or feed 

use subject to section 408 of the FFDCA if the use is not covered by an existing tolerance or 

tolerance exemption. 

Final: 

A petition proposing a numerical tolerance or a tolerance exemption is required for any food or feed 

use subject to section 408 of FFDCA if the use is not covered by an existing tolerance or tolerance 

exemption. If the use is subject to FFDCA section 409, the applicant must identify to EPA an 

applicable section 409 food additive regulation or clearance, or submit a copy of a petition to FDA 

requesting a section 409 food additive regulation or clearance for the food or feed use. 

T110.2: Testnote 2 to the Residue Chemistry Table: 
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Proposed (2): 

An analytical reference standard is required for any food or feed use requiring a tolerance. Material 

safety data sheets must accompany analytical standards as specified by OSHA in 29 CFR 1910.1200. 

Final: 

An analytical reference standard is required for any food or feed use requiring a numeric tolerance or 

exemption. Material safety data sheets as specified by Occupational Safety and Health 

Administration in 29 CFR 1910.1200 must accompany analytical standards. 

T110.3: Testnote 3 to the Residue Chemistry Table: 

Proposed (21): 

Data are required whenever a pesticide is to be used in a food-handling or feed handling 

establishment unless theoretical calculations, radiolabeled laboratory data, the nature of the residue 

study, or other data show that residues will not occur in food or feed. Use in a food-handling 

establishment also includes fresh fruits and vegetables that undergo a rinse with either a sanitizing 

solution, or with a disinfectant followed by a potable water rinse. 

Final: 

Data are required if a pesticide may be used in a food-handling establishment unless data including, 

but not limited to, theoretical (high-end) estimates, radiolabeled laboratory data, or the nature of the 

residue on surfaces study, show that residues will not occur in food or feed. 

T110.4: Testnote 4 to the Residue Chemistry Table: 

New testnote for new study (110.36) 

Final: 

If an antimicrobial pesticide may be applied to a food-contact surface or impregnated into a foodcontact material and if theoretical (high-end) estimates of exposure exceed EPA’s risk level of 

concern, then the nature of the residue on surfaces study is required. Protocols must be approved by 

the Agency prior to the initiation of the study. 

T110.5: Testnote 5 to the Residue Chemistry Table: 

Proposed (23): 

Migration of residue data are required for antimicrobial pesticides applied to hard food surfaces or 

incorporated into substrates (wood, plastic, paper, cloth, rubber or similar products) intended for 

contact with food or feed when theoretical (modeled) estimates of the amount of antimicrobial 

residue transferred to the food or feed may result in a risk of concern. Protocols must be approved 

by the Agency prior to the initiation of the study. Details for developing protocols are available from 

the Agency. 
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Final: 

Based on the results of the nature of the residue on surfaces study, if residues of concern are 

identified, then the migration study will be required. Protocols must be approved by the Agency 

prior to the initiation of the study. 

T110.6: Testnote 6 to the Residue Chemistry Table: 

Proposed (10): 

A residue analytical method suitable for collecting data to establish tolerances must quantitate all 

residues of concern, as determined by the Agency. 

Final: 

If a magnitude of the residue study is required as specified in §158.2290(d), then a residue analytical 

method suitable for collecting data is also required. The method must be capable of determining all 

residues of concern to permit calculation of dietary risk or to establish a tolerance or tolerance 

exemption. 

T110.7: Testnote 7 to the Residue Chemistry Table: 

Proposed (12) 

Data are required for any food or feed use requiring magnitude of the residue studies unless 

analytical samples are stored frozen for 30 days or less, and the active ingredient is not known to be 

volatile or labile. 

Final: 

If a magnitude of the residue study, as specified in §158.2290(d), is required, then storage stability 

data are also required, unless analytical samples are stored for 30 days or less. During hazard 

characterization, if a residue of concern is known to be volatile or labile, then storage stability data 

are required regardless of sample storage time. 

T110.8: Testnote 8 to the Residue Chemistry Table: 

Proposed: 

(3)For agricultural premises, data are required for postharvest storage of plant commodities. 

(4)Data are required for direct food contact uses, excluding egg washes, to determine the 

transformation products in representative foods. 

(5)Data are required to support applications to water if any residues could occur in irrigated crops, 

or to crops treated directly in the field. 

Final: 

If crop plants or metabolically active raw agricultural commodities of food crops may be directly or 

indirectly exposed to an antimicrobial, plant metabolism studies are required to determine the 

transformation products that may enter the human diet. Such exposure could include, but is not 

limited to: 

 i. treatment of storage or shipping containers, 
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 ii. postharvest fruit and vegetable treatment prior to shipping or storage, 

 iii. use of antimicrobial-treated water for irrigation, and 

 iv. any direct food contact use. 

T110.9: Testnote 9 to the Residue Chemistry Table: 

Proposed: 

(6)Data are required when an antimicrobial pesticide is applied directly to livestock, to livestock 

premises, to livestock drinking water, to livestock feed, or to crops used for livestock feed. 

(7)Data are required for aquatic uses if there is the potential that the treated water could be used 

eventually for drinking purposes by livestock. 

(8)If results from the plant metabolism study show differing metabolites in plants from those found 

in animals, then additional livestock metabolism study(ies) involving dosing with the plant 

metabolite(s) may be required. 

Final: 

If livestock may be exposed to an antimicrobial, then hen and ruminant metabolism studies are 

required to determine the identities of residues of concern that may enter the human diet from 

consumption of livestock commodities. Livestock may be exposed via the oral, dermal, or inhalation 

route following treatment or contamination of sites including, but not limited to, livestock premises, 

feed, and drinking water. Shell eggs and other metabolically active livestock products may also be 

treated. If livestock may be exposed to one or more residues of concern differing from those found 

in animals, then one or more additional livestock metabolism studies involving dosing with these 

residues may be required. 

T110.10: Testnote 10 to the Residue Chemistry Table: 

Proposed (9): 

A residue analytical method suitable for enforcement purposes is required whenever a numeric 

tolerance is proposed. Enforcement methods must be supported by results of an independent 

laboratory validation. 

Final: 

If there is a numerical level to enforce, then a residue analytical method suitable for enforcement 

purposes is required. The method must be supported by an independent laboratory validation. 

T110.11: Testnote 11 to the Residue Chemistry Table: 

Proposed (11): 

Data are required to determine whether the Food and Drug Administration/United States 

Department of Agriculture multiresidue methodology would detect and identify the antimicrobial 

active ingredient and its metabolites. 

Final: 
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Master Responses: 

Residue Chemistry Section (110) Page 163 

If there is a numerical level to enforce, then testing is required to determine whether the 

FDA/USDA multiresidue methodology would detect and identify the antimicrobial and its residues 

of concern, as part of programs to monitor pesticides in the U.S. food supply. 

T110.12: Testnote 12 to the Residue Chemistry Table: 

Proposed (18): 

Data are required for antimicrobial pesticides applied directly to water, if there is the potential that 

the treated water could be used for drinking purposes by man or animals. 

Final: 

Data are required if an antimicrobial may be applied directly to water or if there is the potential that 

the antimicrobial-treated water could be used directly for drinking water purposes by humans or 

animals or that contaminated water could run-off, leach, or be discharged from treated sites or 

materials and make its way into potable water. 

T110.13: Testnote 13 to the Residue Chemistry Table: 

Proposed (19): 

For aquatic uses, data for fish are required for antimicrobial pesticides applied directly to water 

inhabited, or which will be inhabited, by fish that may be caught or harvested for human 

consumption. 

Final: 

Data are required if an antimicrobial may be applied directly to water inhabited by fish or that will be 

inhabited by fish or if contaminated water could run-off, leach, or be discharged from treated sites 

or materials and make its way into bodies of water containing fish that may be used for human 

consumption. 

T110.14: Testnote 14 to the Residue Chemistry Table: 

Proposed (20): 

Data are required for antimicrobial pesticides applied directly to water that could be used for 

irrigation or to irrigation facilities such as ditches. 

Final: 

Data are required if an antimicrobial may be applied directly to water used for irrigation of food 

crops or such that contaminated water could run-off, leach, or be discharged from treated sites or 

materials to make its way into water used for irrigation of food crops. 

T110.15: Testnote 15 to the Residue Chemistry Table: 

Proposed: 

(16)Data are required when the pesticide use is a direct application to livestock. 
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Master Responses: 

Residue Chemistry Section (110) Page 164 

(17)Data are required if livestock premises are treated or if pesticide residues are present in or on 

livestock feed items or intentionally added to drinking water. These studies, however, may not be 

required in cases where the livestock metabolism studies indicate negligible transfer of pesticide 

residues of concern to tissues, milk, and eggs at the maximum expected exposure level for the 

animals. 

Final: 

Livestock or their products may be exposed via the oral, dermal, or inhalation route following 

treatment or contamination of sites including, but not limited to, livestock premises, feed, and 

drinking water. Shell eggs and other metabolically active livestock products may also be treated. If 

the antimicrobial may be applied directly to livestock, livestock commodities, or livestock premises, 

or a livestock metabolism study indicates that residues of the antimicrobial may result in livestock 

commodities, studies are required to determine the magnitude of the residues of concern in meat, 

meat by-products, milk, poultry, and eggs that may be consumed by humans. These studies, 

however, may not be required in cases where the livestock metabolism studies indicate that transfer 

of pesticide residues of concern to tissues, milk, and eggs is not expected to occur at the maximum 

expected exposure level for the animals. 

T110.16: Testnote 16 to the Residue Chemistry Table: 

Proposed (13): 

Residue data are required if antimicrobial chemicals are to be applied to mushroom houses, 

empty or occupied bee hives, wood used to construct bee hives, or any use which could result in 

residues in food or feed. 

Final: 

If food crops or metabolically active raw agricultural commodities of food crops may be exposed to 

an antimicrobial, then residue studies are required to determine the magnitude of the residues of 

concern that may enter the human diet. Such exposures include, but are not limited to, postharvest 

fruit and vegetable treatments and application of antimicrobial chemicals to field crops, mushroom 

houses, empty or occupied beehives, or wood used to construct beehives. 

T110.17: Testnote 17 to the Residue Chemistry Table: 

Proposed (15): 

Data on the nature and level of residues in processed food or feed are required if residues could 

potentially concentrate on processing, thus requiring the establishment of a separate tolerance higher 

than that of the raw agricultural commodity. 

Final: 

Data on the nature and magnitude of residues in processed food or feed are required if antimicrobial 

residues could potentially concentrate on processing. If so, the establishment of a separate tolerance 

higher than that in the raw agricultural commodity may be required. 

T110.18: Testnote 18 to the Residue Chemistry Table: 
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Residue Chemistry Section (110) Page 165 

Proposed (22): 

Data are required when estimates of risk using residues at the tolerance level may result in a risk of 

concern. These data may include washing, cooking, processing or degradation studies as well as 

market basket surveys for a more precise residue determination. 

Final: 

Data are required when dietary exposure values at the tolerance level or screening-level (high-end) 

result in estimates of dietary or aggregate risk that meet or exceed the Agency’s level of concern. 

These data may include, but are not limited to, washing, cooking, processing, or degradation studies 

as well as market basket surveys for a more realistic residue determination. Protocols must be 

approved by the Agency prior to the initiation of the study. 

Proposed testnote 14: 

If the antimicrobial chemical may be applied to a field crop, then the residue chemistry data 

requirements of §158.1410 apply, unless otherwise determined by the Agency on a case-by-case 

basis. 

Removed from testnotes and placed in text before table. 

§158.2290(e) If the antimicrobial chemical is applied to a field crop, then the residue chemistry data 

requirements of §158.1410 apply, unless otherwise determined by the Agency on a case-by-case 

basis. 
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Master Responses: 

Environmental Risk Assessment Section (120) Page 166 

Environmental Risk Assessment (120) 

Master Responses for the Environmental Risk Assessment Section 

Please note that EPA responses are presented in numerical order. However, in the course of response development, 

some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are missing. 

Comment 120.1: Some commenters contended that the proposed environmental fate data 

requirements would not provide useful environmental exposure information for the wood 

preservative use pattern. Their main concerns are as follows: 

(1) the leach rate test is required for all wood preservative products without regard to whether or not 

the end-use would result in any environmental exposure, and 

(2) the results from the leach rate test (American Wood Preservers’ Association Standard Method 

E11-97) would seriously overestimate the environmental exposure, particularly since aquatic 

exposure with every use is assumed. 

Response 120.1: EPA disagrees with the commenter’s contention that the proposed leach rate test 

would not provide useful environmental exposure information for the wood preservative use 

pattern. As discussed in response 50.4, environmental exposure to wood preservatives can occur at 

multiple points in the life-cycle of a product treated with the wood preservative, independent of its 

end-use. Hence, the leach rate test is required for all wood preservatives because leaching from 

treated materials is the primary source of environmental exposure to wood preservatives. The 

Agency uses the results of the leach rate test to help determine the amount of a parent compound 

and its transformation/degradates or leachates that are likely to be released into the environment. 

Even under circumstances in which the leach rate test overestimates exposure, the information 

provides an upper bound estimate of potential exposure and risk, which is crucial for a screeninglevel risk assessment. An upper bound for an estimate represents the greatest expectation of 

potential exposure. If a risk assessment based on upper bound estimates does not exceed the 

Agency’s level of concern, then no further analysis is necessary. 

Comment 120.2: A commenter maintained that EPA has not addressed the June 1997 Scientific 

Advisory Panel (SAP) recommendation to consider when “testing from one [EPA] Office may be 

substituted for the requirements of the Office of Pesticide Programs.” The commenter also stated 

that EPA has not provided “triggers” for requiring down the drain testing as recommended by the 

1997 SAP. 

Response 120.2: At the June 1997 session of the FIFRA SAP (“A Set of Scientific Issues Being 

Considered by the Agency to Determine Antimicrobial Issues”), EPA sought the SAP’s input on 

OPP’s proposed approach for requiring minimal ecological effects and environmental fate data for 

eight “use scenarios” for which OPP contended that ecological risk assessments are not necessary 

and a tiered set of ecological effects and environmental fate data for four “use scenarios” for which 

EPA would perform an ecological risk assessment. The eight “use scenarios” for which OPP 

contended an assessment would not be necessary were agricultural premises and equipment; food 

handling/storage establishments premises and equipment; commercial, institutional, and industrial 
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Master Responses: 

Environmental Risk Assessment Section (120) Page 167 

premises and equipment; residential and public access premises; medical premises and equipment; 

human drinking water systems; materials preservatives; and swimming pools. The four “use 

scenarios” for which EPA would perform an ecological risk assessment were industrial processes 

and water systems; antifouling coatings; wood preservatives; and aquatic areas. 

The SAP responded that requiring a reduced data set for these specified eight use scenarios appeared 

justified only if data available from other programs both within and outside the Agency are adequate 

to assess risk. The SAP expressed concern over the lack of chemical fate data. In addition, the Panel 

expressed concern about the lack of inclusion of any microbial testing and responded that additional 

non-target microbial data should be provided for all antimicrobial pesticides. The SAP contended 

that these tests are needed not only to ensure the safety of environmental discharge, but also for 

protection of POTWs (publicly-owned treatment works) and other treatment systems which often 

rely on microbial treatment processes. 

The SAP also agreed with OPP that full ecological risk assessments are necessary for the four major 

“use categories” (i.e., industrial processes and water systems, antifoulant coatings, wood 

preservatives, and aquatic outdoor uses). The SAP also noted that the Agency’s presentation of its 

proposed approach indicated that there is concern about possible redundancy of testing 

requirements across Agency Program Offices. The SAP commented that if redundancy of 

requirements is a concern then this should be addressed through harmonization among other 

Agency Program Offices of fate and effects testing where possible, noting that “experience should 

indicate those cases where testing from one Agency Office may be substituted for the requirements 

of the Office of Pesticide Programs.” 

A summary of EPA’s questions and SAP’s responses in this session on antimicrobial issues can be 

found at http://www.epa.gov/scipoly/sap/meetings/1997/june/antimicr.htm. 

The Agency has undertaken efforts to harmonize its ecological effects and environmental fate 

methodologies. Response 20.3 discusses the EPA’s recent efforts since the June 1997 SAP to not 

only harmonize methodologies among Agency Offices, but also to include both the scientific and 

regulated community in its efforts to develop a common framework. The results of those long-term 

efforts that might affect the data requirements needed for an ecological risk assessment of 

antimicrobial pesticides would be included in future rule-making. 

EPA disagrees with the commenters statement that “EPA has not provided triggers” for requiring 

down-the-drain testing as recommended by the 1997 SAP.” In the preamble to the proposed rule 

[59407], EPA discusses its proposed tiered approach for determining the data needed to assess 

exposure and risk from antimicrobial pesticides released to the environment via down-the-drain use 

patterns. The lower-tiered studies included three ecotoxicity studies and up to seven fate studies. 

Higher-tiered studies are triggered on a weight-of-evidence evaluation of the results of lower-tiered 

studies. In response to public comments on the proposed rule, EPA has revised data requirements 

for assessing down-the-drain uses of antimicrobial pesticides. To summarize, OPP’s Antimicrobial 

Division will perform a down-the-drain analysis for every product with an applicable use or 

exposure scenario that has the potential for waters containing antimicrobials to reach a wastewater 

treatment plant. EPA has concluded that an analysis of down-the-drain releases is needed for all use 

patterns except aquatic areas. A complete discussion of these changes and the associated rationale, as 
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Master Responses: 

Environmental Risk Assessment Section (120) Page 168 

well as changes in the proposed environmental fate data requirements for assessing down-the-drain 

releases, can be found in response to comment 134.1. 

Comment 120.4: A commenter argued that EPA has included an assumption of product misuse in 

determining the data requirements for an environmental risk assessment on p. 59405 of the 

proposed rule. 

Response 120.4: In formulating this response, EPA has assumed that the commenter is referring to 

EPA’s statement [59405] that “treated wood intended for a use with little potential aquatic exposure 

could be inadvertently diverted to other uses, such as marine docks or pilings, which would have 

considerable aquatic exposure.” 

EPA believes that wood that has been treated for land-only application could end-up in contact with 

water and vice versa, or lead to other environmental exposures (e.g., the inadvertent mixing of 

treated wood with untreated wood at construction sites). In addition, consumers who work with 

treated wood are generally encouraged to conduct post-treatment actions, including sawing, sanding 

and machining of treated wood, outdoors. Some consumers might also inadvertently use sawdust or 

remnants from treated wood as compost or mulch. Because of these potential environmental 

exposures, EPA believes the same data requirements for conducting an environmental risk 

assessment are generally appropriate for all wood preservatives. 

EPA disagrees that recognizing the potential for inadvertent diversion amounts to “an assumption 

of product misuse." EPA does not assume that the wood treater misuses a pesticide-containing, 

wood-treatment product during the actual wood-treatment process. Wood treaters and treated wood 

distributors/retailers who may be intentionally diverting legally-treated wood for use in unregistered 

use sites may be subject to enforcement action by the Agency. 

Comment 120.5: A commenter noted that Canada’s PMRA and USEPA conduct risk assessment for 

wood preservatives differently. The commenter maintained EPA’s risk assessment is based on the 

treated wood when used at the final use site, while the PMRA’s risk assessment is based at the site 

where the wood is treated. The commenter also maintained PMRA also does not distinguish 

between terrestrial-only or aquatic-only use for anti-sapstains and heavy-duty wood preservatives. 

 

Response 120.5: The Agency acknowledges differences between its risk assessment of wood 

preservatives and that of Canada’s PMRA. Based on comments received (see response to comment 

50.4), EPA has re-evaluated its practice of determining the data required for a wood preservative 

product. As part of the re-evaluation, EPA considered the human and ecological risks based on 

exposure pathways identified in OECD’s Emissions Scenario Document (ESD) for Wood 

Preservatives. This ESD identifies potential human and ecological exposures for both treatment of 

wood at processing facilities and in-service uses on land and in water. The Agency determined that 

all treated wood should be considered as having the potential to come into contact with surface 

water. This determination reflects EPA’s concern about the potential for the indirect release to 

surface waters of wood preservatives. As a result, EPA is changing its practice for requiring 

environmental and ecological effects studies for wood preservatives. All wood preservative risk 

assessments will now be performed considering that the treated wood could end-up either on the 

land or in the aquatic environment. 
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Master Responses: 

Environmental Risk Assessment Section (120) Page 169 

Comment 120.6: A commenter argued that “before a wholesale list of new data requirements are 

approved for antimicrobial pesiticides” EPA should consider for antimicrobials the PBT approach 

proposed by OPP’s Environmental Fate and Effects Division at the October 2008 SAP. The PBT 

approach was developed for pesticides with combined persistence (P), bioaccumulative (B), and 

toxic characteristics (T), collectively referred to as PBT. 

Response 120.6: EPA agrees that the PBT approach could be considered for antimicrobial 

pesticides. A description of the PBT approach can be found at the SAP part of EPA’s website, 

(http://www.epa.gov/scipoly/sap/meetings/2008/102808_mtg.htm ). The proposed PBT 

approach is described in “White Paper on Methods for Assessing Ecological Risks of Pesticides with 

Persistent, Bioaccumulative and Toxic Characteristics” (October 28-31, 2008). This approach is 

based on the Stockholm Persistent Organic Pollutant treaty (http://chm.pops.int/default.aspx ). 

The approach proposed raised such issues as: 

 persistence (i.e., assessing total residues of concern, assessing solubility issues, interpreting 

degradation half-life data, and quantifying long-term accumulation); 

 sediment dynamics (processes such as settling, re-suspension, and burial of sediment, 

particles, which can affect the distribution of pesticides in the water column-, pore water-, 

and suspended- and benthic-sediment compartments); 

 bioaccumulation (including chemical exposure to aquatic organisms via the diet (i.e., trophic 

transfer) and terrestrial bioaccumulation (i.e., pesticide dietary uptake from direct deposition 

on food items); 

 long-range transport (i.e., far-field pesticide loading); and toxicity, including combined 

toxicity of parent and degradate mixtures and assessing aquatic toxicity from multiple routes 

of exposure. 

EPA has implemented one or more aspects of the PBT approach in its environmental fate and 

ecological risk assessments for conventional pesticides, including endosulfan, pyridalyl, 

pentachloronitrobenzene (PCNB), and metaflumizone. The PBT-related aspects of the 2010 

environmental fate and ecological risk assessment for endosulfan, which can be accessed at 

www.regulations.gov (Document ID: EPA-HQ-OPP-2002-0262-0162), include: 1) use of field, 

laboratory and model-derived estimates of bioaccumulation in aquatic food webs and subsequent 

risks to fish-eating birds and mammals; 2) modeling and monitoring data pertaining to long range 

transport (LRT); 3) proper interpretation of aquatic metabolism rates and consideration of the 

degradates; 4) sediment toxicity and risk to benthic-dwelling invertebrates; 5) tissue residue-based 

effects assessment; and 6) evaluation of the impact of different assumptions regarding sediment 

'burial' of the pesticide. 

Implementation of the PBT approach in assessing environmental fate and potential ecological risk 

of a pesticide does not focus on defining a specific set of data that would always be needed if a 

chemical was classified as a PBT, but instead focuses on identifying different risk assessment 

approaches for addressing the unique characteristics of PBT compounds and some types of data 

that would aid in reducing uncertainty in the risk assessments. In many cases, models are used to 

address certain aspects of pesticides with PBT profiles, but it is usually beneficial to supplement the 

model estimates with the available data. 
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Master Responses: 

Environmental Risk Assessment Section (120) Page 170 

In summary, the Agency has found that chemicals with PBT profiles that conform to specific 

criteria that indicate persistence, bioaccumulation, and toxicity present a number of risk assessment 

challenges for which many standard test and risk assessment methods are not well suited (for 

further discussion, see Tissue-Based Criteria for “Bioaccumulative” Chemicals. Science Advisory 

Board Consultation Document on USEPA’s Proposed Revisions to Aquatic Life Guidelines, Office 

of Water, USEPA 2005). A summary of numeric ranges of these PBT criteria are presented in Table 

2.1 of “White Paper on Methods for Assessing Ecological Risks of Pesticides with Persistent, 

Bioaccumulative and Toxic Characteristics” (October 28-31, 2008). The ranges of numeric criteria 

presented in Table 2.1 reflect different institutional policies, regulations, and treaties regarding PBT 

classification. If an antimicrobial pesticide meets these criteria for persistence, bioaccumulation, and 

toxicity that are summarized in Table 2.1 of “White Paper on Methods for Assessing Ecological 

Risks of Pesticides with Persistent, Bioaccumulative and Toxic Characteristics,” then EPA could 

consider applying the PBT approach. 
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Master Responses: 

Letter from Environmental Working 

Group Section (125) Page 171 

Letter from Environmental Working Group (125) 

Master Responses for the Letter from Environmental Working Group Section 

The following summary comments and EPA responses refer exclusively to comments received from the Environmental 

Working Group. Their verbatim complete comment letter follows in Section 3 of this document. 

Comment 125.1: A commenter stated that EPA should propose additional data requirements in 

order to strengthen the proposed data requirements for antimicrobial pesticides so as to address 

outstanding gaps in key areas such as: 

 Protecting human health from cumulative exposure to antimicrobial pesticides. 

 Requiring monitoring of pesticide contamination in the environment and in people, 

including in cord blood and statistically representative samples from other vulnerable 

populations. 

 Ensuring that aquatic and terrestrial ecosystems are protected from chronic pesticide 

toxicity. 

Response 125.1: EPA is continually striving to improve the soundness of its regulatory process. 

Based on its review and evaluation of public comments, EPA has revised all of the data requirement 

tables in the proposed 158W rule. EPA routinely evaluates its risk assessment principles and 

practices, and updates its methodologies to include the state-of-the-art exposure and risk assessment 

data and tools for estimating potential risks to humans and ecological organisms from exposure to 

chemical substances. The Agency has developed guidance for performing assessments of cumulative 

risks to humans from exposure to chemical substances 

(http://www.epa.gov/scipoly/sap/meetings/2002/020502_mtg.htm ). 

As discussed in response to comment 125.5, EPA does not require biomonitoring data, as described 

by the commenter. 

The Agency is currently developing additional methods and tools for assessing chronic ecosystem 

toxicity so that such evaluations can be routinely performed in the future. This rule, once effective, 

will assure that the data needed for a chronic non-target organism assessment is submitted to EPA, 

when needed. 

As discussed in the preamble to the proposed rule (73 FR 59383), “this rule, once final, is intended 

to further enhance the Agency’s ability to make regulatory decisions about the human health, and 

environmental fate and effects of antimicrobial pesticide products.” As a result of this rule the 

Agency will be able to consider additional data beyond what has been traditionally-required, i.e., the 

data needed for a down-the-drain assessment. In turn, this will enhance the Agency’s ability to 

conduct an assessment of environmental and human health risks that result from uses of 

antimicrobial pesticides. 

Comment 125.3: A commenter contended that it is completely irrelevant whether exposure to an 

antimicrobial is due to its presence in a product that is regulated by EPA, FDA, or any other 

government agency – what matters is whether or not the overall exposures are safe over a life-time. 

The commenter asserted that environmental and human health risks of antimicrobial pesticides 
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Master Responses: 

Letter from Environmental Working 

Group Section (125) Page 172 

should be addressed with a comprehensive health and safety assessment that would not hide behind 

the artificial separation of pesticide regulation between FDA and EPA. The commenter contended 

that the final EPA rule needs to account for the overall presence of antimicrobial products in 

commerce. 

Response 125.3: EPA understands the commenters’ concerns. When establishing a tolerance for 

a pesticide under the Federal Food Drug and Cosmetic Act (FFDCA), as amended by the Food 

Quality Protection Act (FQPA), EPA is required to consider the combined exposures of 

pesticidal sources of an antimicrobial chemical, as well as other non-occupational sources of 

exposure, in a human health risk assessment. This means that human health risk assessments are 

required to include exposures to a pesticide from food, water, and residential uses of the 

pesticide, and exposures to the substance resulting from use of products not regulated as 

pesticides. For antimicrobials, while we do not regulate use of an antimicrobial in human drugs 

or cosmetics (that is under FDA purview), we do account for the contribution of such uses to 

overall human risk. 

FIFRA, however, does not contain a requirement for EPA to perform aggregate ecological risk 

assessments that would consider the combined impacts of both pesticidal and non-pesticidal uses 

of a chemical. Moreover, EPA has neither the data nor the methodology to conduct such an 

assessment. The Agency hopes in the future to be able to undertake such assessments, and, 

therefore, EPA is working to create the needed methodology. 

Comment 125.4: A commenter stated that the increasing and unnecessary use of antimicrobials in a 

wide range of consumer products raises concerns, because of the prospect of reduced medical 

usefulness due to antimicrobial resistance. 

Response 125.4: EPA agrees that antimicrobial resistance is an important issue. See response to 

comment 70.15. 

Comment 125.5: A commenter asserted that the proposed rule includes “minimal and woefully 

insufficient data requirements for monitoring pesticide contamination of people and the 

environment.” The commenter also stated that “manufacturers should be responsible for 

conducting biomonitoring studies on an ongoing basis” and that collection of such information 

“should be a mandatory condition for a pesticide to remain in commerce.” 

Response 125.5: In the preamble to its proposed rule, EPA discussed biological monitoring or 

biomonitoring studies for both applicator and post-application uses [59398]. Generally, these studies 

are conducted on a small population to measure effects from deliberate pesticide exposures and 

require compliance with the Agency’s regulations governing research with human subjects. 

Biomonitoring studies are conditionally required and can be submitted by the applicant in addition 

to, or in lieu of, dermal and inhalation passive dosimetry exposure data. 

However, the Agency believes that the commenter is using the term biomonitoring in a different 

way, to mean large-scale surveys of blood-levels in the general population and levels of the 

antimicrobial in the environment. The commenter states correctly that EPA does not routinely 
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Master Responses: 

Letter from Environmental Working 

Group Section (125) Page 173 

require surveys of blood-levels in the general population. EPA does, however, sometimes require 

environmental monitoring studies, such as the monitoring of representative U.S. waters. The Agency 

also receives incident reports and, if new or updated monitoring data becomes available, the Agency 

would consider this data. EPA invites the submission of monitoring data that may be available as a 

part of its public process. Additionally, the Centers for Disease Control and Prevention (CDC) does 

have biomonitoring datasets from the National Health Assessment and Nutrition Examination 

Survey (NHANES) that are publicly available. 

EPA disagrees that the human health applicator and post-application exposure data requirements as 

well as the environmental fate data requirements being codified are “woefully insufficient.” The data 

requirements being codified should provide EPA with additional important data to use in risk 

assessments and making regulatory determinations. 

Comment 125.6: A commenter noted that, in the proposed rule, monitoring of representative U.S. 

waters and monitoring of pesticide body burden in people in residential and occupational settings 

are both included as a “conditional requirement” meaning that there is less than 50 percent chance 

for biomonitoring to be required during a pesticide registration process. The commenter asserted 

that EPA should require this data more often. 

Response 125.6: As discussed in response to comment 140.24, EPA expects that the monitoring of 

representative U.S. waters will be rarely required. As discussed in response to comment 125.5, EPA 

does not require biomonitoring data, as it is described by the commenter. 

Comment 125.7: A commenter asserted that EPA should develop a data-based approach for 

comprehensive assessment and mitigation of chronic ecotoxicity risks. The commenter futher 

asserted that these studies should be driven by the real-life findings of pesticide levels in the 

environment and their effects on ecosystems. The commenter maintained that conducting chronic 

ecotoxicity tests on laboratory organisms would not be sufficient to answer this question; instead, 

ecosystem health monitoring should be used as a key parameter for addressing ecological risks of 

antimicrobial pesticides. 

Response 125.7: EPA believes that ecotoxicity studies performed in the laboratory provide valuable 

information that is needed for identifying dose response and conducting an environmental risk 

assessment. EPA agrees that it can be a challenge to extrapolate laboratory findings to the “real 

world;” however, laboratory studies offer a standardization needed to compare across studies. . This 

is why the use of laboratory data on a smaller scale in a more controlled environment is used as the 

basis for EPA’s risk assessments, and in the event that environmental monitoring data is available, 

then it is considered. 

Comment 125.8: A commenter strongly urges EPA to strengthen the proposed data requirements 

for antimicrobial pesticides so as to address outstanding data gaps in key areas such as cumulative 

human and environmental exposures, potential risks to human health, and the chronic ecosystem 

toxicity. The commenter asserted that decisions on the use of antimicrobial pesticides should be 

based on extensive research and data collection that would provide necessary information for the 

risk assessment and mitigation. 
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Master Responses: 

Letter from Environmental Working 

Group Section (125) Page 174 

Response 125.8: The intent of the proposed rule is to ensure that EPA has sufficient information to 

make regulatory decisions for antimicrobial pesticides. 

For all scientific disciplines, a tiered approach is used by EPA that is both chemical- and use patternspecific. When conducting a risk assessment, whether for human health or for environmental health, 

the entire data set for a given chemical is systematically evaluated, a hazard characterization is 

conducted, exposure estimates are generated, the findings are internally peer-reviewed, and then a 

decision is made whether to require additional (special) studies not specifically required under part 

158W. All special studies, including EPA’s rationale describing the need for the study, must then be 

approved by the Office of Management and Budget, under the terms of clearance for the 

Information Collection Request (ICR) approved under the Paperwork Reduction Act, OMB Control 

No. 2070-O174 (EPA ICR No. 2288.01), before a Data Call-In Notice is issued. 
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Master Responses: 

Down-the-Drain Section (130) Page 175 

Down-the-Drain (130) 

Master Responses for the Down-the-Drain Section 

Please note that EPA responses are presented in numerical order. However, in the course of response development, 

some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are missing. 

Comment 130.1: A commenter contended that Down-the-Drain (DtD) models may not be suitable 

or practical for some antimicrobials, including oxidizers, reactive substances, certain inorganics, and 

volatile substances, noting, for example, that hypochlorite may react during use, in the sewer, or in 

the wastewater treatment plant (WWTP). Thus, according to the commenter, a simple removal 

factor is likely insufficient to fully account for hypochlorite fate after use. The commenter also 

asserted that estimates of indoor products that are destined down the drain may be excessive if they 

do not take into account volatility (air), or post-application wipe-up (trash disposal) or other relevant 

activities and characteristics. The commenter stated that there is a critical need to identify how 

factors such as reactivity, degradation of the active ingredient, volatility, adsorption to wastes affect 

how much reaches the WWTP. 

Response: 130.1: An environmental fate assessment must be completed before deciding whether or 

not it is appropriate to run the Down-the-Drain model. An assessment of the environmental fate of 

an antimicrobial pesticide always includes a thorough examination of the antimicrobial’s 

physical/chemical properties, an analysis of degradation processes, products, and half-lives, as well 

as an analysis of the extent to which an antimicrobial is expected to partition to environmental 

media, such as air, water, soil, bottom sediments, and sludge. EPA agrees that not all antimicrobials 

are candidates for Down-the-Drain modeling and therefore, the Down-the-Drain model would not 

be run for those antimicrobials that are so reactive or unstable that they would degrade or form 

another chemical before reaching a wastewater treatment facility. The Down-the-Drain model, 

however, could be run for stable chemicals formed from highly reactive or unstable antimicrobial 

pesticides. 

A key input parameter to the Down-the-Drain model is the wastewater treatment plant influent 

volume. This volume reflects the amount of antimicrobial pesticide that is expected to enter a 

wastewater treatment plant based on use characteristics of products into which an antimicrobial 

pesticide is incorporated. For some products, including but not limited to laundry detergents, toilet 

bowl cleaners, liquid fabric softeners, and dishwashing detergents, virtually all of the product is 

expected to be disposed down the drain during use. For these types of products, the wastewater 

treatment plant influent volume of the antimicrobial pesticide would be assumed to be roughly equal 

to the portion of the antimicrobial pesticide’s production volume expected to be incorporated into 

these types of products. For other products such as surface cleaners, paints, and adhesives, to name 

a few, only a fraction of the product might be expected to be disposed down the drain following use. 

For these types of products, the wastewater treatment plant influent volume of the antimicrobial 

pesticide would be estimated to be considerably less than its production volume. 

 
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Comment 130.3: A commented maintained that since there is evidence that some compounds pass 

through wastewater treatment plants, there should be increased testing of chemicals to assure 

protection of wildlife. The commenter contended that it is not acceptable to continue allowing new 

compounds to be manufactured or distributed in commercial products before the full extent of 

impact is understood. The commenter maintained that is more effective both in terms of cost and in 

terms of results to control these items before they are allowed to be manufactured or used in 

commercial products. 

Response 130.3: EPA understands the commenter’s concerns and believes that such concerns are 

addressed via the EPA pesticide registration process. Federal law requires that before selling or 

distributing a pesticide in the United States, a person or company must obtain a registration, or 

license from EPA. Before registering a new pesticide or new use for a registered pesticide, EPA must 

first ensure that the pesticide, when used according to label directions, can be used with a reasonable 

certainty of no harm to human health and without posing unreasonable risks to the environment. To 

make such determinations, EPA requires more than 100 different scientific studies and tests from 

applicants. Where pesticides may be used on food or feed crops, EPA also sets tolerances (i.e., 

maximum pesticide residue levels) for the amount of the pesticide that can legally remain in or on 

foods. 

Additionally, under the Registration Review Program, all pesticides are re-evaluated on a regular 

cycle. The program’s goal is to review each pesticide active ingredient every 15 years to make sure 

that as the ability to assess risks to human health and the environment evolves and as policies and 

practices change, all pesticide products in the marketplace can still be used safely. 

As explained in the proposed rule [59407-8], based on evidence that certain antimicrobial pesticides 

are not completely removed from wastewater treatment plant influent and/or are transferred to 

other environmental media (e.g., wastewater treatment plant sludge) during wastewater treatment, 

EPA proposed to require additional fate studies to determine the transport and fate of an 

antimicrobial in a WWTP. Using this information, EPA can determine whether the antimicrobial 

would be released to the environment and pose a potential concern to non-target organisms and 

plants. If so, EPA could then require additional studies to assure protection of non-target organisms 

and plants. Based on comments received, EPA is also requiring a study to ascertain potential toxicity 

of antimicrobials to wastewater treatment plant microorganisms to ascertain the concentration of an 

antimicrobial pesticide that may inhibit the effectiveness of wastewater treatment plant 

microorganisms. 

Comment 130.4: A commenter recommended that when using the down-the-drain model, the 

Agency also takes into account transformation and degradation products of the antimicrobial 

substances under review and their impacts on surface waters, microbial communities in WWTPs, as 

well as in sewage sludge, because some of these degradation/transformation products can be even 

more persistent and bioaccumulative than their parent chemical. 

Response 130.4: EPA agrees that certain degradation/transformation products can be more 

persistent and/or bioaccumulative than the parent chemical. EPA identifies 

degradation/transformation products through an environmental fate assessment. As mentioned in 

the response to comment 130.1, an environmental fate assessment must be completed prior to 

running the Down-the-Drain model. If EPA’s evaluation of the antimicrobial pesticide, reveals that 
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transformation/degradation products would be expected to be formed between the time the 

product containing the antimicrobial pesticide is disposed down the drain and the time the 

antimicrobial pesticide would be expected to enter a wastewater treatment facility, the Down-theDrain model would be used to estimate potential exposures to these transformation/degradation 

products based on an analysis of their environmental fate and effects. The following guideline is 

used by EPA’s Office of Pollution Prevention and Toxics (OPPT) to determine whether to assess 

risks from a chemical substance and/or its degradation products when conducting a down-the-drain 

analysis: 

If the half-life in the environment (e.g., hydrolysis half-life) is less than one hour, then only the 

degradation products are assessed. If the half-life is greater than one hour, but less than 14 days, 

then both the intact chemical and its products are assessed. If the half-life is greater than 14 days, 

then generally only the parent chemical is assessed (Interpretive Assistance for Sustainable Futures 

Summary Assessment”, updated January 22, 2007). 

OPPT’s criteria for whether to assess parent chemicals and/or degradates are based on 

consideration of travel time of a chemical substance from source of release via a wastewater 

treatment system to surface water (i.e., indirect release to surface water). OPP believes these criteria 

provide reasonable guidance for determining whether or not to take into account potential exposure 

and risk to degradates when conducting a down-the-drain analysis. 

Comment 130.5: A commenter argued that EPA has developed a screening-level assessment of the 

fate of antimicrobials that reach wastewater treatment plants (WWTPs) but lacks a risk assessment 

procedure to determine the true fate of antimicrobials that go down-the-drain. 

Response 130.5: The Agency disagrees with this comment. To assess whether the proposed tiered 

approach for determining data requirements for antimicrobial pesticides provides the data needed to 

assess exposure and risk from antimicrobial pesticides released to the environment via effluent 

released from a WWTP, the Agency conducted four case studies, as described in support document 

44 in the proposed rule docket. These four case studies are examples of the procedure that could be 

used to evaluate environmental fate and effects of antimicrobial pesticides while accounting for their 

partitioning to air, water, and biosolids in wastewater treatment plants and corresponding deposition 

to environmental compartments such as surface water, air, benthic sediments, and soil. Once EPA 

has determined the fate and partitioning of the antimicrobial, then EPA would use its existing risk 

assessment procedures to develop exposure and risk assessments. The Agency’s exposure and risk 

assessment procedures have been presented in numerous exposure and risk assessments for 

antimicrobial pesticides that are available to the public through EPA/OPP’s website. EPA’s 

assessments reflect the best available data and state of the science of exposure and risk assessment 

models, methods, and procedures. 

Comment 132.1: A commenter argued that it is essential that there be adequate protection in the 

terrestrial environment for the application of biosolids containing antimicrobial pesticides. The 

commenter asserted that if the DtD assessment indicates that antimicrobials would partition into the 

biosolids, then a risk assessment methodology should exist for the situation. The commenter also 

contended that OPP and EPA’s Office of Wastewater Management (OWM) should work together 

to develop a methodology to assess the risk of land application of biosolids containing 
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antimicrobials. The commenter thought the existing Office of Pesticide Programs’ guidelines for the 

study of chemicals in the terrestrial environment could be modified to address biosolids amended 

soil systems. In addition, the evaluation should include an analysis of bioaccumulation, toxicity to 

microbes, and toxicity to worms, all of which have OPP guidelines. 

Response 132.1: EPA agrees that assessing the risk of land application of antimicrobials in biosolids 

is important. Historically, EPA/OPP’s assessment has not extended to identifying potential risks 

from biosolids. However, with the promulgation of the environmental fate data requirements, 

OPP’s Antimicrobial Division will be performing an ecological risk assessment which will evaluate 

the extent to which antimicrobial pesticides would be expected to partition to biosolids. 

The OPP ecological risk assessment would be based on modeling performed using the Sewage 

Treatment Plant (STP) model which is run before the Down-the-Drain modeling is performed. The 

STP model predicts fate and transport of chemical substances in wastewater treatment plants during 

conventional activated sludge treatment, including the extent to which a chemical substance would 

partition to the biosolids. OPP’s down-the-drain analysis could also prove useful to EPA’s Biosolids 

Program conducted under 40 CFR part 503. 

EPA’s Office of Water’s Office of Science and Technology (OST) has been working on developing 

a methodology for assessing the risk of land application of biosolids containing chemical substances. 

OPP and OW are coordinating closely on OST’s progress to finalize this methodology and on 

sharing antimicrobial risk assessment information developed by OPP. 

Comment 134.1: Some commenters expressed concern regarding EPA’s proposal to exclude 

antifoulants and wood preservatives from testing designed to protect publicly-owned treatment 

works (POTWs) and the aquatic environment. These commenters contended that these compounds 

may reach POTWs through sources such as hull blast water, landfill leachate, and centralized waste 

treatment facilities. They maintained that EPA should revisit this assumption to verify its accuracy. 

Response 134.1: Based on this comment, EPA did re-evaluate its original determination to exclude 

antifoulant coating and paints, wood preservatives, and aquatic areas from down-the-drain analysis. 

EPA still believes that it is appropriate to exclude aquatic areas from a down-the-drain analysis. As 

discussed in the preamble (73 FR 59390) aquatic areas include lakes, ponds, streams, drainage 

ditches, and other bodies of water. These would not be expected to result in down-the-drain releases 

and are therefore unlikely to be discharged to a wastewater treatment plant. 

However, based on its re-evaluation, EPA believes that a down-the-drain analysis is needed for the 

wood preservative and antifoulant paints and coatings use patterns, as well as the “all other” use 

pattern category. There are a number of sources of indirect releases of antifoulants and wood 

preservatives to surface water via wastewater treatment plants. The Emission Scenario Document 

(ESD) for Wood Preservatives, which is part of the Organisation for Economic Co-operation and 

Development (OECD) Series on Emission Scenario Documents, documents numerous sources of 

environmental releases directly to surface water. The ESD also describes various types of wood 

preservative facilities where there may be environmental releases to the facility drain that 

subsequently drains to a wastewater treatment plant. Some of the types of wood preservative 

facilities identified in the OECD ESD for wood preservatives include automated spraying plants, 
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dipping/immersion plants, and plants that employ vacuum-pressure and double vacuum processes. 

According to this OECD ESD for wood preservatives, it is also possible for releases to sewage 

treatment plants to occur from some treated wood products, such as noise barriers. 

According to the OECD Series on Emission Scenario Documents, Emission Scenario Document 

for Antifouling Products, in addition to numerous sources of environmental releases directly to 

surface water as a result of the use of antifoulant paints and coatings, there is the potential for 

antimicrobials to enter sewage treatment plants as a result of application and removal of antifoulant 

paints at boatyards and marinas. 

Thus, OPP’s Antimicrobial Division (AD) will perform a down-the-drain assessment for every 

product with an applicable use or exposure scenario that has the potential for waters containing 

antimicrobials to reach a WWTP. To perform this assessment, the Agency is requiring data on the 

potential toxicity and biodegradation of an antimicrobial pesticide to wastewater treatment plant 

microorganisms in an activated sludge basin. For some antimicrobial pesticides, the Agency will also 

require the activated sludge sorption isotherm test to determine removal from wastewater via 

partitioning to activated sludge. 

To reflect the data needed for performing a down-the-drain assessment will require changes to the 

proposed Environmental Fate Data Requirements Table. 

 The table descriptor for the activated sludge, respiration inhibition study (ASRI) will be 

changed from “NR” to “R” for the antifoulant paints and coatings, and wood 

preservative use patterns 

 For the ASRI test, the proposed Environmental Fate Table specified the modified 

activated sludge, respiration inhibition test, while referencing guideline 850.8600. The 

complete title of this study is “Modified Activated Sludge, Respiration Inhibition Test 

for Sparingly Soluble Chemicals.” As noted by the title, the guideline is most appropriate 

only for sparingly soluble chemicals. Therefore, in addition to OCSPP 850.6800, EPA 

will also add Organisation for Economic Co-operation and Development (OECD) 

Guideline 209 Activated Sludge, Respiration Inhibition Test (Carbon and Ammonium 

Oxidation) to the Guideline Number Column. Applicants will have the choice of which 

study to perform based on the antimicrobial substance’s solubility characteristics. The 

Guideline for OECD 209 can be downloaded from 

http://www.oecdbookshop.org/oecd/display.asp?K=5LMQCR2K7RG4&DS=TestNo.-209-Activated-Sludge-Respiration-Inhibition-Test 

 The results of the ASRI study will trigger the activated sludge sorption isotherm (ASSI) 

test and determine whether or not the applicant has the option of performing the ready 

biodegradability test as opposed to the porous pot or one of the simulation studies. For 

the ASSI and the ready biodegradability study, the table descriptor for the industrial 

processes and water systems use pattern and the “all other” use pattern category 

grouping (previously the low environmental exposure grouping) will be changed from 

“R” to “CR”. The table descriptors for the antifoulant coatings and paints and the wood 

preservative use patterns will be changed from “NR” to “CR.” 

 There are no changes to the porous pot test. 

 Two new studies, the Biodegradation in Activated Sludge Study, as described in 

“Simulation Tests to Assess the Primary and Ultimate Biodegradability of Chemicals 
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Discharged to Wastewater” (OCSPP 835.3280) and the “Simulation Test – Aerobic 

Sewage Treatment: A. Activated Sludge Units” will be added to the Environmental Fate 

Table. Both of these studies would also be triggered based on the results of the ASRI 

study. The aquatic areas use pattern data requirement designation is “NR” and the data 

requirement designation for the “all other” use patterns category is “CR.” 

As discussed on page 1 of Guideline OCSPP 835.3280, this guideline was developed based on 

OECD Guideline 314 “Simulation Tests to Assess the Biodegradability of Chemicals Discharged in 

Wastewater”. Both guidelines contain five separate but related simulation studies to assess chemicals 

whose route of entry into the environment begins with their discharge to wastewater. The five 

studies assess the primary and ultimate biodegradation of chemicals discharged to wastewater 

beginning with transit in the sewer, followed by treatment in a wastewater treatment plant, and 

ending with discharge from the wastewater treatment plant to the effluent-surface water mixing 

zone. 

Both the OECD Guideline 303 and the OCSPP Guideline 835.3280 contain a Figure entitled 

“Pathways for Chemicals Discharged to Wastewater” which illustrates the points in the wastewater 

treatment process that are simulated by the guidelines. The OCSPP 835 guidelines are available at 

http://www.epa.gov/ocspp/pubs/frs/publications/Test_Guidelines/series835.htm 

A table to crosswalk the two guidelines is presented below: 

Title OECD OCSPP 

Biodegradation in a sewer system 314A Begins on page 12 

Biodegradation in activated sludge 314B Begins on page 20 

Mineralization and transformation in 

anaerobic digester sludge 

314C Begins on page 29 

Biodegradation in treated effluent-surface 

water mixing zone 

314D Begins on page 38 

Biodegradation in untreated wastewatersurface water mixing zone 314E Begins on page 46 

The following flowchart explains the approach that will be used by EPA in requiring these studies. 

The triggers for new test notes 3, 18, 19, and 20 to the Environmental Fate Table come from the 

decision points in this flowchart. Also, proposed testnote 4 is revised to include the following: “If 

the antimicrobial fails the ready biodegradability study, then the applicant must conduct one of the 

following studies: The biodegradation in activated sludge study as described in the “Simulation 

Tests to Assess the Biodegradability of Chemicals Discharged in Wastewater,” the porous pot test, 

or the “Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units.” 
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The goal of requiring these studies is to determine potential toxicity to activated sludge 

microorganisms and also percent removal during wastewater treatment, the latter of which would 

then be used in the down-the-drain analysis. Based on the results of the ASRI test, for antimicrobials 

with an EC50 of greater than 20 mg/L, an applicant may need to conduct only one biodegradation 

study.. Applicants have the choice of performing either the Ready Biodegradability Test (choice 2) 

or skip the Ready Biodegradability Test and perform either the Biodegradation in Activated Sludge 

Study, the Simulation Test – Aerobic Sewage Treatment: A. Activiated Sludge Units, or the Porous 

Pot Test (choice 1). 

ASRI test is performed

EC50 ≤ 20 mg/L 

Applicant chooses: 

 Choice 1: BAS, 

AST/ASU, or Porous 

Pot, 

 Choice 2: Ready Bio 

 Require ASSI 

 Require either BAS, AST/ASU, 

or Porous Pot 

Applicant conducts either 

BAS, AST/ASU, or Porous 

Pot

Agency determines percent removal during wastewater 

treatment to use in down-the-drain analysis

Applicant conducts 

Ready Bio

Pass Ready 

Bio? 

Yes No 

Yes

No 

Key: 

ASRI: Activated Sludge 

Respiration Inhibition Study 

ASSI: Activated Sludge 

Sorption Isotherm 

BAS: Biodegradation in 

Activated Sludge 

AST/ASU: Aerobic Sewage 

Treatment/Activated Sludge 

Units 

Ready Bio: Ready 

Biodegradability Study 
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 If the antimicrobial passes the ready biodegradability test, then no more testing is required 

and EPA will assume that 90 percent of the antimicrobial is removed during wastewater 

treatment. 

 If the applicant performs the Ready Biodegradability Test and the antimicrobial fails this test, 

then the applicant is required to perform the Biodegradation in Activated Sludge study, the 

Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or the Porous Pot 

Test as well as the ASSI test. EPA would use the results of the study performed to determine 

percent removal during wastewater treatment. 

EPA notes that the applicant has the option of conducting additional studies to possibly refine (or 

possibly increase) the percent removal. For many classes of chemicals, the Activated Sludge Sorption 

Isotherm study could be used for this purpose. The additional studies could also include 

Biodegradation in a Sewer System and Mineralization and Transformation in Anaerobic Digester 

Sludge. Both of these studies are included in the “Simulation Tests to Assess the Biodegradability of 

Chemicals Discharged in Wastewater” guideline. 

Comment 134.3: A commenter noted that the DtD model recommends modifying production 

volume to account for the percentage expected to go down the drain. The commenter agreed with 

this conceptually, but believes that the values associated with various forms of usage and range of 

volatilities must be standardized to ensure consistency in modifying the production volume to 

determine the wastewater treatment plant influent volume. Other commenters stated that the 

Agency must explain how to determine how much substance actually goes down the drain as 

opposed to an estimate based on annual production volumes. 

Response 134.3: EPA agrees that values associated with various forms of usage and range of 

volatilities must be standardized to ensure consistency in modifying the production volume to 

determine the wastewater treatment plant influent volume. EPA also agrees that it is essential to be 

transparent in explaining how much of an antimicrobial pesticide is assumed to go down the drain. 

As EPA gains experience in using the Down-the-Drain model to assess exposures and risks from 

antimicrobials to ecological organisms, a consistent set of assumptions regarding the percentage of 

end-use product assumed to be disposed down-the-drain will be developed to ensure that model 

estimates are influenced solely by differences in physical/chemical properties. 

Comment 134.4: According to a commenter, EPA staff indicated at the 158W Antimicrobials Data 

Requirements Workshop held on November 6, 2008 that the E-FAST model may have been based 

on municipal wastewater treatment plants that received only “residential” discharges. The 

commenter maintained this to be very unlikely and stated that according to the E-FAST manual, the 

model was based on data from actual U.S. municipal wastewater treatment plants. The commenter 

noted that nearly every municipal wastewater treatment plant receives discharges from many types of 

non-residential sources, like commercial facilities, medical facilities, institutions, and cooling water 

systems (which are common in commercial buildings), and that even in smaller communities, 

POTWs receive wastewater from residential and commercial (e.g., schools, stores, restaurants, 

hotels/motels, and/or medical facilities) sources. The commenter also noted that most municipal 

wastewater treatment plants also receive both process and non-process discharges from industrial 

facilities. Some commenters contended that the E-FAST model is applicable as a screening-level 

model for all antimicrobial use patterns with discharges that are typically rinsed down-the-drain 
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including agricultural premises and equipment, food handling/storage establishments, residential and 

public access premises, medical premises and equipment, industrial processes and water systems, 

swimming pools, and others. 

Response 134.4: The E-FAST documentation manual indicates that the Down-the-Drain module 

was developed as a screening-level model for estimating concentrations of chemicals in surface 

water that may result from the disposal of consumer products into household wastewater. The 

model developers have confirmed, however, that the database of wastewater treatment plants that is 

accessed by this module consists of domestic wastewater treatment plants that receive wastewaters 

predominantly from residential, commercial, and institutional sources and not solely from residential 

sources. In modeling releases of antimicrobial pesticides to environmental media, the appropriate 

data inputs, methods, and tools are dependent upon where the environmental releases come from. 

To assess exposures and risks to releases of antimicrobial pesticides to surface water from 

residential, commercial, and institutional sources, the Down-the-Drain module of E-FAST is the 

most appropriate tool. 

To assess exposures and risks to antimicrobial pesticides from manufacturing, processing, and 

industrial use facilities, however, the General Population and Ecological Exposures from Industrial 

Releases module of E-FAST is the most appropriate tool. The decision to use the General 

Population and Ecological Exposures from Industrial Releases module is made on a case-by-case 

basis considering the availability of data required as inputs to the module, and the potential for 

significant exposure. For example a low volume use may not require use of this module. 

The input data requirements for these two modules are considerably different. In addition to using 

the Down-the-Drain module of E-FAST to estimate human and ecological exposures from releases 

of antimicrobial pesticides via domestic wastewater treatment plants to surface water, EPA has 

recently demonstrated the feasibility of adapting OPPT’s methodology to estimate releases to 

surface water and exposures to aquatic organisms from processing and industrial use of 

antimicrobial pesticides, such as those used in recirculating cooling towers and metalworking fluids. 

EPA agrees that the E-FAST model is applicable as a screening-level model for all antimicrobial use 

patterns with discharges that are typically rinsed down-the-drain including agricultural premises and 

equipment, food handling/storage establishments, residential and public access premises, medical 

premises and equipment, industrial processes and water systems, swimming pools, and others. 

Comment 134.5: Some commenters questioned the justification for exceedance levels used by EPA 

to evaluate potential risks to aquatic organisms including those used to evaluate: (1) Potential risks 

from effects to aquatic invertebrates and fish exceedance of the chronic concentration of concern 

(COC) for 20 or more days triggers potential for concern; (2) Potential risks from effects to aquatic 

invertebrates and fish exceedance of the acute COC for 4 or more days triggers potential for 

concern; and (3) Potential risks from effects to algae exceedance of the COC for algae for 4 days or 

less may trigger a concern and is evaluated on a case-by-case basis. 

Response 134.5: EPA notes that mathematical models used to estimate exposures and risks can be 

characterized as probabilistic or deterministic. Probabilistic modeling is a technique that utilizes the 

entire range of input data to develop a probability distribution of risk or exposure rather than a 
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single point value. Deterministic modeling is based on select input data that result in a single point 

estimate. Models such as E-FAST that include modules that are used to estimate potential exposures 

of aquatic organisms to antimicrobials from releases of antimicrobial pesticide-containing products 

via wastewater treatment plants to surface water have the capability of providing either deterministic 

or probabilistic results. These modules use probability distributions as inputs to estimate the number 

of days per year that the concentration of a chemical in surface waters downstream of wastewater 

treatment plants exceed concentrations of concern for aquatic life. These probability distributions 

are based on the ratio of receiving stream flows to wastewater treatment plant flows for a 

distribution of wastewater treatment plants in the United States. Whereas deterministic models 

predict whether or not a concentration of concern for aquatic organisms is exceeded for a 

hypothetical set of input data, these probabilistic models also consider the magnitude of releases and 

associated exposures expressed as the number of days of exceedance of concentrations of concern 

to aquatic organisms relative to the number of days of release of antimicrobial pesticides to surface 

water. Consequently, criteria for determining whether or not testing on aquatic organisms is required 

need to take into account the additional information regarding magnitude of exposure that these 

probabilistic modeling results provide. 

These exceedance levels and corresponding number of days of exceedance that trigger potential for 

concern are those cited on page 7-7 of EPA/OPPTS/OPPT’s “Revised Draft New Chemicals 

Decision Guidelines Manual” dated April 17, 2001. The justification that the potential for chronic 

risk to aquatic organisms may exist if the predicted environmental concentration (PEC) exceeds the 

chronic COC and the exceedance occurs for 20 days or more per year is documented on page 11 of 

“Interpretive Assistance for Sustainable Futures Summary Assessment”, updated January 22, 2007: 

“...although there is a potential for the concentration of the chemical in the water to reach levels 

exceeding the hazardous level, the levels are not exceeded for a sufficient duration of time to induce 

any chronic effects. The 20-day criterion is derived from partial life-cycle tests (daphnid chronic and 

fish early life-stage tests) that typically range from 21 to 28 days in duration. Low concern for 

chronic risk exists if the COC is exceeded on fewer than 20 days per year or the PEC is less than the 

chronic COC”. 

Therefore, two test notes in the proposed Nontarget Organism Data Requirements Table have been 

revised to include a probabilistic trigger for down-the-drain analyses, while retaining the existing 

deterministic trigger for releases of antimicrobials that are expected to enter wastewater treatment 

plants. Testnote 7 triggers the acute freshwater invertebrate toxicity study (TEP testing) and the 

acute freshwater fish toxicity study (TEP testing). Testnote 12 triggers the fish life-cycle study. 

Comment 134.7: A commenter noted that more modern approaches are available to estimate surface 

water concentrations of chemicals - for example, GIS (Geographical Information Systems)-based 

tools such as the P&G-developed GIS-ROUT that allow estimation of surface water concentrations 

on a site-specific basis,. The commenter maintained that these approached would facilitate sitespecific evaluations of risk due to these materials, since these tools directly address some of the 

limitations in the DtD model and should be further investigated. The commenter thought that the 

Agency should further investigate GIS-based tools to predict surface water concentrations due to 

their ability to include a range of dilution factors, wastewater treatment types, and integrate releases 

from commercial, industrial, and domestic sectors. 
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Response 134.7: EPA agrees that GIS-based tools are useful for estimating surface water 

concentrations at specified locations where environmental releases are identified. EPA, however, 

currently does not routinely receive location information regarding use of antimicrobial pesticides. 

Generally, antimicrobial pesticides have the potential to be used throughout the United States and 

are not usually limited to specific geographic locations. In the event that EPA is provided with 

information specifying geographic locations where antimicrobial pesticides are used, EPA would 

consider using a GIS-based approach to allow estimation of surface water concentrations on a sitespecific basis. 

Comment 134.9: A commnter thought that it is unclear how generic DTD modeling would be 

applied in different geographic regions, like desert or water-restricted areas. 

Response 134.9: The Down-the-Drain model is not intended to provide estimates for select 

geographic regions or areas with specific climatologic or hydrogeologic characteristics (i.e., deserts or 

water-restricted areas). The Down-the-Drain model uses probability distributions as inputs to 

estimate the number of days per year that the concentration of a chemical in surface waters 

downstream of domestic wastewater treatment plants exceeds concentrations of concern (COCs) for 

aquatic life. The distributions of inputs are ratios of stream flows downstream of wastewater 

treatment plants to wastewater treatment plant effluent flows. These distributions are intended to be 

representative of all geographic regions in the conterminous United States where domestic 

wastewater treatment plants are located. 

Comment 134.10: A commenter asserted that other validated models and means to estimate 

potential environmental exposures should be accepted by EPA. This would include the use of 

EpiWin and EPI Suite, SAR/QSAR, and open literature references as a testing alternative to 

estimate endpoints for use in environmental modeling. As an example, the commenter maintained 

that the removal values entered for modeling can be estimated from the biodegradability rate 

constant, volatility, and the Koc using a variety of models, a lab scale WWTP, or monitoring data. 

Models used to do this include STP (Sewage Treatment Plant), which was developed by the 

Canadian Environmental Modeling Centre and adapted for use in EPI Suite by OPPT, and 

ASTREAT. According to the commenter, the Canadian government evaluated a range of models 

and concluded that ASTREAT was superior to OPPT’s STP model. The commenter stated that, it 

should be acceptable to run an environmental risk assessment screen using means other than downthe-drain and conduct fate testing only if there is a need to show a loss during wastewater treatment. 

Thus, the commenter maintained that if assuming 100 percent of the substance goes into effluent 

and is still regarded as safe, there is no need for environmental or ecotoxicity testing. 

Response 134.10: OPP believes that physical/chemical property estimates from EPI Suite as well as 

data from the open literature could be used to supplement environmental fate data on antimicrobial 

pesticides. In addition, OPP would use wastewater treatment plant partitioning and removal 

estimates from the STP module of EPI Suite, and data on wastewater treatment plant removal from 

EPA’s Office of Water’s publications and the open literature, to supplement available lab and field 

test data on percent removal of antimicrobial pesticides during wastewater treatment. 

OPP would consider using structure activity relationships (SAR) and Quantitative SAR (QSAR) 

modeling if the antimicrobial pesticide is one of the chemical classes and/or functional groups with 
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an adequate database to permit SAR approaches and QSAR modeling. EPA’s Ecological Structure 

Activity Relationships (ECOSAR) Class Program, developed by OPPT, is a computerized predictive 

system that estimates the aquatic toxicity of industrial chemicals. The program estimates a chemical’s 

acute (short-term) toxicity and chronic (long-term or delayed) toxicity to aquatic organisms such as 

fish, aquatic invertebrates, and aquatic plants by using SAR. OPP is familiar with and has used 

predictive results from ECOSAR. Applicants interested in using results of the ECOSAR program as 

part of their submission to OPP are urged to consult the ECOSAR User’s Guide, and Technical 

Reference Manual which can be accessed through EPA’s website at 

www.epa.gov/opptintr/newchems/tools/21ecosar.htm. 

EPA would consider using models other than the Down-the-Drain model provided that such 

models are applicable to domestic wastewater treatment plants in the United States, are welldocumented, are transparent, and meet EPA’s quality assurance standards. Generally, for EPA to 

use a model, three criteria must be met. Ideally, the model should be publicly available, although 

proprietary models will be considered. Second, the model must be peer-reviewed. This could mean 

review by the FIFRA Scientific Advisory Panel, or another appropriate body. And, last, the model 

should be transparent, so that the data, algorithms, and procedures used can be seen and evaluated. 

Since the source code of proprietary models is not publicly available, its use should be accompanied 

by comprehensive, publicly available documentation. Before accepting the results of a model, EPA 

must have a sufficient basis for concluding that the model and its analytical results are of a quality 

sufficient to serve as the basis for a decision. Additional information on developing models can be 

found in the “Guidance on the Development, Evaluation, and Application of Environmental 

Models” (EPA/100/K-09/003: March 2009) which is available at www.epa.gov/crem. 

Comment 134.11: A commenter requested guidance on standard test methods which can be used to 

estimate input parameters for the model. The commenter asserted that such guidance should specify 

how volatilization, hydrolysis, and biodegradation during product use, disposal, and transport to the 

WWTP (i.e., in sewer) are to be estimated and incorporated into the DtD model. The commenter 

thought that neither the amount disposed down the drain, the removal, or the concentration of 

concern (COC), the key input parameters affecting DtD, are clearly defined or explained. Noting 

that there is no clear definition for how “Days exceeding COC” will be used in decision making, the 

commenter asserted that the Agency should explain whether the COC is an acute value, a chronic 

value, or the lowest value in all cases, and why. The commenter inquired about the regulatory 

implications of “failing” the model and stated that the Agencyould provide more explanation as to 

the intended use of the model and results. 

Response 134.11: For aquatic exposures, down-the-drain modeling requires the following inputs: 

 Concentrations-of-concern for aquatic organisms, including acute and chronic values for 

fish, aquatic invertebrates, and aquatic plants 

 Production volume (more specifically, the WWTP influent volume) 

 Percent removal during wastewater treatment, which includes a consideration of 

volatilization, hydrolysis, and biodegradation, and sorption to sludge during wastewater 

treatment 
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EPA has developed guidance on how to use the Down-the-Drain model: Applicants wishing to 

access guidance on running the Down-the-Drain model or to use results from this model as part of 

a submission or application to OPP are urged to consult the following sources of information: 

 

 Guidance on estimating input parameters and values such as the COC 

http://www.epa.gov/oppt/sf/pubs/InterpretiveAssistance0107.pdf and 

http://www.epa.gov/oppt/sf/meetings/train.htm#materials . 

 Information on uses of the Down-the-Drain model is available in Exposure and Fate 

Assessment Screening Tool (E-FAST), version 2.0, Documentation Manual, dated April 

2006. This manual is also available on EPA’s website 

(www.epa.gov/oppt/exposure/pubs/efast.htm). 

Use of the Down-the-Drain Model is appropriate for estimating down-the-drain releases and 

associated exposures from domestic wastewater treatment plants, however, for releases of 

antimicrobial pesticides from industrial wastewater treatment facilities, an estimate of releases of an 

antimicrobial pesticide to an environmental medium (i.e., air, water, soil) is required. See response to 

comment 134.18 regarding guidance on the E-FAST module, “General Population and Ecological 

Exposure from Industrial Releases” for sources of information on estimating these environmental 

releases. 

If the modeled results indicate concern, then EPA may require higher-tier ecological effects testing 

and/or the applicant may choose to perform simulation tests to asses the primary and ultimate 

biodegradability of chemicals discharged to wastewater other than that required to determine 

biodegradation in activated sludge. Another possibly, is that the antimicrobial’s registration could 

include limitations on the amount of the antimicrobial that could be used or on the types of uses of 

the antimicrobial pesticide. 

Comment 134.14: Some commenters contend that the DtD model should not be part of the 

regulation as a requirement, but only serve as an example of environmental modeling for products in 

“those relevant use patterns” and that it should be used only in relation to very limited use patterns 

for antimicrobial pesticides, be used only with appropriate chemistries, and must fully identify the 

significant limitations associated with the use of this model in any regulatory decision. These 

commenters further contend that the Agency has not identified how the output from this model 

would be used in a regulatory decision. These commenters assert that no decisions should be made 

on the basis of the results of this modeling until the model has been fully and appropriately reviewed 

for such purposes and the Agency has clarified how the information will be used. 

Response 134.14: The Agency disagrees with this comment. For over 20 years, the Down-the-Drain 

model has been used here at EPA by the Office of Pollution Prevention and Toxics (OPPT) to 

assess potential concerns for humans and aquatic organisms from exposures to a wide range of 

chemical substances that would be discharged to domestic wastewater treatment plants as the result 

of their use in a variety of chemically-based products that would be released down-the-drain. 

EPA/OPPT has significant experience in identifying use patterns and chemical substances that are 

appropriate for use of the Down-the-Drain model. Their record for using results from this model in 

chemical regulatory decision-making is well-established. OPP intends to build on OPPT’s 
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established processes and procedures in developing the processes and procedures that will be used 

for antimicrobial pesticide regulatory decision-making. 

EPA also wishes to clarify that the Down-the-Drain model was not proposed for inclusion as a data 

requirement in proposed part 158W. The results of Down-the Drain modeling would be used by 

Agency scientists as part of the exposure and risk assessment process. EPA has required several new 

studies to be used to develop inputs for the modeling. This was described in the preamble to the 

proposed rule. EPA developed four case studies to illustrate and describe how the outputs from 

down-the-drain modeling would be considered in an antimicrobial risk assessment. 

Comment 134.15: Commenters would like to know the technical basis (rationale) for assuming the 

surface water concentrations obtained from the 10th and 50th percentile SDFs as acute and chronic 

concentrations in national down-the-drain assessments. The commenter noted that some POTWs 

discharge to effluent-dominated receiving waters, providing essentially the only source of water to a 

surface water body during dry periods, and NPDES permits for these facilities do not include a 

stream dilution factor. In addition, other facilities in the country do not have dilution credits in their 

NPDES permits for other environmental reasons. Therefore, according to these commenters, EPA 

should not include stream dilution factors in national down-the-drain assessments for pesticides. 

Response 134.15: No “stream dilution factors” or “dilution credits” are applied in the Down-theDrain model. The terminology “stream dilution factor” as used in the Down-the-Drain model refers 

to the ratio of the stream flow downstream of a wastewater treatment plant to the effluent flow of 

the wastewater treatment plant. In those instances in which a POTW discharges to “effluentdominated receiving waters,” the ratio of the stream flow to the wastewater treatment plant effluent 

flow would be 1. For the distribution of wastewater treatment plants in the Down-the-Drain model, 

the 10th percentile 7Q10 (i.e., lowest consecutive 7-day average stream flow over any 10-year period) 

is 1. Surface water concentrations based on the 7Q10 are routinely used by EPA/OPPT and 

EPA/OW to assess potential concerns for exposure to aquatic organisms. LC50 values for aquatic 

organisms serve as a basis for establishing end-points for determining potential for acute toxicity. 

(LC50, also sometimes referred to as lethal concentration 50 or median lethal concentration, is the 

concentration of a chemical substance which kills 50 percent of test animals exposed.) NOAEC 

values for aquatic organisms serve as a basis for establishing end-points for determining potential for 

chronic toxicity. (NOAEC, referred to as the No-Observed-Adverse-Effect Concentration, is the 

maximum concentration of a substance that is found to have no adverse effects upon the test 

subject.) Surface water concentrations based on the harmonic mean flow (which is derived from the 

arithmetic mean flow by taking the inverse mean of reciprocal daily arithmetic mean flow values) 

and the 30Q5 (i.e., the lowest consecutive 30-day average stream flow over any 5-year period) are 

used by EPA/OPPT and EPA/OW to assess potential concerns for exposure to humans from 

ingestion of drinking water and fish. OPP intends to use this same approach. 

Comment 134.16 : A commenter maintained that the DtD model has uncertainties as follows: the 

model does not address the possibility of degradation of the parent; does not estimate the 

concentration of any degradates; and does not address actions to be taken to avoid contamination of 

POTWs when a chemical remains in water and does not biodegrade. 

Response 134.16: The Down-the-Drain model is used to estimate potential exposures to a chemical 

substance based on environmental fate and physical/chemical property inputs. Thus, the Down-the-
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Drain model is a risk assessment tool, not a risk management tool. As such, it is not intended to 

“address actions to be taken to avoid contamination of POTWs when a chemical remains in water 

and does not biodegrade” (or be removed or transported from wastewater and/or surface water by 

other means). The Down-the-Drain model is also not an environmental fate assessment tool. 

Environmental fate and physical/chemical properties of a chemical substance must be assessed prior 

to running the Down-the-Drain model. If the environmental fate assessment identifies degradates of 

the parent chemical that are stable and should be considered, then the Down-the-Drain model can 

be used to predict concentrations for assessing the potential for human and ecological exposure and 

associated risk. 

Comment 134.17: A commenter argued that model results are highly dependent on streamflow 

(dilution). The commenter noted that there is no guidance on what value should be used. In 

addition, the commenter maintained that 1Q10 (i.e., the lowest stream flow in a single day over any 

10-year period), 7Q10, and 30Q5 are extremely conservative values that are unrealistic, and that even 

the harmonic mean flow is lower than EPA has used in the past. The commenter asserted that the 

Agency should clarify the dilution factor at WWTP (flow rates, population served, industrial 

contributions to WWTP, seasonal variations, geographic differences, etc.). The commenter also 

maintained that the Agency should address which percentile to use for highly variable modeling 

assumptions (e.g., average surface water concentration, stream dilution factor for streams to which 

wastewater treatment facilities discharge). 

Response 134.17: EPA agrees that the results of any model are dependent on the data used as 

inputs. EPA, however, has provided guidance on the values used as inputs. As mentioned in 

Response 134.15, surface water concentrations based on the 7Q10 are routinely used here at EPA to 

assess potential concerns for exposure to aquatic organisms; surface water concentrations based on 

the harmonic mean flow and the 30Q5 are used by EPA/OPPT and EPA/OW to assess potential 

concerns for exposure to humans from ingestion of drinking water and fish. OPP intends to use the 

same approach. The use of a probabilistic distribution in the Down-the-Drain model is intended to 

reflect seasonal variations in hydrologic characteristics as well as geographic differences in 

wastewater treatment plant characteristics, including effluent flow rates and populations served. 

Comment 134.18: A commenter contended that during the 158W Antimicrobial Data Requirements 

Workshop held on November 6, 2008, EPA staff indicated that evaluation of discharges to still 

water and to salt water would be challenging. According to the commenter, the E-FAST model 

manual suggests that these discharges can be readily evaluated with appropriate input data and 

elimination of the PDM (Probabilistic Dilution Model) option. 

Response 134.18: Information provided by EPA staff in the proposed ruke and in the presentation 

on the Down-the-Drain Model at the 158W Antimicrobial Data Requirements Workshop on 

November 6, 2008 focused exclusively on discharges to surface water from domestic wastewater 

treatment plants. 

The PDM option uses probability distributions of the ratio of domestic wastewater treatment plant 

flows to stream flows immediately downstream of those plants as inputs and calculates the resulting 

probability distribution of the concentration in the stream. When the Down-the-Drain module of EFAST is run without the PDM option, the results are limited to estimates of concentrations in 
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surface water downstream of domestic wastewater treatment facilities based on a distribution of the 

ratio of domestic wastewater treatment plant flows to stream flows immediately downstream of 

those plants. The Down-the-Drain module has no option for estimating concentrations in lakes, 

bays, estuaries, and oceans. 

E-FAST, however, has the capability for evaluating discharges to still water and to salt water from 

discharges to wastewater treatment plants that receive manufacturing, processing, and industrial use 

releases, but not from discharges to surface water via domestic wastewater treatment plants. 

 

E-FAST includes a module referred to as the General Population and Ecological Exposure from 

Industrial Releases module that estimates human and ecological exposures from industrial releases. 

This module is designed to estimate releases to air, water, and land from manufacturing, processing, 

and industrial use of chemical substances. The database for estimating releases to wastewater 

treatment plants that primarily receive wastewater from manufacturing, processing, and industrial 

uses requires estimates of releases to environmental media from models such as ChemSTEER 

(Chemical Screening Tool for Exposures and Environmental Releases), a model developed by 

EPA’s OPPT or from data and calculations included in standard scenarios, also developed by OPPT 

(www.epa.gov/oppt/exposure/pubs/chemsteerdl.htm). The General Population module includes 

an option for estimating concentrations in lakes, bays, estuaries, and oceans. 

Comment 134.19: A commenter argued DtD modeling is highly site-specific due to its reliance on a 

single WWTP removal value to model the entire United States and would be very difficult to obtain 

meaningful environmental exposure estimates for generic use. 

Response 134.19: As illustrated by the case studies, the use of the DtD model will eliminate 

variability due to wastewater treatment plant characteristics and will ascertain the relative difference 

between antimicrobial pesticides as a result of their physical/chemical properties, fate and transport 

in wastewater treatment plants and the environment, and potential adverse effects to ecological 

organisms. For this reason, EPA uses results from well-documented, scientifically-sound published 

lab data and/or field data, such as those published by EPA’s Office of Water, or model estimates, 

such as those from the Sewage Treatment Plant (STP) model, to ascertain removal of antimicrobial 

pesticides during wastewater treatment. The sewage treatment plant characteristics used in this 

model are based on a typical wastewater treatment plant in the United States that provides secondary 

treatment using the activated sludge process. Wastewater treatment plants that employ secondary 

treatment using the activated sludge process are presently the most common types of domestic 

wastewater treatment plants in the United States. 

Comment 134.20: Several commenters argued that EPA’s approach for down the drain chemicals 

separates the exposure and the effects of the assessment and subjects chemicals to similar testing 

requirements regardless of the mass of chemical disposed in the environment. According to these 

commenters, the fact that EPA does not guide testing by the extent of environmental exposure is 

wasteful for ingredients which will reach the environment at low levels. Even for chemicals which 

are used at greater volume, there is no proof that EPA’s program will achieve its goal without being 

wasteful and some commenters believer that EPA’s approach will likely result in significant 

unwarranted costs in animals, time, and dollars. The commenters asserted that this will result in 

unnecessary loss of animals, increased costs to the consumer and will negatively affect product 
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Down-the-Drain Section (130) Page 191 

innovation as new product development will be slowed due to the extra regulatory burden. The 

benefit to the environment of the EPA approach, according to the commenters, approach is likely 

to be small and not commensurate with its costs. 

Response 134.20: EPA disagrees with this comment. Three key input parameters for the Down-theDrain model are (1) percent removal of antimicrobial pesticide during wastewater treatment; (2) 

concentrations of concern for antimicrobial pesticides based on acute and chronic end-points for 

freshwater fish, freshwater invertebrates, and freshwater plants; and (3) wastewater treatment plant 

influent volume of antimicrobial pesticide. 

As demonstrated in the sensitivity analysis of the Down-the-Drain model in the document, “Four 

Case Studies of Antimicrobial Pesticides in the Down-the-Drain Screening Model, Using the 

Proposed Approach for a Screening-Level Environmental Fate Assessment” (available at in the 

docket at http://www.regulations.gov), the amount of chemical disposed in the environment 

strongly influences the results of the Down-the-Drain model. It is possible that if the amount of 

chemical disposed is small (i.e., wastewater treatment plant influent volume is low), that the 

predicted concentration of the antimicrobial, even for a chemical of high toxicity, would not exceed 

the Agency’s level of concern. Under such circumstances, higher tier testing (environmental fate, 

ecotoxicity, and plant protection) is unlikely to be triggered. Since, higher-tier testing is triggered 

only if the down-the-drain model indicates that the predicted concentration of the antimicrobial may 

adversely affect aquatic organisms this reduces the number of tests required, and therefore the 

animals, time, and dollars. 

EPA also notes that two of the three key input parameters needed to run the down-the-drain model, 

percent removal during wastewater treatment and wastewater treatment plant influent volume do 

not involve animal testing and would not lead to loss of animals. Fate tests required to determine 

removal during wastewater treatment via biodegradation and adsorption are inexpensive. No costs 

are associated with wastewater treatment plan influent volume. 

Comment 134.21: A commenter noted that, at the 158W Antimicrobial Data Requirements 

Workshop held on November 6, 2008, EPA staff indicated that chronic aquatic toxicity endpoints 

might not be used to evaluate antimicrobial discharges from municipal wastewater treatment plants. 

The commenter asserted that since EPA/OW requires municipal wastewater treatment plants to 

conduct both acute and chronic toxicity tests regularly as conditions of CWA-regulated National 

Pollution Discharge Ellimination System (NPDES) permits, both acute and chronic endpoints 

should be evaluated by EPA/OPP to ensure that antimicrobial discharges will not cause toxicity in 

municipal wastewater treatment plant effluent. 

Response 134.21: EPA/OPP proposed a tiered approach to determine the aquatic toxicity and 

environmental fate data required to ensure that discharges of antimicrobial pesticides in wastewater 

treatment plant effluent will not cause toxicity to downstream nontarget organisms. In addition to 

evaluating aquatic toxicity, it is important to evaluate the stability and persistence of an antimicrobial, 

degradates of potential concern, and the extent to which the antimicrobial and/or its degradates 

partition to environmental media. 
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To assess whether the proposed screening level assessment and tiered system of data requirements 

provides the data needed to assess exposure and risk of antimicrobial pesticides released to the 

environment via down-the-drain use patterns, the Agency conducted four case studies. In two of the 

case studies, A and B, the Agency had Tier 1 acute toxicity studies for aquatic organisms, but no 

chronic toxicity studies. Based on the screening level assessment, which considered such factors as 

stability to hydrolysis, probability of exceedance of levels of concern, widespread detections in 

surface water, potential to partition to sludge and sediment, potential to occur in estuarine and 

marine environments due to discharge or wastewater treatment effluents, and need for endangered 

species risk assessment, the Agency required several non-target organism studies, including three 

chronic toxicity tests, in addition to the Tier 1 studies that were available. In case study D, acute 

toxicity studies on aquatic organisms conducted using chemical D indicated no potential for 

concern. In addition, chemical D was not determined to be persistent. As a result of these two 

factors, the potential for chronic toxicity was assumed to be negligible and no chronic aquatic 

toxicity studies were required for chemical D. 

Based on this comment, EPA has re-evaluated the approach used for the case studies. EPA agrees 

with the commenter that both acute and chronic toxicity endpoints should be evaluated by 

EPA/OPP to ensure that antimicrobial discharges will not cause toxicity to aquatic organisms 

downstream of wastewater treatment plant effluents. This means that the chronic toxicity data needs 

to be submitted at the same time as the acute toxicity data, so both types of studies are available for 

EPA to use for the ecological risk assessment. Also see response to comments 134.1 and 134.4. 

Consequently, in the table, “Nontarget Organism Data Requirements”, the table descriptors for the 

fish early-life stage and aquatic invertebrate life cycle tests have been changed from “CR” to “R” for 

the wood preservatives use pattern and the “all other” use patterns category. Testnote 10 will be 

modified to remove the trigger since it is no longer needed. 

Comment 134.22: Several commenters believe that potential environmental impacts of cross-media 

transfers need to be addressed in U.S. EPA’s environmental risk assessments. These commenters 

support higher-tier environmental studies in cases where the screening-level assessment indicates 

that the pesticide would partition to biosolids or into air. These commenters think that EPA 

considers partitioning to the biosolids as “removal” in some of its outreach materials for the 

proposal. They asserted that pesticide residuals that are adsorbed to the sludge should not be 

considered removed, but instead transferred to another medium. 

Response 134.22: EPA agrees that pesticide residuals that are adsorbed to the sludge have been 

transferred to another medium. In its materials EPA used the term “wastewater treatment plant 

removal” as it is used in reference to the Down-the-Drain model. The documentation for the model 

refers to removal from wastewater entering the wastewater treatment plant and reflects the 

reduction of chemical concentration in wastewater treatment plant influent relative to wastewater 

treatment plant effluent. As such, transfers from wastewater to air and to biosolids are considered as 

transport processes that can lead to reduction of the concentration of an antimicrobial pesticide in 

wastewater that enters a treatment plant. This terminology is consistent with the terminology, “total 

removal”, that is used in the (STP) Sewage Treatment Plant model of EPI Suite that EPA uses to 
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Down-the-Drain Section (130) Page 193 

calculate overall chemical mass balance expressed as percent for influent, partitioning to sludge, 

volatilization, aeration off gas, biodegradation, and final water effluent. 

Comment 134.23: A commenter stated that at the November workshop EPA staff suggested that 

“expert judgment” would be needed to estimate metals removal at municipal wastewater treatment 

plants. The commenter maintained that the EPA Office of Water has datasets suitable for the 

purpose – “expert judgment” is not needed. The commenter maintained that whenever possible, 

instead of estimates, actual data should be used to model removal efficiencies for all pollutants. 

Since removal efficiencies are input parameters into E-FAST, several commenters asserted that 

actual data should be used for modeling discharges of well-characterized substances like copper and 

silver. 

Response 134.23: At the presentation on the Down-the-Drain model that was given at the Part 

158W Antimicrobial Data Requirements Workshop on November 6, 2008, slide 107 states, “For 

estimating removal of metals during wastewater treatment, must use expert judgment or lab or field 

test data since no models for estimating removal of metals during wastewater treatment have been 

identified.” EPA agrees with the commenters that, when available, measured data should be given 

preference over predicted data to model efficiencies for all pollutants. EPA acknowledges that OW 

has datasets for some metals that are suitable for indicating the likely degree of removal at 

wastewater treatment plants. However, such datasets are not available for all metals and expert 

judgment would need to be used in their absence. EPA has cited data on removal of silver during 

wastewater treatment from EPA/OW publications, such as, “Development Document for the Final 

Effluent Limitations Guidelines and Standards for the Metal Products and Machinery Point Source 

Category”, (EPA-821-B-03-001), and would characterize the source of these data as field studies. 
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Environmental Fate (140)

Master Responses and Testnotes for the Environmental Fate Section 

Please note that EPA responses and testnotes are presented in numerical order. However, in the course of response 

development, some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are 

missing. 

Comment 140.1: A commenter contended that the proposed environmental fate data requirements 

for indoor uses of antimicrobials greatly exceed those in part 158 for conventional pesticide 

chemicals. Antimicrobials are not directly broadcast into the environment. The commenter 

maintained that there are limited situations under which any assessment of environmental exposure 

is relevant for antimicrobial pesticides. 

Response 140.1: EPA believes that it is taking a flexible approach to the antimicrobial data 

requirements and has built a tiered system for its testing requirements. As explained in the proposed 

rule, there is now a greater emphasis on indoor uses of antimicrobials, particularly for those 

antimicrobials that go down-the-drain. The Agency and the scientific community have more recently 

become concerned with pharmaceuticals and personal care products (PPCPs), which are now 

recognized as environmental contaminants. A subset of these PPCPs includes antimicrobial 

pesticide products, some of which are being detected in various environmental compartments [e.g., 

surface water and wastewater treatment plant (WWTP) biosolids]. These findings are notable, 

because many of the antimicrobial pesticides detected are registered for only indoor use patterns. 

There are many uses for which a high potential for exposure exists, especially outdoor uses such as 

wood preservatives, ballast water, antifoulant paints/coatings, once-through water circulating 

systems, aquatic areas, and others. These uses may require a more extensive data set that could 

include aerobic and anaerobic metabolism studies. There also are indoor uses that may result in 

environmental exposure through down-the-drain exposure. However, these uses will typically 

require a much reduced first tier data set with additional testing required only if the results of the 

required data indicate a potential risk that needs further characterization. 

Comment 140.2: A commenter asserted that there should not be any environmental fate data 

requirements for material preservatives. 

Response 140.2: EPA disagrees with this comment. Under the Federal Insecticide, Fungicide, and 

Rodenticide Act (FIFRA) for each pesticide registration, the Agency needs sufficient scientific 

information (chemistry, toxicity, exposure data etc.) to make the required statutory finding 

concerning “unreasonable adverse effects.” For some uses, like material preservatives, EPA 

proposed to require five environmental exposure studies to perform a down-the-drain assessment. 

As explained in the preamble to the proposed rule most material preservatives are added during 

industrial processes and are therefore indoor uses. EPA believes that a down-the-drain analysis is 

needed for material preservatives. 

Comment 140.3: A commenter argued that the high and low exposure groupings are inappropriate 

for environmental fate data requirements and that EPA has not provided an adequate explanation. 
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Environmental Fate Section (140) Page 195 

Response 140.3: In response to comments, EPA has removed the “low” and “high” exposure 

descriptors. Instead EPA will use its 12 antimicrobial use patterns to define the required data. 

Comment 140.4: A commenter asserted that there should not be any environmental fate data 

requirements for indoor industrial uses. 

Response 140.4: EPA disagrees with this comment. Under the Federal Insecticide, Fungicide, and 

Rodenticide Act (FIFRA) for each pesticide registration, the Agency needs sufficient scientific 

information (chemistry, toxicity, exposure data etc.) to make the required statutory finding 

concerning “unreasonable adverse effects.” Indoor (industrial or residential) uses are likely to result 

in the disposal of antimicrobial chemicals down-the-drain, which then triggers certain data 

requirements. 

Comment 140.5: A commenter contended that the Agency has not clearly stated when 

environmental fate data on the transformation products would be required, noting that some 

substance degrades quickly. 

Response 140.5: For environmental fate data, the Agency evaluates transformation products on a 

case-by-case basis, using several sources of information. First, the transformation products need to 

be identified. While product chemistry data can provide some information on degradates, 

environmental fate data provide data specific to a particular environmental compartment. 

Environmental fate studies provide information on the stability and persistence of the active 

ingredient and its degradation products in the various environmental media. For example, in the 

hydrolysis study, a half-life >30 days indicates that the substance is stable to hydrolytic processes, 

i.e., the substance did not degrade. Similar determinations are made based on the results of the 

photodegradation in soil and water studies, and the aerobic and anaerobic metabolism in soil and 

water studies after review of the required fate data. Monitoring and incident data, if available, also 

may indicate stability and persistence. There could also be information on a related chemical or from 

the open literature. 

EPA proposed criteria to require testing of transformation/degradation products or leachate 

residues in proposed §158.2280(a)(2) and (3). In response to this comment and also in response to 

comment 160.3, as part of re-evaluating these criteria, EPA determined to clarify and revise the 

criteria to read as follows: 

(2) Data on transformation/degradation products or leachate residues of the parent 

compound are also required to support registration, if the Agency determines that the 

transformation/degradation/leachate products meet one of the following criteria: 

(i) More toxic, persistent, or bioaccumulative than the parent, 

(ii) Have been shown to cause adverse effects in mammalian or aquatic reproductive studies, 

or 

(iii) The moiety of concern (i.e., functional group in the parent chemical molecule that 

imparts adverse effects) remains intact. 
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Environmental Fate Section (140) Page 196 

EPA would use these criteria to determine if environmental fate data on the 

transformation/degradation products or leachate residues are required. Therefore, if the 

environmental fate studies on the parent indicate the transformation product(s) is, for example, 

more persistent in soils, then the same environmental fate data required for the parent are then 

required for the transformation product(s). If concerns are identified, then higher-tiered 

environmental fate and/or ecological effects data on the transformation/degradation product(s) 

would be required. 

Also see response to comments 80.73 and 160.3 for an explanation of transformation products for 

toxicity and ecological effects, respectively. 

It should be noted that the criteria for determining whether to assess risks from a chemical 

substance and/or its degradation products when conducting a down-the-drain analysis are different 

from those discussed above. Those criteria are discussed in response to comment 130.4. 

Comment 140.6: A commenter stated that there are many models that could be used to estimate the 

environmental exposures of antimicrobials. The commenter also maintained that these models have 

not been fully vetted. 

Response 140.6: The Agency agrees with the commenter that many fate models are available and can 

be used for EPA’s risk assessments. We have worked with stakeholders (both industry (such as the 

Biocides Panel of the American Chemistry Council) and organizations such as the American Society 

for Testing and Materials) to understand the robustness of existing models and/or discuss 

development of new models. Currently EPA is working with the Biocides Panel to develop a 

method for estimating the amount of copper in the aquatic medium from antimicrobial uses. For 

models to be applied for environmental fate risk assessments, the model must be validated and must 

be applicable for antimicrobial scenarios. Usage of a validated model is sound science, giving results 

that are more reliable and defensible. 

Comment 140.7: A commenter contended that EPA should evaluate mixtures of antimicrobials that 

occur in the environment. 

Response 140.7: 

The Agency agrees with the commenter that the possible risks that may arise from the presence of 

multiple pesticides, drugs, and cosmetic chemicals should be monitored, and their impact on human 

health and the environment should be assessed. The presence of multiple chemicals in 

environmental media clearly indicates that resolution of such environmental risks can not be done 

by one Agency or a part of one Agency but should be based on a harmonized approach by various 

Agencies and stakeholders. OPP has kept itself abreast of some national monitoring programs like 

the United States Geological Survey’s National Water Quality Assessment Monitoring Program 

which has a huge monitoring database on pesticides in US Waterways, soils, and aquatic species like 

fish. The data indicates reduction of key pesticides in all these three environmental media. 
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Comment 140.8: A commenter stated that the potential environmental impacts of cross-media 

transfers of pesticides need to be addressed in EPA’s environmental risk assessments. 

Response 140.8: The Agency has always been cognizant of the fact that pesticides can transfer from 

one environmental media to another. For this reason we require submission of studies that are used 

to determine various partition coefficients: 

 water/air (Henry Law Constant), which helps in understanding the volatilization from 

surface water. 

 water/soil (Koc), which helps in determining if the pesticide will bind strongly with the 

surface soil and stay on the surface, or will not bind with soil surfaces but instead migrate 

down and result in ground water contamination. 

 octanol/water partition coefficient (Kow), and its components bioconcentration and 

biomagnifications, help in estimating the possibility of bioaccumulation into aquatic 

organisms and the potential of transferring the chemical up the food chain. 

These partition coefficients enable EPA to estimate or predict the environmental fate and transport 

behavior of pesticide chemicals in water, soils/ sediments, and tissues of aquatic organisms. Also see 

response to comment 134.22. 

Comment 140.9: A commenter noted that effluent from some WWTPs discharges to salt water. 

Therefore, according to the commenter, EPA should require at least one marine/estuarine 

invertebrate, one vertebrate, and one plant species to properly assess the potential impacts to 

municipal wastewater treatment plants and receiving waters. 

Response 140.9: Acute Testing with a fish and two aquatic invertebrate species including a bivalve is 

required when the Agency believes there is potential for an active ingredient or potentially toxic 

degradate to reach the estuarine/marine environment from a treatment site. Chronic testing also 

may be required if the Agency believes that chronic exposure is likely. 

Comment 140.10: One commenter indicated that EPA should be using more tiered approaches to 

requiring data. Another commenter asked for clarification on how the environmental fate 

assessment is used to require higher-tiered testing. 

Response 140.10: The approach proposed by EPA for environmental fate data requirements was a 

tiered approach. However, based on comments, the proposed approach has been revised. The 

approach being codifed in the final rule is also a tiered approach. The approach being codified 

specifies that the degradation studies and the activated sludge, respiration inhibition (ASRI) test are 

required immediately. The other studies listed under “Toxicity and Fate in Wastewater Systems” are 

triggered based on the results of the ASRI study. The results of the studies required under “Toxicity 

and Fate in Wastewater Systems” are then used as inputs for the drain-the-drain analysis, and as part 

of a weight-of-evidence evaluation to determine if the higher-tiered studies should be required. For 

additional information on EPA’s use of a tiered data approach in other scientific disciplines, see 

response to comments 80.62, 80.64, 80.71, 160.32, and 160.40. 
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Comment 140.11: The commenter provided information to EPA on the fate of biocides in 

recirculating (non-single-pass) cooling water systems. The commenter asserted that EPA should 

restructure the rule to reflect that recirculating cooling water systems discharge biocides to both 

municipal wastewater treatment plants and directly to surface waters via storm drains. 

Response 140.11: The Agency evaluated the information provided and agrees that there should not 

be a distinction between industrial process and water systems that recirculate water and those that 

are once-through systems. Instead, EPA will refer to “Industrial Processes and Water Systems.” 

Comment 140.12: A commenter stated that the photodegradation in water study is not needed. 

Response 140.12: EPA disagrees with this comment, but believes that additional clarification is 

needed in the testnotes. The photodegradation in water study provides information to ascertain if 

the chemical is likely to degrade or not degrade in surface water due to the action of sunlight. The 

photodegradation in water study would not be required if the hydrolysis study indicates that the 

antimicrobial degrades just by being in water (i.e., the half-life is less than 30 days) at all three pHs 

(5, 7, and 9). To clarify, EPA will add this condition for not requiring the photodegradation in water 

study to proposed testnote 2. 

Comment 140.13: A commenter does not believe that EPA has sufficiently explained why a 

photodegradation in soil study would be required if a substance hydrolyzes and its behavior is 

known from its soil profile. 

Response 140.13: EPA proposed to require the photodegradation in soil study for only one use 

pattern: wood preservative. Wood products that have been treated with wood preservatives are 

often in contact with soil, and therefore it is possible for the wood preservative chemical as well as 

its transformation and degradation products to leach out from the treated wood product. To 

understand the fate of wood preservative chemicals in soil, first requires an understanding of the 

soils properties. Soil profiles are descriptions of soil properties, both physical and chemical. 

Examples of physical characteristics would include: color, bulk density, and texture. Examples of 

chemical characteristics would include: pH of the soil, organic matter content, and chemical 

exchange capacity (CEC). Depending on the soil profile, an antimicrobial pesticide can undergo 

chemical and/or biochemical (biodegradation) processes. For example, if the pH of the soil is less 

than 7, the antimicrobial can undergo hydrolysis and become nonpersistent, or if the pH of the soil 

is basic, the antimicrobial can stay stable and become persistent. If the organic carbon content of a 

soil is high, then the soil has a high microbial population which facilitates the biodegradation 

process. Hence the nature of a soil (soil profile) is an important indicator of how a pesticide may 

behave in a soil. 

Many applicants are well aware of soil profiles, since EPA asks for the soil profile to be submitted 

along with the results of the studies in soils. A number of soil profile databases are available; two of 

the databases used by OPP are one from USDA and the other one called CLARION. 

In the final rule, EPA will retain the photodegradation in soil study for the wood preservatives use 

pattern. If data from the standardized soil profiles show that the chemical is likely to readily degrade 

microbially or undergo redox reactions (degrade chemically) then the photodegradation study in 
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soils may not be required. EPA will add a new testnote 10 to the environmental fate table to replace 

proposed testnote 10, which was removed. New testnote 10 will explain this condition for not 

requiring the photodegradation in soil study. 

Comment140.14: A commenter asserted that nutrient removal test should also be required. 

Response 140.14: This proposed rule focuses specifically on data requirements for antimicrobial 

pesticides. Testing for nutrient removal is not within the scope of this proposed rule. 

Comment 140.15: A commenter argued that biodegradability testing cannot be applied to inorganic 

chemicals. 

Response 140.15: If by inorganic chemicals the commenter means metal ions, then the Agency 

agrees with the commenter; however, inorganic species like chlorite/chlorate, sulfate, nitrate, etc are 

known to interact microbially, and hence biodegradability tests are possible for such species. 

Comment 140.16: A commenter contends that the porous pot study is one of several required 

studies that may not be suitable or practical for antimicrobials. The commenter thinks the Agency 

should clarify whether other factors may be considered in determining whether or not an 

antimicrobial is suitable for porous pot testing (e.g., physical/chemical (P/C) properties, whether the 

chemical belongs to a class of chemicals that will not biodegrade (i.e., inorganics), sludge adsorption 

and removal), or whether studies that simulate WWTPs may substitute for this test (e.g., bioreactor 

test, OECD 303). 

Response 140.16: In the proposed rule, the porous pot test was intended to be a “second tier” test 

that would be required if an antimicrobial pesticide failed the ready biodegradability test. The 

Agency agrees with the commenter that a different study could substitute for the porous pot study 

and has identified two alternative tests that can be used in place of the porous pot test. The first 

alternative test, Biodegradation in Activated Sludge, is one of the five tests included in “Simulation 

Tests to Assess the Primary and Ultimate Biodegradability of Chemicals Discharged to Wastewater” 

(Guideline number OCSPP 835.3280). This guideline is based on the Organisation for Economic 

Co-operation and Development (OECD) guideline 314. Both of the OECD and OCSPP guidelines 

were finalized in October 2008, at approximately the same time that the proposed rule published. 

The second alternative test is entitled “Simulation Test – Aerobic Sewage Treatment: A. Activated 

Sludge Units” (OCSPP 835.3240) and is based on OECD guideline 303. This guideline was also 

finalized in October 2008. 

Both the OECD Guideline 303 and the OCSPP Guideline 835.3280 contain a Figure entitled 

“Pathways for Chemicals Discharged to Wastewater” which illustrates the points in the wastewater 

treatment process that are simulated by the five tests in the guidelines. The OCSPP guidelines are 

available at http://www.epa.gov/ocspp/pubs/frs/publications/Test_Guidelines/series835.htm 

A table to crosswalk the two guidelines is below: 
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Title OECD OCSPP 

Biodegradation in a sewer system 314A Begins on page 12 

Biodegradation in activated sludge 314B Begins on page 20 

Mineralization and transformation in 

anaerobic digester sludge 

314C Begins on page 29 

Biodegradation in treated effluent-surface 

water mixing zone 

314D Begins on page 38 

Biodegradation in untreated wastewatersurface water mixing zone 314E Begins on page 46 

The Agency has determined that either of the simulation tests provide adequately similar 

information to the Porous Pot test and therefore the applicant can have the choice of which study to 

perform. In selecting which study to perform, the applicant should be aware that EPA would 

consider results from either of the simulations tests or the porous pot study to be more conclusive 

than results from the ready biodegradability test. Since these two simulations studies or the porous 

pot study simulate more realistic conditions, they are considered to be much more precise than the 

ready biodegradability test, which is more of a screen. 

Comment 140.17: A commenter did not understand the term “intermittently dry” in proposed 

testnote 9? 

Response 140.17: Proposed testnote 9 triggers the aerobic soil metabolism study. Based on the 

timing of and amounts of water released, soil surfaces can dry-out, thus alternating between wet and 

dry (intermittently dry). This is important because if the soil surfaces are constantly wet (waterlogged) then a different soil metabolism study would be required. In response to this comment, the 

descriptor -- alternating between wet and dry – has been added to proposed testnote 9. 

Comment 140.18: A commenter did not understand the expression “in soils which may become 

flooded or waterlogged” in proposed 10? 

Response 140.18: Proposed testnote 10 was meant to trigger the anaerobic soil metabolism study 

and the aquatic metabolism studies. The process for conducting these studies is to flood the soil 

system in the test environment (water-logging it) to mimic conditions in which the soil is 

continuously wet. However, based on comments received proposed testnote 10 is removed, since 

these studies are now required. See response to comment 50.4. 

Comment 140.19: According to a commenter, it is not clear what EPA means by a weight-ofevidence (WOE) evaluation to trigger aerobic and anaerobic aquatic metabolism studies. 

Response 140.19: Proposed testnotes 5 and 6 (now renumbered to 7) specify that the soil and 

aquatic metabolism studies are a WOE evaluation based on the results of the degradation and 

biodegradation studies conducted in the laboratory. 
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In conducting the WOE evaluation, the Agency first considers the abiotic degradation studies 

(hydrolysis, photodegradation in water and soil), which are chemical methods of degradation. Next , 

the Agency would consider biotic studies (activated sludge sorption isotherm; ready biodegradability; 

and modified activated sludge, respiration inhibition test) which are biological methods of 

degradation. The Agency would evaluate if the antimicrobial would degrade or not degrade within 

30 days. If the antimicrobial does not degrade then the metabolism studies would be required. If the 

exposure happens to be in the terrestrial medium, then terrestrial biodegradation studies such as the 

aerobic and anaerobic soil metabolism may be required. If the aquatic medium is the exposure 

pathway, then aerobic and anaerobic aquatic metabolism studies may be required. 

Comment 140.20: A commenter maintained that EPA’s statement that the dissipation pathway in 

aquatic environments are “almost always” different than in terrestrial environments is not true. 

Response 140.20: EPA agrees with the commenter, and believes “sometimes” would be a better 

word choice. 

Comment 140.21: A commenter states that EPA is unclear about the triggers that would lead to the 

requirement for an aquatic sediment study, and how D-t-D modeling could affect the need for this 

study. 

Response 140.21: Proposed testnotes 5 and 13 trigger the aquatic sediment study for all use patterns 

except the aquatic areas use pattern. EPA has re-evaluated the need for the aquatic sediment study 

and the appropriate triggers. EPA agrees that having two triggers, both of which use a weight-ofevidence evaluation process, is confusing, and believes that one trigger (testnote 13) would be 

sufficient for triggering the aquatic sediment study. EPA will remove testnote 5 from the testnote 

no. column for the aquatic sediment study. Based on this re-evaluation, EPA believes that the 

aquatic sediment study should also be required for the antifoulant coatings and paints use pattern 

since an antifoulant use would meet the criteria of the trigger: Testnote 13. “...data are required 

based on the potential for aquatic exposure and if the weight-of-evidence indicates that the active 

ingredient or principal transformation products are likely to have the potential for persistence, 

mobility, nontarget aquatic toxicity, or bioaccumulation.” Antifoulants are released/applied directly 

to the aquatic environment. These products are often manufactured to be persistent and because of 

the continuous release process some of the active ingredient is likely to be transferred to the bottom 

of the water column and then be adsorbed to the sediment. This is likely to result in adverse effects 

on non-target benthic organisms. Since, this meets the triggers for requiring the study, EPA will 

change the “CR” for the aquatic sediment study for the antifoulant coatings and paints use patterns 

to “R”. 

The aquatic sediment study provides information about the degradation/dissipation processes under 

field conditions. The results of Down-the-Drain (D-t-D) modeling are unlikely to provide 

appropriate information to determine the need for the aquatic sediment study. The current version 

of the D-t-D model estimates concentrations of chemical substances in the water column 

downstream of wastewater treatment facilities, but does not estimate concentrations in the sediment. 

Comment 140.22: A commenter notes that there is no guidance on how to conduct a “monitoring 
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Environmental Fate Section (140) Page 202 

of representative US waters” study, and that EPA has not provided the criteria for triggering a 

“monitoring of representative US waters” study. 

Response 140.22: The commenter is correct: EPA does not have a guideline for conducting this 

study. For all pesticides, such monitoring (studies) of representative US waters is a very rare 

occurrence. If EPA were to require such a monitoring study, protocols would have to be developed 

to specify a great deal of information: 

 At which locations would the monitoring occur and how often would the monitoring occur? 

 Is the sampling for groundwater, surface water, or the estuarine/marine environment? 

 Which chemical substances would be monitored: Is just the antimicrobial to be analyzed or 

would the transformation/degradation products also be analyzed? 

Such a protocol would be specific to a particular pesticide, where that pesticide is used, and where 

the pesticide has been detected, and could not necessarily be used for a different pesticide. 

For the monitoring of representative US waters data requirement, the term “residue of concern” 

(ROC) is currently specified in the Environmental Fate Data Requirements Table in the Test 

Substance to Support column. Since the ROC would be determined during protocol development, 

EPA has added this information as part of a new testnote 17. 

As stated in the preamble to the proposed rule, a WOE approach would be used to determine if a 

monitoring of representative US waters study should required. The preamble to the proposed rule 

discusses this aspect in more detail [59413]. EPA expects this study to be rarely required. 

Comment 140.24: A commenter asserted that the “monitoring of representative US waters” study 

should be required more often. 

Response 140.24: At this time, a monitoring of representative US waters study is very rarely 

triggered. EPA does not expect this to change. 

Comment 140.25: Some commenters contended that AWPA method E11-97 or E20-04, and ASTM 

Method D5108-90 “are of limited or no relevance to estimating environmental exposures” for wood 

preservatives, or antifoulants, respectively. According to the commenters, the results of the ASTM 

method are not suitable for “estimating release rate limits for regulation purposes.” The commenters 

argued that both methods “overestimate leach rates and are not intended for use in risk 

assessments.” The commenters also provided information to indicate that ASTM Method D5108-90 

has been replaced by ASTM D6442-06. 

Response 140.25: Proposed test note 15 triggers the special leaching data requirement for the wood 

preservative use pattern. The commenter stated that the methods referenced by EPA “are known to 

significantly overestimate leach rates and are not intended for use in risk assessments.” Since the 

commenters believe that this method is inappropriate, but have not offered alternative methods, 

proposed testnote 15 will be revised to remove the AWPA methods. Testnote 12 is added to require 

protocol review. 
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Proposed testnote 16 triggers the special leaching data requirement for the antifoulant coatings and 

paints. Since the commenter finds these methods are inappropriate, but have not offered alternative 

methods, proposed testnote 16 will be revised to remove the ASTM methods. Testnote 12 is added 

to require protocol review. 

Comment140.26: A commenter asserted that first tier environmental fate testing should only be 

conducted if there are environmental exposures of concern and that higher tiered testing should 

only be required if triggered. 

Response 140.26: EPA disagrees. The degradation and biodegradation studies provide information 

on the chemical’s stability and persistence in various environmental compartments. This provides 

EPA with information about the antimicrobial’s concentration in the environment. Higher tiered 

testing is triggered based on the results of these studies. 

Comment 140.27: A commenter wants EPA to use a RQ (risk/quotient) approach for assessing 

pesticide risks to terrestrial and aquatic animals and plants. 

Response 140.27: An RQ approach is used for assessing acute and chronic risks of antimicrobial 

pesticides to aquatic plants and animals. RQs are not currently used to assess risks to terrestrial 

organisms due to lack of appropriate exposure estimates needed to derive an RQ. Terrestrial 

exposure is an area that is being further developed, including exposure models, before an RQ 

methodology can be employed. Currently a weight-of evidence approach is used that includes 

available information, including toxicity, monitoring and incident data available, and any relevant 

information from open literature indicating potential risks to terrestrial organisms. 

For plants, EPA believes that an RQ approach would be useful for triggering the seedling 

emergence study. See response to comment 151.1. 

Comment 140.28: A commenter argued that some outdoor uses of antimicrobials could be 

considered as both “low” and “high”, or alternatively that all outdoor uses are considered as “high.” 

Response 140.28: In response to comments, EPA has removed the “low” and “high” exposure 

descriptors. Instead EPA will use its 12 antimicrobial use patterns to define the required data. 

Comment 140.29: A commenter stated that the European approach for addressing wood products 

and their environmental exposure would be useful for EPA to consider. 

Response 140.29: Recently the Agency worked closely with European Union (EU) and OECD 

Countries including Canada to develop and harmonize test guidelines for wood preservative leaching 

test methodologies: OECD 313 (see http://www.oecd.org/dataoecd/33/45/43403332.pdf) and 

OECD 107 (see http://www.oecd.org/dataoecd/33/45/43403332.pdf). 
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EPA agrees with the commenter that these studies could provide useful information for regulatory 

decisions, and would review and evaluate studies submitted to EPA that were conducted according 

to OECD 313 or 107. 

Comment 140.30: A commenter did not understand what EPA meant by expression “chemicals that 

degrade quickly in soil”? 

Response 140.30: Generally, any pesticide chemical that takes less than 60 days in soils to degrade is 

considered to degrade “quickly,” and is therefore not considered stable and hence will not be 

regarded as persistent in soils. If the half-life of the chemical in soil is 60 to 180 days, then the 

chemical is regarded as moderately persistent. If the half-life is greater than 180 days, then the 

chemical is regarded as persistent. 

Comment 140.31: A commenter maintained that EPA should define “likely to occur in non-target 

organisms.” 

Response 140.31: Generally, this means an adverse effect on an organism that was not the target 

pest to be killed or repelled, i.e., a non-target organism. 

Comment 140.32: A commenter asserted that EPA should make its assessments and methodologies 

publicly available. 

Response 140.32: The Agency’s exposure and risk assessment procedures have been presented in 

numerous exposure and risk assessments for antimicrobial pesticides. EPA’s assessments reflect the 

best available data, and the state of the science of exposure and risk assessment models, methods, 

and procedures. 

Comment 140.33: With regards to the “three pronged approach,” a commenter asked: (1) Is the 

modeling approach appropriate for all DtD uses, and if alternatives are acceptable; (2) If the 

hydrolysis or photodegradation in water demonstrates rapid and complete conversion of the 

antimicrobial, are the other three biodegradability studies still needed; (3) Is there a threshold or de 

minimus exposure estimate where the study results are not significant for risk assessment; and (4) if 

a degradate is readily biodegradable, does that satisfy the criteria of both 

environmental chemistry and aquatic toxicity? 

Response 140.33: The responses to the four-part question are as follows: 

(1) The E-FAST model developed by OPPT has two modules that are appropriate for 

estimating exposures to aquatic organisms from releases of antimicrobial pesticides to 

wastewater treatment plants. The Down-the-drain module of E-FAST 2.0 is appropriate for 

discharges to surface water from domestic wastewater treatment facilities that receive 

wastewater containing antimicrobial pesticide primarily from commercial, institutional, and 

residential sources. The General Population Exposures module of E-FAST 2.0 is 

appropriate for discharges to surface water from industrial wastewater treatment facilities 
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that receive wastewater containing antimicrobial pesticides primarily from manufacturing, 

processing, and industrial uses. Paragraph 3 of the response to Q 134.10 discusses the 

criteria EPA would use in considering models other than the Down-the-Drain model. 

(2) Paragraph 1 of the response to comment 130.1 addresses this question. 

(3) The Agency has not determined a threshold or de minimus exposure estimate where the 

study results are not significant for risk assessment. Since risk is a product of hazard and 

exposure, it would not be appropriate to develop a threshold or de minimus level based on 

exposure alone. 

(4) If a degradate is readily biodegradable, that is, meets the criteria of passing the ready 

biodegradability test, the Agency would assume that 90 percent of the degradate is removed 

during wastewater treatment. 

Comment 140.34: A commenter contended that the ready biodegradability study is one of several 

required studies that may not be suitable or practical for antimicrobials, including inorganics. The 

commenter claims that at the dosing level necessary to see CO2 evolution caused by the compound 

above background evolution, many biocides will be toxic to the microbial community. 

Response 140.34: The Agency agrees that many biocides may be toxic to microorganisms at fairly 

low concentrations. This is the primary reason that the Agency is requiring the Activated Sludge 

Respiration Inhibition (ASRI) test for all antimicrobial pesticides, and then triggering the other 

studies listed under the Toxicity and Fate in Wastewater Systems section of the Environmental Fate 

Table according to the results of the ASRI study. According to information in the Ready 

Biodegradability Test Guideline (OCSPP 835.3110), chemical substances with EC50 values of less 

than or equal to 20 mg/L are likely to pose serious problems for subsequent testing. Based on these 

considerations, for antimicrobials with an EC50 of 20 mg/L or less as determined from the ASRI 

study, the Agency will not require the Ready Biodegradability Test but will, however, require either 

the Biodegradation in Activated Sludge study, the Simulation Test - Aerobic SewageTreatment: A. 

Activated Sludge Units, or the Porous Pot Test. In addition, the results of the ASRI study are one of 

the triggers for requiring the Activated Sludge Sorption Isotherm (ASSI) study. 

For antimicrobials with an EC50 of greater than 20 mg/L, based on the ASRI test, applicants must 

perform a biodegradation test, but can choose whether to perform the Ready Biodegradability Test 

or skip the Ready Biodegradability Test and perform either the Biodegradation in Activated Sludge 

study, the Simulation Test - Aerobic SewageTreatment: A. Activated Sludge Units, or the Porous 

Pot Test. If the applicant performs the Ready Biodegradability Test and the antimicrobial fails this 

test, then the applicant must then perform either the Biodegradation in Activated Sludge study or 

the Porous Pot Test, and the ASSI test (unless the conditions of new testnote 19 are met). If the 

antimicrobial passes the ready biodegradability test, the Agency will assume that 90 percent of the 

antimicrobial is removed during wastewater treatment. If the Biodegradation in Activated Sludge 

study, the Simulation Test - Aerobic SewageTreatment: A. Activated Sludge Units, or the Porous 

Pot Test study is performed, then the Agency will use these test results to determine percent 

removal during wastewater treatment. Also see response to comment 134.1. 

Comment 140.35: For environmental fate, as part of their comments, a commenter suggested an 

alternative table approach that is triggered for each of the commenter’s suggested use patterns. 
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Response 140.35: The Environmental Fate Data Requirements table suggested by the commenter, as 

part of their comments, would not provide EPA with the data needed to understand the 

environmental fate and transport of antimicrobials. The commenter’s table demonstrated an 

approach of requiring fate data only when there is “significant environmental exposure.” The table 

submitted did not include test guideline numbers, changed and reduced the number of use patterns, 

and proposed that most fate studies are either not required or only conditionally required. The 

commenter contends that “ [a]ssessment of environmental exposure for antimicrobial pesticides is 

relevant under very limited circumstances” and that indoor uses should not be subject to 

environmental exposure data requirements. EPA disagrees with the commenter’s overall approach 

and the submitted Environmental Fate Data Requirements table for the reasons discussed below. 

Also see response to comments 140.10 and 140.26. 

EPA disagrees with the commenter’s assertion that there are few circumstances where 

environmental exposure of antimicrobials is relevant. Given the detections of antimicrobials in 

surface water and other environmental compartments, minimal exposure cannot be assumed. (see 

response to comments 140.1, 140.2, and 140.4). Moreover, there are many outdoor uses of 

antimicrobials. FIFRA mandates that EPA conduct a risk assessment for any uses for which 

exposure may occur in the various environmental compartments/media. Knowledge of the fate and 

transport in the various environmental compartments is critical to triggering higher-tiered 

environmental fate studies and the nontarget organism risk assessment. 

EPA disagrees that the test substance for many of the studies (in the commenter’s table) should be 

identified simply as the “residue of concern (ROC).” In its proposed Environmental Fate Data 

Requirements Table, EPA specified the test material (TGAI, PAIRA, TEP) to be used for each 

study. Generally, the testing is done first on the TGAI and then as described in response to 

comment 140.5, the determination whether further testing is also needed is made after reviewing the 

required environmental fate and physical/chemical properties data and any other available 

information (e.g., open literature, closely related chemicals). 

The submitter also omitted most of the Testing Guideline Numbers from their data table. At this 

time, all of the data requirement tables in 40 CFR part 158 have Guideline Numbers since this is a 

method of providing information to applicants. The guidelines were developed by EPA scientists 

and others with a particular interest or expertise in the subject matter covered, including 

representatives from the scientific community, industry, non-profit organizations, and other 

governments. Some of these guidelines harmonize EPA's guidelines with guidelines established by 

the Organization for Economic Cooperation and Development (OECD), an international 

organization whose membership includes most industrialized nations which maintain comprehensive 

testing requirements for pesticides and industrial chemicals. When necessary, significant scientific 

issues were presented for external peer review to the FIFRA Scientific Advisory Panel, or to another 

group of scientific experts for that particular topic. Applicants are not required to use these guidance 

documents but are encouraged to use these test guidelines when developing data. Since these 

guidelines have been developed via a rigorous process, as discussed in the preamble to the proposed 

rule (73 FR 59387), “they represent the recommended approach to developing high-quality data that 

should satisfy EPA’s data needs for risk assessment.” Applicants may develop their own test 

protocols; but, are encouraged (and for certain studies required) to submit them to EPA for review 
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Master Responses: 

Environmental Fate Section (140) Page 207 

and acceptance prior to testing to assure that the study would provide EPA with the needed 

information. 

Based on the comments received, the Testnotes to the Environmental Fate Table in the 

final rule will read as follows: 

T140.1 Testnote 1 to the Environmental Fate Table 

Proposed: 

For testing antifoulant paints and coatings, testing is to be performed with both sterile buffered 

distilled water and sterile synthetic seawater at pH 5, 7, and 9. 

Final: 

For testing antifoulant paints and coatings, testing is to be performed separately with both sterile 

buffered distilled water and sterile synthetic seawater at pHs 5, 7, and 9. 

T140.2 Testnote 2 to the Environmental Fate Table 

Proposed: 

Not required when the electronic absorption spectra, measured at pHs 5, 7 and 

9, of the chemical and its hydrolytic products, if any, show no absorption or tailing between 290 and 

800 nm. 

Final: 

Not required if: 

 (i) the electronic absorption spectra, measured at pHs 5, 7 and 9, of the chemical and its 

hydrolytic products, if any, show no absorption or tailing between 290 and 800 nm, inclusive, or 

 (ii) the results of the hydrolysis study at all three pHs (5, 7, and 9) demonstrates a half-life of 

less than 30 days. 

T140.3 Testnote 3 to the Environmental Fate Table 

Proposed: 

The selection of the particular biodegradation study depends on the physical and chemical 

properties of the test substance, and the results of the activated sludge sorption isotherm and the 

modified activated sludge studies. 

Final: 

The results of the Activated Sludge, Respiration Inhibition (ASRI) Test determine which of the 

following tests are required: Ready biodegradability, porous pot, or the Biodegradation in Activated 

Sludge Study as described in the “Simulation Tests to Assess the Biodegradability of Chemicals 

Discharged in Wastewater” or simulation test – aerobic sewage treatment: activated sludge units. 
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Master Responses: 

Environmental Fate Section (140) Page 208 

i. If the ASRI EC50 is equal to or less than 20 mg/L, then the applicant must choose either 

to: 

(A). Conduct a Biodegradation in Activated Sludge as described in the “Simulation Tests to 

Assess the Biodegradability of Chemicals Discharged in Wastewater”; 

(B). Conduct the Porous Pot Test; or 

(C). Conduct the simulation test – aerobic sewage treatment: activated sludge units. 

ii. If the ASRI EC50 is greater than 20 mg/L, then the applicant must choose either to: 

(A). Conduct a Ready Biodegradability Study; or 

(B). Conduct one of the following studies: The biodegradation in activated sludge study as 

described in the “Simulation Tests to Assess the Biodegradability of Chemicals Discharged 

in Wastewater,” the porous pot test, or the simulation test – aerobic sewage treatment: 

activated sludge units. 

T140.4 Testnote 4 to the Environmental Fate Table 

Proposed: 

Required if the pass criteria for the ready biodegradation study are not met. This means 70% or 

greater removal of dissolved organic carbon and 60% or greater of theoretical oxygen demand or 

theoretical carbon dioxide. These pass values must be reached in a 10–day window within the 28–

day period of the test. 

Final: 

Pass criteria for the ready biodegradability study are: 70% removal of dissolved organic carbon 

(DOC) and 60% removal of theoretical oxygen demand (ThOD) or theoretical carbon dioxide 

(ThCO2) production for respirometric methods. These pass levels must be reached in a 10-day 

window within the 28-day period of the test. If the antimicrobial passes the ready biodegradability 

study, then no further testing is required. If the antimicrobial fails the study, then the applicant must 

conduct one of the following studies: The biodegradation in activated sludge study as described in 

the “Simulation Tests to Assess the Biodegradability of Chemicals Discharged in Wastewater,” the 

porous pot test, or the simulation test – aerobic sewage treatment: activated sludge units. 

T140.5 Testnote 5 to the Environmental Fate Table 

Proposed: 

For low environmental exposure uses, data are required based on a weight-ofevidence evaluation of 

the results of the hydrolysis, photodegradation in water, activated sludge sorption isotherm, ready 

biodegradability, and modified activated sludge, respiration inhibition tests. 

Final: 

For the “All Other” use patterns category (as specified in § 158.2280(a)(3)),, data are required based 

on a weight-of-evidence evaluation of the results of the hydrolysis, photodegradation in water, 

activated sludge sorption isotherm, biodegradability, and activated sludge, respiration inhibition 

tests. . 
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Master Responses: 

Environmental Fate Section (140) Page 209 

 

T140.6 Testnote 6 to the Environmental Fate Table 

Proposed: 

For industrial processes and water systems (once-through), data are required based on a weight-ofevidence evaluation of the results of the hydrolysis, photodegradation in water, activated sludge 

sorption isotherm, ready biodegradability, and modified activated sludge, respiration inhibition tests. 

Final: 

Adsorption and desorption using a batch equilibrium method is preferred. In some cases, as when 

the antimicrobial pesticide degrades rapidly, soil column leaching with unaged or aged columns may 

be more appropriate to fully characterize the potential mobility of the parent compound and major 

transformation products. 

T140.7 Testnote 7 to the Environmental Fate Table 

Proposed: 

Adsorption and desorption using a batch equilibrium method is preferred. In some cases, as when 

the antimicrobial pesticide degrades rapidly, soil column leaching with unaged or aged columns may 

be more appropriate to fully characterize the potential mobility of the parent compound and major 

transformation products. 

Final: 

For industrial processes and water systems, aquatic areas, and the “all other” use patterns category 

(as specified in § 158.2280(a)(3)), data are required based on a weight-of-evidence evaluation of the 

results of the hydrolysis, photodegradation in water, activated sludge sorption isotherm, 

biodegradability, and activated sludge, respiration inhibition tests. 

T140.8 Testnote 8 to the Environmental Fate Table 

Proposed: 

The environmental media (soil, water, hydrosoil, and biota) to be utilized in these studies must be 

collected from areas representative of potential use sites. 

Final: 

The environmental media (soil, water, hydrosoil, and biota) to be utilized in these studies must be 

collected from areas representative of potential use sites. 

T140.9 Testnote 9 to the Environmental Fate Table 

Proposed: 

For industrial processes and water systems (once-through), and aquatic areas, data are required for 

use sites that are intermittently dry. 
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Master Responses: 

Environmental Fate Section (140) Page 210 

Final: 

For industrial processes and water systems, and aquatic areas, data are required for use sites that are 

intermittently dry. 

T140.10 Testnote 10 to the Environmental Fate Table 

Proposed: 

For wood preservatives, data are required if treated wood is used in aquatic environments or in soils 

which may become flooded or waterlogged. 

Final: 

For non-metallic antimicrobials, not required if the standardized soil profiles demonstrate that the 

antimicrobial is likely to readily degrade either microbially or via redox reactions (chemically). 

T140.11 Testnote 11 to the Environmental Fate Table 

Proposed: 

Environmental chemistry methods used to generate data associated with this study must include 

results of a successful confirmatory method trial by an independent laboratory. 

Final: 

Analytical methods used to generate data associated with this study must include results of a 

successful confirmatory method trial by an independent laboratory. 

T140.12 Testnote 12 to the Environmental Fate Table 

Proposed: 

Protocols must be approved by the Agency prior to the initiation of the study. 

Details for developing protocols are available from the Agency. 

Final: 

Protocols must be approved by the Agency prior to the initiation of the study. 

T140.13 Testnote 13 to the Environmental Fate Table 

Proposed: 

For industrial processes and water systems (once-through), antifoulant paints and coatings, and 

wood preservatives, data are required based on the potential for aquatic exposure and if the weightof evidence indicates that the active ingredient or principal transformation products are likely to 

have the potential for persistence, mobility, nontarget aquatic toxicity, or bioaccumulation. 

Final: 

For industrial processes and water systems, wood preservatives, and the “all other” use patterns 

category (as specified in § 158.2280(a)(3)), data are required based on the potential for aquatic 
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Master Responses: 

Environmental Fate Section (140) Page 211 

exposure and if the weight-of-evidence indicates that the active ingredient or principal 

transformation products are likely to have the potential for persistence, mobility, nontarget aquatic 

toxicity, or bioaccumulation. 

T140.14 Testnote 14 to the Environmental Fate Table 

Proposed: 

Data are required if the weight-of evidence indicates that the active ingredient or principal 

transformation products are likely to occur in nontarget freshwater, estuarine, or marine waters such 

that human or environmental exposures are likely to occur. The Agency takes into account other 

factors such as the toxicity of the chemical(s), available monitoring data and the vulnerability of the 

freshwater, estuarine, or marine water resources in the antimicrobial use area. 

Final: 

Data are required if the weight-of-evidence indicates that the active ingredient or principal 

transformation products are likely to occur in non-target freshwater, estuarine, or marine waters 

such that human or environmental exposures are likely to occur. In making that determination, the 

Agency takes into account other factors such as the toxicity of the chemical(s), available monitoring 

data and the vulnerability of the freshwater, estuarine, or marine water resources in the antimicrobial 

use area. 

 

T140.15 Testnote 15 to the Environmental Fate Table 

Proposed: 

For wood preservatives, an aquatic leaching study is required. A soil leaching study is required if 

human or environmental exposures are likely to occur from leachates that contain the active 

ingredient or principal transformation products from wood treated with a preservative product. For 

these studies, the Agency accepts the following methods or their equivalents: American Wood 

Preservers’ Association (AWPA) Method E11–97 (aquatic leaching), and AWPA Method E20–04 

(soil leaching). Prior approval of studies conducted according to E11–97 is not required. All other 

protocols must be approved by the Agency prior to the initiation of the study. Details for 

developing protocols are available from the Agency. 

Final: 

For wood preservatives, an aquatic leaching study is required. A soil leaching study is required if 

human or environmental exposures are likely to occur from leachates that contain the active 

ingredient or principal transformation products from wood treated with a preservative product. 

Protocols must be approved by the Agency prior to the initiation of the study. 

T140.16 Testnote 16 to the Environmental Fate Table 

Proposed: 
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Master Responses: 

Environmental Fate Section (140) Page 212 

For antifoulant paints and coatings, a leaching study is required. The Agency accepts the following 

method or its equivalent: American Society for Testing and Materials (ASTM) Method D5108–90. 

Prior approval of studies conducted according to D5108–90 is not required. All other protocols 

must be approved by the Agency prior to the initiation of the study. Details for developing 

protocols are available from the Agency. 

Final: 

For antifoulant paints and coatings, a leaching study is required. Protocols must be approved by the 

Agency prior to the initiation of the study. 

T140.17 Testnote 17 to the Environmental Fate Table 

Proposed: 

N/A 

Final: 

Protocols, which include the residues of concern (such as parent, degradate/transformation product, 

and/or leachate residues) that would be monitored, must be approved by the Agency prior to the 

initiation of the study. 

T140.18 Testnote 18 to the Environmental Fate Table 

Proposed: 

N/A 

Final: 

A biodegradation study is not required if the antimicrobial meets one or more of the following 

criteria: 

i. Classified as a metal; 

ii. Relatively volatile, but not hydrophobic; 

iii. Highly reactive. 

T140.1 Testnote 19 to the Environmental Fate Table 

Proposed: 

N/A 

Final: 

The Activated Sludge Sorption Isotherm test cannot be performed and therefore is not required if 

the antimicrobial is: 

i. Relatively volatile, but not hydrophobic; 

ii. Highly reactive. Or 

iii. The log Kow is less than 3.0. 
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Master Responses: 

Environmental Fate Section (140) Page 213 

T140.20 Testnote 20 to the Environmental Fate Table 

Proposed: 

N/A 

Final: 

If the criteria of testnote (19) of this paragraph are not met, then the Activated Sludge Sorption 

Isotherm test is required if one or more of the following criteria are met: 

i. The antimicrobial is a metal. 

ii. The log Kow is greater than or equal to 3.0. 

iii. The antimicrobial is positively charged or polycationic. 

iv. The EC50 in the Activated Sludge, Respiration Inhibition Test is less than or equal to 20 

mg/L. 

v. The EC50 in the Activated Sludge, Respiration Inhibition Test is greater than 20 mg/L, 

and the antimicrobial fails the Ready Biodegradability study. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Master Responses: 

Non-Target Plant Protection Section (150) Page 214 

Non-Target Plant Protection (150) 

Master Responses and Testnotes for the Non-Target Plant Protection Section 

Please note that EPA responses and testnotes are presented in numerical order. However, in the course of response 

development, some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are 

missing. 

Comment 151.1: One commenter asked EPA to explain the criteria used to trigger higher-tiered 

plant studies based on the results of the algal studies. 

 

Response 151.1: The criteria to trigger higher- tiered plant studies are specified in proposed testnotes 

2 and 5 to the proposed nontarget plant protection table. A toxicity level (EC50 <1ppm) indicates 

that the antimicrobial pesticide would have serious adverse affect(s) on algae at low concentrations. 

This could have serious consequences to nontarget algae species. Therefore, at this toxicity level, 

additional higher-tiered testing is required to further characterize the potential adverse affects to 

aquatic plants. EPA is retaining the toxicity trigger of (<1 ppm) in proposed testnote 5 to the 

nontarget plant protection table. 

In evaluating proposed testnote 2 to the nontarget plant protection table, EPA has considered the 

commenter’s suggested table for nontarget plants. For the seedling emergence study, the commenter 

used “CR” for most use patterns and suggested that the seedling emergence study should only be 

required “when environmental exposure is likely to result under normal usage conditions as 

determined by appropriate assessment methods.” Also, comment 140.27 advocated for the use of an 

Risk Quotient (RQ) approach for assessing plants. 

Based on this evaluation, EPA believes using “CR” for the seedling emergence study when triggered 

by a level of concern approach (RQ approach) would provide EPA with the required data when 

needed. Proposed testnote 2 to the final nontarget plant protection table is replaced by: 

“Data are required if the risk quotient from any aquatic plant growth Tier II study exceeds a level of 

concern for aquatic plants.” 

However, proposed testnote 2 also triggers the aquatic plant growth (aquatic vascular plant) study, 

and is still the appropriate trigger for that study. A new testnote 10 to the final nontarget plant 

protection table will be created to replace testnote 2 and which will read: 

“For the ‘All Other’ use patterns category (as specified in § 158.2250(c)), data are required if the 

aquatic (algal) plant growth Tier II study demonstrates detrimental effects at less than 1.0 ppm or 

mg/L.

Comment 152.1: A commenter noted that in testnote 3 to the proposed table for nontarget plant 

protection data requirements: (1) Hydrolysis indicates half-life of greater than 4 days but now 

includes metabolites and/or transformation products; (2) pH levels are not discussed. The 

commenter also noted that this differs from testnote 13 to the proposed nontarget organism data 

requirements which addressed active and/or metabolites if persistence greater than 5 days at pHs 

5,7,9. The commenter believe these two testnotes should be consistent. 

 
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Master Responses: 

Non-Target Plant Protection Section (150) Page 215 

Response 152.1: EPA re-evaluated and compared these two testnotes. Both of these testnotes 

specify the circumstances when a study would not be required, and given the similarities of the two 

scientific disciplines, there should be some similarities in the triggers. The commenter is correct that 

there are differences between proposed testnote 13 of the Nontarget Organism Table and proposed 

testnote 3 of the Nontarget Plant Protection Table. The following changes are made to proposed 

testnote 3. 

 EPA has reconsidered the octanol/water partition coefficent as a trigger (3i) for the 

Nontarget Plant Protection Table. While this trigger is appropriate for nontarget organisms 

(used as a measure of bioconcentration factor in fish), the octanol/water partition factor 

cannot serve the same function for plants. Therefore, EPA will remove proposed trigger 3i. 

 However, in re-evaluating and comparing proposed testnote 13 of the Nontarget Organism 

Table, EPA noted that proposed testnote 13ii with some revisions would be an appropriate 

trigger to replace proposed trigger 3i. The new trigger 3i will read “There are no potential 

exposures to plants.” 

 EPA agrees that the two testnotes should be consistent in their approach to pH levels used 

as a trigger. EPA will revise proposed testnote 3ii of the Nontarget Plant Protection Table to 

read the same as proposed testnote 13iii of the Nontarget Organism Table 

 EPA intends to retain proposed trigger 3iii with a modification to replace the phrase “the 

ready biodegradability study [158.2280]” with the phrase “a biodegradation study.” This 

accounts for changes in the environmental fate table. 

As part of the re-evaluation of proposed testnote 3, EPA also considered if, based on the revised 

testnote, the wood preservative use pattern and the antifoulant coatings and paints use pattern could 

be “CR” instead of “R” for the vegetative vigor study. Based on the revised testnote 3 to the 

Nontarget Organism Table and most particularly on the new trigger included in testnote 3i, as 

described above, EPA believes that using “CR” for the vegetative vigor study would provide EPA 

with the required data when needed. 

Comment 153.1: According to a commenter, testnote 5 to the proposed nontarget plant protection 

data requirements references four different algal species but does not differentiate on the basis of 

freshwater versus saltwater species. 

Response 153.1: Four test species are specified in both proposed testnotes 5 and 6. Two of the 

species Navicula pelliculosa and Skeletonema costatum are marine species 

Comment 154.1: A commenter asked how the terrestrial field study data requirements are related to 

antimicrobial uses, noting that antimicrobials are not applied directly to the environment. 

 

Response 154.1: EPA agrees that most antimicrobials are not applied directly to the terrestrial 

environment: there are many indoor uses. However, there are uses such as wood preservatives, that 

are in placed in contact with soil or leaches to the soil. As explained in the preamble to the proposed 

rule [59416], the terrestrial field study provides more realistic information than a laboratory study 

and would be required on a very infrequent basis. Proposed testnote 8 specifies the triggers for 

requiring a terrestrial field study, on a case by case basis. 

 

 
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Master Responses: 

Non-Target Plant Protection Section (150) Page 216 

Comment 154.2 A commenter asked how the data from the terrestrial field study would be used in a 

risk assessment. 

 

Response 154.2: If the terrestrial field study data requirement were triggered, then the results would 

be used to determine any adverse affects (such as mortality or reproductive impacts under actual 

field considerations) on terrestrial organisms (birds, mammals, insects, etc). These results from the 

terrestrial field study would be incorporated into an environmental risk assessment that would detail 

the adverse affects of using the antimicrobial pesticide in the environment. EPA notes that the 

requirement to conduct a terrestrial field study would be a rare occurrence, and only under unusual 

circumstances, such as the antimicrobial could not be adequately tested in the laboratory. 

Comment 155.1: A commenter argued that the plant protection data requirements for antimicrobials 

are inconsistent with those of conventional pesticides, noting that for conventionals, these studies 

are required for several outdoor use patterns, yet for antimicrobials they are required for both indoor 

and outdoor use patterns. 

 

Response 155.1: As explained herein, EPA believes that the plant protection data requirements for 

antimicrobials should not be the same as those for conventional pesticides. Antimicrobial pesticides 

have very different use patterns than the indoor conventional pesticides. As discussed in the 

proposed rule preamble, it is expected that most of the "indoor use" antimicrobial pesticides will 

enter the environment since, either after or during use, the antimicrobial ends up down-the-drain. 

 

Comment 155.2: One commenter noted that Tier II testing is required for all antimicrobials while 

only Tier 1 testing is required for conventionals. 

 

Response 155.2: Based on the rationale in the preamble which discussed the expected phytotoxicity 

of many antimicrobials (73 FR 59416), EPA continues to believe that only Tier II testing is 

appropriate for antimicrobial pesticides. Antimicrobials are different from conventional pesticides, 

particularly in their large use volumes, multiple source use patterns and environmental exposure 

from down the drain uses and disposal, and therefore differences in testing requirements from 

conventionals is expected. 

Comment 155.3: As part of their comments, a commenter suggested an alternate Antimicrobial 

Plant Protection Data Requirements Table. 

Response 155.5: As explained herein, the Ecotoxicity (Nontarget Plant) Data Requirements table 

suggested by the commenter is not adequate to evaluate the hazards and risks to nontarget plants 

from antimicrobial pesticides. The suggested table did not include test guideline numbers, changed 

and reduced the number of use patterns, and proposed that all ecotoxicity plant studies are either 

not required or only conditionally required. The commenter contends that there are no 

circumstances where ecological effects plant data are relevant for antimicrobial pesticides, and that 

indoor uses should not be subject to environmental exposure or nontarget plant species risk 
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Master Responses: 

Non-Target Plant Protection Section (150) Page 217 

assessments. EPA disagrees with many aspects of these comments and the suggested Ecotoxicity 

Data Requirements Table for plant species. 

EPA disagrees that exposure should be presumed to be minimal or nonexistent for antimicrobials 

applied indoors or that tests are not required if the test organism is the target species for the 

pesticide (see testnotes 1 and 2 to the commenter’s suggested table). Moreover, there are many 

outdoor uses of antimicrobials that are not addressed in the commenter’s suggested table. FIFRA 

mandates that EPA conduct a risk assessment for any uses for which exposure may occur in the 

various environmental compartments/media. Those risks are assessed separately for the various taxa 

including plants, categories (e.g., freshwater, saltwater), and short-term (i.e., acute) and longer-term 

(i.e., chronic) exposures. Assessing these potential risks necessitates having an appropriate 

ecotoxicity data base for plant exposure and toxicity. This can only be accomplished by requiring 

plant studies for the initial assessment. A tiered approach can not be driven solely by risk quotients 

derived from a Tier 1 study. The fact that an acute risk quotient for a plant species does not exceed a 

Level of Concern for acute risk does not imply that a chronic risk does not exist or that data are not 

needed to assess that risk. The trigger for a chronic test is more likely driven by the frequency, 

duration, or magnitude of the chronic exposure and the environmental properties of the pesticide. 

For example, plants might be subjected to repeated low-level exposure that is not acutely lethal but 

which may impact reproductive success and plant growth. 

EPA disagrees that the test substance for plant studies (in the commenter’s table) should be 

identified simply as the “residue of concern (ROC).” In its proposed Nontarget Plant Data 

Requirements Table, EPA specified the test material (TGAI, TEP) to be used for each 

study. The test substance determination is made after reviewing the required environmental fate and 

physical/chemical properties data and any other available information (e.g., open literature, closely 

related chemicals) to determine the substance of concern for exposure of non-target 

organisms. For example, if an applicant can adequately demonstrate that the TGAI dissipates so 

rapidly that there would be no acute or chronic exposure, TGAI testing may be waived, and 

degradate testing may be required. 

The commenter also omitted all Testing Guideline Numbers from its data table. At this time, all data 

requirement tables in 40 CFR part 158 have Guideline Numbers since this is a method of providing 

information to applicants. Applicants are not required to use these guidance documents but are 

encouraged to use these test guidelines when developing data. Since these guidelines have been 

developed via a rigorous process, as discussed in the preamble to the proposed rule (73 FR 59387), 

“they represent the recommended approach to developing high-quality data that should satisfy 

EPA’s data needs for risk assessment.” Applicants may develop their own test protocols, but, are 

encouraged (and for certain studies required) to submit them to EPA for review prior to testing to 

assure that the study would provide EPA with the needed information. 

Based on the comments received, the Testnotes to the Non-Target Plant Protection Table 

in the final rule will read as follows: 

T152.1 Testnote 1 to the Nontarget Plant Protection Table 
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Master Responses: 

Non-Target Plant Protection Section (150) Page 218 

Proposed: 

Data on only one plant species (rice, Oryza sativa) are required. 

Final: 

Data on only one plant species (rice, Oryza sativa) are required 

T152.2 Testnote 2 to the Nontarget Plant Protection Table 

Proposed: 

For low environmental exposures, data are required if the aquatic (algal) plant growth Tier II study 

demonstrates detrimental effects at less than 1.0 ppm or mg/L. 

Final: 

Data are required if the risk quotient from any aquatic plant growth Tier II study exceeds a level of 

concern for aquatic plants. 

T152.3 Testnote 3 to the Nontarget Plant Protection Table 

Proposed: 

For low environmental exposures, and industrial processes and water systems (once-through), data 

are required if one or more of the following criteria are met: 

 i. The octanol/water partition coefficient (Kow) for the active ingredient or principal 

transformation products ≥ 1,000 for the active ingredient or principal transformation products; 

 ii. The hydrolysis half-life of the active ingredient or principal transformation products in 

water is > 4 days. 

 iii. The results of the ready biodegradability study [§ 158.2280] indicate that the active 

ingredient or principal degradation products are not biodegradable in 28 days, i.e. the biodegradation 

curve has not reached a plateau for at least three determinations within the 28 days. 

Final: 

Not required when: 

 i. There are no potential exposures to plants; 

 ii. The hydrolytic half-life is less than 5 days at pH 5, 7, and 9; or 

 iii. The results of a biodegradation study indicate that the active ingredient or principal 

degradation products are not biodegradable in 28 days, i.e. the biodegradation curve has not reached 

a plateau for at least three determinations within the 28 days. 

T152.4 Testnote 4 to the Nontarget Plant Protection Table 

Proposed: 

For TEP testing, data are required for the applicant’s end-use product if an ingredient in the end-use 

product, other than the active ingredient, is expected to enhance the toxicity of the active ingredient. 

Final: 
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Master Responses: 

Non-Target Plant Protection Section (150) Page 219 

For TEP testing, data are required for the applicant’s end-use product if an ingredient in the end-use 

product, other than the active ingredient, is expected to enhance the toxicity of the active ingredient. 

T152.5 Testnote 5 to the Nontarget Plant Protection Table 

Proposed: 

One Tier II (dose response) study, conducted with Selenastrum capricornutum, is required for the low 

environmental exposure category grouping. If the results of this study exhibits detrimental effects (is 

less than 1.0 ppm or mg/L), then additional Tier II (dose response) studies are required on three 

species (Anabaena flos-aquae, Navicula pelliculosa, and Skeletonema costatum. 

Final: 

One Tier II (dose response) study, conducted with Selenastrum capricornutum, is required for the “all 

other” use patterns category (as specified in §158.2250(c)). If the results of this study exhibits 

detrimental effects (EC50 less than 1.0 ppm or mg/L), then additional Tier II (dose response) studies 

are required on three species (Anabaena flos-aquae, Navicula pelliculosa, and Skeletonema costatum). 

T152.6 Testnote 6 to the Nontarget Plant Protection Table 

Proposed: 

For industrial processes and water systems (once-through), antifoulant coatings and paints, wood 

preservatives, and aquatic areas, Tier II (dose response) studies are required on four species 

(Anabaena flosaquae, Navicula pelliculosa, Skeletonema

costatum, and Selenastrum capricornutum.

Final: 

For industrial processes and water systems, antifoulant coatings and paints, wood preservatives, and 

aquatic areas, Tier II (dose response) studies are required on four species (Anabaena flos-aquae, 

Navicula pelliculosa, Skeletonema costatum, and Selenastrum capricornutum). 

T152.7 Testnote 7 to the Nontarget Plant Protection Table 

Proposed: 

Environmental chemistry methods used to generate data must include the results of a successful 

confirmatory method trial by an independent laboratory. 

Final: 

No change from proposal. 

T152.8 Testnote 8 to the Nontarget Plant Protection Table 

Proposed: 
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Master Responses: 

Non-Target Plant Protection Section (150) Page 220 

Tests are required on a case-by-case basis based on the results of lower tier plant protection studies, 

adverse incident reports, intended use pattern(s), and environmental fate characteristics that indicate 

potential exposure. 

Final: 

Tests are required on a case-by-case basis based on the results of lower tier plant protection studies, 

adverse incident reports, intended use pattern(s), and environmental fate characteristics that indicate 

potential exposure. 

T152.9 Testnote 9 to the Nontarget Plant Protection Table 

Proposed: 

Protocols must be approved by the Agency prior to the initiation of the study. Details for 

developing protocols are available from the Agency. 

Final: 

Protocols must be approved by the Agency prior to the initiation of the study. 

T152.10 Testnote 10 to the Nontarget Plant Protection Table 

Proposed: 

N/A 

Final: 

For the “All Other” use patterns category (as specified in § 158.2250(c)), data are required if the 

aquatic (algal) plant growth Tier II study demonstrates detrimental effects at less than 1.0 ppm or 

mg/L.
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Master Responses: 

Non-Target Organism Exposure Section (160) Page 221 

Non-Target Organism Exposure (160) 

Master Responses and Testnotes for the Non-Target Organism Exposure 

Section 

Please note that EPA responses and testnotes are presented in numerical order. However, in the course of response 

development, some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are 

missing. 

Comment 160.1: A commenter asserted that if there is no expectation of environmental exposure, 

then no ecotoxicity data are needed. The commenter maintained that there are few antimicrobial use 

patterns where ecological effects information would be relevant to an assessment under FIFRA. 

According to the commenter, it is unclear why extensive ecotoxicity data are required for indoor 

uses of antimicrobials 

Response 160.1: EPA believes that it is taking a flexible approach to the antimicrobial data 

requirements for non-target organisms and has built a tiered system for its testing requirements. As 

explained in the proposed rule, there is now a greater emphasis on indoor uses of antimicrobials, 

particularly for those antimicrobials that go down-the-drain. The Agency and the scientific 

community have more recently become concerned with pharmaceuticals and personal care products 

(PPCPs), which are now recognized as environmental contaminants. A subset of these PPCPs 

includes antimicrobial pesticide products, some of which are being detected in various 

environmental compartments/media [e.g., surface water and wastewater treatment plant (WWTP) 

biosolids]. These findings are notable, because many of the antimicrobial pesticides detected are 

registered for only indoor use patterns. 

There are many uses for which a high potential for exposure exists, especially outdoor uses such as 

wood preservatives, ballast water treatments, antifoulant paints and coatings, aquatic areas, and 

others. These uses may require a more extensive data set that could include acute and chronic tests 

in both freshwater and saltwater, and possibly in the sediment as well as the water column. There 

also are indoor uses that may result in environmental exposure through down-the-drain release. If 

the effluent from a wastewater treatment plant (WWTP) is likely to contain an antimicrobial 

pesticide, or if the antimicrobial is likely to partition to the sludge that is derived during the 

treatment process, then indoor uses could require additional testing to further characterize the 

hazard and the risk. 

Comment 160.2: A commenter questioned why Tier 1 nontarget organism acute toxicity data are 

needed “in case of unintended or coincident exposure to antimicrobials, such as a transportation 

accident” for antimicrobials, but not for conventionals or biochemicals? 

Response 160.2: As discussed in the preamble to the proposed rule (73 FR 59413), acute ecological 

effects studies are currently required for an application for registration for an antimicrobial pesticide. 

These studies allow EPA to develop precautionary labeling language, which can provide needed 

information in case of unintended or co-incident exposure to antimicrobials. Additionally, these data 

are also used as during the down-the-drain assessment. The results of the down-the-drain 

assessment would provide EPA with estimated environmental concentrations (EECs) which when 
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combined with the results of the Tier 1 ecotoxicity studies could indicate a potential risk that needs 

further characterization. 

Comment 160.3: A commenter asserted that EPA should explain what is considered “stable” in the 

environment in proposed testnote 3. Some commenters questioned how would a registrant 

determine if “transformation products” would need to be tested. One commenter stated their belief 

that any data developed to assess the potential risk to nontarget organisms should be developed with 

the appropriate residue of concern (ROC) (i.e. degradation product, metabolite, or TGAI) rather 

than always testing with the TGAI. Still another commenter asked how would EPA determine that 

the transformation products are “more toxic, persistent, bioaccumulative or have been shown to 

cause adverse effects in mammalian or aquatic reproductive studies” 

Response 160.3: The Agency evaluates transformation products on a case-by-case basis, using 

several sources of information. As explained in response to comment 140.5, environmental fate 

studies provide information on the stability and persistence of the active ingredient and degradation 

products in the various environmental media. Monitoring and incident data, if available, also may 

indicate stability and persistence. There could also be information on a related chemical or from the 

open literature. 

If the environmental fate studies on the parent indicate the transformation/degradation product(s) 

is, for example, more persistent in soils, then it is possible that non-target plants or animals could be 

exposed to the degradate. Once the transformation products and the environmental compartment in 

which they occur are identified, then the available toxicology data (e.g., reproduction tests, 

developmental tests, non-rodent chronic studies) are reviewed to determine toxicity. 

EPA proposed criteria to require testing of transformation/degradation products or leachate 

residues in proposed §158.2240(a)(3) and (4) for non-target organisms. In response to this comment 

and response to comment 140.5, as part of re-evaluating these criteria, EPA determined to clarify 

and revise the criteria to read as follows: 

Data on transformation/degradation products or leachate residues of the parent compound 

are also required to support registration, if the Agency determines that the 

transformation/degradation/leachate products meet one of the following criteria: 

(i) more toxic, persistent, or bioaccumulative than the parent, 

(ii) have been shown to cause adverse effects in mammalian or aquatic reproductive studies, 

or 

(iii) the moiety of concern (i.e., functional group in the parent chemical molecule that 

imparts adverse effects) remains intact. 

After reviewing all available information, EPA would use these criteria to determine if ecological 

effects data on the transformation/degradation products or leachate residues are required for either 

non-target organisms or non-target plants. These criteria will also be added to the non-target plant 

table as new §158.2250(b). EPA believes that non-target plant protection data may sometimes be 

needed when the Agency begins conducting species-specific endangered species assessments for 

antimicrobial pesticides. 

EPA does not use the term “residue of concern (ROC)” in the Nontarget Organisms Data 

Requirements Table. Instead the appropriate test material(s) such as TGAI, degradate, or TEP is 
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specified in the data requirements table in proposed 40 CFR 158.2240. This approach is also used 

for the conventional nontarget organism table in part 158. Generally, for ecological testing, the 

TGAI testing is performed first, and then additional testing on a transformation product may be 

required based on the process described above. Depending on how fast a substance decays, a nontarget organism or plant could actually be exposed to a mixture of the parent and the 

degradation/transformation products. 

EPA notes that ROC is used in the Residue Chemistry Data Requirements Tables for both 

conventionals and antimicrobials. The term ROC is defined for conventionals as the parent 

pesticidal compound and its metabolites, degradates, and impurities of toxicological concern. The 

ROC is determined by the Agency using the results of residue chemistry metabolism studies 

(mammalian or plant) or nature of the residue on surfaces and then combining those results with the 

results of mammalian toxicity studies. Taken together, EPA uses these studies to identify the 

residues that would be a concern in a food item. 

Comment 160.4: A commenter noted that EPA did not include any studies to assess endocrine 

disruption effects for avian and aquatic species. 

Response 160.4: The commenter is correct that EPA has not included within the proposed subpart 

W, studies whose sole purpose is to assess endocrine disruption effects in avian and aquatic species. 

The Agency has developed, through a separate effort, a screening battery to identify chemicals that 

may have effects on the hormone systems of people and animals. 

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor Screening 

Program (EDSP) to determine whether certain substances (including pesticide active and other 

ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally 

occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP 

employs a two-tiered approach to making the statutorily required determinations. Tier 1 consists of a 

battery of 11 screening assays to identify the potential of a chemical substance to interact with the 

estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 

screening and are found to have the potential to interact with E, A, or T hormonal systems will 

proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests 

are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine 

related effects caused by the substance, and establish a dose-response relationship between the dose 

and the E, A, or T effect. 

Between October 2009 and February 2010, EPA issued test orders/data call-ins for 58 pesticide 

active ingredients and nine inert ingredients. This list of chemicals was selected based on the 

potential for human exposure through pathways such as food and water, residential activity, and 

certain post-application agricultural scenarios. This list should not be construed as a list of known or 

likely endocrine disruptors. 

Under FFDCA sec. 408(p) the Agency must screen all pesticide chemicals, including antimicrobials. 

Accordingly, EPA anticipates issuing future EDSP test orders/data call-ins for all pesticide active 

ingredients. 
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For further information on the EDSP including the status and test guidelines, please visit our 

website: http://www.epa.gov/endo/. 

Comment 160.5: A commenter asked why the species selected for the acute avian toxicity data 

requirement (proposed testnote 1) are different from those selected for conventional pesticides 

(testnote 3 in the 2007 final rule). 

Response 160.5: Proposed testnote 1 to the antimicrobial data requirements table for non-target 

organisms specifies testing in two species: a waterfowl species and an upland game bird species for 

four use patterns and one species for the “all other” use patterns category. For most use patterns, 

testnote 3 in 40 CFR 158.630 (the non-target organism data requirements for conventional 

pesticides) would require testing in two species: a passerine species and either a waterfowl species or 

an upland game bird species. In contrast to most antimicrobials, many conventional pesticides are 

applied extensively and repeatedly as foliar sprays in agricultural and non-agricultural areas (e.g., turf, 

roadside right-of-ways) and have a greater potential to impact a broader variety of terrestrial birds. 

Standard OPP policy for avian testing always has been to use the mallard (waterfowl species) and/or 

the northern bobwhite (aka bobwhite quail) (upland game bird) as test species for both antimicrobial 

and conventional pesticides. The Agency is continuing this policy by requiring the mallard and/or 

bobwhite species for acute avian toxicity testing of antimicrobial pesticides. 

Comment 160.7: A commenter noted that proposed testnote 7 specifies the triggers for requiring 

TEP testing for the acute freshwater invertebrate study and acute freshwater fish study; however, 

the wood preservatives use pattern is specified as NR. The commenter asked whether TEP testing 

could be required because of the triggers in testnote 7, even though it is NR. 

Response 160.7: Proposed testnote 7 also triggers the testing for the TEP acute estuarine and marine 

organisms toxicity testing. EPA agrees that the combination of Rs, CRs, NRs and the current 

structure of proposed testnote 7, is confusing and that clarification is needed. 

The data requirements for TEP testing and proposed testnote 7 was also considered in light of the 

Agency’s recent determination based on comments received (see response to comment 50.4) on 

EPA’s current practice of conducting risk assessments for wood preservatives based on land-only 

versus a land and aquatic predetermined use pattern. All wood preservative risk assessments will 

now be performed considering that the treated wood could end-up either on the land or in the 

aquatic environment. As previously discussed there are multiple pathways for wood preservative 

degradates and/or leachates to reach surface water. EPA has also determined to conduct a downthe-drain assessment for all appropriate use patterns which would include wood preservatives and 

antifoulant paints and coatings (see response to comment 134.1). For wood preservatives, these 

determinations mean that additional ecological testing is required to conduct an ecological risk 

assessment, and the following changes are being made to the wood preservative testing column: 

Acute freshwater invertebrates toxicity (TEP testing): change from NR to CR 

Acute freshwater fish toxicity (TEP testing): change from NR to CR 

Acute estuarine and marine organisms toxicity (TEP testing): change from NR to CR 
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For antifoulant paints and coatings, the determination to conduct a down-the-drain assessment also 

means that additional data could be needed for the down-the-drain assessment, and the following 

changes are being made to the antifoulant paints and coatings testing column: 

 

Acute freshwater invertebrates toxicity (TEP testing): change from NR to CR 

Acute freshwater fish toxicity (TEP testing): change from NR to CR 

Acute estuarine and marine organisms toxicity (TEP testing): change from NR to CR 

EPA believes that simplifying the data requirements that reference testnote 7 so that these 

requirements are CR for all use patterns is clearer, and also closer to the suggestions made by the 

commenters in their suggested nontarget organism data requirements table. Their suggested table 

was predominantly CR for aquatic uses. 

Therefore, proposed testnote 7 will trigger the “CR” studies. 

However, changing all the use patterns to “CR” for the TEP studies means changing the “R” 

proposed for the aquatic use, and industrial processes and water systems use patterns for the acute 

freshwater invertebrates toxicity study and the acute freshwater fish toxicity study, to “CR.” To 

account for this change proposed testnote 7 will be revised to include an additional trigger: Data are 

required when “the end-use antimicrobial product will be applied directly into an aquatic 

environment.” EPA believes that this trigger is equivalent to the “R” and essentially this is a nonchange. These changes are summarized below for both the aquatic areas and industrial processes and 

water systems testing column: 

Acute freshwater invertebrates toxicity (TEP testing): change from R to CR 

Acute freshwater fish toxicity (TEP testing): change from R to CR 

Acute estuarine and marine organisms toxicity (TEP testing): no change 

 TEP testing should be infrequently required for the antifoulant paints and coatings use patterns 

because for these use patterns, the TEP could be the paint. Testing for aquatic organisms is done in 

water. Therefore, the test material must be soluble in water, or made soluble by addition of an 

appropriate solvent, if one exists, or other appropriate mechanical methods. Paint is not soluble and 

there may not be a way to make it soluble. Since these studies are often run in glass aquaria, the paint 

could coat the sides of the glass and the test animals themselves. The paint could ruin test 

equipment by clogging lines and injection nozzles. Therefore EPA has added a new testnote, which 

is replacing proposed testnote 5 (which was removed). This new testnote states that an applicant 

should request a waiver if the TEP cannot be tested. 

EPA also notes that a testnote specifying the number of species to be tested was omitted in the 

proposed rule for the TEP testing for acute freshwater fish toxicity. This testnote is needed for 

clarity. Testnote 3 is added to the line for acute freshwater fish toxicity. 

Comment 160.8: A commenter asserted that it is essential to have both acute and chronic toxicity 

test results for at least one freshwater invertebrate, vertebrate, and plant species, and at least one 

marine/estuarine invertebrate, vertebrate, and plant species. 
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Response 160.8: EPA proposed to require acute tests for both a coldwater and warmwater 

freshwater fish, an invertebrate, and one or more aquatic plants. For marine/estuarine species, for 

most use patterns, EPA proposed to conditionally require acute testing with a fish and two aquatic 

invertebrate species, including a bivalve, when the Agency believes there is a potential for the active 

ingredient or a potentially toxic degradate to reach the estuarine/marine environment through 

transport (e.g., leaching, runoff) from the treatment site. In such a situation, chronic testing with one 

or more marine/estuarine species also may be required if the Agency believes that chronic exposure 

is likely. These studies are required for those uses where the pesticide product is applied directly into 

the marine/estuarine environment. 

For chronic testing EPA also proposed to require the fish early life stage and the aquatic 

invertebrate life-cycle studies for the industrial (once-through), antifoulant and aquatic areas use 

patterns. EPA proposed to conditionally require the same two studies for the low environmental 

grouping (now called the “all other” use patterns category) and wood preservatives. 

Based on this and other comments, EPA has re-evaluated the non-target organism data needed for a 

registration decision and concluded that additional acute and chronic data are needed. See response 

to comments 160.7, 50.4, and 134.21 for discussions on the rationale for and descriptions of the 

changes. 

EPA does not require chronic testing for plants. Plant species encompass many different life spans. 

Phytoplankton reproduce quickly and have extremely short life spans. Annuals live for one year. 

Many perennials do not actually live for multiple years, but reproduce from seeds year after year. 

The plant species that live the longest would be woody species, such as trees. EPA does not believe 

that antimicrobial use patterns impact terrestrial areas such that chronic exposures occur: To EPA’s 

knowledge, no adverse chronic effects caused by pesticides has been documented. Any effect on 

terrestrial plant species has been categorized as an acute effect and would be covered by our current 

testing procedures. Chronic effects of aquatic plants are covered by the acute testing guidelines. 

Algae is used as the primary test species for acute testing of aquatic plants. The testing is based on 

growth parameters and the tests normally run for periods of time that would include several 

generations of the algae. The results from the acute algal studies would be similar to those obtained 

from chronic testing in other species, and could be used to assess any chronic effects to aquatic 

plant species. 

Comment 160.9: A commenter asked for clarification on the trigger point in proposed testnote 7(i). 

Response 160.9: Proposed testnote 7 specifies the triggers when TEP testing would be required. In 

7(i), when the EEC (estimated environmental concentration) is greater than one-half the LC50 or 

EC50 of the TGAI, then the Level of Concern (LOC) is exceeded. This exceedance means that EPA 

would presume that there is an acute risk, and may need additional data to characterize that risk. 

Comment 160.10: In proposed testnote 4 (which triggers the avian dietary study), EPA specified a 

trigger of 100 mg ai/kg (milligrams active ingredient/kilogram) for additional testing. A commenter 

requested information on why this trigger was selected. The commenter also stated that EPA could 
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use exposure tools to conduct an initial assessment based on Tier 1 data and then trigger additional 

testing based on risk. 

Response 160.10: OPP has long used this value as an indication of toxicity to birds. As specified in 

40 CFR 156.85(b)(3), any pesticide (including conventional pesticides) that is intended for outdoor 

use with an avian acute oral LD50 of 100 mg ai/kg or less requires a precautionary label statement 

that the pesticide is toxic to birds. EPA believes that if 100 mg ai/kg is appropriate to trigger a 

precautionary label statement, then it is also appropriate to use as a trigger for testing. Therefore, if 

the avian oral acute toxicity study indicates an oral LD50 of 100 mg ai/kg or less, then an avian 

dietary study is required.. 

In the proposed rule, for the avian dietary toxicity study, EPA proposed to require testing on two 

species for the aquatic areas and to conditionally require testing on one avian species for all of the 

other use patterns. The comments reviewed and evaluated by EPA on avian toxicity testing included 

the commenter’s suggested data requirements table for nontarget organisms, which specified only 

“CR” for avian testing. EPA agrees with the commenter that “CR” is appropriate for the avian 

dietary toxicity and avian reproduction studies for all use patterns. This simplifies the testnotes and 

with the appropriate triggers EPA would be able to require the needed testing. 

The following changes are being made to the aquatic areas column: 

 

Avian dietary toxicity: change from R to CR 

Avian reproduction: change from R to CR 

Proposed testnote 4 will trigger the avian dietary toxicity study based on the results of the avian 

acute toxicity study. For the avian dietary study, testing in a second species would be triggered based 

on the results of the avian dietary testing in the first species. Since the second test species will be 

required based on the results of the first species proposed testnote 5 is no longer needed and will be 

removed. Proposed testnote 6 would trigger the avian reproductive study based on one or more of 

four specific criteria: the specific criteria are the same as in the proposed rule. 

Comment160.11: A commenter asked why a Kow of greater than 3 was selected to trigger avian 

reproductive studies in proposed testnote 6(iii). 

Response 160.11: A Kow (octanol-water partition coefficient) equal to or greater than 1000 (log 

Kow of 3) is used by OPP as a standard value for indicating whether a compound might have 

adsorptive potential, in which case it has a potential for sublethal (e.g., reproductive, growth) effects 

in birds. Since the Kow has proven useful, AD will continue using this value as an indicator for 

potential bioaccumulation in non-targets. 

Comment 160.12: A commenter maintained that proposed testnotes 1 and 6 (for the avian 

reproduction study) are contradictory as testnote 1 specifies the study is required for low exposures 

and testnote 6 specifies the triggers for requiring the study. The same commenter also asked for 

additional clarification on the inter-relationship of the triggers in testnote 6. 
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Response 160.12: Proposed testnote 1 specifies for both the acute avian oral toxicity study and the 

avian reproduction whether testing is to be conducted with one or two species. EPA agrees that 

there could be some confusion, and has reworked testnote 1 to clarify. 

Proposed testnote 6 specifies four criteria that are used to trigger the requirement for conducting an 

avian reproduction study. The criteria focus on the exposure of birds to either the antimicrobial 

pesticide or a transformation product of the pesticide. The four criteria of proposed testnote 6 are 

independent of each other: only one of the criteria needs to be met to trigger the study. Once testing 

has been triggered according to proposed testnote 6, and is required, then revised testnote 1 

describes whether one or two species are to be tested, which depends on the use pattern. 

Comment 160.13: A commenter contended that proposed testnotes 9 and 10 do not provide 

sufficient information for a registrant to figure out what is required. The commenter asked what is 

meant by “likely to enter.” 

Response 160.13: Proposed testnote 9 triggers the acute estuarine/marine organism toxicity study. 

Proposed testnote 10 triggers the fish early-life stage and the aquatic invertebrate life-cycle study. 

Both testnotes use “if the parent compound and/or transformation products are likely to enter the 

‘freshwater (testnote 10 only) or’ estuarine/marine environment” as the trigger for requiring the test. 

In making its determination about the potential of a substance to enter the environment, EPA 

considers a variety of factors to determine the potential for exposure to organisms inhabiting the 

estuarine/marine environment. These factors can include including proximity of use sites to coastal 

areas or streams and rivers emptying in to coastal waters, potential environmental transport of the 

active ingredient or transformation products and modeling of estimated environmental 

concentrations, and any other relevant information (e.g., monitoring data, incident data, open 

literature). 

Also see response to comment 134.21. As described in that response to comments, proposed 

testnote 10 will be revised to remove the trigger. 

Comment 160.14: A commenter asserted that higher-tiered testing should only be required when 

“an environmental risk assessment has been conducted with Tier 1 data and additional data are 

needed.” 

Response 160.14: The Agency is taking a flexible approach to its ecotoxicity data requirements by 

using a tiered system of data requirements. The three required acute non-target organism studies 

(and one algae study) required for the Tier 1 dataset are not sufficient to conduct even a cursory 

ecological risk assessment for antimicrobials with outdoor uses (e.g., wood preservatives, antifoulant 

paints and coatings, ballast water, aquatic areas). Given the direct release into the aquatic or 

terrestrial environment, more studies are required for outdoor uses. The higher-tier data 

requirements for outdoor uses were identified using EPA’s experience in conducting environmental 

risk assessments of antimicrobial pesticides. Based on its experience in conducting these risk 

assessments, AD considers it highly likely that non-target organisms will be exposed when 

antimicrobial pesticide products are applied in the outdoors. EPA also requires the same Tier 1 

dataset for indoor uses that may result in environmental exposure through down-the-drain exposure. 

The results of the down-the-drain assessment would provide EPA with estimated environmental 
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concentrations (EECs) which when combined with the results of the Tier 1 ecotoxicity studies could 

indicate a potential risk that needs further characterization. If the effluent from a wastewater 

treatment plant (WWTP) is likely to contain an antimicrobial pesticide, or if the antimicrobial is 

likely to partition to the sludge that is derived during the treatment process, then indoor uses could 

require additional testing to further characterize the hazard and the risk to non-target organisms. 

In effect, the tiered system is designed to minimize the number of studies needed for an ecological 

assessment. 

Comment 160.15: A commenter stated that proposed testnote 8 is confusing when compared to the 

guideline numbers, noting that that three studies are required, but five guidelines are included. 

Response 160.15: Proposed testnote 8 states that three studies are required for estuarine/marine 

organisms: one fish species, one mollusk species, and one other invertebrate species. In the Data 

Requirements table, five OCSPP (Office of Chemical Safety and Pollution Prevention) Harmonized 

Guideline numbers are listed for the estuarine/marine organism testing. Four of those guidelines are 

for invertebrate tests and one for fish (850.1075). Therefore for the mollusk and the other 

invertebrates EPA has offered applicants some flexibility in how the studies can be conducted. 

Different guidelines are specified for different species or different tests. For example, the one 

required mollusk test can be conducted using either the guideline for an embryo-larval test 

(850.1055) or for a shell-deposition test (850.1025). The one required invertebrate test is typically 

conducted with a shrimp. Guideline 850.1035 is for the mysid shrimp, the preferred invertebrate 

species, but a penaeid shrimp test (850.1045) also is acceptable for the invertebrate species. 

Comment 160.18: A commenter wanted to know whether the the fish early life stage study should 

be conducted with fresh or salt water species? 

Response 160.18: Proposed testnote 10 specifies testing must be conducted with the most sensitive 

fish species (either freshwater or estuarine/marine): the most sensitive species is determined by the 

acute toxicity test(s). If acute toxicity testing is not required for the estuarine/marine species, then 

the test would be conducted with a freshwater fish. 

Comment 160.19: A commenter asserted that exposure based risk assessment should be considered 

as a factor in proposed testnote 12. 

Response 160.19: Proposed testnote 12, describes the criteria to trigger the fish life-cycle study. 

Exposure based risk is one of the factors that can trigger the fish life cycle study. Proposed testnote 

12(i) bases the need for the fish life cycle test on a comparison of the Estimated Environmental 

Concentration (EEC) (an estimate of exposure of the pesticide in the water column) to the noobserved-effect concentration as determined in the fish early-life stage test. If the ratio is equal to or 

greater than 0.1, then the test is triggered. Additionally, it should be realized that the fish life-cycle 

study is rarely required and is needed only if there is potential for chronic exposure. 

Comment 160.20: A commenter requested the following clarification on proposed testnote 12.ii: 
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Would the fish life cycle test be triggered by mammalian and/or avian reproduction effects even if 

no effects on reproductive physiology were seen in the fish life cycle test? 

Response 160.20: The fish-life cycle study has typically been requested only on a case-by-case basis 

and only when the early life-stage test has not been adequate to assess potential chronic risks. 

Information from mammalian and/or avian reproduction effects alone is not likely to trigger the 

criteria in testnote12.ii, but such data may help corroborate other available information (e.g., open 

literature) in determining if the study is needed. 

Comment 160.21: A commenter asserted that the registrants of any antimicrobial pesticide that has 

the potential to be discharged either directly or indirectly to surface water should be required to 

supply any additional data needed to derive a water quality criterion for the pesticide in question. 

Response 160.21: As discussed in the conventionals Response to Comment document [page 104], 

the Agency is confident that the pesticide registration process, including its data requirement 

regulations, adequately considers the endpoints that are protected under the Clean Water Act (CWA) 

as administered by the Office of Water (OW). When acceptable data are available, OPP uses these 

data in its risk assessment process. 

The purpose of a water quality criterion under the CWA is to determine the level at which a water 

body may be at risk for environmental damage. The purpose of certain data requirements for 

pesticide registration is to allow the Agency to determine ecological risk of using a pesticide. Thus, 

these programs have similar goals. While EPA has developed guidelines for developing Water 

Quality Criteria (WQC), the Agency has also recognized that WQC can be developed with a more 

limited data set. 

Pesticide registration data are valuable in assessing water quality risks. As noted in EPA’s 2005 

response to comments on the conventional pesticides, EPA’s OW and OPP together developed 

aquatic life benchmarks for 71 pesticides or pesticide degradation products for States to use to 

establish targets for safe levels of pesticides for aquatic plants and animals. The benchmarks are 

derived from data submitted to EPA for pesticide registration. Currently, there are a total of 144 

chemicals for which there are OPP benchmarks. These chemicals are a combination of active 

ingredients and primary degradates. As of April 18, 2011, there are 242 pesticide chemicals with 

aquatic benchmarks on the website 

(http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm ) Protecting America’s 

waters is one of Administrator Jackson’s priorities. 

Comment 160.22: A commenter has concerns about the quality assurance built into the testing 

guidelines for aquatic toxicity. 

Response 160.22: EPA agrees that quality assurance is an important part of testing. 40 CFR part 160 

includes the Good Laboratory Practices regulations that must be satisfied for studies submitted to 

OPP. Under 40 CFR 160.12, studies submitted to EPA in support of a registration must complete a 

certification statement of compliance or non-compliance concerning Good Laboratory Practices. 

The submitter of the study must certify that (1) the study meets the requirements for 40 CFR Part 
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160, (2) the study does not meet the requirements of 40 CFR Part 160, and then explain how the 

study differs, or (3) does not know whether it has been conducted in accordance with 40 CFR Part 

160. There are reasons that a study might not have been conducted under GLPs. It could be an 

older study, conducted before the GLP regulations. The submitter of an article from open literature 

would have access only the information in the article and is unlikely to know if the study were 

conducted under GLPs. If, for some reason, a study has not been conducted according to GLPs, 

then EPA would be aware of this fact 

Comment 160.23: A commenter argued that higher tier tests for biomagnification are necessary to 

determine potential exposure levels throughout the food chain. The commenter maintained that 

since this does not equate to a toxic effect, additional studies would be necessary to determine the 

ecological impact of any biomagnification on the food web. 

Response160.23: EPA appreciates the commenter’s concern regarding higher tier tests for 

biomagnification. For antimicrobial pesticides, OPP proposed to conditionally require two studies to 

evaluate bioconcentration (fish and oyster) and one study to evaluate the aquatic food chain transfer. 

As the environmental risk assessment process continues to evolve, the Agency could determine that 

additional biomagnification testing is needed. 

Comment 160.24: A commenter inquired into whether EPA/OPP has considered the potential for 

antimicrobials to impact air emissions from the POTW as the chemical degrades during the 

treatment process? 

Response160.24: OPP has not typically addressed air emissions from the POTW. OW also does not 

regularly address air emissions from a POTW. Air emissions falls under the purview of the Clean Air 

Act and jurisdiction of the EPA Office of Air. 

Comment 160.26: A commenter asserted that for the simulated or actual field testing for aquatic 

organisms that the low environmental exposures should be NR. 

Response 160.26: The Agency is no longer using the term “low environmental exposure grouping” 

as a descriptor for identifying data requirements for non-target organisms. Instead, EPA is using the 

term “All Other” as a use pattern category. EPA disagrees that the simulated or actual field testing 

for aquatic organisms should be “NR.” EPA believes that a simulated or actual field test for aquatic 

organisms could be required to adequately characterize environmental exposures when laboratory 

derived data are not sufficient to adequately characterize risk. This decision would be made on a 

case-by-case basis and likely would be an infrequent occurrence, but one that could occur. EPA will 

continue to use “CR.” 

Comment 160.27: A commenter argued that EPA has not considered the environmental fate of a 

compound (such as the tendency of a chemical to absorb/desorb) when considering the need for 

sediment testing. 
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Response 160.27: EPA disagrees with this comment. Proposed testnotes 17 and 18 trigger the 

sediment studies based on the results of the aerobic soil or aquatic metabolism studies and 

knowledge of the physical/chemical properties which express the environmental fate of the 

antimicrobial pesticide chemical. The soil partition coefficient (Kd) is used as an expression of 

binding capability of the chemical to sediments. The Agency’s justification for using Kd >50 as a 

criterion for requiring sediment testing is that this value would capture those chemicals with about 

80 percent adsorption to sediments (relative to organic carbon). 

The octanol-water partition coefficient (Kow) and the soil organic carbon-water partition coefficient 

(Koc) also are used by EPA as part of its decision process. Both values are frequently more available 

than either the Kd or half-life values. Proposed testnote 17, the trigger for requiring an acute 

sediment study, considers all three of these values. 

Next, as explained in proposed testnote 18, the chronic sediment study is triggered based on the 

results of the acute sediment study as well as a re-examination of the three values. 

Comment 160.28: A commenter referred to the comments submitted to the conventional pesticides 

proposed rule for sediment testing. 

Response 160.28: EPA responded to a large number of comments (43) on sediment testing 

submitted to the docket for the conventional chemicals. EPA responded to those comments on 

pages 53-61 of that document. Those comments were considered in determining the data 

requirements proposed for antimicrobial pesticides. 

In response to all of the comments received on sediment testing, EPA re-evaluated the need for 

sediment testing for antimicrobials. EPA continues to believe these studies are needed, when 

triggered. For the Antifoulant Coatings and Paints column for the whole sediment acute freshwater 

invertebrates and whole sediment acute marine invertebrates studies, EPA has determined that “R’ is 

not needed, and that “CR” is appropriate. EPA believes that simplifying the data requirements for 

sediment testing so that these requirements are CR for all use patterns is clearer, and also closer to 

the suggestions made by the commenters in their nontarget organism data requirements table. Their 

suggested table was predominantly CR for aquatic uses, which they consider to include antifoulants. 

Additionally, changing to CR harmonizes with the conventional data requirements. 

Comment 160.29: A commenter noted that it seems likely that all antimicrobials will have sediment 

testing, given the multiple criteria that are given in proposed testnotes 17 and 18. The commenter 

asked whether sediment testing for marine environments would be required for a chemical that does 

not enter marine or brackish water, and whether the invertebrate testing that has already been 

performed would be considered in determining when sediment testing is required. 

Response 160.29: EPA disagrees with this comment. Sediment testing is conditionally required for 

all use patterns: testing would be triggered based on the criteria in proposed testnotes 17 and 18 for 

any use patterns potentially impacting the aquatic environment. Sediment testing will be requested 

only for those antimicrobial chemicals expected to be adsorbed onto the sediment. 
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EPA begins its process of determining the need for these studies by analyzing what is happening in 

the water column: we look at the concentrations of the antimicrobials in the water and the toxicity 

of the chemicals. The toxicity portion is determined by the invertebrate testing that has already been 

performed. This is done by calculating the EECs to determine the risk of the pesticide to fish and 

invertebrates in the water column. Next we analyze the potential for the benthic organisms in the 

sediment to be exposed. This means that the antimicrobial would need to be adsorbed onto the 

sediment. If the chemical is unlikely to be adsorbed onto the sediments, then sediment testing would 

not be required. As discussed in response to comment 160.27, the decision to require the data 

considers multiple sources of data and could be considered a weight-of-evidence process. 

Proposed testnote 19 specifies the trigger for estuarine/marine testing. If the antimicrobial is directly 

applied to the marine environment, or could reach the estuarine/marine environment, then testing is 

required. 

Comment 160.30: With regards to sediment testing, a commenter asserted that EPA should explain 

which testing protocols are to be followed. 

Response 160.30: For acute sediment testing, there are two OCSPP Harmonized Guidelines 

(850.1735 and 850.1740). Both of these guidelines are available on the EPA website 

(http://www.epa.gov/ocspp/pubs/frs/home/draftguidelines.htm). There is no guideline for 

conducting a chronic sediment study, since it has been rarely required. Therefore, if a chronic study 

were triggered, then the protocol must be approved by the Agency prior to initiation of the study. 

Comment 160.31: A commenter asked why EPA is requiring honey bee testing for antimicrobials. 

Response 160.31: Insect pollinator testing is required when a potential exists for exposure of bees to 

an antimicrobial. This could occur if the beehive were to be treated with an antimicrobial pesticide. 

This could also occur when wood that has been treated with a wood preservative is used to 

construct beehives, and bees would then be in contact with the wood. EPA has now determined 

that all wood preservative risk assessments will now be performed considering that the treated wood 

could end-up on the land or in the aquatic environment. Based on that same logic, EPA is also 

determining that all wood preservative risk assessments will now be performed considering that the 

treated wood could end-up in a beehive. This means that for the wood preservative use pattern the 

honeybee acute contact study and the toxicity of residues to honeybees are changed from “CR” to 

“R.” With this change, only the “all other” use pattern category remains as “CR”. Testnote 20 to 

the non-target organism table will be revised to reflect this change. 

Comment 160.32: A commenter maintained that EPA has not provided sufficient rationale for 

requiring significant and costly testing of nontarget species for antimicrobials. Additionally, the 

commenter argued that EPA has not provided meaningful tiering. 

Response 160.32: EPA believes that it has provided meaningful tiering for nontarget organism 

testing. As stated in response to comment 160.1, EPA believes that it is taking a flexible approach 

that includes the tiering of data requirements and is designed to minimize the number of ecotoxicity 
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tests required to support pesticide registrations. There is a continuum of exposures, with some being 

greater than others. EPA uses this distinction in evaluating the amount of data needed to properly 

assess the risks of using an antimicrobial pesticide. Based on its experience EPA is able to 

distinguish between those use patterns where fewer studies need to be required immediately and 

more studies need to be required immediately. Without this distinction, a complete data set would 

be required for all antimicrobials, regardless of the use pattern. 

Comment 160.34: A commenter asserted: “EPA should reconsider its use of TEP as a test article. 

Since TEPs vary greatly, validity of TEP testing is questionable. Also, nontarget species will not be 

exposed to TEP because TEP is not applied in the environment.” 

Response 160.34: TEP testing for nontarget organisms is of value when the product is applied 

directly to the environment. TEPs are sometimes applied directly into the aquatic environment (e.g., 

antifoulant) or may contain an inert ingredient that enhances the toxicity of the active ingredient or 

may contain multiple active ingredients. TEP testing would be required with a specified product or 

formulation. If there is variability of inert ingredients within a specific product registration, then the 

Agency will need to determine the appropriate test material. Also, as discussed in response to 

coment 160.7, EPA has added a new testnote 5, which is replacing proposed testnote 5 to the 

proposed nontarget organism table (proposed testnote 5 was removed). New testnote 5 to the 

nontarget organism table states that an applicant should request a waiver if the TEP cannot be 

tested. 

Comment 160.36: A commenter does not believe that any avian testing should be required and asks 

that EPA provide greater detail on its rationale for requiring avian reproductive studies for 

antimicrobials. 

Response 160.36: EPA believes that avian reproductive testing for antimicrobials, while rare, should 

be required when triggered. Avian reproductive studies would be triggered only for those 

circumstances where birds might be exposed to an active ingredient during or preceding the 

breeding season, and an ecological risk assessment is needed to characterize the risk and, if 

necessary, to mitigate the risk. 

Comment 160.37: A commenter disagrees with the triggers in testnote 13(iii). The commenter 

argued that the hydrolytic effects at pH 5 are environmentally irrelevant, and that EPA should drop 

the criteria for pH 5 and 9 and include marine water instead, so that the BCF (bioconcentration 

factor) test would not be required if the hydrolytic half-life is less than 5 days at pH 7 and in marine 

water. 

Response 160.37: The Agency believes that effects at pH 5 and 9 are relevant. pH can vary widely 

among natural lakes, ranging from 4.5 in poorly buffered bog lakes to greater than 9.0 in hard water 

lakes. An hydrolysis study (conducted according to guideline 835.2120) is conducted in buffered 

water. OPP does not require hydrolysis testing in marine water, neither for antimicrobial pesticides 

nor for conventional pesticides. 
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Comment 160.38: A commenter asserted that there should not be any ecotoxicity data requirements 

for indoor industrial uses. 

Response160.38: EPA disagrees with this comment. Exposure from indoor industrial uses occurs 

primarily through water via point-source discharges directly to the environment or indirectly via 

passage through Waste Water Treatment Plants (WWTPs). Leachates, rinsates, or flushes are often 

released down-the-drain and eventually reach a WWTP. After treatment, effluents (water or 

biosolids) are released into the aquatic environment or in wastewater treatment plant sludge (aka 

biosolids) that may be land-applied, deposited in surface impoundments, or disposed of in landfills, 

thereby leading to potential for non-target organisms to be exposed. 

Comment 160.39: With regard to ecotoxicity data requirements, a commenter stated that the 

European approach for addressing wood products and their environmental exposure would be 

useful for EPA to consider. 

Response 160.39: As part of their comments, the commenter also provided a table specifying classes 

of wood products and the products expected environmental exposures. Classes 1 and 2 are 

described as interior uses of wood. Classes 3, 4, and 5 are exterior, in-ground, and marine, 

respectively. The commenter noted that only classes 3-5 “would be subject to the more extensive 

requirements to assess ecotoxicity and environmental fate.” 

EPA believes that only classes 3, 4, and 5 would be treated with a wood preservative and therefore 

agrees that classes 3, 4, and 5 would be subject to EPA’s data requirements for wood preservatives. 

EPA is aware of the differences and similarities of how an ecological assessment for a wood 

preservative is performed in Europe and the U.S. There are differences in the protocols used for 

assessing leaching. Some of the scenarios developed by the Europeans have been used as part of 

EPA’s modeling approach for estimating the exposures then used to assess the risks of terrestrial 

wood preservative uses. 

Comment 160.40: A commenter argued the low exposure use pattern is subjective and arbitrary.

Response 160.40: As a result of comments received, EPA is no longer using the terms “high 

environmental exposure” and “low environmental exposure” as table headers as proposed for the 

Antimicrobial Nontarget Organism Data Requirements Table [59436] and the Nontarget Plant 

Protection Data Requirements Table [59439]. Instead EPA in the final rule is now using its 12 

antimicrobial use patterns to define the required data. Using the 12 use patterns as the table headers 

means that EPA can distinguish the use patterns with higher exposure that need more data from 

those that need less. Accordingly, the table headers for both the Nontarget Organism and the 

Nontarget Plant Protection Data Requirements Tables in the final rule are: Industrial Processes and 

Water Systems, Antifoulant Coatings and Paints, Wood Preservatives, Aquatic Areas, and “All 

Other.” The “All Other” Use Patterns Category includes the following eight use patterns: 

“Agricultural Premises and Equipment;” “Food-handling/Storage Establishments, Premises and 

Equipment;” “Commercial, Institutional and Industrial Premises and Equipment;” “Residential and 
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Public Access Premises;” “Medical Premises and Equipment;” “Human Drinking Water Systems;” 

“Materials Preservatives, and Swimming Pools.” 

EPA also notes that the terms “high environmental exposure” and “low environmental exposure” 

can be appropriate when discussing a particular antimicrobial use. A statement that a particular use 

results in “high environmental exposure” provides information and alerts the reader that more data 

is likely to be needed, rather than less data. 

Comment 160.41: For nontarget organisms, as part of their comments,a commenter suggested a 

tiered testing approach that is triggered for each of the commenter’s suggested use patterns through 

a deterministic or risk quotient methodology. 

Response 160.41: The Ecotoxicity (Nontarget Organism) Data Requirements table suggested by 

industry, as part of their comments, is not adequate to evaluate the hazards and risks of 

antimicrobial pesticides. The suggested table did not include test guideline numbers, changed and 

reduced the number of use patterns, and proposed that most ecotoxicity studies are either not 

required or only conditionally required. The commenters contend that “. . . there are only a few 

circumstances where certain ecological effects data are relevant for antimicrobial pesticides.” and 

that indoor uses should not be subject to environmental exposure or nontarget species risk 

assessments. EPA disagrees with many aspects of these comments and the suggested Ecotoxicity 

Data Requirements table for the reasons discussed below. 

EPA disagrees that exposure should be presumed to be minimal or nonexistent for antimicrobials 

applied indoors (see response to comments 160.1 and 160.38). Moreover, there are many outdoor 

uses of antimicrobials. FIFRA mandates that EPA conduct a risk assessment for any uses for which 

exposure may occur in the various environmental compartments/media. Those risks are assessed 

separately for the various taxa (e.g., fish, invertebrates, plants), categories (e.g., freshwater, saltwater), 

and short-term (i.e., acute) and longer-term (i.e., chronic) exposures. Assessing these potential risks 

necessitates having an appropriate ecotoxicity data base, and that cannot be accomplished by 

requiring only two acute studies (fish, aquatic invertebrates) for the initial assessment. A tiered 

approach can not be driven solely by a risk quotient derived from a Tier 1 study. The fact that an 

acute risk quotient for fish does not exceed a Level of Concern for acute risk does not imply that a 

chronic risk does not exist or that data are not needed to assess that risk. The trigger for a chronic 

test may be driven by the frequency, duration, or magnitude of the chronic exposure and the 

environmental properties of the pesticide. For example, fish might be subjected to repeated lowlevel exposure that is not acutely lethal but which may impact reproductive success and growth of 

young. 

EPA disagrees that the test substance for Tier 2 studies (in the commenter’s table) should be 

identified simply as the “residue of concern (ROC).” In its proposed Nontarget Organism Data 

Requirements Table, EPA specified the test material (TGAI, degradate, TEP) to be used for each 

study. In some cases, studies may be needed both on the TGAI and a degradate. Generally, the 

testing is done first on the TGAI and then as described in response to comment 160.3, the 

determination whether degradate testing is also needed is made after reviewing the required 

environmental fate and physical/chemical properties data and any other available information (e.g., 

open literature, closely related chemicals) to determine the substance of concern for exposure of 
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non-target organisms. For example, if an applicant can adequately demonstrate that the TGAI 

dissipates so rapidly that there would be no acute or chronic exposure, TGAI testing may be waived. 

The submitter also omitted all Testing Guideline Numbers from their data table. At this time, all of 

the data requirement tables in 40 CFR part 158 have Guideline Numbers since this is a method of 

providing information to applicants. The guidelines were developed by EPA scientists and others 

with a particular interest or expertise in the subject matter covered, including representatives from 

the scientific community, industry, non-profit organizations, and other governments. Some of these 

guidelines harmonize EPA's guidelines with guidelines established by the Organization for 

Economic Cooperation and Development (OECD), an international organization whose 

membership includes most industrialized nations which maintain comprehensive testing 

requirements for pesticides and industrial chemicals. When necessary, significant scientific issues 

were presented for external peer review to the FIFRA Scientific Advisory Panel, or to another group 

of scientific experts for that particular topic. Applicants are not required to use these guidance 

documents but are encouraged to use these test guidelines when developing data. Since these 

guidelines have been developed via a rigorous process, as discussed in the preamble to the proposed 

rule [59387], “they represent the recommended approach to developing high-quality data that should 

satisfy EPA’s data needs for risk assessment” Applicants may develop their own test protocols; but, 

are encouraged (and for certain studies required) to submit them to EPA for review prior to testing 

to assure that the study would provide EPA with the needed information. 

EPA has used certain aspects of the commenter’s suggested table to reconsider and ultimately revise 

the Nontarget Organism Data Requirements Table. These revisions are discussed in response to 

comments 160.7 and 160.28. 

Based on the comments received, the Testnotes to the Non-Target Organism Table will 

read as follows: 

T160.1: Testnote 1 to the Non-Target Organism Table

Proposed: 

For low environmental exposures, data are required for one avian species. For industrial processes 

and water systems (once-through), antifoulant paints and coatings, wood preservatives, and aquatic 

areas data are required for one waterfowl species and one upland game bird species. 

Final: 

For industrial processes and water systems, antifoulant paints and coatings, wood preservatives, and 

aquatic areas, data are required for two avian species: one waterfowl species and one upland game 

bird species. For the “All Other” use patterns category (as specified in §158.2240(a)(5)), data are 

required for one avian species. 

T160.2: Testnote 2 to the Non-Target Organism Table 

Proposed: 

Data are required on one freshwater aquatic invertebrate species. 
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Non-Target Organism Exposure Section (160) Page 238 

Final: 

Data are required on one freshwater aquatic invertebrate species. 

T160.3: Testnote 3 to the Non-Target Organism Table 

Proposed: 

For low environmental exposures, data are required on one species of fish, either one cold water 

species or a warm water species. Testing on a second species is required if the active ingredient or 

principal transformation products are stable in the environment and the LC50 in the first species is 

greater than 1 ppm or 1mg/L. For the “All Other” use patterns, data are required on two species of 

fish, one cold water species and one warm water species. 

Final: 

For the industrial processes and water systems, antifoulant paints and coatings, wood preservatives, 

and aquatic use patterns areas, data are required on two species of fish, one coldwater species and 

one warmwater species. For the “All Other” use patterns category (as specified in §158.2240(a)(5)), 

data are required on one species of fish, either one coldwater species or a warmwater species. 

Testing on a second species is required if the active ingredient or principal transformation products 

are stable in the environment and the LC50 in the first species is greater than 1 ppm or 1 mg/L. 

T160.4: Testnote 4 to the Non-Target Organism Table 

Proposed: 

For low environmental exposures, industrial processes and water systems (once-through), 

antifoulant paints and coatings, and wood preservatives data are required for one waterfowl species, 

if the avian acute oral LD50 ( TGAI testing) is less than or equal to 100 mg a.i./kg and a.i. residues or 

its principal transformation products are likely to occur in avian feed items. Data on one upland 

game bird species are required if the avian dietary LC50 in the first species tested is less than or equal 

to 500 ppm a.i. in the diet. 

Final: 

Data are required on one avian species, either one waterfowl species or one upland game bird 

species, if the avian acute oral LD50 ( TGAI testing) is less than or equal to 100 mg. a.i./kg and a.i. 

residues or its principal transformation products are likely to occur in avian feed items. Data on the 

second species are required if the avian dietary LC50 in the first species tested is less than or equal to 

500 ppm a.i. in the diet. 

T160.5: Testnote 5 to the Non-Target Organism Table 

Proposed: 

This is a new testnote; proposed testnote was no longer needed and removed. 

Final: 

If TEP testing cannot be conducted due to the physical characteristics of the test substance (for 

example, a paint), then the applicant should request a waiver. 
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T160.6: Testnote 6 to the Non-Target Organism Table 

Proposed: 

For low environmental exposures, industrial processes and water systems (once-through), 

antifoulant paints and coatings, and wood preservatives, data are required if one or more of the 

following criteria are met: 

 i. Birds may be subjected to repeated or continued exposure to the pesticide or any of its 

transformation products, especially preceding or during the breeding season. 

 ii. The pesticide or any of its major metabolites or degradation products are stable in the 

environment to the extent that a potentially toxic amount may persist in avian feed. 

 iii. The pesticide or any of its major metabolites or degradation products are stored or 

accumulated in plant or animal tissues, as indicated by the octanol/water partition coefficient (Kow is 

greater than or equal to 1,000), accumulation studies, metabolic release and retention studies, or as 

indicated by structural similarity to known bioaccumulative chemicals. 

 iv. Any other information, such as that derived from mammalian reproduction studies that 

indicate that reproduction in terrestrial vertebrates may be adversely affected by the anticipated use 

of the pesticide product. 

Final: 

Data are required if one or more of the following criteria are met: 

 i. Birds may be subjected to repeated or continued exposure to the pesticide or any of its 

transformation products, especially preceding or during the breeding season. 

 ii. The pesticide or any of its major metabolites or degradation products are stable in the 

environment to the extent that a potentially toxic amount may persist in avian feed. 

 iii. The pesticide or any of its major metabolites or degradation products are stored or 

accumulated in plant or animal tissues, as indicated by the octanol/water partition coefficient (Kow is 

greater than or equal to 1,000), accumulation studies, metabolic release and retention studies, or as 

indicated by structural similarity to known bioaccumulative chemicals. 

 iv. Any other information, such as that derived from mammalian reproduction studies that 

indicate that reproduction in terrestrial vertebrates may be adversely affected by the anticipated use 

of the pesticide product. 

T160.7: Testnote 7 to the Non-Target Organism Table 

Proposed 

TEP testing is required for any product which meets one or more of the following conditions: 

 i. The estimated environmental concentration (EEC) in the aquatic environment is equal to 

or greater than one-half the LC50/EC50 of the TGAI when the end-use product is used as directed. 

 ii. An ingredient in the end-use product other than the active ingredient is expected to 

enhance the toxicity of the active ingredient or to cause toxicity to aquatic organisms. 

Final: 

TEP testing is required for any product which meets one or more of the following conditions: 
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 i. When based on deterministic modeling results: If the estimated environmental 

concentration (EEC) in the aquatic environment is equal to or greater than one-half the LC50/EC50

of the TGAI. 

 ii. When based on probabilistic modeling results: If the estimated 10th percentile 7Q10 

Surface Water Concentration exceeds the acute concentration of concern (i.e., one-half the 

LC50/EC50) for 4 or more days 

 iii. If an ingredient in the end-use product other than the active ingredient is expected to 

enhance the toxicity of the active ingredient or to cause toxicity to aquatic organisms. 

 iv. The end-use antimicrobial product will be applied directly into an aquatic environment. 

T160.8: Testnote 8 to the Non-Target Organism Table 

Proposed: 

Data are required on one estuarine/marine mollusk, one estuarine/marine invertebrate, and one 

estuarine/marine fish species. 

Final: 

Data are required on one estuarine/marine mollusk, one other estuarine/marine invertebrate, and 

one estuarine/marine fish species. 

T160.9: Testnote 9 to the Non-Target Organism Table

Proposed: 

For low environmental exposures, industrial processes and water systems (once-through), wood 

preservatives, and aquatic areas, data are required if the pesticide residues from the parent 

compound and/or transformation products are likely to enter the estuarine/marine environment. 

Final: 

For the “All Other” use patterns category (as specified in §158.2240(a)(5)), industrial processes and 

water systems, wood preservatives, and aquatic areas, data are required if the pesticide residues from 

the parent compound and/or transformation products are likely to enter the estuarine/marine 

environment. 

T160.10: Testnote 10 to the Non-Target Organism Table 

Proposed: 

For low environmental exposures data are required if pesticide residues from the parent compound 

or transformation products are likely to enter freshwater or estuarine/marine environments, as 

determined by the Agency. For wood preservatives, data are required if pesticide residues from the 

parent compound, transformation products, and/or leachates from preservative-treated wood are 

likely to enter freshwater or estuarine/marine environments, as determined by the Agency. Testing 

should be conducted with the most sensitive organism (either freshwater or estuarine/marine 

vertebrates, or freshwater or estuarine/marine invertebrates), as determined from the results of the 

acute toxicity tests (acute EC50 freshwater invertebrates; acute LC50/EC50 estuarine and marine 

organisms; acute freshwater fish LC50). 
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Non-Target Organism Exposure Section (160) Page 241 

Final: 

Testing must be conducted with the most sensitive organism (either freshwater or estuarine/marine 

vertebrates, or freshwater or estuarine/marine invertebrates), as determined from the results of the 

acute toxicity tests (acute EC50 freshwater invertebrates; acute LC50/EC50 estuarine and marine 

organisms; acute freshwater fish LC50). 

T160.11: Testnote 11 to the Non-Target Organism Table 

Proposed: 

Data are required on estuarine /marine species if the product is intended for direct application to 

the estuarine or marine environment, or the product is expected to enter this environment in 

significant concentrations (as determined by the Agency) because of its expected use or mobility 

patterns. 

Final: 

Data are required on estuarine /marine species if the product is intended for direct application to 

the estuarine or marine environment, or the product is expected to enter this environment in 

significant concentrations because of its expected use or mobility patterns. 

T160.12: Testnote 12 to the Non-Target Organism Table 

Proposed: 

Data are required on freshwater species if the end-use product is intended to be applied directly to 

water, or is expected to be transported to water from the intended use site, and when one or more 

of the following conditions apply: 

i. If the Estimated Environmental Concentration (EEC) in water is equal to or greater than 0.1 of 

the no-observed-adverse-effect concentration or no-observed-adverse-effect level 

(NOAEC/NOAEL) in the fish early-life stage or invertebrate life cycle tests. 

ii. If studies of other organisms indicate that the reproductive physiology of fish may be affected. 

Final: 

Data are required on freshwater species if the end-use product is intended to be applied directly to 

water, or is expected to be transported to water from the intended use site, and when one or more 

of the following conditions apply: 

 i. When based on deterministic modeling results: If the Estimated Environmental 

Concentration (EEC) in water is equal to or greater than 0.1 of the no-observed-effect 

concentration or no-observed-effect level (NOEC/NOEL) in the fish early-life stage or invertebrate 

life cycle tests. 

 ii. When based on probabilistic modeling results: If the estimated 10th percentile 7Q10 

Surface Water Concentration based on probabilistic modeling exceeds for 20 days or more the 

chronic concentration of concern (i.e., one-tenth the NOAEC or NOAEL) determined in the fish 

early-life stage or invertebrate life cycle tests. 

 iii. If studies of other organisms indicate that the reproductive physiology of fish may be 

affected.
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Non-Target Organism Exposure Section (160) Page 242 

T160.13: Testnote 13 to the Non-Target Organism Table 

Proposed: 

Not required when: 

 i. The octanol/water partition coefficients of the pesticide and its major degradates are less 

than 1,000; or 

 ii.There are no potential exposures to fish and other nontarget aquatic organisms; or 

 iii. The hydrolytic half-life is less than 5 days at pH 5, 7, and 9. 

Final: 

Not required when: 

 i. The octanol/water partition coefficients of the pesticide and its major degradates are less 

than 1,000; or 

 ii. There are no potential exposures to fish and other nontarget aquatic organisms; or 

 iii. The hydrolytic half-life is less than 5 days at pH 5, 7, and 9. 

T160.14: Testnote 14 to the Non-Target Organism Table 

Proposed: 

Environmental chemistry methods used to generate data associated with this study must include 

results of a successful confirmatory method trial by an independent laboratory. Test standards and 

procedures for independent laboratory validation are available as addenda to the guideline for this 

test requirement. 

Final: 

Environmental chemistry methods used to generate data associated with this study must include 

results of a successful confirmatory method trial by an independent laboratory. Test standards and 

procedures for independent laboratory validation are available as addenda to the guideline for this 

test requirement. 

T160.15: Testnote 15 to the Non-Target Organism Table 

Proposed: 

Protocols must be approved by the Agency prior to the initiation of the study. Details for 

developing protocols are available from the Agency. 

Final: 

Protocols must be approved by the Agency prior to the initiation of the study. 

T160.16: Testnote 16 to the Non-Target Organism Table 

Proposed: 

Data are required if the intended use pattern, and the physical/chemical properties and 

environmental fate characteristics of the antimicrobial indicate significant potential exposure and 
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Master Responses: 

Non-Target Organism Exposure Section (160) Page 243 

based on the results of the acute and chronic aquatic organism testing significant impairment of 

nontarget aquatic organisms could result. 

Final: 

Data are required if the intended use pattern, and the physical/chemical properties and 

environmental fate characteristics of the antimicrobial indicate significant potential exposure and 

based on the results of the acute and chronic aquatic organism testing significant impairment of 

nontarget aquatic organisms could result. 

T160.17: Testnote 17 to the Non-Target Organism Table 

Proposed: 

Data are required if the half-life of the pesticide in the sediment is equal to or less than 10 days in 

either the aerobic soil or aquatic metabolism studies, and if one or more of the following conditions 

are met: 

 i. The soil partition coefficient (Kd) is equal to or greater than 50. 

 ii. The log Kow is equal to or greater than 3. 

 iii. The Koc is equal to or greater than 1,000. 

Final: 

Data are required if the half-life of the pesticide in the sediment is equal to or less than 10 days in 

either the aerobic soil or aquatic metabolism studies, and if one or more of the following conditions 

are met: 

 i. The soil partition coefficient (Kd) is equal to or greater than 50 L/kg. 

 ii. The log Kow is equal to or greater than 3. 

 iii. The Koc is equal to or greater than 1,000. 

T160.18: Testnote 18 to the Non-Target Organism Table 

Proposed: 

Data are required if the EEC in sediment is > 0.1 of the acute LC50/EC50 values and if one or more 

of the following conditions are met: 

 i. The soil partition coefficient (Kd) is equal to or greater than 50 L/kg. 

 ii. The log Kow is equal to or greater than 3. 

 iii. The Koc is equal to or greater than 1,000. 

Final: 

Data are required if the EEC in sediment is greater than 0.1 of the acute LC50/EC50 values and if one 

or more of the following conditions are met: 

 i. The soil partition coefficient (Kd) is equal to or greater than 50 L/kg. 

 ii. The log Kow is equal to or greater than 3. 

 iii. The Koc is equal to or greater than 1,000. 

T160.19: Testnote 19 to the Non-Target Organism Table 
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Master Responses: 

Non-Target Organism Exposure Section (160) Page 244 

Proposed: 

Sediment testing with estuarine/marine test species is required if the product is intended for direct 

application to the estuarine or marine environment or the product is expected to enter this 

environment in significant concentrations (as determined by the Agency) either by runoff or erosion, 

because of its expected use or mobility pattern. 

Final: 

Sediment testing with estuarine/marine test species is required if the product is intended for direct 

application to the estuarine or marine environment or the product is expected to enter this 

environment in significant concentrations either by runoff or erosion, because of its expected use or 

mobility pattern. 

T160.20: Testnote 20 to the Non-Target Organism Table 

Proposed: 

Data are required only for beehive applications when the beehive (empty or occupied) is treated. 

Final: 

For the “All Other” use patterns category (as specified in § 158.2240(a)(5)), data are required only 

for beehive applications when the beehive (empty or occupied) may be treated. 

T160.21: Testnote 21 to the Non-Target Organism Table 

Proposed:

If beehives are constructed of treated wood a study similar to “Honey Bee Toxicity of Residues on 

Foliage” is required using treated wood instead of the foliage. Protocols must be approved by the 

Agency prior to the initiation of the study. Details for developing protocols are available from the 

Agency. 

Final: 

A study similar to “Honey Bee Toxicity of Residues on Foliage” is required using treated wood 

instead of the foliage. Protocols must be approved by the Agency prior to the initiation of the study. 
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Master Responses: 

White Paper on Use of SAR and QSAR (170) Page 245 

White Paper on the Use of SAR and QSAR (170) 

Master Responses for the White Paper on the Use of SAR and QSAR Section 

Please note that EPA responses are presented in numerical order. However, in the course of response development, 

some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are missing. 

Comment 170.1: A commenter stated EPA should provide clear guidance on its policies, 

procedures, and processes on the use of alternative technologies such as structure-activityrelationships (SAR) and Quantitative SAR (QSAR), and the weight-of-evidence (WOE) approach. In 

addition, the commenter asserted that EPA should also provide education and training on these 

approaches. 

 

Response 170.1: The Agency encourages applicants to create submissions that include predictive 

techniques such as SAR, and QSAR to fulfill data requirements. As described in the white paper to 

the proposed rule which is entitled “Use of Structure-Activity Relationship (SAR) Information and 

Quantitative SAR (QSAR) Modeling For Fulfilling Data Requirements for Antimicrobial Pesticide 

Chemicals and Informing EPA’s Risk Management Process” (document 45 in the docket at 

http://www.regulations.gov) an important part of the applicant’s submission is the rationale. The 

rationale, or weight-of-evidence (WOE) evaluation, is the part of the submission that explains the 

applicant’s belief as to why and how the predictive data would fulfill the data requirement. The 

WOE approach requires a critical analysis of the entire body of available data for consistency and 

biological plausibility. In support of a request that predictive data be considered, the applicant would 

need to explain why it believes the surrogate data or the modeling are appropriate for the intended 

use and are of sufficient completeness and quality, and therefore would fulfill the data requirement. 

The general types of information that are considered appropriate for a WOE approach would 

include: 

• Sufficiency of data. Studies that completely characterize both the effects and exposure of the agent 

have more credibility and support than studies that contain data gaps. 

• Quality of the data. Potentially relevant studies are judged for quality and studies of high quality are 

given more weight than those of lower quality. 

• Evidence of causality. The degree of correlation between the presence of an agent and some adverse 

effect is an important consideration 

The Agency would evaluate each submission with a WOE rationale on a case-by-case basis. 

Regarding SAR/QSAR, the white paper to the proposed rule discusses on page 30 the five criteria 

set by the Organization for Economic Co-operation and Development (OECD) for evaluating a 

model. EPA encourages submitters to follow the established criteria set by OECD and show how 

the model is validated for that particular pesticide chemical structure as a measure of the model’s 

applicability. 

Different computer software programs are used to estimate/predict different hazards (see: 

http://www.epa.gov/oppt/sf/tools/methods.htm). This means that predictive software models for 

different scientific disciplines are not at the same level of development. The Agency has long 

standing experience in predicting (modeling) physical-chemical properties, environmental fate, 
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Master Responses: 

White Paper on Use of SAR and QSAR (170) Page 246 

ecotoxicity, and experience in predicting carcinogenesis for certain classes of chemicals. However, 

the Agency is still gaining experience to become familiar with predictive approaches that look at 

other human health endpoints (e.g., reproductive, development), which have not been widely used at 

EPA. Given the different levels of development, EPA would expect to undertake a case-by-case 

evaluation of submitted WOEs. EPA encourages the use of integrated approaches that combine the 

knowledge from existing databases about the chemical of interest with data from appropriate 

surrogate chemicals. 

EPA agrees that guidance on the policies, procedures, and processes for using alternative 

approaches such as SAR/QSAR is needed. EPA is developing such a guidance document for 

pesticides and is seeking to harmonize its approach with that of Canada’s Pest Management 

Regulatory Authority. It is anticipated that the guidance document would be issued as a North 

American Free Trade Agreement guidance document during 2011. [update] This guidance document 

will adhere to the five OECD principles that were discussed in the white paper. Once finalized, this 

document will be the definitive source of information for applicants seeking to use SAR and QSAR 

approaches for fulfilling data requirements for pesticide registration. 

 

 

Comment 170.2: A commenter asserted that there should be an explicit statement that SAR and 

QSAR can be considered to fulfill data requirements. Another commenter had concerns on 

codifying the use of SAR in Part 158, Subpart A since that would mean that “SAR/QSAR 

Techniques would be applicable to conventional, biochemical and microbial, and antimicrobials 

pesticide chemicals.” Another commenter requested that SAR/QSAR be fully integrated within the 

rule. 

 

Response 170.2: EPA has and will continue to consider accepting SAR/QSAR to fulfill its data 

requirements on a case-by-case basis. Acceptance would be based on the information provided and 

most especially on the supporting rationale submitted to EPA. The Agency would evaluate the 

information submitted to determine if the applicant has provided information that is of sufficient 

quality and completeness. The Agency notes that validation of QSAR models is necessary before the 

predictions from those models can be fully integrated into the testing requirements. To that end, 

QSAR models must be inclusive of pesticide toxicology data and chemical structures. Until these 

models become customized with pesticide information, full incorporation of predictive tools likely 

will be limited to a case-by-case basis. 

 

EPA agrees that if use of SAR/QSAR were to be codified in Subpart A, that it would be applicable 

to all pesticide chemicals. EPA will not at this time codify the use of SAR and QSAR in Subpart A. 

 

 

Comment 170.3: A commenter asserted that the Mode-of-Action should be a consideration for 

using a SAR approach. 

 

Response 170.3: In a weight of evidence approach, all empirical data would be considered in the 

characterization of hazard, especially when relying on structure activity relationship data. We agree 

that a mechanistic interpretation strengthens the SAR approach and is a very important piece of 

information that would be factored into the analysis, if available. 
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Master Responses: 

White Paper on Use of SAR and QSAR (170) Page 247 

 

Comment 170.4: A commenter does not believe that SAR and QSAR should be used to fulfill 

physiochemical and biodegradation data requirements, noting that these are quick and inexpensive 

tests. 

 

Response 170.4: The Agency disagrees with this comment. As discussed in response to comment 

170.2, EPA encourages submitters to use SAR, QSAR, read across and a WOE approach to fulfill 

data requirements. 

 

 

Comment 170.6: A commenter sought clarification on the criteria for determining the “nearest 

analog.” 

Response 170.6: Evaluating the potential hazard (toxicity) of chemicals that have not been 

experimentally tested is usually done by comparing the untested chemical to analogs (chemicals with 

similar structures) that have been tested. There are no absolute criteria for determining the nearest 

analog. It is based on a weight- of-evidence approach, utilizing all available information on that 

chemical, including structural information, mode of action, and physical/chemical properties. 

 

Comment 170.7: A commenter asked about the role of bridging data and the rationale for the use of 

that data? 

 

Response 170.7: An integral part of an analysis of any chemical of interest (new or existing) is 

evaluating the structure/sub-structures of the chemical to compare it with analogous chemicals 

("analogs"). An accepted approach used within the Office of Chemical Safety and Pollution 

Prevention (OCSPP) for addressing data gaps is to consider closely related chemicals as a group, or 

chemical category, rather than as individual chemicals. This is referred to as "Bridging" or “Read 

across”. To “read across” is to apply data from a tested chemical for a particular property or effect 

(cancer, reproductive toxicity, etc.) to a similar untested chemical. The read across technique is often 

applied within groups of similar chemicals assembled for assessment using either analog approach 

(grouping based on a very limited number of chemicals) or category approach (grouping based on a 

larger number of chemicals). In an analog/category approach, not every chemical needs to be tested 

for every endpoint. Read more about “Read Across from Analogs/Categories. [For more 

information see: 

http://www.oecd.org/document/23/0,3343,en_2649_34377_33957015_1_1_1_37465,00.html

In 2007, NAS [National Research Council (NRC) (2007) Toxicity Testing in the 21st Century: A 

Vision and a Strategy. National Academy of Sciences, Washington, D.C. 

http://www.nap.edu/catalog.php?record_id=11970#toc] proposed, that the unnecessary use of 

animal studies could be reduced by fully utilizing all available information to better focus our testing 

requirements to endpoints relevant to human health. EPA believes that a rationale for use of 

bridging data should include various types of information, such as: chemical class, the structural 
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Master Responses: 

White Paper on Use of SAR and QSAR (170) Page 248 

similarities of the known to the unknown, the similarity or dissimilarity of the results of the same 

studies conducted on both chemicals, and/or knowledge of the mode-of-action. 

 

Comment 170.8: A commenter contended that SAR and QSAR are not sufficiently robust to form 

the basis of aquatic toxicity data or environmental fate data. 

Response 170.8: EPA disagrees with this comment and believes that various SAR techniques and 

QSAR models are sufficiently robust for use in risk assessment, including environmental risk 

assessment. As discussed in response to comment 170.1, EPA has long standing experience in 

modeling aquatic toxicity and environmental fate data. EPA’s white paper to the proposed rule [page 

12] discusses the ECOlogical Structure Activity Relationship (ECOSAR) model which is publicly 

available on EPA’s website and has been used in various OPP environmental risk assessment 

documents. Also, OECD released its guidance document “Strategies for Grouping Chemicals for 

Data Gap Filling for Acute Aquatic Toxicity Endpoints” during April 2010. (see 

http://www.oecd.org/dataoecd/4/47/45133663.pdf) See also response to comment 170.4. 
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Master Responses: 

Endangered Species Section (180) Page 249 

Endangered Species (180) 

Master Responses for the Endangered Species Section 

Please note that EPA responses are presented in numerical order. However, in the course of response development, 

some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are missing. 

Comment 180.1: A commenter contended that EPA needs to recognize the manner in which 

antimicrobials may result in environmental exposure and the regulations under statutes other than 

FIFRA in order to promote an effective and efficient approach to regulating antimicrobial pesticides 

with regard to endangered and threatened species. According to the commenter, antimicrobials are 

not applied directly to the environment, but environmental exposures from antimicrobial pesticides 

result from point-source discharges or slow release from pesticide-containing materials. 

Response 180.1: EPA agrees that there are differences between antimicrobial pesticides and 

agricultural pesticides. As discussed in the proposed rule (October 8, 2008; 73 FR 59425), for 

agricultural pesticides, there is generally greater specificity relative to where a pesticide may be used 

compared to antimicrobial pesticides. Agricultural pesticides are typically used on crops. As part of 

its endangered species assessment, EPA extracts information on county-level crop occurrence and 

acreage within counties of particular crops from the most recent U.S. Department of Agriculture’s 

National Agricultural Statistical Services’ Census of Agriculture. Because antimicrobial pesticides are 

typically not applied directly to the environment, it is easier to delineate and overlay agricultural 

pesticide use with endangered or threatened species locations than to delineate and overlay

antimicrobial pesticides use. Nevertheless, antimicrobial uses, including uses in swimming pool 

water, industrial slimicides used in recirculating water cooling towers, and paper mills, have the 

potential for environmental exposures. The Agency is working to refine its endangered species 

assessment for antimicrobial pesticides to account for the unique mechanisms involved in 

application and use of antimicrobial pesticides, and the different routes through which antimicrobial 

pesticides enter the environment. 

EPA recognizes that antimicrobials, like any other pesticide product, may be subject to other federal, 

state and local laws. FIFRA requires that, before a pesticide may be lawfully sold or distributed in 

the United States, the product must be registered by EPA, unless the product is exempt from 

registration requirements. Prior to registering a pesticide product, EPA must first ensure that the 

pesticide, when used according to label directions, can be used without posing unreasonable risks to 

humans and the environment. The registration of a pesticide product, whether it is an antimicrobial 

or other type of pesticide product, is considered an “action” subject to the Endangered Species Act 

(ESA). The ESA requires all federal agencies to determine that any action they permit or authorize 

will not jeopardize the continued existence of endangered or threatened species, or adversely modify 

habitat designated as critical by the U.S. Fish and Wildlife Service (FWS) or National Marine 

Fisheries Service (NMFS). 

In order to ensure EPA’s actions are consistent with the ESA, the Agency must assess the potential 

for both direct and indirect effects to any potentially exposed threatened or endangered species and 

critical habitat, independent of whether exposure results from a point-source discharge or the slow 

release of a pesticide containing material. If effects may occur, EPA consults with the FWS or 
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Master Responses: 

Endangered Species Section (180) Page 250 

NMFS to determine whether there may be jeopardy to the species or destruction or adverse 

modification to habitat designated as critical. 

Comment 180.2: A commenter does not believe that EPA/OPP has a mature program currently in 

place for antimicrobial environmental risk assessment generally. More specifically, the commenter 

stated that EPA does not have a program in place for assessing potential impacts on endangered and 

threatened species relevant to antimicrobials and their uses. The commenter maintained that until 

EPA scientifically substantiates data requirements to use in estimating antimicrobial environmental 

exposures and modeling the potential for risks from such exposures, it will not be feasible to make 

any meaningful determinations on potential impacts to endangered species. The commenter 

contended that it is thus premature for the EPA to determine how it should approach antimicrobials 

with regard to endangered species. 

Response 180.2: EPA disagrees with the commenter. EPA has a robust program for completing 

antimicrobial environmental risk assessments, as outlined in the preamble to the proposed rule 

[59405]. Environmental fate studies evaluate the mobility, distribution and dissipation of a pesticide 

in various compartments of the environment, such as water, soil, air, and sediment. Ecological 

effects data are used by the Agency to determine the toxicological hazards of pesticides to various 

nontarget organisms, such as birds, mammals, fish, bees, terrestrial and aquatic invertebrates, and 

plants. The required environmental fate studies and ecological effects (both plant and animal) data 

provide the foundation for an environmental risk assessment. EPA’s environmental risk assessment 

for antimicrobials combines environmental fate studies with ecological effects data to determine the 

potential of the pesticide to cause harmful effects to nontarget organisms and plants. The data 

requirements that will be codified in the final rule will provide sufficient information for EPA to 

perform an ecological risk assessment. 

EPA/OPP’s process for assessing the potential risks of a pesticide to federally listed threatened or 

endangered species and their designated critical habitat is described in the document titled 

“Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs, U.S. 

Environmental Protection Agency – Endangered and Threatened Species Effects Determinations” 

released in January, 2004. Appendix A to that document – Overview of OPP’s Screening-Level 

Ecological Risk Assessment Process for Antimicrobial Pesticides – explains both the data needed 

and the process that would be used by EPA to assess potential risks to endangered and threatened 

species from antimicrobial pesticides. 

EPA’s assessment of potential impacts on endangered and threatened species begins with a 

screening level assessment to determine if there is a potential concern. When the screening-level 

ecological risk assessment raises potential concerns related to a listed species, EPA then conducts a 

species-specific evaluation to refine the assessment. The more refined assessment should involve clear 

delineation of the action area associated with the proposed use of the pesticide and the best available 

information on the temporal and spatial co-location of the listed species with respect to the action 

area. EPA notes that with the publication of the proposed rule, the discussion in Appendix A is out 

of date. In the response to comments received on the proposed antimicrobial data requirements, 

EPA indicated it is no longer relying on its proposed approach classifying use patterns as high/low 

or minimal/significant exposure uses with regard to ecological effects testing. However, the 

Agency’s basic approach to endangered species risk assessments, which combine environmental fate 
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Master Responses: 

Endangered Species Section (180) Page 251 

studies with ecological effects data to determine the potential of the pesticide to cause harmful 

effects to threatened and endangered species, has not changed. In addition, the Agency will conduct 

an assessment for antimicrobial pesticides with down-the-drain uses, as described in the response to 

comment 134.1. The codified data requirements and the down-the-drain assessment will extend the 

Antimicrobial Division’s ability to understand the potential impacts of antimicrobial pesticides on 

endangered species. 

EPA cannot wait to comply with the ESA until newer, more advanced, models are available or 

additional data needs are determined: Federal agencies must comply with the ESA by performing 

their assessments and analyses using the best scientific and commercial data available. As a part of 

Registration Review, EPA is conducting species-specific environmental risk assessments that will 

allow EPA to determine whether the antimicrobial pesticide product has “no effect” or “may affect” 

federally-listed threatened or endangered species (listed species) or their designated critical habitats. 

When an assessment concludes that a pesticide product’s use “may effect” a listed species or its 

designated critical habitat, the Agency will consult with the FWS and/or NMFS, as appropriate. 

Comment 180.5: A commenter stated that it will take several years to identify and develop a 

database of information, sources, and programs that would be useful for the evaluation of the 

impact of antimicrobials on endangered and threatened species. According to the commenter, EPA 

should conduct an evaluation of other federal, state and local laws and regulatory schemes that 

regulate antimicrobial pesticides, and similarly should evaluate other EPA-administered programs 

such as the Clean Water Act to evaluate the types of data that could be provided to EPA. 

Response 180.5: EPA agrees that it will take time to develop one comprehensive set of information 

and tools that could be used to refine evaluations of the potential effects of a pesticide to a listed 

species or critical habitat. A variety of information is used in these assessments, which are intended 

to refine the screening-level risk assessments to more specifically determine exposure and 

characterize risk to a listed species or critical habitat. Examples of the types of information used in 

species/habitat specific assessments include county-level occurrence information for listed species; 

county-level information on agricultural crops and their acreage; biological requirements and habits 

of listed species; incident information; sales and use information; local use practices; and monitoring 

data. .

In the proposed rule [59425], EPA sought comment on what additional data and information may 

be needed to develop and/or refine endangered species risk assessments for antimicrobial species. 

EPA will consider those comments, and comments on the proposed and final rules issued for 

conventional, biochemical and microbial pesticides, to inform any future review of overall 

endangered species data requirements with the purpose of determining whether new data 

requirements for endangered species assessments need to be determined and promulgated in a new 

rule. If in the future EPA finds that specific additional data need to be generally required for 

purposes of assessing the potential risks to endangered and threatened species, EPA will issue a 

proposed rule to amend subpart W of part 158, relative to those specific data needs. 
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Master Responses: Guidelines Section (190) Page 252 

Guidelines (190) 

Master Responses for the Guidelines Section 

Please note that EPA responses are presented in numerical order. However, in the course of response development, 

some have been combined, thus there are some jumps in the sequential numbering scheme; no responses are missing. 

Comment 190.1: A commenter contends that antimicrobial pesticide data requirements for uses that 

discharge to POTWs should require both acute and chronic toxicity test results for at least one 

freshwater invertebrate, vertebrate, and plant species and at least one marine/estuarine invertebrate, 

vertebrate, and plant species conducted according to EPA’s Office of Water’s (OW) Whole Effluent 

Toxicity (WET) methods instead of according to OPP’s guidelines. The commenter further 

contends that acute and chronic toxicity data are essential for screening-level environmental 

assessments since U.S. EPA will need to use adverse effect concentrations in the Exposure and Fate 

Assessment Screening Tool (E-FAST) to evaluate potential impacts. 

Response 190.1: As described in response to comments 50.4, 134.1, 134.21, 140.21, and 160.7 EPA 

revised the table descriptors for certain data requirements from “conditionally required (CR)” or 

“not required (NR),” to “required (R).” Thus the overall effect of EPA’s responding to comments 

received is that in the final rule for antimicrobial data requirements, EPA is requiring “R” more 

environmental fate and ecotoxicity data than originally proposed. As contended by the commenter 

above, for many antimicrobial use patterns, EPA is now requiring both acute and chronic toxicity 

studies for freshwater and/or marine invertebrates and vertebrates, and acute studies for plant 

species. 

However, in the data requirement tables that will be codified in part 158W, OPP is specifying 

EPA/OPP’s Harmonized Test Guidelines. Studies conducted according to the Harmonized Test 

Guidelines are specifically designed to provide information for assessing risk and then making a 

regulatory decision under FIFRA or FFDCA. 

EPA WET test methods (40 CFR Part 136) are performed differently than chemical-specific 

analyses used for required aquatic toxicity studies for pesticide registration. WET tests are designed 

to detect aggregate toxic impacts from a pollutant or mixture of pollutants that can either cause, 

contribute to, or potentially cause an exceedance of a state aquatic life protection (ALP) water 

quality standard (WQS) due to the possible toxicity from permitted point source effluents discharges 

and non-point sources into waters of the U.S. For WET testing, the sample may be taken either at 

the end of the discharge pipe or in the receiving waterbody. The WET assessment is used for 

determining whether reasonable potential (RP) to exceed a WQS exists (thus requiring a WET limit) 

and for compliance with a permit’s WET limit(s). WET tests use diluted and undiluted (100 percent 

effluent) samples of the permitted effluent in a minimum of five dilution (the effluent is diluted with 

the same water used as the control sample) series (each with multiple replicates according to the 

particular WET test) to assess at which concentration the acute (survival/death) or chronic 

(inhibition of growth, reproduction, etc.) effects are observed due to exposure to the effluent. 

Thus, a limitation of WET testing is that since the effluent often contains a mixture of chemicals, 

the testing does not provide information on acute and chronic toxicity to aquatic organisms as a 

result of exposure to a specific chemical substance. 
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Master Responses: Guidelines Section (190) Page 253 

This is different from the chemical-specific nontarget organism testing required for a pesticide 

registration in which the test species is placed into a diluted mixture of water (the same water used as 

the control sample, which meets the appropriate quality parameters to ensure species survival) and 

the candidate antimicrobial pesticide at one or more specific concentrations. 

Thus, the toxicity data requirements developed by OPP are designed to predict potential adverse 

effects as a result of exposure of aquatic organisms to a specific pesticide chemical. 

EPA agrees that acute and chronic toxicity data are essential for screening-level environmental 

assessments and that EPA will need to use adverse effects concentrations in E-FAST to evaluate 

potential impacts to aquatic organisms. However, EPA/OPP disagrees that results from WET 

testing methods would provide the chemical-specific measurement endpoints needed as input values 

for the E-FAST model, whereas OPP acute and chronic toxicity methods provide such endpoints. 

Comment 190.2: A commenter contended that the proposed data requirements for aquatic toxicity 

of antimicrobial pesticides do not include a sufficient number of species to meet EPA/OPP’s 

environmental risk assessment needs. EPA/OW requires data from eight families of aquatic animals 

as the minimum data set for water quality criteria development. The commenter also argued that salt 

water species aquatic toxicity data need to be included in the minimum data set for antimicrobials 

that may be used outdoors in urban areas. The commenter asserted that, if these data are not 

included among the minimum data set, the regulation should be revised to clarify that 

implementation of this requirement is expected to be quite common. The commenter further states 

that aquatic organism testing guidelines [sic for antimicrobial pesticides] should be updated to 

harmonize with Office of Water methods. 

Response 190.2: The commenter is correct that the number of species for which OW requires 

aquatic toxicity test data to establish a national ambient water quality criteria is greater than the 

number of species required by OPP that are used to establish levels of concerns for freshwater and 

estuarine/marine vertebrates, and plants. Data conducted according to the Harmonized Test 

Guidelines or similar protocols are used to establish levels of concern for freshwater and 

estuarine/marine vertebrates, invertebrates, and plants. EPA does not agree that the process OPP 

uses to establish these levels of concern does not include sufficient species. OPP establishes levels of 

concern for aquatic organisms based on the most sensitive species for which verifiable toxicity data 

are available. In establishing levels of concern for aquatic organisms, EPA considers not only 

toxicity data based on results from OPP test guidelines for the most sensitive species of aquatic 

vertebrates, invertebrates, and plants for which testing is required, but also considers results of acute 

and chronic tests for aquatic species that are included in EPA ORD’s Ecotoxicology database, 

ECOTOX. ECOTOX integrates three previously independent databases, ACQUIRE, 

PHYTOTOX, and TERRETOX into a unique system which includes toxicity data derived 

predominantly from the peer-reviewed literature for aquatic life, terrestrial plants, and terrestrial 

wildlife, respectively. If more sensitive aquatic species are identified based on verifiable data from 

the ECOTOX database than results from OPP toxicity guideline tests indicate, OPP uses the data 

from the ECOTOX database to establish levels of concern for aquatic vertebrates, invertebrates, 

and plants. 
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Master Responses: Guidelines Section (190) Page 254 

Comment 191.1: Several commenters maintained that the current Harmonized Guidelines have 

significant problems, which include: 

 Lack of guidelines could create an unevenness from one company to another in how the data 

requirements are applied 

 Data requirements for which guidelines are not available 

 Older, outdated guidelines that need revision 

 Draft guidelines that need to be finalized 

 Older exposure guidelines that do not include information about the Human Studies Review 

Board 

 Guidelines that were adopted without the opportunity for public comment 

According to the commenters, the Agency needs to provide current, consistent, and reliable 

guidance and standards for each data requirement. The commenters believe EPA should finalize all 

of its guidelines before the final rule is published per the recommendation from OMB. 

Response 191.1: EPA’s Harmonized Test Guidelines are publicly-available at 

http://www.epa.gov/ocspp/pubs/frs/home/guidelin.htm. The Harmonized Guidelines contain 

recommendations on how to conduct a study that is most likely to provide the information needed 

by EPA for making a registration decision. 

EPA’s Harmonized Guidelines are organized in the following series: 

 810 - Product Performance Test Guidelines 

 830 - Product Properties Test Guidelines 

 835 - Fate, Transport and Transformation Test Guidelines 

 840 - Spray Drift Test Guidelines 

 850 - Ecological Effects Test Guidelines 

 860 - Residue Chemistry Test Guidelines 

 870 - Health Effects Test Guidelines 

 875 - Occupational and Residential Exposure Test Guidelines 

 880 - Biochemicals Test Guidelines 

 885 - Microbial Pesticide Test Guidelines 

890 - Endocrine Disruptor Screening Program Test Guidelines

The Harmonized Guidelines are guidance. The guidelines themselves do not impose mandatory 

requirements. Applicants are not required to submit studies developed according to the guidelines to 

fulfill a data requirement. However, EPA encourages applicants to use the guidelines. These 

guidelines were developed to provide applicants, who would be conducting the studies, with 

recognized approaches for developing high quality data, guidance on evaluating and reporting data, 

definition of terms, and suggested study protocols. It would not be possible to address every 

conceivable circumstance that could occur when conducting a particular study. Instead the 

guidelines provide a framework that provides recommended approaches for conducting studies 

while offering flexibility and accommodation for individual circumstances where appropriate. EPA 

has reviewed and accepted many studies, on a case-by-case basis, that were not conducted in 
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Master Responses: Guidelines Section (190) Page 255 

accordance with current guidelines, but which provided suitable information for risk assessment 

purposes. 

Since guidelines cannot account for every conceivable circumstance, EPA, for certain studies, 

proposed a “required” or “highly suggested” protocol submission and review step in the testnotes to 

the tables in the proposed rule. Generally, these pertain to those studies that are “newer” or have 

not been routinely conducted. Given that the applicant community and contracting laboratories 

would have less experience in conducting these kinds of “newer” studies, protocol submission, 

review, and meetings about proposed protocols are beneficial to both the applicant and EPA, and 

help assure that the study submitted for review should provide the information needed by EPA for 

its registration decision. Such an approach also helps assure that the studies would provide sufficient 

information to EPA. It is designed to help minimize instances in which the applicant conducts and 

submits a study and EPA reviews the study only to discover that the study provided insufficient 

information. It should be noted that EPA can indicate to an applicant that data that are key to 

assessing their particular product that may not be provided by using an existing guideline to conduct 

a study. Or alternatively, an applicant may offer to conduct a study for which there is no guideline to 

address issues in the risk assessment. EPA offers to work with applicants to provide guidance on 

study methods prior to the conduct of the study. 

EPA acknowledges that there are: data requirements for which guidelines are not available; outdated 

guidelines that need revision; and draft guidelines that need to be finalized. Ideally, up-to-date final 

guidelines would be available for every data requirement. Up-to-date guidelines increase the 

possibility that EPA will receive useful data and that applicants can produce such data in the most 

cost-efficient and consistent manner. However, given the rapidly evolving scientific methods for 

conducting toxicity, exposure and ecological studies with pesticides, study guidelines will need 

frequent updating to include the latest techniques and methods. Moreover, the need for openness 

and transparency means that developing a guideline or updating an existing one can be a lengthy 

process. In a recent letter to CropLife America (June 26, 2009), the Agency discussed the timeframe 

for developing the Terrestrial Field Dissipation Guideline (835.6100) which spanned 15 years. 

During that time period, there were presentations to the SAP, at various symposia including ones 

conducted by the American Chemical Society and the American Society of Agronomy, and to a 

workshop in Washington, DC co-hosted by EPA and Canada’s Pest Management Regulatory 

Agency. Thus, the reality is that test guidelines will always be a work in progress. At the same time, 

EPA is implementing a regulatory program under FIFRA and FFDCA section 408 under which it 

must make timely decisions on the safety of pesticide products based on toxicity and exposure 

testing. Guidance on optimal testing procedures remains an Agency goal but the absence of testing 

guidelines is not a barrier to the imposition of testing requirements necessary to make the required 

statutory findings. 

EPA understands that an applicant may be “uneasy” about using a protocol that has not yet been 

designated as final. On its Harmonized Guidelines website, EPA maintains the listing of draft 

guidelines separately from those that have been finalized. (see 

http://www.epa.gov/ocspp/pubs/frs/home/draftguidelines.htm) The webpage clearly states that 

while draft guidelines are to be consulted during protocol development, that before using a draft 

guidelines, to “please check with the appropriate EPA office.” 
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Master Responses: Guidelines Section (190) Page 256 

At times for certain scientific disciplines, the science, as well as practices and policies are rapidly 

evolving, and even recently finalized guidelines can be suddenly subject to the need for change. For 

example, the Harmonized Guidelines for Exposure Assessment need revisions to account for new 

advances in how exposure is measured and modeled. As discussed above developing a guideline can 

be a multi-year process. Before a guideline can be finalized and posted to the website, there also 

needs to be general agreement by the experts on how the study is to be conducted. In such 

circumstances, when the guidelines are in draft or under development, EPA can provide applicants 

with the most up-to-date and appropriate information it has available. Applicants often meet with 

EPA on a pre-submission basis to discuss the potential acceptability of a protocol or to review the 

possible adequacy of the available data. Such discussions are valuable as it is mutually beneficial to 

discover that a planned study might not provide the quality or completeness of data needed for a 

licensing decision before study conduct or submission occurs. 

In 2008, OMB, during its Executive Order 12866 review of the proposed rule, recommended that 

certain draft guidelines be finalized before publishing the Antimicrobial Data Requirements final 

rule. These guidelines were: 

 Applicator product use information 

 Post application product use information 

 Indoor surface residue dissipation 

 Non-dietary ingestion 

In the proposed rule (October 8, 2008; 73 FR 59382), EPA discussed that that the publicly-available 

versions of these guidelines were only available on the SAP portion of EPA’s website (73 FR 59399 

– 59401). EPA intends to finalize these guidelines in the near future. Also as previously discussed, 

the data requirement referencing the non-dietary ingestion guideline was removed from the final 

post-applicator exposure table in § 158.2270 (see response to comment 100.13). 

As the guidelines for exposure studies are updated, information regarding the requirements for 

ethical conduct of research involving intentional exposure of humans will be incorporated into the 

appropriate exposure guidelines as they are revised. If any studies undertaken to address these 

requirements involve intentional exposure of a human subject (as defined at 40 CFR 26.1102(i)), 

then the study must not be initiated before submission of protocols and supporting documentation 

for review by EPA and the Human Studies Review Board. The requirements for protocol 

submissions and Agency review are specified at 40 CFR 26.1125 and 40 CFR 26.1601, respectively. 

If there is any question, however, about whether a proposed study intended for submission to EPA 

falls within or outside this regulatory definition, consultation with EPA is recommended before 

initiating the study. If EPA did not review the protocol for a study involving intentional exposure of 

a human subject, the study, if subsequently submitted to the Agency, would not be acceptable under 

40 CFR 26.1705. 

To acknowledge those exposure guidelines that are not up-to-date and to provide needed 

information to the public and applicants, EPA will change the way these guidelines are referenced 

on the Harmonized Guidelines website by adding links to the SAP and HSRB meetings at which the 

changes needed to conduct one of these studies were publicly discussed. 
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Master Responses: Guidelines Section (190) Page 257 

Before finalizing a guideline, EPA provides many opportunities for public comment. EPA’s 

commitment to transparency is not new. Transparency allows all stakeholders to know what, how, 

and why EPA is adopting a guideline. EPA’s procedures for developing a guideline is described in a 

Notice of Availability that published on August 28, 1996 (61 FR 44308): 

 Guidelines under development (whether new or being substantially revised) are made 

available for public comment. 

 Guidelines under development (whether new or being substantially revised) undergo an 

external peer review process. Most commonly, the peer review process would be a review by 

the FIFRA SAP. 

 Reformatted guidelines (no substantial revisions) are not subject to review and comment. 

 Public review and comment is also used when EPA guidelines are being harmonized with 

OECD guidelines. 

Since the publication of the proposed rule on October 8, 2008, EPA has worked to update and 

finalize a number of guidelines. On April 15, 2009, EPA published in the Federal Register (74 FR 

17479) a Notice of Availability describing updates to 16 environmental fate guidelines. On January 

27, 2010, (75 FR 4380) EPA published four draft product performance guidelines for comment. 

These four guidelines (810.2000, 810.2100, 810.2200, and 810.2300) were developed over an 

extended period of time with multiple levels of review across divisions and program offices in EPA, 

expert external peer review by the FIFRA Scientific Advisory Panel, and discussions with and 

comments from the regulated community. Many of the technical changes described in the four draft 

guidelines have been in use by the Agency for several years. Three additional product performance 

guidelines (810.2400, 810.2500, and 810.2600) should be published for comment in a timeframe 

similar to that of the publication of the final rule for Antimicrobial Data Requirements. Similarly, 

the nontarget organism and plant protection guidelines should be finalized by the end of this year. 

 

As of May 4, 2011, additional information on EPA/OPP’s work to update and finalize its guidelines 

is in the table below. EPA notes that the information in the “Guideline Status According to ACC 

Comments” column was taken from the alternative data requirements tables suggested by ACC for 

residue chemistry, environmental fate, and applicator and post-application exposure, as well as the 

table beginning on page 17 of their comments. 

Guideline Data Requirement Guideline Status 

According to ACC 

Comments 

EPA’s Response on 

Status 

§158.2210 Product chemistry 

830.1550 Product Identity and Composition No comment Final 

830.1600 Description of Materials used to 

Produce the Product 

No comment Final 

830.1620 Description of Production Process No comment Final 

830.1650 Description of Formulation Process No comment Final 

830.1670 Description of Formulation 

Impurities 

No comment Final 

830.1700 Preliminary Analysis No comment Final 

830.1750 Certified Limits No comment Final 

830.1800 Enforcement Analytical Method No comment Final 
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Master Responses: Guidelines Section (190) Page 258 

Guideline Data Requirement Guideline Status 

According to ACC 

Comments 

EPA’s Response on 

Status 

830.1900 Submittal of Samples No comment Final 

830.6302 Color No comment Final 

830.6303 Physical State No comment Final 

830.6304 Odor No comment Final 

830.6313 Stability to Normal and Elevated 

Temperature, Metals, and Metal 

Ions 

No comment Final 

830.6314 Oxidation/Reduction; Chemical 

Incompatibility 

No comment Final 

830.6315 Flammability No comment Final 

830.6316 Explodability No comment Final 

830.6317 Storage Stability No comment Final 

830.6319 Miscibility No comment Final 

830.6320 Corrosion characteristics No comment Final 

830.6321 Dielectric Breakdown Voltage No comment Final 

830.7000 pH No comment Final 

830.7050 UV/Visible Light Absorption No comment Final 

830.7100 Viscosity No comment Final 

830.7200 Melting Point/Melting Range No comment Final 

830.7220 Boiling Point/Boiling Range No comment Final 

830.7300 Density/Relative Density/Bulk 

Density 

No comment Final 

830.7370 Dissociation Constants in Water No comment Final 

830.7520 Particle Size, Fiber Length, and 

Diameter Distribution 

No comment Final 

830.7550 

830.7560 

830.7570 

Partition Coefficient (noctanol/water) No comment Final 

830.7840 

830.7860 

Water Solubility No comment Final 

830.7950 Vapor Pressure No comment Final 

§158.2220 Product performance 

810.2100 Sterilants – Efficacy Data 

Recommendations 

Guideline has not been 

made available for 

public comment. 

Draft * 

Expected to Final 2011 

Also, Series 91 guidelines 

available 

810.2200 Disinfectants for Use on Hard 

Surfaces – Efficacy Data 

Recommendations. 

Guideline has not been 

made available for 

public comment. 

810.2300 Sanitizers for Use on Hard Surfaces 

– Efficacy Data Recommendations 

Guideline has not been 

made available for 

public comment. 
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Master Responses: Guidelines Section (190) Page 259 

Guideline Data Requirement Guideline Status 

According to ACC 

Comments 

EPA’s Response on 

Status 

810.2400 Disinfectants and Sanitizers for Use 

on Fabrics and Textiles -- Efficacy 

Data Recommendations. 

Guideline has not been 

made available for 

public comment. 

Under development; draft 

guidelines expected to 

publish for comment in 

2011 

Also, Series 91 guidelines 

available 

810.2500 Air Sanitizers – Efficacy Data 

Recommendations 

Guideline has not been 

made available for 

public comment. 

810.2600 Disinfectants for Use in Water -- 

Efficacy Data Recommendations. 

Guideline has not been 

made available for 

public comment. 

§158.2230 Toxicology 

870.1100 Acute oral toxicity – rat No comment Final 

870.1200 Acute dermal toxicity No comment Final 

870.1300 Acute inhalation toxicity - rat No comment Final

870.2400 Primary eye irritation - rabbit No comment Final

870.2500 Primary dermal irritation No comment Final 

870.2600 Dermal sensitization No comment Final 

870.6200 Acute neurotoxicity - rat No comment Final

870.3100 90-Day oral toxicity - rodent No comment Final 

870.3150 90-Day oral toxicity - nonrodent No comment Final 

870.3200 21/28-Day dermal toxicity No comment Final 

870.3250 90-Day dermal toxicity No comment Final 

870.3465 90-Day inhalation - toxicity - rat No comment Final 

870.6200 90-Day neurotoxicity - rat No comment Final

870.4100 Chronic oral toxicity - rodent No comment Final 

870.4200 Carcinogenicity – two rodent 

species – rat and mouse preferred 

No comment Final 

870.3700 Prenatal developmental toxicity - rat 

and rabbit preferred 

No comment Final

870.3800 Reproduction and fertility effects No comment Final

870.6300 Developmental neurotoxicity No comment Final

870.5100 Reverse mutation assay No comment Final

870.5300 

870.5375 

In vitro mammalian gene mutation No comment Final

870.5385 

870.5395 

In vivo cytogenetics No comment Final

870.7485 Metabolism and pharmacokinetics No comment Final 

870.7200 Companion animal safety No comment Final 

870.7600 Dermal penetration No comment Final 

870.7800 Immunotoxicity No comment Final 

§ 158.2240 Nontarget organisms. 

850.1010 Acute freshwater invertebrates 

toxicity 

Not Final Draft** 

850.1075 Acute freshwater fish toxicity Not Final Draft** 
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Master Responses: Guidelines Section (190) Page 260 

Guideline Data Requirement Guideline Status 

According to ACC 

Comments 

EPA’s Response on 

Status 

850.1025 

850.1035 

850.1045 

850.1055 

850.1075 

Acute estuarine and marine 

organisms toxicity 

Not Final Draft** 

850.1400 Fish early-life stage Not Final Draft** 

850.1300 

850.1350 

Aquatic invertebrate life- cycle Not Final Draft** 

850.1500 Fish life-cycle Not Final Draft** 

850.1710 

850.1730 

850.1850 

Aquatic organisms, bioavailability, 

biomagnification, toxicity tests 

Not Final Draft** 

850.1950 Simulated or actual field testing for 

aquatic organisms 

Not Final Draft** 

850.1735 Whole sediment; acute freshwater 

invertebrates 

Not Final Draft** 

850.1740 Whole sediment; acute marine 

invertebrates 

Not Final Draft** 

none Whole sediment; chronic 

invertebrates freshwater and marine

Not Final There is an Agency-wide 

guidance document. 

Protocol must be 

approved by the Agency 

prior to the initiation of 

the study (case-by-case). 

850.2100 Acute avian oral toxicity Not Final Draft** 

850.2200 Avian dietary toxicity Not Final Draft** 

850.2300 Avian reproduction Not Final Draft** 

850.3020 Honeybee acute contact Not Final Draft** 

850.3030 Toxicity of residues to honeybees Not Final Draft** 

§158.2250 Nontarget plant protection 

850.4225 Seedling emergence, Tier II – dose 

response 

Not Final Draft** 

850.4250 Vegetative vigor , Tier II – dose 

response 

Not Final Draft** 

850.4400 Aquatic plant growth (aquatic 

vascular plant) Tier II – dose 

response 

Not Final Draft** 

850.5400 Aquatic plant growth (algal) Tier II 

(dose response) 

Not Final Draft** 

850.4300 Terrestrial field Not Final Draft** 

850.4450 Aquatic field Not Final Draft** 

§158.2260 Applicator exposure 
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Guideline Data Requirement Guideline Status 

According to ACC 

Comments 

EPA’s Response on 

Status 

875.1100 

875.1200 

Dermal exposure Cited† Final 

These 3 guidelines need to 

be updated*** 

875.1300 

875.1400 

Inhalation exposure Cited†

875.1500 Biological monitoring Cited†

875.1600 Data reporting and calculations Cited† Final 

875.1700 Product use information Not available, even in 

draft 

Under development and is 

substantially similar to the 

draft post-application 

guideline available at the 

SAP website. 

§158.2270 Post-application exposure 

875.2200 Soil residue dissipation Cited† Final 

875.2300 Indoor surface residue dissipation Not available, even in 

draft

Draft guideline is 

available at SAP website 

875.2400 Dermal exposure Cited† Final 

These 3 guidelines need to 

be updated*** 

875.2500 Inhalation exposure Cited†

875.2600 Biological monitoring Cited†

875.2700 Product use information Not available, even in 

draft

Draft guideline is 

available at SAP website 

875.2800 Description of human activity Cited† Final 

875.2900 Data reporting and 

 calculations 

Cited† Final 

§158.2280 Environmental fate 

835.2120 Hydrolysis Not available, even in 

draft

Final

835.2240 Photodegradation in water Not available, even in 

draft 

Final 

835.2410 Photodegradation in soil Not available, even in 

draft 

Final 

850.6800 

OECD 

209 

Activated Sludge, Respiration 

Inhibition Test 

Cited† Draft 

(OECD guideline is 

available on the OECD 

website) 

835.1110 Activated Sludge Sorption Isotherm Cited† Final 

835.3110 Ready Biodegradability Cited† Final 

835.3220 Porous Pot Study Cited† Final 

835.3280 Simulation Tests to Assess the 

Biodegradability of Chemicals 

Discharged in Wastewater 

NA Final 
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Master Responses: Guidelines Section (190) Page 262 

Guideline Data Requirement Guideline Status 

According to ACC 

Comments 

EPA’s Response on 

Status 

835.3240 Simulation Test – Aerobic Sewage 

Treatment: A. Activated Sludge 

Units 

NA Final 

835.1230 

835.1240 

Leaching and adsorption/ 

desorption 

Not available, even in 

draft 

Final 

835.4100 Aerobic soil metabolism Not available, even in 

draft 

Final 

835.4200 Anaerobic soil metabolism Not available, even in 

draft 

Final 

835.4300 Aerobic aquatic metabolism Not available, even in 

draft 

Final 

835.4400 Anaerobic aquatic metabolism Not available, even in 

draft 

Final 

835.6200 Aquatic (sediment) Not available, even in 

draft 

Final 

none Monitoring of representative U.S. 

waters 

Not available, even in 

draft 

Protocol must be 

approved by the Agency 

prior to the initiation of 

the study (case-by-case). 

none Special leaching Not available, even in 

draft 

Protocol must be 

approved by the Agency 

prior to the initiation of 

the study (case-by-case). 

§ 158.2290 Residue Chemistry 

860.1100 Chemical identity Cited† Final 

860.1200 Directions for use Cited† Final 

860.1550 

Proposed tolerance/ 

tolerance exemption 

Cited† Final 

860.1560 

Reasonable grounds in support of 

petition 

Cited† Final 

860.1650 

Submittal of analytical reference 

standards 

Cited† Final 

860.1460 Food-handling Different# Final 

none Nature of residues on surfaces NA Protocol must be 

approved by the Agency 

prior to the initiation of 

the study (case-by-case). 

none Migration studies Not available, even in 

draft 

FDA protocols available. 

Protocol must be 

approved by the Agency 

prior to the initiation of 

the study (case-by-case). 
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Master Responses: Guidelines Section (190) Page 263 

Guideline Data Requirement Guideline Status 

According to ACC 

Comments 

EPA’s Response on 

Status 

860.1340 Residue analytical method for data 

collection 

None## and Cited† Final 

860.1380 Storage stability None## and Cited† Final 

860.1300 

Nature of the residue in plants Different# Final 

860.1300 

Nature of the residue in livestock None## Final 

860.1340 Residue analytical methods for 

tolerance/tolerance exemption 

enforcement 

None## Final 

860.1360 Multiresidue method testing None## Final 

860.1400 Potable water Different# Final 

860.1400 Fish Different# Final 

860.1400 Irrigated crops Different# Final 

860.1480 Meat/milk/poultry/eggs None## Final 

860.1500 Crop field trials Different# Final 

860.1520 Processed food or feed Different# Final 

none Anticipated residues Not available, even in 

draft 

Draft Policy documents 

are available. 

Protocol must be 

approved by the Agency 

prior to the initiation of 

the study (case-by-case). 

* These three draft guidelines were published, and have completed the public comment period. 

EPA is working on the response-to-comments document and revisions to the guidelines. Target for 

publication of final guidelines is 2011. 

** Revision activities are almost completed. Target for publication of final guidelines is 2011 

*** The final guidelines for dermal (875.1100, .1200, .1300, .1400, .2400), inhalation (875.1300, 

.1400, .2500), and biological (875.1500, .2600) along with the draft guideline for indoor surface 

residue dissipation (875.2300) need to be revised based on the emerging science of human exposure 

monitoring. Additionally, there is also a need to update the guidelines to include information 

regarding the ethical conduct of research involving intentional exposure of humans. EPA plans to 

change the way these guidelines are referenced on the Harmonized Guidelines website by providing 

researchers links to the most recent available monitoring methods and protocols that are available 

on the SAP, HSRB, and CPSC web sites. 

†

 Cited means that the ACC cites EPA’s Guideline number in their alternative data requirements 

table 

#

 Different means ACC’s alternative data requirements tables for residue chemistry used different 

nomenclatures or did not reference this data requirement or the guideline. 
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Master Responses: Guidelines Section (190) Page 264 

## None means guideline column is marked as “none” in one of commenter’s suggested residue 

chemistry data requirements table, meaning that ACC did not believe in the existence of that 

guideline 

OCSPP Harmonized Test Guidelines are available on the internet at the following locations: 

Final Guidelines http://www.epa.gov/ocspp/pubs/frs/home/guidelin.htm

Draft Guidelines http://www.epa.gov/ocspp/pubs/frs/home/draftguidelines.htm

Comment 191.3: A commenter maintained that the absence of guidelines makes it impossible to: 

 Gauge the impact of the regulation 

 Determine if requirements are rational 

 Comply with the final regulation 

 Determine if a particular date requirement is applicable and how to address it 

 Fully comment on the proposal 

 Determine what data are expected and under what circumstances 

Response 191.3: EPA disagrees with this comment, and believes the impact of the regulation is 

defined by the data requirements, not the presence or absence of guidelines. The types of data 

needed for EPA to make a registration decision are clearly identified in its proposed rule. As 

discussed in EPA’s Response to Comment 191.1, guidelines can be useful to both EPA and 

regulated parties; however, the presence of a guideline is not a mandatory requirement for 

promulgation of a data requirement. EPA believes that the comments received on the proposed 

data requirements demonstrated a good understanding of the data requirements and the comments 

were key to determining the data requirements for the final rule. Further, as discussed in the 

preamble to the proposed rule, the applicant may use a protocol (i.e., study design) of their choice as 

long as the study produces data of sufficient quality and completeness for a registration decision. 

This is based on 40 CFR 158.70, “Satisfying Data Requirements,” where EPA has specified its 

general policies on evaluating if a submitted study fulfills a data requirement. In 40 CFR 158.70(d), 

EPA discusses that a particular protocol is not required, and that any protocol that meets the 

purpose of the test standards specified in the pesticide assessment guidelines, and provides data of 

suitable quality and completeness may be used to generate the data required under Part 158. The 

Harmonized Guidelines are not the only means to provide quality data. Notably, the commenters 

have not given a single example of how the absence of a guideline has made it “impossible” to 

“gauge the impact of the regulation,” “determine if the requirements are rational,” etc. Rather, the 

comments have been limited to lists of uncompleted or draft guidelines and generic assertions about 

the effect of this situation. 
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Master Responses: Guidelines Section (190) Page 265 

Comment 191.4: A commenter asserted that EPA should harmonize its guidelines with those of 

OECD. 

 

Response 191.4: EPA agrees with this comment and is continuing to harmonize guidelines, to the 

extent practicable, as they are revised. As noted on its website 

http://www.epa.gov/pesticides/science/guidelines.htm, EPA has several harmonization activities 

underway with the Organisation for Economic Co-operation and Development (OECD). The 

Master List of Harmonized Test Guidelines includes a reference to an OECD guideline, when 

harmonized. All harmonized OECD test guidelines 

(http://www.epa.gov/epahome/exitepa.htm)fall under the OECD Mutual Acceptance of Data 

decision, which calls for acceptance for regulatory use by all OECD member nations. Additionally, 

in 40 CFR 158.70(d)(2), testing conducted in accordance with OECD protocols is described. 

Harmonized test guidelines reduce the burden on chemical producers and conserve scientific 

resources, including the minimal use of laboratory test animals. They also form a basis for work 

sharing and cooperation among all OECD countries. U.S. experts are engaged in harmonization 

activities through OECD to revise toxicology and ecotoxicology test guidelines. These revisions will 

emphasize reduction, refinement, or replacement of animal testing, while incorporating the latest 

advances in science. Animal welfare concerns and international regulatory needs are being 

considered in the course of these revisions of the test guidelines. In addition, EPA is actively 

engaged in OECD’s development and harmonization efforts for guidelines to address 

environmental fate, endocrine disruptor screening, and efficacy of antimicrobial pesticides. 

Tests conducted in accordance with the requirements and recommendations of the applicable 

OECD protocols can be used to develop data necessary to meet the data requirements. However, 

some of the OECD recommended test standards, such as test duration and selection of test species, 

are less restrictive than those recommended by EPA. When using OECD protocols, applicants 

should be careful to observe the test standards so that the data generated will satisfy the EPA data 

requirements. 

 

Comment 191.5: A commenter noted that there is a need for guidance on risk assessment for 

antimicrobials. 

 

Response 191.5: Risk assessment is not unique to OPP. The principles used by OPP, and in fact, by 

EPA are those used by the scientific community in general. OPP follows the processes and 

procedures in the many risk assessment guidance documents that have been issued by EPA. (see 

http://www.epa.gov/riskssessment/guidance.htm) The Agency’s exposure and risk assessment 

procedures have been presented in numerous exposure and risk assessments for antimicrobial 

pesticides. EPA’s assessment reflects the best available data, and the state of the science of exposure 

and risk assessment models, methods, and procedures. 

For several reasons, new detailed guidance on antimicrobial risk assessment is not needed in 

conjunction with this rulemaking. First, EPA’s approach to risk assessment of pesticides, including 

antimicrobial pesticides, is publicly available. EPA has recently concluded the process of completing 

Reregistration Eligibility Decision Documents for all pesticides under FIFRA and reassessing all 
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Master Responses: Guidelines Section (190) Page 266 

FFDCA pesticide tolerances. This was a very open process involving multiple public comment 

opportunities as to each pesticide. Further, all regulatory decision documents as well as the 

underlying risk assessments have been made available to the public. EPA has now begun new 

pesticide reviews under the Registration Review program, and that process is equally open and 

transparent. Second, the proposed rule does not represent a change to EPA’s existing risk 

assessment procedures. Rather, the proposal is merely designed to tailor the existing data 

requirements that apply to all pesticides in a way that is more specific to antimicrobial pesticides, as 

well as including some new requirements applicable to antimicrobials. Finally, EPA has explained 

the need for each study and provided background information on the purpose for which each study 

would be required. Part 158, subpart B contains an extensive description of the need for and use of 

submitted studies. Additionally, as explained in the preamble to the proposed rule (73 FR 59384), 

the proposals for establishing data requirements for conventional pesticides (March 11, 2005; 70 FR 

12276) and biochemical and microbial pesticides (March 8, 2006; 71 FR12072) “ state the rationales 

for requiring and/or revising particular data requirements. With few exceptions, these rationales are 

also applicable to antimicrobial pesticide chemicals, and as such have not been repeated in today’s 

proposed rule. Today’s proposal discusses in detail only those revisions that are singularly applicable 

to antimicrobial pesticides, including antifoulants and wood preservatives.” Examples of studies 

applicable to antimicrobial pesticides and therefore included in the proposed rule for antimicrobials 

include the need for the 90-day dermal and 90-day inhalation studies for a heating, ventilation, air 

conditioning, and refrigeration uses (73 FR 59395), the need for a food migration study (73 FR 

59404), and the need for environmental fate studies to support a down-the-drain assessment (73 

FR59408). 

 

Comment 191.6: A commenter stated that guidelines specific to antimicrobials are needed, and in a 

meeting here at EPA on May 17, 2011 provided EPA with examples of guidelines that they 

considered to be “inapplicable” to antimicrobials. 

Response 191.6: EPA agrees that for certain scientific disciplines or certain studies that 

antimicrobial-specific guidance may be needed. The data required to demonstrate product 

performance would be very different for an insect repellent or a termiticide versus that needed for 

sanitizers and disinfectants. Exposure studies could be conducted differently for an antimicrobial 

used in a food-processing plant versus a conventional pesticide sprayed on an agricultural field. 

Exposure studies could also be conducted the same: a spray can with an insecticide is assessed using 

the same techniques as a spray can with a disinfectant. For other scientific disciplines such as 

toxicology or product chemistry, generally, with a few exceptions, the guidance would be the same: 

A carcinogenicity, developmental, or reproductive toxicity study would be conducted similarly for an 

antimicrobial or a conventional pesticide. However, as noted in response to comment 80.41, the 

Ames assay may not be useful for assessment of mutagenic potential of antimicrobial pesticides. 

The commenters May 17, 2011 submission appears to have defined “inapplicable” in two different 

ways: The first is their belief that the guideline is not specific to antimicrobials, and the second is 

that the data requirement is not appropriate to the circumstances of antimicrobials. 

 

EPA’s Harmonized Test Guidelines are not intended to be specific to only a specific class of 

chemicals, such as antimicrobials or conventional pesticides. As noted on EPA’s website (see 

http://www.epa.gov/ocspp/pubs/frs/home/guidelin.htm), these guidelines are used for “testing of 
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Master Responses: Guidelines Section (190) Page 267 

pesticides and toxic substances...” While the guidelines may contain specific information to assist 

pesticide registrants, the guidelines also contain information for testing of other chemicals. 

ACC/CSPA Comment EPA Response 

Post-Application Exposure, Descriptions of Human Activity, 875.2800 

This is clearly stated as relevant only for 

determining reentry intervals following crop 

treatments. 

EPA disagrees. The purpose of the guideline is 

stated as, “to delineate the requirements for 

developing and submitting descriptions of 

human activities likely to occur at a site that has 

been treated with a specific pesticide.” The 

guideline later states that “the applicant should 

state which activity is the most like[ly] to result in 

maximum human exposure to pesticide residue 

for each site” and then discusses that the most 

significant human exposure to pesticide residues 

occurs when harvested commodities are 

transferred and handled. Once the applicant has 

selected his maximum exposure activity, then the 

guideline states, “The activity selected will 

represent the maximum expected exposure 

activity for that specific use, and may be 

employed as the exposure standard for future 

calculations under OPPTS 875.2900 if that 

guideline is used for calculating a reentry 

interval.” [emphasis added] 

Ready Biodegradability, 835.3110 and Porous Pot Test, 835.3220 

These studies may not be suitable or practical for 

antimicrobial testing, including biodegradability 

testing with inorganic chemicals, or chemical 

elements. Also, at the dosing level necessary to 

see CO2 evolution caused by the compound 

above background evolution, many biocides will 

be toxic to the microbial community. 

As noted above, the Harmonized Guidelines are 

not intended to be specific to only a specific 

class of chemicals. The Ready Biodegradability 

guideline contains six different protocols that 

“permit the screening of chemicals for ready 

biodegradability in an aerobic aqueous medium.” 

“[D]epending on the physical characteristics of 

the substance to be tested, a particular method 

may be preferred.” Ready Biodegradability 

studies are routinely submitted to OPP/AD, 

therefore it is possible to perform this study with 

an antimicrobial. 

EPA has considered that some biocides may be 

too toxic for a screening type of study such as 

the Ready Biodegradability study to be useful. 

That is why the Activated Sludge Respiration 

Inhibition study is performed first, and then 

based on the results of that study, the applicant 

has the choice of several biodegradation studies, 

including the Porous Pot, to perform. For 
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Master Responses: Guidelines Section (190) Page 268 

additional information see response to comment 

134.1. 

Aerobic Soil Metabolism, Anaerobic Soil Metabolism, Aerobic Aquatic, Metabolism, 

Anaerobic Aquatic Metabolism, 835.4100 through 835.4400 

These guidelines are clearly identified as 

designed for terrestrial applications to crops and 

noncrop areas; they do not include appropriate 

guidance for antimicrobial pesticides at are, by 

definition, not applied in such terrestrial 

environments. For example, OPPTS 

835.410/4200 says: “The treatment rate should 

correspond to the highest application rate of a 

crop protection product recommended in the 

use instructions and uniform incorporation to an 

appropriate depth in the field (e.g., top 10 cm 

layer of soil).” These guidelines further depend 

on maintenance of an appropriate microbial 

population in the soils. Since antimicrobial 

pesticides are designed to control 

microorganisms, the relevance of these testing 

protocols is questionable, particularly given what 

likely are significant limitations on the dosing 

levels to avoid toxicity to the microorganisms. 

EPA disagrees. The purpose of 

835.4100/835.4200 is to evaluate the aerobic and 

anaerobic transformation of chemicals in soil. 

“Such studies are used for chemicals which are 

directly applied to soil or which are likely to 

reach the soil environment.” An example of an 

antimicrobial that could reach the soil 

environment is a wood preservative. The 

guideline also provides an exclusion: “The test 

should not be applied to chemicals which are 

highly volatile from soil...” 

The commenter is correct that on page 7, there 

is information on treatment rates that would be 

useful to those testing crop protection products. 

However, the guideline also states, “For general 

chemicals, the application rate should be 

estimated based on the most relevant route of 

entry.” 

The purpose of 835.4300/835.4400 is described 

as: “Chemicals can enter shallow or deep 

surface waters by such routes as direct 

application, spray drift, run-off, drainage, waste 

disposal, industrial, domestic or agricultural 

effluent and atmospheric deposition.....Such 

studies are used for chemicals which are directly 

applied to water or which are likely to reach the 

aqueous environment by the routes described 

above.” 

EPA also notes that these studies have been 

conducted with antimicrobials and submitted to 

EPA. 

Mutagenicity Testing, particularly 870.5100 (Ames Assay) 

Inclusion of the Ames Assay as a requirement is 

inconsistent with the Agency’s prior conclusions 

on the relevance of that assay for antimicrobial 

pesticides. The Agency has long recognized that 

it is inappropriate... The testing guidance does 

not address how this study should be 

appropriately conducted for compounds that are 

intended to control bacteria. 

EPA has revised the testnote 32 to this data 

requirement to read as follows: Due to the 

nature of antimicrobials, if testing with bacterial 

strains has not been conducted, then testing 

using a mammalian cell assay such as the mouse 

lymphoma TK +/- assay is preferred. If reverse 

mutation assay testing with bacterial strains has 

already been conducted, and the testing was 
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Master Responses: Guidelines Section (190) Page 269 

conducted at levels that did not cause toxicity to 

the bacterial strains tested, then the applicant 

may submit the study to fulfill this data 

requirement. 

Companion Animal Safety Testing, 870.7200 

[The] application of antimicrobials to companion 

animals removes those uses from the definition 

of pesticide, as such uses would be considered as 

animal drugs. This testing guidance is not 

applicable to antimicrobial pesticides. 

See response to comment 80.97 

Residues in Meat/Milk/Poultry/Eggs, 860.1480 

This testing guideline addresses direct 

application to livestock or addition to livestock 

feed. If there is such direct application of an 

antimicrobial pesticide, it would be exempt from 

FIFRA. Similarly, direct application of an 

antimicrobial pesticide to livestock feed is not 

applicable to FIFRA. Further the statutory 

authority to regulate products used to clean 

and/or sanitize eggs is unclear. 

See response to comment 30.26 

Plant Metabolism, 860.1300; Crop Field Trials, 860.1500; Processed Food or Feed, 860.1520 

Direct application to edible crops removes the 

product from the definition of an antimicrobial 

pesticide. Direct application of an antimicrobial 

pesticide to animal feed removes the use from 

the definition of a pesticide and from regulation 

under FIFRA. The guidance for testing 

provided in these testing procedures does not 

provide appropriate direction for antimicrobial 

pesticides. For example, all guidance in these 

testing procedures is based solely on application 

to crops in the field. There is no relevant 

guidance for testing of antimicrobial pesticides I 

any of these guidelines. 

See response to comment 30.26 

 
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Comments and Response References: 

General Comments on the Rule (10) Page 270 

3. Verbatim Comments and Response References by Topic Area 

General Comments on the Rule (10) 

Verbatim Comments and Response References for the General Comments on 

the Rule Section 

Comment Code: 10000 General comments on the rule 

Commenter Name: Eileen J. Moyer 

Commenter Organization: Reckitt Benckiser, Inc. 

Letter ID: 0076 

Comment ID: 25419 

Comment Code: 10000 

Comment: IV. CONCLUSION 

Reckitt appreciates the opportunity to comment on the proposed regulation and encourages the 

Agency to consider our recommendations. We urge the Agency to consider CSPA and the ACC 

Biocides Panel's recommendations to address the significant issues that have been raised and publish 

a revised proposal for public comment. 

Response: EPA acknowledges Reickitt Benckiser, Inc.'s support for the comments submitted by 

CSPA and the ACC Biocides Panel. 

Also see response 2. 

Commenter Name: Kelly K. Naujock 

Commenter Organization: S.C. Johnson & Son, Inc. 

Letter ID: 0063 

Comment ID: 25425 

Comment Code: 10000 

Comment: The comments that have been forwarded to this docket are numerous and lengthy. They 

highlight multiple, major issues of concern rather than minor adjustments. We believe that it would 

be premature to finalize this proposed rule without thorough revisions to the document. Industry 

and EPA are partners dedicated to the safe and effective use of antimicrobial pesticides. As such, we 

offer our assistance as EPA continues to craft this proposed rule. 

Response: See response 2 

Commenter Name: Jamie S. Heisig-Mitchell 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 

Comment ID: 25437 

Comment Code: 10000 
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Comments and Response References: 

General Comments on the Rule (10) Page 271 

Comment: HRSD strongly supports increased data requirements designed to protect publicly 

owned treatment works (POTWs) and applauds EPA's pursuit of this effort. For too long, the 

potential for these downthe- drain antimicrobial compounds to negatively affect the critical and 

sensitive biological treatment systems present in most POTWs has been disregarded. 

Response: EPA acknowledges Hampton Road Sanitation District's support of increased data 

requirements to protect POTWs. 

Commenter Name: Sally Hayes 

Commenter Organization: Scientific & Regulatory Consultants, Inc. (SRC) 

Letter ID: 0066 

Comment ID: 25456 

Comment Code: 10000 

Comment: Scientific & Regulatory Consultants, Inc. (SRC) is providing comments on the proposed 

rule Data Requirements for Antimicrobial Pesticides, 73 Federal Register 59382. The purpose of the 

proposed rule is to revise and update the existing data requirements for antimicrobial pesticides. 

SRC appreciates the opportunity to comment on the proposed changes to 40 CFR Part 158. In 

general, SRC supports the comments submitted by the Consumer Specialty Products Association 

(CSPA). SRC also wants to take this opportunity to emphasize some of the points in the CSPA 

comments. 

Response: EPA acknowledges Scientific & Regulatory Consultants' support of the comments 

submitted by the Consumer Specialty Products Association (CSPA). 

Commenter Name: Abigail Trueblood 

Commenter Organization: Dow Chemical Company 

Letter ID: 0082 

Comment ID: 25472 

Comment Code: 10000 

Comment: Dow has worked with the American Chemistry Council (ACC) Biocides Panel ("the 

Panel") in the development of comments submitted to the Agency on this Proposed Rule, and is in 

general agreement with those comments. We do not intend to address here all of the subjects 

contained within the Panel comment letter, but rather confine our comments to a few areas of 

particular interest. 

Dow wishes to commend the Agency for the enormous effort which has gone into the development 

of the Proposal. Its publication has been anticipated by the regulated community for some time, and 

this Proposal as published, contains many positive aspects. We make special note of the recognition 

of exposure as a critical component of risk assessment and the acknowledgement of alternative 

approaches to traditional toxicological testing. However, Dow does agree with the conclusion of the 

Panel that there are serious shortfalls in the Proposal requiring considerable rework and recommend 

a reproposal of this proposed regulation. 
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Comments and Response References: 

General Comments on the Rule (10) Page 272 

Response: EPA acknowledges Dow Chemical Company's support for the comments submitted by 

the ACC Biocides Panel. 

Also see response 2 

Commenter Name: Abigail Trueblood 

Commenter Organization: Dow Chemical Company 

Letter ID: 0082 

Comment ID: 25487 

Comment Code: 10000 

Comment: The Dow Chemical Company submits these comments to EPA in the spirit of working 

with the Agency to finalize a regulation which will best serve both the regulated community and 

EPA. The issuance of this Proposal is a step in this process, but we sincerely hope the Agency will 

recognize that considerable work is still required. We stand with the ACC Biocides Panel in 

requesting the Agency to repropose this rule. 

Response: See response 2 

Commenter Name: Patrick H. Quinn 

Commenter Organization: Innovation and Reform Group (IRG) 

Letter ID: 0080 

Comment ID: 25501 

Comment Code: 10000 

Comment: Finally, the IRG fully supports the more comprehensive comments of the ACC 

Biocides Panel on the Proposed Subpart 158W Rule, including the Panel’s suggestion that EPA 

should re-propose the Regulation with the benefit of public comment. This action will avoid hasty 

adoption of a flawed Final Rule while producing a far better antimicrobial data requirements rule 

consistent with the Agency’s 21st Century toxicology strategic plan. 

Response: EPA acknowledges IRG's support for the comments submitted by the ACC Biocides 

Panel. 

Also see responses 2 and 4. 

Commenter Name: Elizabeth Tannehill 

Commenter Organization: Mason Chemical Company 

Letter ID: 0078 

Comment ID: 25506 

Comment Code: 10000 

Comment: Mason Chemical Company also strongly supports the comments submitted by the 

Consumer Specialty Products Association (CSPA) and the American Chemistry Council Biocides 

Panel and encourages the Agency to carefully consider these comments and recommendations prior 

to finalizing the rule. 
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Comments and Response References: 

General Comments on the Rule (10) Page 273 

Response: EPA acknowledges Mason Chemical Company's support for the comments submitted 

by CSPA and the ACC Biocides Panel. 

Commenter Name: Susan E. Little 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0068 

Comment ID: 25522 

Comment Code: 10000 

Comment: Beyond our advocacy in inclusion of AEJV data in the Proposed Rule, the AEJV 

supports the more complete comments submitted by the Consumer Specialty Product Association 

and the American Chemistry Council Biocides Panel. These trade associations address the entire 

proposed rule and we fully support their comments. 

Response: EPA acknowledges AEJV's support for the comments submitted by the Consumer 

Specialty Product Association and American Chemistry Council Biocides Panel. Also see response 

90.7. 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25537 

Comment Code: 10000 

Comment: CSPA is pleased that the Part 158 regulations have been proposed. CSPA offers the 

following comments on the overall framework of the rule as well as specific comments on the 

following areas: Product Performance Efficacy; Residue Chemistry; Toxicology; and Human 

Exposure. CSPA has worked cooperatively with the ACC Biocides Panel on these and other 

comments and support the comments submitted by the Panel. 

Response: EPA acknowledges CSPA's support for the comments submitted by the ACC Biocides 

Panel. 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25573 

Comment Code: 10000 

Comment: Detailed Considerations 

Section Number IV. 

Title Introduction to Subpart W 

Paragraph D. Clarifying How to Use the Data Tables Paragraph 4 and 5, p.59386 
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Comments and Response References: 

General Comments on the Rule (10) Page 274 

Excerpt from Federal Register The use of R does not necessarily indicate that a study is always 

required, but that it is more likely to be required than not. For example, if the applicant wanted to 

apply his pesticide to apples, then crop field trials would be required almost always on apples. 

However, if the physical/chemical properties of the chemical did not lend themselves to the test, 

such as performing an inhalation test with a chemical that is a solid and has an extremely low vapor 

pressure, then a waiver might be granted. Generally test notes for R studies discuss any particular 

circumstances when the testing might not be required. The use of CR means a study is less likely to 

be required. Triggers in the test notes indicate the circumstances under which the Agency has 

learned through experience that the information is needed. Although only an approximation, if 

percentages were to be assigned to indicate the need for a particular study, then R could be viewed 

as representing the submission of a study 50% to 100% of the time and CR would be up to 50%. 

Thus, NR, R, and CR are used for convenience to make the table format feasible, but serve only as a 

general indication of the applicability of a data requirement. 

HC Comment Descriptors of "R" - Required, "CR" - Conditionally Required and "NR" - Not 

Required are used in the data tables to signify the need for a study or data waiver to fulfil a data 

requirement. As noted above (in the general considerations), the PMRA requests confirmation that 

data requirements listed as ‘R’ must always be addressed by the applicant, whether by the submission 

of an actual study or alternatively, through submission of a scientifically valid waiver request, such as 

the case at the PMRA. The text in this section, suggests that the actual data requirement itself may 

not be required to be addressed by the Agency. 

The PMRA suggests replacing the text in paragraphs 4 & 5 with the following (which is similar to 

the system used by the PMRA): "Applicants must address data elements listed as "R"; those listed as 

"CR" must be addressed when the conditions triggering the requirement are met (as outlined in the 

test notes accompanying the tables in Subpart W). Required data elements (and conditionally 

required data elements, when triggered) may be addressed by the submission of scientific 

data/studies, or alternatively, through submission of a scientifically valid waiver request." 

Response: see response 20.2 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25658 

Comment Code: 10000 

Comment: We appreciate this opportunity to comment on EPA’s proposed revised data 

requirements for antimicrobial pesticides. These comments are made jointly with the Wastewater 

Enterprise of the San Francisco Public Utilities Commission (SFPUC), a separate department of the 

City and County of San Francisco, whose mission is to safely and cost effectively manage San 

Francisco’s sewage, stormwater, and biosolids in order to protect public health and the environment. 

This is a function that may be directly challenged by the disposal of antimicrobial pesticides and 

other products for which sufficient environmental data are not obtained prior to registration. In our 

previous comments to EPA about pesticides, we have stressed the need for EPA to ensure it 

receives all data necessary for complete, scientifically sound reviews of pesticides. In general, we 
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Comments and Response References: 

General Comments on the Rule (10) Page 275 

support the proposed changes to the data requirements for antimicrobial pesticides. These changes 

significantly improve EPA’s ability to obtain data needed to ensure that pesticides are registered in a 

manner protective of human health and the environment. In this letter, we request several changes 

to improve the draft requirements. We request these changes because we feel that it is important for 

EPA to take full advantage of this opportunity to exercise leadership, clarify its procedures, and 

resolve longstanding problems that we have identified in our previous comments on individual 

pesticide reregistrations. In the pages that follow, we have organized our comments into four main 

categories: general comments, comments on the human health protection data requirements, 

comments on the ecotoxicity data requirements, and comments on other requirements. Due to the 

length and complexity of the proposed rule changes, we do not have the resources to comment in 

detail on all aspects of the proposal and have limited our comments to what we believe are some of 

the more important issues raised. 

 GENERAL COMMENTS 

Support redesign to improve water quality assessments 

EPA has proposed to redesign its antimicrobials data requirements to clarify the nature of 

antimicrobial pesticide use patterns-and to identify specifically those use patterns that would have 

the greatest potential to release antimicrobials to surface water. By identifying such use patterns and 

requiring the data necessary to evaluate their impacts on surface water quality, EPA will have the 

ability to prevent potential water quality impacts at the time that pesticides are initially registered and 

when their registrations are reviewed. SFE and the SFPUC support this overall approach. 

Response: EPA acknowledges SF Environment's support for the proposed revisions to the data 

requirements for antimicrobial pesticides. Also see responses 30.2 and 30.25. 

Commenter Name: Lisa M. Amadio 

Commenter Organization: JohnsonDiversey, Inc. 

Letter ID: 0084 

Comment ID: 25689 

Comment Code: 10000 

Comment: The purpose of the proposed rule is to revise and update the existing data requirements 

for antimicrobial pesticides. JDI supports the comments submitted by both the Consumer Specialty 

Products Association (CSPA) and the American Chemistry Council Biocides Panel. JDI encourages 

the Agency to carefully consider these comments and recommendations prior to finalizing the rule. 

Response: EPA acknowledges Johnson Diversey, Inc.'s support for the comments submitted by 

CSPA and the ACC Biocides Panel. 

Commenter Name: Jay Feldman 

Commenter Organization: Beyond Pesticides 

Letter ID: 0067 

Comment ID: 25702 

Comment Code: 10000 
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Comments and Response References: 

General Comments on the Rule (10) Page 276 

Comment: Beyond Pesticides appreciates the opportunity to comment on the Proposed Rule; Data 

Requirements for Antimicrobial Pesticides. The U.S. Environmental Protection Agency (EPA), with 

these new rules, proposes to revise and update the existing data requirements for antimicrobial 

pesticides. Currently, the agency does not have a separate listing of data requirements for 

antimicrobial pesticides. Often the agency would conduct case-by-case determinations to instruct 

registrants on what data was needed for submission. However, this invariably led to inconsistencies 

among data submissions and data gaps, which continue to plague the agency’s review processes. Due 

to the unique use patterns of antimicrobial pesticides, it is necessary to establish a separate set of 

data requirements for all antimicrobial so that the process is uniform, efficient and reduces 

uncertainties. 

Response: No response is needed. 

Commenter Name: Jay Feldman 

Commenter Organization: Beyond Pesticides 

Letter ID: 0067 

Comment ID: 25705 

Comment Code: 10000 

Comment: These new rules are a step in the right direction when it comes to the impact of 

antimicrobials on human and environmental health. We believe they are indeed necessary 

considering the proliferation of these substances in the consumer marketplace. There are a few 

suggestions that we would like the agency to consider as it moves forward with finalizing these new 

rules: 

Response: EPA acknowledges Beyond Pesticides' belief that the proposed rule is a step in the right 

direction. 

Commenter Name: Jay Feldman 

Commenter Organization: Beyond Pesticides 

Letter ID: 0067 

Comment ID: 25723 

Comment Code: 10000 

Comment: Conclusion 

Beyond Pesticides believes that these rules are long overdue and are necessary if the agency is 

serious about protecting human and environmental health from the impacts of antimicrobials. 

Antimicrobial substances have exploded unto the consumer market place with little to no regulatory 

oversight and little to no data on their fate and effect in the environment. These rules will help to 

ensure that additional scrutiny is placed upon these chemicals and that the risk assessment process is 

strengthened. 

We hope that these new requirements will also help to close many of the outstanding data gaps that 

plague the risk assessment process of many chemicals under the EPA’s jurisdiction. The agency 

must move expeditiously to establish these new requirements so as to ensure that antimicrobial 

substances do not pose unreasonable hazards to human and environmental health. 
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Comments and Response References: 

General Comments on the Rule (10) Page 277 

As the agency moves forward, these new requirements must be implemented in a context that 

enables EPA to take restrictive action in the face of incomplete and inadequate data. Since 

widespread exposure to antimicrobials through contaminated water, aquatic life, sludge and food 

exposes human and environmental health to unknown and unstudied risks, urgent and restrictive 

action is needed now to prevent the further release of antimicrobial substances into the 

environment. 

Response: EPA acknowledges Beyond Pesticides' support for the proposed rule. 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25776 

Comment Code: 10000 

Comment: U.S. EPA has proposed to update and revise data requirements for the registration, reregistration, and registration review of antimicrobial pesticides under the Insecticide, Fungicide and 

Rodenticide Act (FIFRA). The proposed data requirements are intended to ensure that U.S. EPA 

has all the information necessary to evaluate the environmental and human health risks of pesticide 

use. The risk benefit standards of FIFRA require U.S. EPA to ensure that pesticides are used in such 

a manner that mitigation under the Clean Water Act is minimal or unnecessary. Without a complete 

set of data relevant to water quality, U.S. EPA cannot fulfill this obligation. Tri-TAC supports the 

proposed revisions to the data requirements and believes that the proposed rule significantly 

improves U.S. EPA's ability to obtain data needed to ensure that pesticides are registered in a 

manner protective of water quality. 

Response: EPA acknowledges Tri-TAC's support for the proposed revisions to the data 

requirements. 

Commenter Name: William C. Balek 

Commenter Organization: ISSA 

Letter ID: 0074 

Comment ID: 25860 

Comment Code: 10000 

Comment: ISSA is are aware of and familiar with the comments being provided by the ACC 

Biocides Panel particularly with regards to tiered data requirements, transparency and the use of 

alternative animal testing measures as a means to address pesticide data requirements, ISSA supports 

these comments as well as comments on the additional technical issues raised on the data tables 

within the draft 158 W rule. In particular, ISSA supports the following aspects of the ACC Biocides 

Panel Comments: 

Response: EPA acknowledges ISSA's support for the comments submitted by the ACC Biocides 

Panel. 

Commenter Name: William C. Balek 
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Comments and Response References: 

General Comments on the Rule (10) Page 278 

Commenter Organization: ISSA 

Letter ID: 0074 

Comment ID: 25868 

Comment Code: 10000 

Comment: ISSA urges EPA to thoroughly review our and the Biocides Panel comments in order to 

develop a set of regulatory criteria that are practical and pertinent to the entire antimicrobial industry 

and its downstream users. 

Response: No response is needed. 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25871 

Comment Code: 10000 

Comment: U.S. EPA has proposed to update and revise data requirements for the registration, reregistration, and registration review of antimicrobial pesticides under the Insecticide, Fungicide and 

Rodenticide Act (FIFRA). The proposed data requirements are intended to ensure that U.S. EPA 

has all the information necessary to evaluate the environmental and human health risks of pesticide 

use. The risk benefit standards of FIFRA require U.S. EPA to ensure that pesticides are used in such 

a manner that mitigation under the Clean Water Act is minimal or unnecessary. Without a complete 

set of data relevant to water quality, U.S. EPA cannot fulfill this obligation. CASA supports the 

proposed revisions to the data requirements and believes that the proposed rule significantly 

improves U.S. EPA's ability to obtain data needed to ensure that pesticides are registered in a 

manner protective of water quality. 

Response: EPA acknowledges CASA's support for the proposed revisions to the data requirements. 

Also see responses 30.2 and 30.25. 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25905 

Comment Code: 10000 

Comment: In general, Clorox (EPA Company Nos. 5813 and 67619) supports the comments 

provided by the following associations: American Chemistry Council Biocides Panel, Consumer 

Specialty Products Association (CSPA), Innovative Reform Group (IRG), Alternative Toxicology 

Working Group (ATWG) and the Antimicrobial Exposure Joint Venture (AEJV). Clorox 

participated in the development of comments by all the associations mentioned above. By this letter, 

we wish to emphasize particular issues in the comments made by various Associations that are of 

critical interest to our company. Lastly, we are providing comments on areas where Associations' 

comments do not fully address Clorox's specific concerns. 
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Comments and Response References: 

General Comments on the Rule (10) Page 279 

We are in support of the overall recommendation that, upon consideration of all comments, the 

Agency should redraft and re-propose Part 158W. Clorox is concerned that EPA's proposal 

regarding data requirements does not provide enough guidance to the regulated community to 

determine what would be needed to file for registration. Furthermore, the financial commitment is 

vastly underestimated and needs to be revised. 

Response: EPA acknowledges Clorox's support for the comments submitted by the ACC Biocides 

Panel, CSPA, IRG, ATWG and AEJV. 

Also see responses 2, 3, and 40.1. 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25917 

Comment Code: 10000 

Comment: [In the Panel's comments, 12 major discussion points are presented as follows:] * 

Current Part 158 should be Amended to Clarify Which Provisions Apply to Antimicrobials 

Response: See Response 50.16 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25921 

Comment Code: 10000 

Comment: In addition, the Biocides Panel has made many recommendations that should be 

incorporated into the proposed guidelines. An important recommendation to the Agency is to look 

at these guidelines from an antimicrobial perspective rather than as conventional pesticides. While it 

is important that the Agency coordinates data requirements throughout its divisions, it must take 

into consideration the unique role antimicrobials have. 

Response: See response 191.6 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25932 

Comment Code: 10000 

Comment: The Data Rule is not the Place to Make Policy Changes 

The proposed rule is meant to communicate the data requirements necessary to obtain antimicrobial 

pesticide registration. However, EPA is proposing a number of policy changes that must not be 

included within the scope of the proposed regulation. These policy changes occur throughout the 
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Comments and Response References: 

General Comments on the Rule (10) Page 280 

proposal but are particularly evident in the definitions subsection (§ 158.2203). We agree with CSPA 

that this rule is not the appropriate venue for making policy changes. If EPA intends to modify 

statutory definitions and/or long standing policies, it should provide justification and specific 

information to support the need to make such changes. EPA needs to include this justification when 

this rule is re- proposed. 

Response: see response 2 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25969 

Comment Code: 10000 

Comment: The National Association of Clean Water Agencies (NACWA) appreciates the 

opportunity to comment on the proposed additions and revisions to the existing data requirements 

for antimicrobial pesticides (October 8, 2008; 73 Fed. Reg. 59382). 

Response: No response is needed. 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25975 

Comment Code: 10000 

Comment: While NACWA was unable to conduct a thorough review of the fate and transport 

considerations in the proposal, NACWA strongly supports the proposed revisions to the data 

requirements and believes that the proposal would improve EPA’s ability to ensure that 

antimicrobial pesticides are registered in a manner protective of the municipal wastewater treatment 

process and water quality. 

NACWA offers the following comments on the proposal and suggestions for improving the data 

requirements. 

Response: EPA acknowledges the National Association of Clean Water Agencies (NACWA)'s 

support for the proposed revisions to the data requirements. 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26097 

Comment Code: 10000 

Comment: U.S. EPA has proposed to update and revise data requirements for the registration, reregistration, and registration review of antimicrobial pesticides under the Insecticide, Fungicide and 

Rodenticide Act (FIFRA). The proposed data requirements are intended to ensure that U.S. EPA 
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Comments and Response References: 

General Comments on the Rule (10) Page 281 

has all the information necessary to evaluate the environmental and human health risks of pesticide 

use. The risk benefit standards of FIFRA require U.S. EPA to ensure that pesticides are used in such 

a manner that mitigation under the Clean Water Act is minimal or unnecessary. Without a complete 

set of data relevant to water quality, U.S. EPA cannot fulfill this obligation. The Districts support 

the proposed revisions to the data requirements and believes that the proposed rule significantly 

improves U.S. EPA's ability to obtain data needed to ensure that pesticides are registered in a 

manner protective of water quality. 

Response: EPA acknowledges Sanitation Districts of Los Angeles County's support for the 

proposed revisions to the data requirements. 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26157 

Comment Code: 10000 

Comment: P&G recognizes substantial work went into drafting the document and that many 

individuals within EPA have invested significant effort. There are positive aspects to the Proposal, 

such as recognition of structure activity relationships (SAR), alternative toxicological approaches, 

(21st Century Toxicology), and the importance of understanding exposures in performing risk 

assessments. P&G is a strong advocate of progressive toxicology and the use of non-animal 

methods. P&G has taken a leadership role in expanding the use of these methods and look forward 

to working with the Agency to incorporate these methodologies into the Agency’s risk assessment 

process. 

Despite the substantial time and effort that have gone into it, P&G believes the Proposal has many 

opportunities for improvement. In particular, P&G believes that the Proposal leaves too many 

standards and decisions to the case-by-case discretion of EPA and fails to provide much of the 

background necessary to meaningfully provide comments on the approaches outlined. In particular 

there are numerous OPPT guidelines cited in the Proposal that have not been issued. Further, the 

Proposal expands the situations in which it applies FQPA-type analyses, and imposes data 

requirements that exceed those for conventional chemicals without providing any rationale. 

Overall, P&G believes that the Proposal, while a very substantial step forward, should not be the 

basis of final regulation. As the comments below make clear, P&G believes there are too many 

places in which EPA has not provided adequate information to allow complete comments, too 

many unexplained deviations from precedent and occasions where the wording is vague and open to 

interpretation. P&G has reluctantly concluded that the best course of action for EPA is to 

repropose the regulation in ways that respond to concerns raised by P&G, CSPA, the Panel and 

others. This reproposal is critical to enable meaningful input on a draft prepared with the benefit of 

input from this round of comments. Furthermore, it may also be worthwhile for EPA to consider 

another round of scientific review. 

P&G would welcome any opportunity to work with the Agency to address any of the concerns 

raised in these comments, whether individually as a company or as members of the Biocides Panel 

or CSPA. 
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Comments and Response References: 

General Comments on the Rule (10) Page 282 

P&G’s comments focus on three key areas of the Proposal; 1) product efficacy, 2) human safety and 

3) environmental fate/effects. P&G is also providing comments on EPA’s SAR/QSAR white paper. 

Response: See responses 1, 2, 3, 30.26, and 110.1. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26176 

Comment Code: 10000 

Comment: There are many positive aspects to the Proposal. These include EPA’s recognition of 

structure activity relationships (SAR), alternative toxicological approaches (21st Century 2 

Toxicology), and the importance of understanding exposures in performing risk assessments. The 

Panel appreciates the fact that EPA has made this rulemaking a priority and supports the Agency’s 

goal of issuing comprehensive regulations and guidance to the regulated community. 

Response: No response is needed. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26178 

Comment Code: 10000 

Comment: Despite the substantial time and effort that have gone into the Proposal, the Panel 

believes the Proposal has many shortcomings. In particular, the Proposal leaves too many standards 

and decisions to the case-by-case discretion of EPA, fails to provide sufficient background necessary 

to provide meaningful comments on the data requirements, expands the situations in which EPA 

applies FQPA-type analyses, and imposes data requirements that exceed those for conventional 

chemicals without providing any apparent rationale. 

The Panel’s comments address both the positive aspects and short comings of the Proposal. The 

comments are organized to provide an overview of the Panel’s positions on issues of greatest 

concern, followed by a section-by-section analysis that provides more detailed input on specific 

aspects of the Proposal. Throughout, the Panel offers suggestions for improvement or for 

alternative approaches where appropriate. 

Response: see responses 1, 3, 30.26, and 110.1. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26186 

Comment Code: 10000 
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Comments and Response References: 

General Comments on the Rule (10) Page 283 

Comment: Overall, the Panel believes that the Proposal, while a very substantial step forward, 

should not be the basis for the issuance of a final regulation. As the comments below make clear, 

there are too many places in which EPA has not provided adequate information to allow complete 

comments, too many unexplained deviations from precedent, many examples of imprecise wording, 

and inadequate analysis of the likely burdens of the regulation on EPA and the regulated 

community. For these reasons, the Panel reluctantly has concluded that the best course of action for 

EPA is to repropose the regulation in ways that respond to concerns raised by the Panel and others. 

This reproposal is critical to enable meaningful input on a draft prepared with the benefit of input 

from this round of comments. It may also be worthwhile for EPA to consider another round of 

scientific review. 

The Panel is committed to working cooperatively with EPA to address the issues raised in this initial 

comment period to develop a state of the art regulation that provides transparency and lends 

certainty to the process. The Panel hopes EPA will review these comments with a view toward 

developing the best possible antimicrobial data requirements regulation and will agree that 

reproposal before attempting to issue final regulations is the most prudent and productive path 

forward. 

Response: See response 2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26188 

Comment Code: 10000 

Comment: The many benefits of antimicrobial pesticides are well-known and substantial. 

Antimicrobial pesticides are essential to control microorganisms that otherwise would result in 

economic losses, wasted resources, and human and animal illness. Antimicrobials serve important 

public health purposes, such as ensuring human drinking water is not contaminated by pathogenic 

microorganisms, safeguarding against diseases and pathogens associated with food handling, and 

preventing the spread of disease in institutions such as schools and health care facilities. 

Antimicrobial pesticides also include a diverse range of material preservative products that provide 

protection against microbial degradation, contamination or fouling to inanimate articles, substances, 

systems or processes. Prevention of attack by microorganisms helps preserve critical resources, 

extend the useful life of the items, and minimize unnecessary waste. In sum, antimicrobials are 

integral to industrial, institutional, and commercial users, as well as to individual consumers. 

Response: No response is needed. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26225 

Comment Code: 10000 
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Comments and Response References: 

General Comments on the Rule (10) Page 284 

Comment: * The use of alternative techniques to address data requirements is not addressed as fully 

as it needs to be, nor does the Proposal move from the traditional study-by-study approach to a 

more modern integrative risk management approach. 

* The Proposal states that any final rule on antimicrobial data requirements would apply to pending 

applications. This would be unfair, wasteful of EPA and industry resources, and contrary to 

applicable legal principles. 

Response: See responses 4, 30.15, and 170.1. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26420 

Comment Code: 10000 

Comment: B. Recommendations 

The Panel fully supports the inclusion of alternative approaches to risk assessment and management 

for antimicrobial pesticides as well as for other pesticides, and is willing to work with the Agency to 

achieve the necessary improvements. An example of Agency cooperation with the Panel is a 

cooperative project through ILSI-Research Foundation to consider whether alternative approaches 

to risk assessment using a threshold-type approach may be appropriate for assessment of some 

antimicrobials. 

Response: See responses 4 and 80.3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26484 

Comment Code: 10000 

Comment: Conclusion The Panel appreciates the opportunity to provide comments on the 

Proposal, and encourages EPA to consider its recommendations and attached appendices in its final 

rulemaking. However, as stated above, there are significant issues that must be fully addressed 

before the Proposal can be finalized. In fact, the issues are significant and extensive enough that a 

revised Proposal should be issued, with an additional opportunity for public comment. 

Response: See response 2. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26491 

Comment Code: 10000 
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Comments and Response References: 

General Comments on the Rule (10) Page 285 

Comment: The Agency has identified the intended applicability of the proposed rule at 158.2200 

and further explains its intent in the Preamble 73 Fed. Reg. at 59385-86. The Panel recommends 

that the terms used in the context of scope be better defined. Moreover, the Panel requests that 

EPA clarify the manner in which the responsibilities among the registering divisions within OPP are 

distributed and the impact of these distributions on the data required for various uses of pesticide 

active ingredients. The Panel’s recommendations are discussed below. 

Response: See responses 10.1 and 30.24 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26583 

Comment Code: 10000 

Comment: II. Comments on Proposed Rule (page 59391-7, section 158.2230), Toxicology Data 

Requirements 

The Panel provides the following comments on the rule as proposed. In a subsequent section, the 

Panel offers an alternative proposal that is consistent with the statutory requirements and the 

identification of potential toxicology data requirements for antimicrobial pesticides. A regulation on 

antimicrobial pesticides should accurately reflect the uses to which these requirements apply and to 

be relevant to antimicrobial pesticides rather than to conventional pesticides. 

Response: See response 1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26693 

Comment Code: 10000 

Comment: There are many positive aspects to the Proposal. These include EPA’s recognition of 

structure activity relationships (SAR), alternative toxicological approaches (21st Century 

Toxicology), and the importance of understanding exposures in performing risk assessments. 

LANXESS appreciates the fact that EPA has made this rulemaking a priority and supports the 

Agency’s goal of issuing comprehensive regulations and guidance to the regulated community. 

Response: No response is required. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26695 

Comment Code: 10000 
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Comments and Response References: 

General Comments on the Rule (10) Page 286 

Comment: Despite the substantial time and effort that have gone into the Proposal, LANXESS 

believes the Proposal has many shortcomings. In particular, the Proposal leaves too many standards 

and decisions to the case-by-case discretion of EPA, fails to provide sufficient background necessary 

to provide meaningful comments on the data requirements, expands the situations in which EPA 

applies FQPA-type analyses, and imposes data requirements that exceed those for conventional 

chemicals without providing any apparent rationale. 

LANXESS’s comments address both the positive aspects and short comings of the Proposal. The 

comments are organized to provide an overview of the LANXESS ’s positions on issues of greatest 

concern, followed by a section-by-section analysis that provides more detailed input on specific 

aspects of the Proposal. Throughout, LANXESS offers positive suggestions for improvement or for 

alternative approaches where appropriate. 

Response: see responses 1, 3, 30.26 and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26697 

Comment Code: 10000 

Comment: Overall, LANXESS believes that the Proposal, while a very substantial step forward, 

should not be the basis for the issuance of a final regulation. As the comments below make clear, 

there are too many places in which EPA has not provided adequate information to allow complete 

comments, too many unexplained deviations from precedent, many examples of imprecise wording, 

and inadequate analysis of the likely burdens of the regulation on EPA and the regulated 

community. For these reasons, LANXESS has concluded that the best course of action for EPA is 

to re-propose the regulation in ways that respond to concerns raised by LANXESS and others. This 

re-proposal is critical to enable meaningful input on a draft prepared with the benefit of input from 

this round of comments. It may also be worthwhile for EPA to consider another round of scientific 

review. 

LANXESS along with other members of the ACC Biocide Panel is committed to working 

cooperatively with EPA to address the issues raised in this initial comment period to develop a state 

of the art regulation that provides transparency and lends certainty to the process. LANXESS hopes 

EPA will review these comments with a view toward developing the best possible antimicrobial data 

requirements regulation and will agree that re-proposal before attempting to issue final regulations is 

the most prudent and productive path forward. 

Response: see response 2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26711 

Comment Code: 10000 
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Comments and Response References: 

General Comments on the Rule (10) Page 287 

Comment: The many benefits of antimicrobial pesticides are well-known and substantial. 

Antimicrobial pesticides are essential to control microorganisms that otherwise would result in 

economic losses, wasted resources, and human and animal illness. Antimicrobials serve important 

public health purposes, such as ensuring human drinking water is not contaminated by pathogenic 

microorganisms, safeguarding against diseases and pathogens associated with food handling, and 

preventing the spread of disease in institutions such as schools and health care facilities. 

Antimicrobial pesticides also include a diverse range of material preservative products that provide 

protection against microbial degradation, contamination or fouling to inanimate articles, substances, 

systems or processes. Prevention of attack by microorganisms helps preserve critical resources, 

extend the useful life of the items, and minimize unnecessary waste. In sum, antimicrobials are 

integral to industrial, institutional, and commercial users, as well as to individual consumers. 

Response: No response is needed. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26729 

Comment Code: 10000 

Comment: [LANXESS has other overall concerns with the Proposal, which are set forth more fully 

below in the General Comments section. These include:] * The use of alternative techniques to 

address data requirements is not addressed as fully as it needs to be, nor does the Proposal move 

from the traditional study-by-study approach to a more modern integrative risk management 

approach. 

* The Proposal would apply any final rule on antimicrobial data requirements to pending 

applications. This would be unfair, wasteful of EPA and industry resources, and contrary to 

applicable legal principles. 

Response: See responses 4, 30.15, and 170.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27089 

Comment Code: 10000 

Comment: B. Recommendations 

LANXESS supports the inclusion of alternative approaches to risk management for antimicrobial 

pesticides as well as for other pesticides, and is willing to work with the Agency to achieve the 

necessary improvements. An example of Agency cooperation with industry (through the ACC 

Biocides Panel) is a cooperative project through ILSI-Research Foundation to consider whether 

alternative approaches to risk assessment using a threshold-type approach may be appropriate for 

assessment of some antimicrobials. 
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Comments and Response References: 

General Comments on the Rule (10) Page 288 

Response: See responses 4 and 80.3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27240 

Comment Code: 10000 

Comment: Conclusion 

LANXESS appreciates the opportunity to provide comments on the Proposal, and encourages EPA 

to consider its recommendations and attached appendices in its final rulemaking. However, as stated 

above, there are significant issues that must be fully addressed before the Proposal can be finalized. 

In fact, the issues are significant and extensive enough that a revised Proposal should be issued, with 

an additional opportunity for public comment. 

Response: See response 2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27242 

Comment Code: 10000 

Comment: The Agency has identified the intended applicability of the proposed rule at 158.2200 

and further explains its intent in the Preamble 73 Fed. Reg. at 59385-86. LANXESS recommends 

that the terms used in the context of scope be better defined. Moreover, LANXESS requests that 

EPA clarify the manner in which the responsibilities among the registering divisions within OPP are 

distributed and the impact of these distributions on the data required for various uses of pesticide 

active ingredients. LANXESS’s recommendations are discussed below. 

Response: See responses 10.1 and 30.24 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27289 

Comment Code: 10000 

Comment: II. Comments on Proposed Rule (page 59391-7, section 158.2230), Toxicology Data 

Requirements 

LANXESS provides the following comments on the rule as proposed. In a subsequent section, 

LANXESS offers an alternative proposal that is consistent with the statutory requirements and the 

identification of potential toxicology data requirements for antimicrobial pesticides. A regulation on 

antimicrobial pesticides should accurately reflect the uses to which these requirements apply and to 

be relevant to antimicrobial pesticides rather than to conventional pesticides. 
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Comments and Response References: 

General Comments on the Rule (10) Page 289 

Response: See response 1 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 27308 

Comment Code: 10000 

Comment: Summary: 

P&G appreciates the opportunity to comment on this Proposal that is so important to the regulated 

antimicrobial community. While it is recognized that important concepts have been introduced by 

the Proposal, P&G recommends that the Proposal be withdrawn and the issues highlighted in these 

comments be addressed in a transparent public fashion before reproposing the Rule. 

Response: See response 2. 

Comment Code: 12000 Comments on other rules/issues (can include FIFRA, FFDCA, 

requirements, etc.) 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25538 

Comment Code: 12000 

Comment: I. Overall Framework 

a. EPA’s Part 158 W Data Requirements for Antimicrobials Must Reflect That They Are Unique 

Congress has reminded EPA that antimicrobials are unique among FIFRA-regulated pesticides. 

Thus, FIFRA has its own definition of "antimicrobial pesticides". (FIFRA 2(mm)). The Food 

Quality Protection Act of 1996 required EPA to implement "reforms to the antimicrobial 

registration process" consistent with the "degrees of risk presented by an antimicrobial pesticide." 

(FIFRA 3(h)(1)). CSPA respectfully submits that the environmental and human hazards of 

antimicrobials, together with human and environmental exposure to antimicrobials, demonstrate 

that antimicrobials pose low risks. CSPA urges the Agency to consider these unique characteristics 

of antimicrobials when it adopts final Subpart W rules. 

Response: See response 1 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25778 
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Comments and Response References: 

General Comments on the Rule (10) Page 290 

Comment Code: 12000 

Comment: In addition, U.S. EPA Office of Pesticide Programs has increased coordination with the 

U.S. EPA Office of Water. Tri-TAC supports these efforts and encourages U.S. EPA's Office of 

Pesticide Programs, Office of Water, and Office of Wastewater Management to continue to work 

together to assess data needs for the water quality-related portions of its registration, re-registration, 

and registration review risk assessments. Coordination between U.S. EPA offices in reviewing 

pesticide data needs is essential to Clean Water Act implementation; it also provides an appropriate 

method of meeting FIFRA's goal of preventing unreasonable adverse impacts from pesticide use. 

Response: EPA acknowledges Tri-TAC's support for increased coordination between EPA's Office 

of Pesticide Programs (OPP) and Office of Water (OW). 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25873 

Comment Code: 12000 

Comment: In addition, U.S. EPA Office of Pesticide Programs has increased coordination with the 

U.S. EPA Office of Water. CASA supports these efforts and encourages U.S. EPA's Office of 

Pesticide Programs, Office of Water, and Office of Wastewater Management to continue to work 

together to assess data needs for the water quality-related portions of its registration, re-registration, 

and registration review risk assessments. Coordination between U.S. EPA offices in reviewing 

pesticide data needs is essential to Clean Water Act implementation; it also provides an appropriate 

method of meeting FIFRA's goal of preventing unreasonable adverse impacts from pesticide use. 

Response: EPA acknowledges CASA's support for increased coordination between EPA's Office 

of Pesticide Programs (OPP) and Office of Water (OW). 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26224 

Comment Code: 12000 

Comment: The Panel has other overall concerns with the Proposal, which are set forth more fully 

below in the General Comments section. These include: 

* The proposed Part 158W obscures the statutory division of jurisdiction with FDA over 

antimicrobial food use products. Without explanation, it appears to assert EPA’s jurisdiction over 

some antimicrobial uses around food to an unprecedented extent and in a manner that does not 

consider the exclusive jurisdiction of FDA under the Federal Food Drug and Cosmetic Act. 

Response: See responses 30.6, 30.26, and 110.1 

Commenter Name: Hasmukh C. Shah 
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Comments and Response References: 

General Comments on the Rule (10) Page 291 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26245 

Comment Code: 12000 

Comment: Finally, as proposed, 158W fails to meet FIFRA’s requirement to "differentiate the types 

of review undertaken for antimicrobial pesticides" and "conform the degree and type of review to 

the risks and benefits presented by antimicrobial pesticides."[FN#18:FIFRA [Section] 

3(h)(3)(A)(ii)(II), (III).] 

Response: See response 1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26254 

Comment Code: 12000 

Comment: For all of these reasons, the Panel believes that the Proposal requires substantial revision 

before being finally issued. If promulgated in its current form, the Panel believes the regulations 

would be invalid because it does not adequately address FIFRA’s requirements under 3(h) and 

provides for the later development of tests, thereby circumventing the requirements of informal 

rulemaking under the APA. 

Response: See responses 1 and 30.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26451 

Comment Code: 12000 

Comment: XII. EPA Must Submit the Antimicrobial Data Requirement Regulation for FIFRA 

Scientific Advisory Panel Review 

EPA "requested that the SAP waive its review of this proposal based on the SAP’s 1997 

review."[FN#82:73 Fed. Reg. at 59427.] The Panel believes, however, that SAP review is necessary. 

Many changes have occurred since the 1997 SAP meeting, including changes to the proposed 

antimicrobial data requirements and these have not been reviewed by the SAP. The Panel believes 

that SAP review of the complete Proposal is essential to ensuring any final regulation is scientifically 

valid. A complete SAP review also is required under the provisions of FIFRA section 25(d). 

EPA has cited the 1994 SAP report on pesticide data requirements, and ten other SAP reports on 

various specific scientific issues or studies in support of the Proposal. The Panel notes that none of 

the discussions in these SAP meetings involved antimicrobials specifically. In fact, antimicrobials 

were not mentioned or referenced. For these reasons, the Panel believes that the SAP reviews cited 

by EPA are insufficient. 
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Comments and Response References: 

General Comments on the Rule (10) Page 292 

Response: See response 20.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26457 

Comment Code: 12000 

Comment: Finally, the SAP in 1997 raised concerns about the absence of any information on the 

risk assessment process EPA intends to use in assessing environmental or ecological end points. 

In terms of the conduct of ecological risk assessments, which the Agency alluded to, that would be 

primarily aquatic risk characterizations, it is unclear as to the focus or endpoints considered in this 

risk characterization process. This process needs to be focused and refined considering the 

increasing amount of data available in this area and improvements in ecological risk assessment 

methodologies.[FN#85:Report at 15.] 

The Panel shares the SAP concerns with regard to the absence of an understanding of how EPA 

intends to use required data for risk assessment purposes. All of these issues illustrate the need for 

SAP review of the entire Proposal, so that current science can be applied to the Agency’s current 

regulatory approach. 

Response: See response 191.5 and 20.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26483 

Comment Code: 12000 

Comment: D. Executive Order 12988 

The EPA has stopped short of providing a clear, unambiguous rule which would reduce litigation as 

required by Section 3 of Executive Order 12988.[FN#103:61 Fed. Reg. 4727 (Feb. 7, 1996) ("The 

agency’s proposed legislation and regulations shall be reviewed by the agency to eliminate drafting 

errors and ambiguity . . . The agency’s proposed legislation and regulation shall be written to 

minimize litigation; and . . . The agency’s proposed legislation and regulations shall provide a clear 

legal standard for affected conduct rather than a general standard, and shall promote simplification 

and burden reduction.").] As explained in Part I and Appendix K, the proposed rule is vague and 

ambiguous. At least thirty-seven sections do not clearly indicate the requirements of the proposed 

rule, thereby consigning regulated parties to subsequent consultations with the Agency. The 

proposed rule does not provide clarity and notice but rather invites litigation. Consequently, the 

Panel suggests that the Agency repropose the rule. 

Response: See responses 2, 3, and 20.4 
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Comments and Response References: 

General Comments on the Rule (10) Page 293 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26492 

Comment Code: 12000 

Comment: II. Definitions, Inclusions and Exclusions 

Antimicrobial pesticides are defined at FIFRA 2(mm) as follows: 

(1) IN GENERAL.--The term ‘‘antimicrobial pesticide’’ means a pesticide that-- 

(A) is intended to-- 

(i)Disinfect, sanitize, reduce, or mitigate growth or development of microbiological organisms; or 

(ii) protect inanimate objects, industrial processes or systems, surfaces, water, or other chemical 

substances from contamination, fouling, or deterioration caused by bacteria, viruses, fungi, protozoa, 

algae, or slime; and 

(B) in the intended use is exempt from, or otherwise not subject to, a tolerance under section 408 of 

the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 346a and 348) or a food additive regulation 

under section 409 of such Act. 

(2) EXCLUDED PRODUCTS.--The term ‘‘antimicrobial pesticide’’ does not include -- 

(A) a wood preservative or antifouling paint product for which a claim of pesticidal activity other 

than or in addition to an activity described in paragraph (1) is made; 

(B) an agricultural fungicide product; or 

(C) an aquatic herbicide product. 

(3) INCLUDED PRODUCTS.--The term ‘‘antimicrobial pesticide’’ does include any other chemical 

sterilant product (other than liquid chemical sterilant products exempt under subsection (u)), any 

other disinfectant product, any other industrial microbiocide product, and any other preservative 

product that is not excluded by paragraph (2). 

EPA, in the Preamble, discussed its interpretation of the intent of this Proposal to be broader than 

the FIFRA definition at section 2(mm) and to "ensure that all pesticides currently considered as 

antimicrobial products for purposes of FIFRA section 33 fees and review periods are covered." 73 

Fed. Reg. at 59385. The Panel is in total agreement with this statement. It is the basis for the Panel’s 

comments on its understanding of the scope of this Proposal. Therefore, it is agreed that the 

Proposal is applicable to antimicrobial pesticides with food uses under FFDCA sec 408, antifoulant 

paints and coatings, wood preservatives that claim activity beyond those in 2(mm)(1), and 

manufacturing use antimicrobials intended for incorporation into registered end-use antimicrobial 

pesticide products.. 
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Comments and Response References: 

General Comments on the Rule (10) Page 294 

However, certain uses of compounds that otherwise might be considered antimicrobial pesticide 

uses are excluded by statute from this regulation based on the FIFRA definition of "pest" at FIFRA 

2(t). It is these uses for which clarification is necessary. In pertinent part, FIFRA section 2(t) 

provides that 

[t]he term "pest" means (1) . . . virus, bacteria, or other micro- organisms (except viruses, bacteria, or 

other micro-organisms on or in living man or other living animals) .... 

EPA has further defined the scope of its regulatory reach for antimicrobials in its regulations at 40 

CFR 152.5, which further defines a pest as 

(d) Any fungus, bacterium, virus, or other microorganism, except for those on or in living man or 

other living animals and those on or in processed food or processed animal feed, beverages, drugs 

(as defined in FFDCA sec. 201(g)(1)) and cosmetics (as defined in FFDCA sec. 201(i)). 

Moreover, FIFRA section 2(u) excludes animal drugs and animal feed from the definition of 

"pesticide." 

Response: See responses 30.24 and 80.97 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26712 

Comment Code: 12000 

Comment: Congress recognized the unique issues surrounding regulation of antimicrobials when it 

added section 3(h) to FIFRA in 1996. Section 3(h) requires EPA to issue regulations on the 

registration requirements for antimicrobial pesticides that recognize the unique uses of 

antimicrobials.[FN1: Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), 7 U.S.C. 

[section]136a(h)(3) ("FIFRA").] FIFRA provides that these regulations should "accelerate and 

improve the review of antimicrobial pesticide products."[FN2: Id. [section]136a(h)(1).] In addition, 

the regulations should: 

(1) define the various classes of antimicrobial use patterns . . . ; 

(2) differentiate the types of review undertaken for antimicrobial pesticides; 

(3) conform the degree and type of review to the risks and benefits presented by antimicrobial 

pesticides, and the function of the review under [FIFRA]; 

(4) ensure that the registration process is sufficient to maintain antimicrobial pesticide efficacy and 

that antimicrobial pesticide products continue to meet product performance standards and 

effectiveness levels for each type of label claim made; and 
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General Comments on the Rule (10) Page 295 

(5) implement effective and reliable deadlines for process management.[FN3: Id. [section] 

136a(h)(3)(ii).] 

LANXESS believes that many of the considerations in section 3(h) of FIFRA are not reflected in 

the Proposal. LANXESS has identified many issues with the Proposal that should be addressed 

before any final regulation is issued. In many cases the issues have prevented meaningful comment 

on portions of the Proposal, which is why LANXESS believes re-proposal is appropriate. These 

issues can best be viewed in context of 3(h) statutory goals. 

Response: See responses 1 and 2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26724 

Comment Code: 12000 

Comment: In the detailed comments that follow, LANXESS explains the reasons for its position 

and proposes an alternative approach that, in the Panel’s view, is more consistent with the goals of 

FIFRA and better suited to the uses of antimicrobials. 

LANXESS also believes that the Proposal does not fully implement the directive in section 3(h) of 

FIFRA to "conform the degree and type of review to the risks and benefits presented by 

antimicrobial pesticides..."[FN5: Id.] The Proposal includes numerous requirements that LANXESS 

believes are not appropriate for particular antimicrobial uses. 

Response: See response 1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26728 

Comment Code: 12000 

Comment: LANXESS has other overall concerns with the Proposal, which are set forth more fully 

below in the General Comments section. These include: 

* The proposed Part 158W obscures the statutory division of jurisdiction with FDA over 

antimicrobial food use products. Without explanation, it appears to assert EPA’s jurisdiction over 

some antimicrobial uses around food to an unprecedented extent and in a manner that does not 

consider the exclusive jurisdiction of FDA under the Federal Food Drug and Cosmetic Act. 

Response: See responses 30.6, 30.26, and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 
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Comment ID: 26768 

Comment Code: 12000 

Comment: Finally, as proposed, 158W fails to meet FIFRA’s requirement to "differentiate the types 

of review undertaken for antimicropesticides" and "conform the degree and type of review to the 

risks and benefits presented by antimicrobial pesticides."[FN18: FIFRA [section] 

3(h)(3)(A)(ii)(II),(III).] 

Response: See response 1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26770 

Comment Code: 12000 

Comment: For all of these reasons, LANXESS believes that the Proposal requires substantial 

revision before being finally issued. If promulgated in its current form, LANXESS believes the 

regulations would be invalid because it does not adequately address FIFRA’s requirements under 

3(h) and provides for the later development of tests, thereby circumventing the requirements of 

informal rulemaking under the APA. 

Response: See responses 1 and 30.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27157 

Comment Code: 12000 

Comment: XII. EPA Must Submit the Antimicrobial Data Requirement Regulation for FIFRA 

Scientific Advisory Panel Review 

EPA "requested that the SAP waive its review of this proposal based on the SAP’s 1997 

review."[FN84: 73 Fed. Reg. at 59427.] LANXESS believes that this request was improper, and that 

the SAP cannot waive its statutory review obligation. Many changes have occurred since the 1997 

SAP meeting, including changes to the proposed antimicrobial data requirements and these have not 

been reviewed by the SAP. LANXESS believes that SAP review of the complete Proposal is 

essential to ensuring any final regulation is scientifically valid. A complete SAP review also is 

required under the provisions of FIFRA section 25(d). 

EPA has cited the 1994 SAP report on pesticide data requirements, and ten other SAP reports on 

various specific scientific issues or studies in support of the Proposal. LANXESS notes that none of 

the discussions in these SAP meetings involved antimicrobials specifically. In fact, antimicrobials 

were not mentioned or referenced. For these reasons, LANXESS believes that the SAP reviews 

cited by EPA are insufficient. 
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Response: See response 20.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27207 

Comment Code: 12000 

Comment: Finally, the SAP in 1997 raised concerns about the absence of any information on the 

risk assessment process EPA intends to use in assessing environmental or ecological end points. 

"In terms of the conduct of ecological risk assessments, which the Agency alluded to, that would be 

primarily aquatic risk characterizations, it is unclear as to the focus or endpoints considered in this 

risk characterization process. This process needs to be focused and refined considering the 

increasing amount of data available in this area and improvements in ecological risk assessment 

methodologies."[FN87: Report at 15.] 

LANXESS shares the SAP concerns with regard to the absence of an understanding of how EPA 

intends to use required data for risk assessment purposes. All of these issues illustrate the need for 

SAP review of the entire Proposal, so that current science can be applied to the Agency’s current 

regulatory approach. 

Response: See response 20.1 and 191.5 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27238 

Comment Code: 12000 

Comment: D. Executive Order 12988 

The EPA has stopped short of providing a clear, unambiguous rule which would reduce litigation as 

required by Section 3 of Executive Order 12988.[FN103: 61 Fed. Reg. 4727 (Feb. 7, 1996) ("The 

agency’s proposed legislation and regulations shall be reviewed by the agency to eliminate drafting 

errors and ambiguity...The agency’s proposed legislation and regulation shall be written to minimize 

litigation; and...The agency’s proposed legislation and regulations shall provide a clear legal standard 

for affected conduct rather than a general standard, and shall promote simplification and burden 

reduction.").] As explained in Part I and Appendix J, the proposed rule is vague and ambiguous. At 

least thirty-seven sections do not clearly indicate the requirements of the proposed rule, thereby 

consigning regulated parties to subsequent consultations with the Agency. The proposed rule does 

not provide clarity and notice but rather invites litigation. Consequently, LANXESS suggests that 

the Agency repropose the rule. 

Response: See responses 2, 3, and 20.4 

Commenter Name: Stanley Oslosky 
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Comments and Response References: 

General Comments on the Rule (10) Page 298 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27241 

Comment Code: 12000 

Comment: APPENDIX A 

COMMENTS ON THE SCOPE OF THE PROPOSED REGULATION 

I. Introduction 

The term "antimicrobial" or "antimicrobial pesticide" has multiple meanings within the context of 

EPA regulation, based on statutory definitions, regulatory definitions, and common Agency practice. 

In reading the Proposal, there are a number of questions about the scope and applicability of the 

"antimicrobial pesticide data requirements," based on these definitions and practices Therefore, 

LANXESS believes it is important that the scope of the Proposal is clarified. 

Response: See response 30.24 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27243 

Comment Code: 12000 

Comment: II. Definitions, Inclusions and Exclusions 

Antimicrobial pesticides are defined at FIFRA 2(mm) as follows: 

(1) IN GENERAL.-The term ‘‘antimicrobial pesticide’’ means a pesticide that- 

(A) is intended to- 

(i) Disinfect, sanitize, reduce, or mitigate growth or development of microbiological organisms; or 

(ii) protect inanimate objects, industrial processes or systems, surfaces, water, or other chemical 

substances from contamination, fouling, or deterioration caused by bacteria, viruses, fungi, protozoa, 

algae, or slime; and 

(B) in the intended use is exempt from, or otherwise not subject to, a tolerance under section 408 of 

the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 346a and 348) or a food additive regulation 

under section 409 of such Act. 

(2) EXCLUDED PRODUCTS.-The term ‘‘antimicrobial pesticide’’ does not include- 

(A) a wood preservative or antifouling paint product for which a claim of pesticidal activity other 

than or in addition to an activity described in paragraph (1) is made; 
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General Comments on the Rule (10) Page 299 

(B) an agricultural fungicide product; or 

(C) an aquatic herbicide product. 

(3) INCLUDED PRODUCTS.-The term ‘‘antimicrobial pesticide’’ does include any other chemical 

sterilant product (other than liquid chemical sterilant products exempt under subsection (u)), any 

other disinfectant product, any other industrial microbiocide product, and any other preservative 

product that is not excluded by paragraph (2). 

EPA, in the Preamble, discussed its interpretation of the intent of this Proposal to be broader than 

the FIFRA definition at section 2(mm) and to "ensure that all pesticides currently considered as 

antimicrobial products for purposes of FIFRA section 33 fees and review periods are covered." 73 

Fed. Reg. at 59385. LANXESS is in total agreement with this statement. It is the basis for 

LANXESS’s comments on its understanding of the scope of this Proposal. Therefore, it is agreed 

that the Proposal is applicable to antimicrobial pesticides with food uses under FFDCA sec 408, 

antifoulant paints and coatings, wood preservatives that claim activity beyond those in 2(mm)(1), 

and manufacturing use antimicrobials intended for incorporation into registered end-use 

antimicrobial pesticide products. 

However, certain uses of compounds that otherwise might be considered antimicrobial pesticide 

uses are excluded by statute from this regulation based on the FIFRA definition of "pest" at FIFRA 

2(t). It is these uses for which clarification is necessary. In pertinent part, FIFRA section 2(t) 

provides that 

"[t]he term "pest" means (1)...virus, bacteria, or other micro-organisms (except viruses, bacteria, or 

other micro-organisms on or in living man or other living animals)...." 

EPA has further defined the scope of its regulatory reach for antimicrobials in its regulations at 40 

CFR 152.5, which further defines a pest as 

"(d) Any fungus, bacterium, virus, or other microorganism, except for those on or in living man or 

other living animals and those on or in processed food or processed animal feed, beverages, drugs 

(as defined in FFDCA sec. 201(g)(1)) and cosmetics (as defined in FFDCA sec. 201(i))." 

Moreover, FIFRA section 2(u) excludes animal drugs and animal feed from the definition of 

"pesticide." 

Response: See responses 30.24 and 80.97 

Comment Code: 13000 Comments on clarity of the proposed data requirements for antimicrobial 

pesticides 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 
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General Comments on the Rule (10) Page 300 

Comment ID: 25555 

Comment Code: 13000 

Comment: Furthermore, the Page 59386 IV A introduces data requirements for the proposed 

regulation; capturing public health but with no mention of non-public health. This is a serious 

omission on the part of the Agency. While Agency policy does not require submission of nonpublic health data, registrants are required to develop data to substantiate label claims. It is the 

position of CSPA that a definition, data requirements and product labeling instructions are necessary 

for a non-public health claim (i.e. odor-causing bacteria). 

Response: See response 70.7 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25564 

Comment Code: 13000 

Comment: *It is unclear how and when conditionally required data are triggered under CFR 158W. 

Are applicants expected to determine when the conditions that trigger the data requirements are met 

for their particular use, and provide these additional data with their original submission? Or, will this 

be determined by the EPA following a review of the originally submitted data? 

Response: see response 20.2 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25663 

Comment Code: 13000 

Comment: Specify criteria for "conditionally required" and "required" data 

The proposed rules refer frequently to various tests as conditionally required or required without 

always clearly defining the criteria used to make such determinations. We understand that neither 

term has an absolute definition but rather includes a range of probabilities that a test will be 

required. We also realize that some flexibility is necessary in determining the need for particular tests 

based on different product uses and exposure patterns. However, if the criteria used to make these 

decisions are not clearly spelled out, there is danger that they will not be applied uniformly and that 

in some cases needed data will not be requested. We request that these criteria be stated in detail so 

that the public can comment on their validity. 

Response: See response 20.2 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 
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Comments and Response References: 

General Comments on the Rule (10) Page 301 

Comment ID: 25667 

Comment Code: 13000 

Comment: Product use information needed for all antimicrobials 

SFE has reviewed many EPA risk assessments indicating that a proper assessment of the human 

health or environmental risks of pesticides could not be completed because the Agency lacked 

pesticide sales and use data. For example, EPA did not complete an assessment of discharges of dphenothrin to municipal wastewater treatment plants due to lack of sales and use data.[FN2: 

Melendez, J. L. and Woodard, V. (2008). Response to Comments of Phase 3 Period on the Draft 

EFED RED Chapter for d- Phenothrin. September 25.] While we support the proposed 

requirement for product use information, the requirement is constructed too narrowly to meet the 

Agency’s needs. Product use information is necessary for environmental risk assessments just as it is 

for human health risk assessment. Neither down-thedrain modeling of discharges to municipal 

wastewater treatment plants nor assessment of impacts to non-target organisms on land and in water 

can be completed without these data. 

Response: See response 10.3 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25670 

Comment Code: 13000 

Comment: Benefits of proposed rule 

SFE agrees with EPA’s assessment that the expanded information that will be obtained about 

antimicrobial pesticides from adoption of this rule will have substantial economic and human health 

benefits. SFE appreciates the benefits noted in the FR Notice (at page 59384), specifically the ability 

to use EPA information to assess hazards of pesticides and to make informed choices about 

alternatives that will be less harmful to our community-including our residents, our children and 

elders, and our workforce. Improving the data available to ensure health protection is particularly 

important to us, because healthcare-for both residents and workers- comprises 21% of our City’s 

annual budget, amounting to $1.38 billion per year. In addition, our city could potentially save 

thousands of dollars currently spent evaluating the toxicity of pesticide products. 

Response: No response is needed. 

Commenter Name: Jamie S. Heisig-Mitchell 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 

Comment ID: 25725 

Comment Code: 13000 
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General Comments on the Rule (10) Page 302 

Comment: *The data quality objectives for risk assessment of these compounds must be outlined in 

advance of study planning and data collection in order to ensure data of the necessary quality to 

inform the decision making process. 

Response: See response 10.2 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25907 

Comment Code: 13000 

Comment: American Chemistry Council Biocides Panel Comments 

The Biocides Panel comments represent considerable input from industry experts and of the various 

Associations' comments, the Panel's are the most comprehensive. Clorox was a participant on the 

Regulatory, Toxicology, Environmental, Use Sites and Human Exposure working groups. In the 

Panel's comments, 12 major discussion points are presented as follows: 

* EPA's proposal does not provide adequate guidance to the regulated community 

Response: See response 3 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25913 

Comment Code: 13000 

Comment: [In the Panel's comments, 12 major discussion points are presented as follows:] * 

Reliance upon alternative approaches should be built into this proposal 

Response: See response 170.2 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25936 

Comment Code: 13000 

Comment: Innovative Reform Group Comments 

IRG was formed by consumer product companies that sell antimicrobial products. The focus of the 

IRG is regulatory optimization that improves processes for both the Agency and the regulated 

community. With this as its focus, the IRG comments stress the need for improved science and risk 

assessments that reflect today's and tomorrow's approaches. We agree that the Agency should leave 

room in the regulations to allow such improvements as they are developed. We specifically wish to 
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Comments and Response References: 

General Comments on the Rule (10) Page 303 

emphasize the work done to establish the Disinfection Hierarchy policy. This is an excellent 

example of the Agency working together with outside stakeholders (IRG, CDC, FDA) to provide a 

science based, action oriented policy that has a public health benefit in emerging pathogen 

situations. 

Alternative Testing Working Group Comments 

The ATWG is an informal working group comprised of seven large consumer product companies. 

The ongoing collaboration with OPP has led to a path forward with a Pilot Program that will allow 

the Agency to gain experience with and review more in vitro data from assays that can serve to 

categorize and label antimicrobial cleaning products for eye irritation. It is with this focus that the 

ATWG's comments emphasize changes to the proposal which make it a flexible plan that genuinely 

integrates alternative and emerging science and has the capacity to quickly respond to future 

advances in toxicology. 

Response: See responses 4 and 70.5 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25950 

Comment Code: 13000 

Comment: The use of this table is just one example of an alternative approach to address the data 

requirements. In other cases it is unclear whether additional data are required to support material 

preservatives; the proposed data table does not adequately address the need for "Required" data 

versus "Conditionally Required" data. 

Response: See response 20.2 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25961 

Comment Code: 13000 

Comment: C. Tiering of Data: The current data requirement proposal is a far cry from 

Antimicrobial Data Call-In which was a measured Agency response to biocides and their potential 

for exposure. While we realize that the science of risk assessment has changed, the use of tiering is 

an important component of any data requirement. It allows companies to properly utilize their 

resources and avoid the unnecessary waste of test animals. Based on the current proposal, tiering is 

not evident and, in fact, is entirely missing in certain parts of the proposal (e.g. non-target 

organism/plant data requirements). The footnotes of many requirements have been proposed with 

multiple endpoints such that they will encompass many, if not all, biocides for additional testing. 

Response: See responses 80.59, 140.10 and 160.32 

Commenter Name: Chris Hornback 
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General Comments on the Rule (10) Page 304 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25995 

Comment Code: 13000 

Comment: * The data quality objectives for risk assessment of these compounds must be outlined 

in advance of study planning and data collection in order to ensure data of the necessary quality to 

inform the decision-making process. 

Response: See response 10.2 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26078 

Comment Code: 13000 

Comment: Waivers of data requirements should be rare. In our reviews of USEPA pesticide 

environmental risk assessments-particularly antimicrobials risk assessments-we have often found 

that required aquatic toxicity data have not been provided to USEPA’s risk assessors. In such cases, 

the risks remain unidentified and unmitigated. USEPA should only waive data requirements under 

extraordinary circumstances, because doing so can efFectively preclude appropriate regulation of the 

pesticide under FIFRA. 

Response: See response 30.12 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26227 

Comment Code: 13000 

Comment: I. EPA’s Proposed Subpart 158W does Not Provide Adequate Guidance to the 

Regulated Community 

A. The Proposal Calls for Many Individual Consultations Rather than Establishing Applicable 

Regulatory Requirements 

One of the most serious concerns with the Proposal is that it leaves many decisions to a case- bycase determination by EPA, instead of providing scientifically based criteria for determining data 

requirements. This would impose significant burdens on both the regulated community and the 

Agency. It also effectively compromises the ability of registrants and applicants to anticipate 

requirements for registration. Thirty-seven specific examples of the need for consultation are listed 

in Appendix K to these Comments. For example, to obtain a registration for a new product or a 

new use, the Proposal seems to require a registrant to consult with the Agency a number of times in 

the early stages of the application process to determine whether data are required. Depending on the 

new product or use, these necessary consultations may include the following, among others:[FN#6: 
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General Comments on the Rule (10) Page 305 

Another example of requiring this type of individual determination is experimental use permits 

("EUP’s"). EPA states in the preamble that it plans to apply, "on a case-by-case" basis, the 

requirements for experimental use permits for conventional pesticides found at 40 CFR [Section] 

158C. Proposed Rule at page 59,385. However, the Proposed Rule has not clearly identified the 

circumstances under which such a permit would be required for antimicrobials or what data 

requirements are applicable.] 

Response: See responses 3 and 30.19 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26256 

Comment Code: 13000 

Comment: There also are strong policy and practical reasons for revising the Proposal to eliminate 

the many situations calling for individual consultations. First, it is important that data requirement 

regulations provide at least one clear path for potential applicants and registrants to follow to obtain 

EPA approval of their products. With so many situations requiring consultation, there is no clarity as 

to requirements. Therefore, the regulated community has no way to determine a path to obtain a 

registration from the regulations. 

Response: See response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26258 

Comment Code: 13000 

Comment: Similarly, neither EPA, the Panel nor any other interested party can meaningfully assess 

the impact the Proposal will have if finalized in its current form - there simply is not sufficient 

information on the content and burdens likely to be imposed by the many individual consultations 

necessitated by the Proposal. At the implementation phase, assuming the Proposal is promulgated as 

proposed, potential applicants will be unable to make informed decisions whether to proceed with 

an application, whether for a new product, formulation, use or otherwise, until after consultation 

with the Agency. 

Response: See response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26267 

Comment Code: 13000 
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General Comments on the Rule (10) Page 306 

Comment: For all of these reasons, the Panel strongly urges EPA to revise the Proposal to 

eliminate most, if not all of the situations calling for individual consultation. Consultation should be 

an option, but the regulations must also provide a clear set of requirements and path forward to 

obtaining regulatory action. Given the number of places this issue arises and their importance to the 

fundamental structure of the Proposal, as well as to address the additional issues described below, 

the Panel believes the Proposal is not sufficiently mature to be converted into a final regulation. 

EPA should propose new 158W standards that enable registrants to determine default data 

requirements from reading the regulation, without having to consult the Agency for many 

registration applications. Consultation should always remain an option for modification or deviation 

from those default requirements and to address complexities, and unusual and unanticipated 

situations. 

B. The Absence of Information on How EPA Plans to Conduct Risk Assessments and How it Plans 

to Use Data Generated by the Rule Is a Critical Shortcoming 

This data requirements regulation is designed to provide EPA with the information it requires to 

evaluate applications for new products and new uses and to reevaluate registered antimicrobial 

pesticides. Information on the manner in which EPA will conduct these processes is not available to 

the public. It is not plausible for the Panel or others to meaningfully comment on the Proposal 

without the benefit of understanding the risk assessment approaches EPA plans to use, (e.g. human 

and ecological), the ways in which the data requirements will provide information to conduct those 

assessments and the ways EPA will use those risk assessments in making regulatory decisions. 

Response: See responses 2, 3, and 191.5. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26268 

Comment Code: 13000 

Comment: The Panel is concerned because, despite making diligent efforts extending well beyond 

the record for this Proposal, it has been unable to find any written policies or guidance documents 

for conducting risk assessments for antimicrobial pesticides. Instead, decisions on necessary data, 

risk assessments to be performed and regulatory decisions all appear to be developed on a case-bycase basis. 

Response: See response 191.5 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26357 

Comment Code: 13000 

Comment: In sum, EPA has significantly broadened the circumstances under which data will be 

required for many antimicrobial uses by imposing requirements based on "limited" rather than 
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General Comments on the Rule (10) Page 307 

"considerable" exposure. However, there is no rationale provided as to why data requirements 

would be predicated based on limited exposures for antimicrobial products, nor is there any clarity 

regarding the term "limited". 

Response: see response 80.16 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26379 

Comment Code: 13000 

Comment: Points of contention in the proposed regulation for data requirements of ecological 

effects: 

* The proposed rule is not a transparent document because many decisions on data requirements 

and the standards against which data will be evaluated are to be "determined by the Agency." 

Response: See response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26416 

Comment Code: 13000 

Comment: VII. Reliance upon Alternate Approaches Should Be Built into a Revised Proposal 

In its proposed and final rules for conventional chemical pesticides, the Agency identified its 

commitment to moving towards a more efficient and refined approach to risk assessment and risk 

management.67 In fact, moving toward alternate approaches is part of EPA’s and OPP’s strategic 

vision68, and substantial resources are being devoted to these activities. The Agency continued to 

discuss that same effort in the preamble to the Proposal for antimicrobials, stating "EPA is 

committed to moving towards alternative testing paradigms that are more efficient, reduce the use of 

animal testing, take full advantage of advances in science, and provide a sufficient credible amount 

of data for use in a risk assessment that will support a risk management decision."[FN#69:29 CFR 

Parts 1900-1910.] 

Response: see response 4 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26417 

Comment Code: 13000 
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General Comments on the Rule (10) Page 308 

Comment: The NRC also recommended that EPA reconsider its approach to data requirements to 

better reflect what actually is needed for risk management: 

The committee cautions against adding testing requirements only for the sake of theoretical 

thoroughness, because such an approach could result in substantial waste of animals and resources 

with little gain. 

[T]he relevant exposure route and exposure durations should be considered in developing a testing 

strategy. 

That it is important to recognize that "toxicity testing for regulatory purposes should be conducted 

primarily to serve the needs of risk management. 

[T]iered testing approaches should be designed to expedite regulatory decisions and to discourage 

toxicity testing that is not used to address regulatory questions.[FN#70:National Research Council 

(NRC) 2006, Toxicity Testing for Assessment of Environmental Agents. Interim Report. National 

Academies Press. p. 8-13. While the NRC report and the Agency’s use of SAR or alternative 

approaches both relate almost exclusively to mammalian toxicity issues, the Panel recommends that 

similar consideration be given to alternative approaches for all data requirement areas.] 

However, the Proposal does not contain any use of alternative techniques, nor is there any evidence 

of a shift away from the traditional study-by-study approach to a more integrative risk management 

approach. In general, the data requirements of the Proposal are less flexible and more burdensome 

than the existing data requirement regulations at 40 CFR Part 158 for conventional chemicals. The 

Panel strongly recommends that the Agency take this opportunity to encourage new science and 

approaches in meeting the data requirements for antimicrobial pesticides, such as structure activity 

relationship analyses, in vitro approaches, or computational toxicology. The regulations should 

explicitly allow the use of these and other new methods and approaches. In addition, guidance 

providing specific direction on the use of alternative techniques should be developed in a 

transparent and manner, with an opportunity for public comment.[FN#71:While the data 

requirement regulation should explicitly permit consideration of alternate approaches, it is also 

essential that the Agency have clear guidance available outside of the regulation itself to allow 

registrants to effectively utilize current and future alternate approaches rather than traditional or outdated testing methodologies. While the Panel is strongly supportive of the use of all available science 

in making regulatory decisions, including the use of predictive techniques such as SAR and the 

appropriate use of a weight of evidence approach, we believe that specific direction regarding the 

use of such alternative techniques should be provided through Agency guidance, rather than as part 

of the data requirement regulations.] 

Response: See responses 4, 170.1, and 170.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26422 

Comment Code: 13000 
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Comments and Response References: 

General Comments on the Rule (10) Page 309 

Comment: The Panel recommends that 40 CFR [Section] 158.70 be amended to include a 

paragraph (e) that explicitly permits the use of alternative approaches to addressing data 

requirements. Wording similar to that in the preamble to Proposal (page 59397) should be 

considered, such as, "applicants may seek to fulfill the data requirements by other appropriate 

means, such as alternative test methods, use of in vitro methods, submission of information from 

the public literature, the use of modeling or predictive methods such as structure activity relations 

and similar. Applicants must have the ability to refer to Agency guidance or confer with the Agency 

if alternative approaches are followed." The wording should clearly permit incorporation of 

additional new approaches, whether the use of structure-activity analyses, in vitro methodology, 

predictive models such as TOXCAST, or others still to be identified. By making this change, the 

Agency will encourage new ideas and be able to incorporate innovative approaches without revising 

its regulations. 

Response: See responses 170.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26449 

Comment Code: 13000 

Comment: XI. Current Part 158 Should Be Amended to Clarify Which Provisions Apply to 

Antimicrobials 

EPA must revise relevant sections of the existing 40 CFR Section 158 to clarify those provisions 

that are applicable to antimicrobials. In particular, Subparts A and B must be amended to include the 

appropriate references to antimicrobial pesticides and to Subpart W. Specifically, 40 CFR 158.1(c)(4) 

must be amended to identify that Subparts A, B, C, D, and W are intended to apply to 

antimicrobials; 40 CFR 158.100 must be amended to include antimicrobial use patterns unless 

replaced by the proposed 158.2201; 40 CFR 158.120(a) must be amended to include Subpart W and 

(b)(2) to address use patterns if use patterns appear other than in 158.100. Without such clear 

references, applicants will not be able to determine what is and is not applicable to antimicrobial 

pesticides. 

Response: see response 50.16 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26718 

Comment Code: 13000 

Comment: The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects: 
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Comments and Response References: 

General Comments on the Rule (10) Page 310 

* The proposed rule is not a transparent document because many decisions on data requirements 

and the standards against which data will be evaluated are to be "determined by the Agency." (See 

Panel’s General Comments at Section I) 

Response: See response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26772 

Comment Code: 13000 

Comment: There also are strong policy and practical reasons for revising the Proposal to eliminate 

the many situations calling for individual consultations. First, it is important that data requirement 

regulations provide at least one clear path for potential applicants and registrants to follow to obtain 

EPA approval of their products. With so many situations requiring consultation, there is no clarity as 

to requirements. Therefore, the regulated community has no way to determine a path to obtain a 

registration from the regulations. This creates a range of problems. 

Response: See response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26774 

Comment Code: 13000 

Comment: Similarly, neither EPA, LANXESS nor any other interested party can meaningfully 

assess the impact the Proposal will have if finalized in its current form - there simply is not sufficient 

information on the content and burdens likely to be imposed by the myriad individual consultations 

EPA will be requiring. At the implementation phase, assuming the Proposal is promulgated as 

proposed, potential applicants will be unable to make informed decisions whether to proceed with 

an application, whether for a new product, formulation, use or otherwise, until after consultation 

with the Agency. 

Response: See response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26783 

Comment Code: 13000 

Comment: For all of these reasons, LANXESS strongly urges EPA to revise the Proposal to 

eliminate most, if not all of the situations calling for individual consultation. Consultation should be 

an option, but the regulations must also provide a clear set of requirements and path forward to 

obtaining regulatory action. Given the number of places this issue arises and their importance to the 
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Comments and Response References: 

General Comments on the Rule (10) Page 311 

fundamental structure of the Proposal, as well as to address the additional issues described below, 

LANXESS believes the Proposal is not sufficiently mature to be converted into a final regulation. 

EPA should propose new 158W standards that enable registrants to determine default data 

requirements from reading the regulation, without having to consult the Agency for many 

registration applications. Consultation would remain an option for modification or deviation from 

those default requirements and to address unanticipated complexities in unusual situations. 

B. The Absence of Information on How EPA Plans to Conduct Risk Assessments and How it Plans 

to Use Data Generated by the Rule Is a Critical Shortcoming 

This data requirements regulation is designed to provide EPA with the information it requires to 

evaluate applications for new products and new uses and to reevaluate registered antimicrobial 

pesticides. To draft these regulations, LANXESS assumes EPA considered the risk assessment 

approaches it plans to apply, the ways in which data generated pursuant to this regulation will be 

used in those risk assessments, and the ways in which decisions will be made once EPA has the data 

and completes its risk assessments. The information regarding these processes is not available to the 

public. It is not plausible for LANXESS or others to meaningfully comment on the Proposal 

without the benefit of understanding the risk assessment approach(es) EPA plans to use, the way(s) 

in which the data requirements will provide information to conduct those assessments and the 

way(s) EPA will use those risk assessments in making regulatory decisions. 

Response: See responses 2, 3, and 191.5 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26784 

Comment Code: 13000 

Comment: LANXESS is concerned because, despite diligent efforts extending well beyond the 

record for this Proposal, it has been unable to find any written policies or guidance documents for 

conducting risk assessments for antimicrobial pesticides. Instead, decisions on necessary data, risk 

assessments to be performed and regulatory decisions all appear to be developed on a case-by-case 

basis. 

Response: See response 191.5 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26791 

Comment Code: 13000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * The use of "as determined by the Agency" as the criteria 

for testing (footnotes 10 and 11) gives no guidance to the registrant on how the Agency will make 
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Comments and Response References: 

General Comments on the Rule (10) Page 312 

this decision. The Agency should provide clear criteria as to when the data requirements are 

applicable. (See Panel’s General Comments at Section I) 

Response: See response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26918 

Comment Code: 13000 

Comment: As discussed in detail in the Panel’s General Comments at section II, and above, the 

guidelines for exposure data requirements are either inapplicable to antimicrobial product types and 

uses, are outmoded based on changes made in response to recommendations by the Human Studies 

Review Board, or have yet to be drafted, proposed and finalized after public comment. In order for 

registrants to be able to understand and comply with EPA’s regulations, current, accurate guidelines 

are essential. All applicable guidelines referenced in this data table must be finalized or updated and 

the proposal reissued for comment, prior to promulgation of this rule. 

Response: See response 191.6 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27072 

Comment Code: 13000 

Comment: VII. Reliance upon Alternate Approaches should be Built into this Proposal 

In its proposed and final rules for conventional chemical pesticides, the Agency identified its 

commitment to moving towards a more efficient and refined approach to risk assessment and risk 

management.[FN69: Proposed rule, 70 Fed. Reg. 12276, March 11, 2005; and final rule72 Fed. Reg. 

60934, October 26, 2007.] In fact, moving toward alternate approaches is part of EPA’s and OPP’s 

strategic vision [FN70: US. EPA’s Strategic Plan for Evaluating the Toxicity of Chemicals, available 

at http://www.epa.gov/osa/spc/toxicitytesting/ as announced at 74 Fed Reg. 12847 (March 25, 

2009)], and substantial resources are being devoted to these activities. The Agency continued to 

discuss that same effort in the preamble to the Proposal for antimicrobials, stating "EPA is 

committed to moving towards alternative testing paradigms that are more efficient, reduce the use of 

animal testing, take full advantage of advances in science, and provide a sufficient credible amount 

of data for use in a risk assessment that will support a risk management decision."[FN71: Section 

XVIII, page 59421.] 

Response: see response 4 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 
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Comments and Response References: 

General Comments on the Rule (10) Page 313 

Comment ID: 27074 

Comment Code: 13000 

Comment: The NRC also recommended that EPA reconsider its approach to data requirements to 

better reflect what actually is needed for risk management: 

"The committee cautions against adding testing requirements only for the sake of theoretical 

thoroughness, because such an approach could result in substantial waste of animals and resources 

with little gain. 

[T]he relevant exposure route and exposure durations should be considered in developing a testing 

strategy. 

That it is important to recognize that "toxicity testing for regulatory purposes should be conducted 

primarily to serve the needs of risk management. [T]iered testing approaches should be designed to 

expedite regulatory decisions and to discourage toxicity testing that is not used to address regulatory 

questions."[FN72: National Research Council (NRC) 2006, Toxicity Testing for Assessment of 

Environmental Agents. Interim Report. National Academies Press. p. 8-13. While the NRC report 

and the Agency’s use of SAR or alternative approaches both relate almost exclusively to mammalian 

toxicity issues, LANXESSrecommends that similar consideration be given to alternative approaches 

for all data requirement areas.] 

However, the Proposal does not contain any use of alternative techniques, nor is there any evidence 

of a shift away from the traditional study-by-study approach to a more integrative risk management 

approach. In general, the data requirements of the Proposal are less flexible and more burdensome 

than the existing data requirement regulations at 40 CFR Part 158 for conventional chemicals. 

LANXESS strongly recommends that the Agency take this opportunity to encourage new science 

and approaches in meeting the data requirements for antimicrobial pesticides, such as structure 

activity relationship analyses, in vitro approaches, or computational toxicology. The regulations 

should explicitly allow the use of these and other new methods and approaches. In addition, 

guidance providing specific direction on the use of alternative techniques should be developed in a 

transparent and manner, with an opportunity for public comment. 

Response: See responses 4, 170.1, and 170.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27091 

Comment Code: 13000 

Comment: LANXESS recommends that 40 CFR § 158.70 be amended to include a paragraph (e) 

that explicitly permits the use of alternative approaches to addressing data requirements. Wording 

similar to that in the preamble to Proposal (page 59397) should be considered, such as, "applicants 

may seek to fulfill the data requirements by other appropriate means, such as alternative test 

methods, use of in vitro methods, submission of information from the public literature, the use of 

modeling or predictive methods such as structure activity relations and similar. Applicants must have 
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Comments and Response References: 

General Comments on the Rule (10) Page 314 

the ability to refer to Agency guidance or confer with the Agency if alternative approaches are 

followed." The wording should clearly permit incorporation of additional new approaches, whether 

the use of structure-activity analyses, in vitro methodology, predictive models such as TOXCAST, 

or others still to be identified. By making this change, the Agency will encourage new ideas and be 

able to incorporate innovative approaches without revising its regulations. 

Response: See response 170.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27155 

Comment Code: 13000 

Comment: XI. Current Part 158 should be Amended to Clarify Which Provisions Apply to 

Antimicrobials 

EPA must revise relevant sections of the existing 40 CFR Section 158 to clarify those provisions 

that are applicable to antimicrobials. In particular, Subparts A and B must be amended to include the 

appropriate references to antimicrobial pesticides and to Subpart W. Specifically, 40 CFR 158.1(c)(4) 

must be amended to identify that Subparts A, B, C, D, and W are intended to apply to 

antimicrobials; 40 CFR 158.100 must be amended to include antimicrobial use patterns unless 

replaced by the proposed 158.2201; 40 CFR 158.120(a) must be amended to include Subpart W and 

(b)(2) to address use patterns if use patterns appear other than in 158.100. Without such clear 

references, applicants will not be able to determine what is and is not applicable to antimicrobial 

pesticides. 

Response: see response 50.16 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27397 

Comment Code: 13000 

Comment: LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects: 

* The proposed rule is not a transparent document because many decisions on data requirements 

and the standards against which data will be evaluated are to be "determined by the Agency." (See 

LANXESS’s General Comments at Section I) 

Response: See response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 
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Comments and Response References: 

General Comments on the Rule (10) Page 315 

Comment ID: 27414 

Comment Code: 13000 

Comment: As discussed in detail in LANXESS’s General Comments at section II, the guidelines 

for exposure data requirements are either inapplicable to antimicrobial product types and uses, are 

outmoded based on changes made in response to recommendations by the Human Subjects Review 

Board, or have yet to be drafted, proposed and finalized after public comment.. In order for 

registrants to be able to understand and comply with EPA’s regulations, current, accurate guidelines 

are essential. All applicable guidelines referenced in this data table must be finalized or updated prior 

to promulgation of this rule. 

Response: See response 191.6 

 
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Comments and Response References: 

Administrative Comments on the Rule Section (20) Page 316 

Administrative Comments on the Rule (20) 

Verbatim Comments and Response References for the Administrative 

Comments on the Rule Section 

Comment Code: 20000 Administrative comments on the rule 

Commenter Name: Lisa M. Amadio 

Commenter Organization: JohnsonDiversey, Inc. 

Letter ID: 0084 

Comment ID: 25693 

Comment Code: 20000 

Comment: Conclusion JohnsonDiversey appreciates the opportunity to comment on the proposed 

158 W regulations. We implore the Agency to consider our recommendations in developing a final 

rule. However, because there are significant issues that need to be addressed before the rule is issued 

in final form, we encourage the Agency to issue a revised draft with another opportunity for public 

comment. 

Response: See response R2 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25918 

Comment Code: 20000 

Comment: [In the Panel's comments, 12 major discussion points are presented as follows:] * EPA 

must submit the Antimicrobial Data Requirement Regulation for FIFRA Scientific Advisory Panel 

review 

Response: see response 20.1 

Comment Code: 21000 Administrative process to develop this proposed rule (including outreach) 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25749 

Comment Code: 21000 

Comment: National Research Council Recommendations and SAP Review Section XV Peer 

Review provides recommendations from the National Research Council (NRC) and the FIFRA 
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Comments and Response References: 

Administrative Comments on the Rule Section (20) Page 317 

Scientific Advisory Panel (SAP). EPA calls out recommendations from a 1993 report entitled 

"Pesticides in the Diets of Infants and Children). EPA cites recommendations from the Council that 

supports the need for acute and subchronic neurotoxicity testing for all food-use pesticides. It also 

encouraged further work in the area developmental toxicity. However, in 2006, the NRC evaluated 

current toxicity testing methods used by the Agency to assess hazards and risks. In NRC's executive 

summary, the Council cautioned against adding testing requirements only for the sake of theoretical 

thoroughness, because such an approach could result in substantial waste of animals and resources. 

As indicated in the CSPA and ACC comments regarding the various data tables, there are more 

efficient and cost effective ways to ascertain relevant data for regulatory decisions. For example, 

tiered testing, as opposed to requiring testing for every data requirement in the section tables. 

In this section the Agency provides a discussion of a 1994 meeting with the SAP where the 

proposed amendments to the data requirements for antimicrobial pesticides were discussed. At a 

subsequent June 1997 meeting, EPA met with the SAP and presented an early version of the Part 

158 W proposal. In the wake of the Food Quality Protection Act (FQPA), EPA consulted with the 

SAP as to the newly mandated FFDCA safety factor required under FQPA. In 2000, EPA met again 

with SAP regarding ecological risk assessment. Recognizing the Agency had met with the SAP up to 

the year 2000 regarding data requirements for 158W, it is important to note that 9 years have elapsed 

since the last recorded meeting. Much has changed regarding risk assessment protocols and end 

points, which could alter some the data requirements proposed in the October 8, 2008 proposed 

rule. For example and in some instances, EPA has accepted FDA's FFDCA 409 clearances rather 

than requiring the needless execution of a separate FFDCA 408 clearance for pesticide registration 

of some food use antimicrobials. 

Due to the 9 year passage of time and that the SAP makeup of experts is most likely very different 

from the late 1990's and 2000, the Agency should again request review and comment from the SAP 

prior to implementation of this data requirement rule. 

Response: See response 20.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26175 

Comment Code: 21000 

Comment: However, given the comparatively short time period for comment allowed by EPA to 

address these complex issues, the Panel may supplement its arguments and/or information to EPA 

and hopes that EPA will consider any additional information the Panel provides. 

Response: As appropriate, EPA has considered additional information provided by the commenter 

after the close of the public comment period. EPA has included the additional information in the 

docket for this action. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 
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Comments and Response References: 

Administrative Comments on the Rule Section (20) Page 318 

Comment ID: 26423 

Comment Code: 21000 

Comment: The Panel further recommends that the Agency expand its efforts to develop 

appropriate guidance for the use of alternative approaches to addressing data requirements through 

the involvement of all stakeholders in a public and transparent process and to provide the necessary 

education and training of both the stakeholder community and OPP staff. 

Response: See response 170.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26464 

Comment Code: 21000 

Comment: XIII. The Proposed Rule Does Not Comply with the Applicable Statutes and Executive 

Orders Governing Notice and Comment Rulemaking 

Given the shortcomings explained in the Panel’s comments and section-by-section analysis, and as 

further explained in this section, the Proposal is not in compliance with the applicable statutes and 

executive orders governing notice and comment rulemaking procedures. Specifically, the proposed 

rule does not comply with (1) Executive Order 12866; (2) the Regulatory Flexibility Act; (3) the 

Paperwork Reduction Act; (4) Executive Order 12988; and (5) the Information Quality Act. 

Response: See response 20.4 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27092 

Comment Code: 21000 

Comment: LANXESS further recommends that the Agency expand its efforts to develop 

appropriate guidance for the use of alternative approaches to addressing data requirements through 

the involvement of all stakeholders in a public and transparent process and to provide the necessary 

education and training of both the stakeholder community and OPP staff. 

Response: See response 170.1 

Comment Code: 22000 Relationship between proposed data requirements and EPA’s statutory 

determinations 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 
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Comments and Response References: 

Administrative Comments on the Rule Section (20) Page 319 

Comment ID: 25539 

Comment Code: 22000 

Comment: EPA's preamble to its proposed Subpart W rules states that [Section] 3(h) "does not 

include provisions pertaining to data requirements." (73 Fed. Reg. at 59385). The plain language of 

[Section]3(h), however, requires EPA to adopt antimicrobial regulations that "conform the degree 

and type of review to the risks and benefits presented by antimicrobial pesticides... considering the 

use patterns of the product, toxicity, expected exposure, and product type." EPA can not meet 

Congress' [Section] 3(h) mandate without assuring in the first instance that the Subpart W data 

requirements reflect the unique risks and benefits of antimicrobials. For this reason, CSPA submits 

that EPA's tiered toxicology, environmental and exposure data requirements for conventional 

pesticides are not in every case suitable or warranted for antimicrobials, and our comments point out 

those data requirements that -- while perhaps proper for conventional agricultural pesticides -- are 

not appropriate for antimicrobials. For example, EPA can assess the risks of a nonfood use 

antimicrobial, even if it presents opportunities for repeated, significant human exposure over a 

considerable portion of the human lifespan, with the benefit of a well conducted 90-day study in the 

rat. 

Response: See response 1 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25664 

Comment Code: 22000 

Comment: Waivers of data requirements should only be allowed under extraordinary circumstances 

In our reviews of EPA pesticide reregistration environmental risk assessments, we have often found 

that required data have not been provided to EPA. The lack of clarity of conditional requirements 

noted above may have contributed to these data gaps, because unclear requirements make it more 

difficult for the Agency to obtain information. Waiving data requirements has all too commonly 

functioned as a method of preventing appropriate regulation of a pesticide under the Federal 

Insecticide, Fungicide and Rodenticide Act (FIFRA). EPA should only waive data requirements 

under extraordinary circumstances. 

Response: See response 20.2 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25740 

Comment Code: 22000 

Comment: 158W Urges Individual Consultation with the Registrant Rather than establishing 

Applicable Regulatory Requirements 
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Comments and Response References: 

Administrative Comments on the Rule Section (20) Page 320 

A significant concern of the proposed 158W rule is that many regulatory decisions regarding 

required data and data generation protocols are left to case by case decisions from the Agency. 

There are 37 specific examples of this as outlined in the ACC Biocides Panel comments. While 

Ecolab agrees that case by case consultations between the registrant and the Agency are necessary 

from time to time to address scientific and regulatory issues, Ecolab remains highly concerned that 

there are 37 instances in the proposed rule addressing the need for Agency consultation. This 

number of conSUltations clearly indicates there is a significant lack of clarity to 158W. Ecolab also 

points out that this will place a significantly increased burden on Agency and industry resources. 

Now is the time to address policy and protocol issues rather than defaulting to a case by case basis. 

Currently there is a lack of transparency of evolving Agency policies and decisions. In many 

instances, new policies emerge in registration letters which have resulted in an increased competitive 

disadvantage. Ecolab urges the Agency to eliminate as many case by case scenarios with clear and 

scientifically sound data requirement policies. 

Response: See response 3 

Comment Code: 23000 Consistency of the proposed regulation with other regulations 

Commenter Name: Ray S. McAlister 

Commenter Organization: CropLife America 

Letter ID: 0079 

Comment ID: 25465 

Comment Code: 23000 

Comment: CLA believes that data requirements for antimicrobial pesticides should be more in line 

with those for conventional pesticides, where there are similar or comparable use patterns, or similar 

possibilities for human or environmental exposure to the pesticide. The American Chemistry 

Council Biocides Panel ("Panel") has detailed specific concerns where the proposed data 

requirements depart from this principle in the section of its comments on this proposed rule, 

entitled, "The Data Requirements for Antimicrobials Exceed those for Conventional Pesticides 

without Justification in Certain Specific Areas." 

Response: See response 1 

Commenter Name: Abigail Trueblood 

Commenter Organization: Dow Chemical Company 

Letter ID: 0082 

Comment ID: 25473 

Comment Code: 23000 

Comment: The Proposal imposes more stringent data requirements on antimicrobial (biocide) 

products than those for conventional pesticides. There is no rationale contained within the Proposal 

justifying this and, as pointed out in greater detail by the Panel comment letter, this is inconsistent 

with Section 3(h) of FIFRA. At the very least, Dow would like to learn the reasoning behind the 

differences in these data requirements in order to make further comment. 
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Comments and Response References: 

Administrative Comments on the Rule Section (20) Page 321 

Response: See response 1 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25695 

Comment Code: 23000 

Comment: Harmonization with Office of Water 

EPA should expand and modify the proposed requirements to harmonize with the aquatic toxicity 

testing methods the Agency requires under the Clean Water Act. Specifically, footnotes in the 

proposed rule should specify test species, to match the species that the Office of Water requires be 

used for effluent toxicity testing (see 40 Code of Federal Regulations Part 136.3, Table 1A). The 

testing Guidelines referenced in the regulations should be updated to harmonize with Office of 

Water methods. 

Response: See response 20.3 

Commenter Name: William C. Balek 

Commenter Organization: ISSA 

Letter ID: 0074 

Comment ID: 25863 

Comment Code: 23000 

Comment: [In particular, ISSA supports the following aspects of the ACC Biocides Panel 

Comments:] * The proposed data requirements for antimicrobials exceed those for conventional 

pesticides without adequate justification in certain areas; 

Response: See response 1 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25910 

Comment Code: 23000 

Comment: [In the Panel's comments, 12 major discussion points are presented as follows:] * Data 

requirements for antimicrobials exceed those for conventional pesticides 

Response: See response 1 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25933 

Comment Code: 23000 
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Comments and Response References: 

Administrative Comments on the Rule Section (20) Page 322 

Comment: The guidelines in the proposal do not adequately address the unique exposures that 

antimicrobials have in comparison to conventional pesticides. 

Response: See response 1 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25955 

Comment Code: 23000 

Comment: After a review of the final rule on the data requirements for conventional chemicals and 

biochemical pesticides it is unclear why the footnotes that are found under these chemicals were 

revised. These footnotes are clear, concise and definitive, whereas those in the current proposal are 

confusing. 

Response: See response 2. 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25974 

Comment Code: 23000 

Comment: In the past, the U.S. Environmental Protection Agency (EPA or Agency) has not 

considered the impacts of antimicrobial pesticides from homes and businesses, believing that 

dilution and degradation in the sewer system would prevent these pesticides from having a negative 

impact. The risk-benefit standards of the Federal Insecticide, Fungicide and Rodenticide Act 

(FIFRA) require EPA to ensure that pesticides are used in a manner such that mitigation under the 

CWA is minimal or unnecessary. Improved analytical capabilities have shown that antimicrobial 

pesticides and other substances that were once dismissed may be present in environmentally relevant 

concentrations. As NACWA’s members now know, the potential for these substances to reach the 

treatment plant in concentrations that can negatively impact the treatment process, effect toxicity 

testing, and pass through the treatment system and reach surface waters can be significant in some 

instances. Without a complete set of data relevant to potential water quality impacts, EPA cannot 

fulfill its obligation under FIFRA. 

Response: See response 20.3 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26019 

Comment Code: 23000 
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Comments and Response References: 

Administrative Comments on the Rule Section (20) Page 323 

Comment: We also have requested modifications to the aquatic toxicity testing requirements to 

harmonize these requirements with to those that USEPA imposes under the Clean Water Act. 

Response: See response 20.3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26177 

Comment Code: 23000 

Comment: There have been many developments during the period these regulations have been in 

development. Most importantly, EPA has promulgated new data requirements for conventional 

pesticides and biochemical pesticides. As EPA recognizes in the preamble to the Proposal, the 

conventional Part 158 provides precedent that should be acknowledged. Where EPA seeks to adopt 

an approach similar to that in the conventional pesticide rule, it should explain why that approach is 

appropriate for antimicrobials; and where it decides to take a different approach, it should explain 

the reasons for deviating from past precedent. 

Response: See response 1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26197 

Comment Code: 23000 

Comment: In many cases, the Proposal would impose more stringent data requirements for 

antimicrobials than for conventional pesticides, without acknowledgment of this fact or any 

purported rationale for doing so. 

Response: See response 1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26320 

Comment Code: 23000 

Comment: IV. Some Data Requirements for Antimicrobials Exceed those for Conventional 

Pesticides without Justification 

The Panel is concerned that EPA’s Proposal imposes more stringent data requirements for 

antimicrobials than for conventional pesticides, without acknowledgment or rationale. 

Response: See response 1 
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Comments and Response References: 

Administrative Comments on the Rule Section (20) Page 324 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26333 

Comment Code: 23000 

Comment: The Proposal also contains many instances of data requirements for antimicrobials that 

are more stringent than those for conventional pesticides without justification. These are discussed 

in the following sections. 

Response: See response 1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26694 

Comment Code: 23000 

Comment: There have been many developments during the period these regulations have been in 

development. Most importantly, EPA has promulgated new data requirements for conventional 

pesticides and biochemical pesticides. As EPA recognizes in the preamble to the Proposal, the 

conventional Part 158 provides precedent that should be acknowledged. Where EPA seeks to adopt 

an approach similar to that in the conventional pesticide rule, it should explain why that approach is 

appropriate for antimicrobials; and where it decides to take a different approach, it should explain 

the reasons for deviating from past precedent. 

Response: See response 1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26703 

Comment Code: 23000 

Comment: Given that neither Subpart G, at 158.630 and 158.660, nor 158.2060 require any 

ecological effects data for indoor use conventional or biochemical pesticides, it is unclear why 

extensive data are required for indoor uses of antimicrobials. The proposed rule is inconsistent with 

the requirements for other types of pesticides, without any clear explanation or justification. While 

the Panel agrees that the Agency may wish to consider different types of assessments for 

antimicrobials than for other types of pesticides and that such an approach would be consistent with 

FIFRA 3(h), the Panel believes that the Agency should do so only when a need has been publicly 

discussed and well justified. An appropriate methodology for the assessment should be developed 

through a transparent process with scientific peer review. 

Response: See response 1. 

Commenter Name: Stanley Oslosky 
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Comments and Response References: 

Administrative Comments on the Rule Section (20) Page 325 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26726 

Comment Code: 23000 

Comment: In many cases, the Proposal would impose more stringent data requirements for 

antimicrobials than for conventional pesticides, without acknowledgment of this fact or any 

purported rationale for doing so. 

Response: See response 1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26839 

Comment Code: 23000 

Comment: IV. The Data Requirements for Antimicrobials Exceed those for Conventional 

Pesticides without Justification in Certain Specific Areas 

LANXESS is concerned that EPA’s Proposal imposes more stringent data requirements for 

antimicrobials than for conventional pesticides, without acknowledgment or rationale. 

Response: See response 1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26840 

Comment Code: 23000 

Comment: First, the use pattern designations for antimicrobial products do not account for indoor 

uses in a manner consistent with that for conventional pesticides, without comment or explanation. 

As discussed below, the use patterns in this Proposal should be more clearly defined to clarify when 

data are required and why. Please see the LANXESS’s alternate proposal regarding use patterns at 

Appendix B. Only when this is done can LANXESS and other interested parties provide meaningful 

comments or input. 

Response: See responses 1 and 50.1. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26853 

Comment Code: 23000 
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Comments and Response References: 

Administrative Comments on the Rule Section (20) Page 326 

Comment: The Proposal also contains many instances of data requirements for antimicrobials that 

are more stringent than those for conventional pesticides without justification. These are discussed 

in the following sections. 

Response: See response 1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27386 

Comment Code: 23000 

Comment: Given that neither Subpart G, at 158.630 and 158.660, nor 158.2060 require any 

ecological effects data for indoor use conventional or biochemical pesticides, it is unclear why 

extensive data are required for indoor uses of antimicrobials. The proposed rule is inconsistent with 

the requirements for other types of pesticides, without any clear explanation or justification. While 

LANXESS agrees that the Agency may wish to consider different types of assessments for 

antimicrobials than for other types of pesticides and that such an approach would be consistent with 

FIFRA 3(h), LANXESS believes that the Agency should do so only when a need has been publicly 

discussed and well justified. An appropriate methodology for the assessment should be developed 

through a transparent process with scientific peer review. 

Response: see response 1 
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Comments and Response References: 

Legal Issues Section (30) Page 327 

Legal Issues (30) 

Verbatim Comments and Response References for the Legal Issues Section 

Comment Code: 30000 Legal issues 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25669 

Comment Code: 30000 

Comment: Implementation timing 

EPA requested comments on the timing of the implementation of the proposed rule. Given the 

importance of the proposed changes, EPA should implement the new rule as quickly as is 

technically feasible. The public’s interest and benefits to human health outweigh any procedural 

reasons for delaying implementation. Given the lengthy discussion of the proposed rule changes and 

6-month comment period on the draft rule, it is clear that registrants have had reasonable notice 

about the updated requirements, many of which have been common practice for quite some time. 

Response: See response 30.15 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25808 

Comment Code: 30000 

Comment: * The Proposed Rule fails to correct the longstanding disparity among U.S. regulatory 

frameworks for antimicrobials, whereby products whose antimicrobial properties are identified on a 

product label are designated "pesticides" and subject to extensive premarketing data and testing 

requirements pursuant to [section]158, while at the same time products containing these same active 

substances are marketed in the U.S. under different regulatory schemes, but without a "germ killing" 

or similar label claim or associated data/testing requirements. 

Response: See response 30.3 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25963 

Comment Code: 30000 
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Comments and Response References: 

Legal Issues Section (30) Page 328 

Comment: D. Alternative Means to Address Regulatory Concerns: The Agency has indicated its 

desire to harmonize its data requirements with the rest of the world. We applaud the Agency for 

taking this approach and indeed look forward to the day when we can use the phrase, "registered 

once, registered everywhere". Unfortunately, the current proposal will not allow this to happen. 

While there are elements of harmonization within the proposal, there are many other instances 

whereby the studies requested are truly U.S. EPA driven (e.g. four biodegradation studies). 

Response: See response 30.13 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26100 

Comment Code: 30000 

Comment: In addition, U.S. EPA Office of Pesticide Programs has increased coordination with the 

U.S. EPA Office of Water. The Districts support these efforts and encourages U.S. EPA's Office of 

Pesticide Programs, Office of Water, and Office of Wastewater Management to continue to work 

together to assess data needs for the water quality-related portions of its registration, re-registration, 

and registration review risk assessments. Coordination between U.S. EPA offices in reviewing 

pesticide data needs is essential to Clean Water Act implementation; it also provides an appropriate 

method of meeting FIFRA's goal of preventing unreasonable adverse impacts from pesticide use. 

Response: See response 30.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26189 

Comment Code: 30000 

Comment: Congress recognized the unique issues surrounding regulation of antimicrobials when it 

added section 3(h) to FIFRA in 1996. Section 3(h) requires EPA to issue regulations on the 

registration requirements for antimicrobial pesticides that recognize the unique uses of 

antimicrobials.[FN#1: Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), 7 U.S.C. 

[Sections] 136a (h) (3) ("FIFRA").] FIFRA provides that these regulations should "accelerate and 

improve the review of antimicrobial pesticide products." [FN#2: Id. [Section] 136a (h) (1).] In 

addition, the regulations should: 

(1) define the various classes of antimicrobial use patterns . . . ; 

(2) differentiate the types of review undertaken for antimicrobial pesticides; 

(3)conform the degree and type of review to the risks and benefits presented by antimicrobial 

pesticides, and the function of the review under [FIFRA]; 
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Comments and Response References: 

Legal Issues Section (30) Page 329 

(4) ensure that the registration process is sufficient to maintain antimicrobial pesticide efficacy and 

that antimicrobial pesticide products continue to meet product performance standards and 

effectiveness levels for each type of label claim made; and 

(5) implement effective and reliable deadlines for process management.[FN3:Id. [Section] 136a (h) 

(3) (ii).] 

The Panel believes that many of the considerations in section 3(h) of FIFRA are not reflected in the 

Proposal. The Panel has identified many issues with the Proposal that should be addressed before 

any final regulation is issued. In many cases the issues have prevented meaningful comment on 

portions of the Proposal, which is why the Panel believes reproposal is appropriate. These issues can 

best be viewed in context of 3(h) statutory goals. 

Response: see responses 1 and 2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26244 

Comment Code: 30000 

Comment: From a legal perspective, a purported regulation that imposes a requirement for private 

negotiations between EPA and the applicant, in many cases, is not a proper rulemaking action. 

Rather the courts have found such a "procedure for the later development of tests" to be invalid 

.[FN#13:Ethyl Corp. v. EPA, 306 F.3d 1144, 1150 (2002) (regulation is "not in accordance with the 

law" if it is merely a promulgation of criteria for the later establishment of methods and procedures 

by private negotiations between the EPA and the applicant).] Courts also have been clear that EPA 

cannot "promulgate mush and then give it concrete form only through subsequent less formal 

‘interpretations.’"[FN#14:Id.] Doing so would circumvent the Administrative Procedures Act (APA) 

notice and comment requirements.[FN#15:Id.; see also United States v. Picotto, 875 F.2d 345, 345-

48 (D.C. Cir. 1989) (holding that the agency could not "interpret" the open-ended phrase "additional 

reasonable conditions" in the legislative rule to mandate a specific condition); Pearson v. Shalala, 164 

F.3d 650, 660-61 (D.C. Cir. 1999) (invalidating a FDA rule because it lacked adequate definitional 

content); Mission Group Kansas, Inc. v. Riley, 146 F.3d 775 (10th Cir. 1998) (finding that the 

Secretary of Education’s interpretation of "entirely unrestricted" regulation was improper).] In Ethyl 

Corp. v. EPA, the Court held that EPA did not meet its statutory obligation to establish regulations 

when the Agency simply established a framework for "case-by-case" approvals after "private 

proceedings with each manufacturer."[FN#16:Ethyl Corp., 306 F.3d at 1146 (holding that instead of 

promulgating regulations explaining how to determine whether carriers met the safety fitness 

requirements, the agency simply required the carrier to "demonstrate that it has adequate controls in 

place" to ensure compliance with the substantive requirements and developed a "safety fitness rating 

methodology" that was not the product of informal rulemaking). The court distinguished between 

(1) vaguely articulated test procedures, which are reviewed deferentially; and (2) procedures for later 

development of tests, which are invalid. Id. Here, the EPA appears to be engaging in the latter by 

requiring consultation with the Agency to develop protocols and tests.] Here, the proposed 

requirements are equally vague as those in the Ethyl case and similarly will achieve concrete form 

only through future case-by-case interpretations.[FN#17:Paralyzed Veterans of America v. D.C. 
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Comments and Response References: 

Legal Issues Section (30) Page 330 

Arena L.P., 117 F.3d 579, 584 (D.C. Cir. 1997) ("a substantive regulation must have sufficient 

content and definitiveness as to be a meaningful exercise in agency lawmaking.").] 

Response: See response 30.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26408 

Comment Code: 30000 

Comment: To meet the mandate of FIFRA 3(h), EPA must promulgate the data requirements for 

antimicrobials based on antimicrobial product types and use patterns. It is necessary and appropriate 

for EPA to consider the conventional pesticide rule in developing the antimicrobial regulation. 

However, if the same requirements are to be imposed, an explanation of why they also are 

appropriate for antimicrobials is needed. Similarly, if EPA imposes different requirements, it must 

explain the reasons for the differences. In either case, EPA should address the manner in which data 

requirements for antimicrobials address the considerations in FIFRA 3(h). 

Response: See response 1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26410 

Comment Code: 30000 

Comment: A. The Proposal Does Not Recognize that Environmental and Occupational Exposures 

to Antimicrobials Are Regulated under Other Statutes 

EPA fails to take in account the extent to which both human and environmental exposures 

antimicrobial uses are regulated under other environmental statutes. For example, as explained 

above, industrial, institutional, and commercial users generally are subject to requirements pursuant 

to the Clean Water Act, which requires pretreatment and compliance with permits if a direct 

discharge to water occurs.[FN#61:CWA section 307. Categorical pretreatment standards for 

discharges to POTWs are found at 40 CFR sec. 403.6 and Parts 405 - 471. For Prohibited discharge 

standards, see 40 CFR sec. 403.5.] 

Given the applicability of the CWA, it is unclear why the Proposal requires activated sludge, ready 

biodegradability, modified activated sludge, Tier II aquatic plant growth, and acute avian and fish 

and invertebrate toxicity studies for industrial recirculating water systems. Many recirculating 

systems are regulated under the Clean Water Act as zero discharge.[FN#62:See the discussion of an 

EPA survey on the occurrence of zero discharge in recirculating water systems and growing reuse of 

water in the preamble to EPA’s Proposed Rule on NPDES -Regulations Addressing Cooling Water 

Intake Structures at New Facilities, 65 Fed. Reg. 49060, 49087 ff. (Aug. 10, 2000).] Yet there is no 

recognition of this fundamental fact in the data requirement regulation. 
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Comments and Response References: 

Legal Issues Section (30) Page 331 

Antimicrobial uses and discharges to the environment are regulated under a range of other statutes: 

* Discharges to POTWs are subject to strict state, local and regional requirements and pretreatment 

regulations.[FN#63:40 CFR Part 403.] 

* The use and discharge of ballast water is regulated by the U.S. Coast Guard.[FN#64:33 CFR Part 

151 Subparts C and D.] 

* Antimicrobials used in the disinfection of municipal drinking water are regulated with regard to 

both efficacy and disinfection by-products (DBPs) under the Safe Drinking Water Act by the EPA 

Office of Water.[FN#65:40 CFR Parts 141, 142 and 143.] The DBP regulations are comprehensive. 

The EPA Pesticide program cannot regulate residues of antimicrobials from drinking water. 

* Occupationally used antimicrobial are subject to the full range of regulations pursuant to the 

Occupational Safety and Health Act administered by the Occupational Safety and Health 

Administration (OSHA).[FN#66:29 CFR Parts 1900-1910.] 

The Proposal does not adequately consider these other regulatory programs and whether additional 

regulation under FIFRA is necessary or appropriate. The Panel submits that, in many instances, the 

Proposal contains requirements that duplicate controls under other federal programs. EPA should 

repropose these regulations after considering regulation under other programs and, where it decides 

to pursue additional regulation under FIFRA, it should explain why this additional burden is 

necessary. Moreover, the recognition of the impact of other regulatory programs on environmental 

exposures is essential if EPA is to effectively regulate antimicrobials’ potential to adversely affect 

endangered and threatened species. See Appendix M for a complete discussion. 

Response: See responses 2, 30.2, and 180.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26490 

Comment Code: 30000 

Comment: APPENDIX A 

COMMENTS ON THE SCOPE OF THE PROPOSED REGULATION 

I. Introduction 

The term "antimicrobial" or "antimicrobial pesticide" has multiple meanings within the context of 

EPA regulation, based on statutory definitions, regulatory definitions, and common Agency practice. 

In reading the Proposal, there are a number of questions about the scope and applicability of the 

"antimicrobial pesticide data requirements," based on these definitions and practices. Therefore, the 

Panel believes it is important that the scope of the Proposal is clarified. 

Response: See responses 30.24 and 30.26 
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Comments and Response References: 

Legal Issues Section (30) Page 332 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26714 

Comment Code: 30000 

Comment: First, the Proposal does not adequately "differentiate the types of review undertaken for 

antimicrobial pesticides."[FN4: Id.] The Proposal does not provide the tools to enable applicants or 

registrants to ascertain the requirements for the varying antimicrobial product types in the 

regulation. The Proposal instead would establish a system under which the types of review that 

would be required for particular products could only be determined by case-by- case consultation 

with the Agency. 

Response: See responses 1, 3, and 30.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26767 

Comment Code: 30000 

Comment: From a legal perspective, a purported regulation that imposes a requirement for private 

negotiations between EPA and the applicant is not a proper rulemaking action. Rather the courts 

have found such a "procedure for the later development of tests" to be invalid .[FN13: Ethyl Corp. 

v. EPA, 306 F.3d 1144, 1150 (2002) (regulation is "not in accordance with the law" if it is merely a 

promulgation of criteria for the later establishment of methods and procedures by private 

negotiations between the EPA and the applicant).] Courts also have been clear that EPA cannot 

"promulgate mush and then give it concrete form only through subsequent less formal 

‘interpretations.’"[FN14: Id.] Doing so would circumvent the Administrative Procedures Act (APA) 

notice and comment requirements.[FN15: Id.; see also United States v. Picotto, 875 F.2d 345, 345-

48 (D.C. Cir. 1989) (holding that the agency could not "interpret" the open-ended phrase "additional 

reasonable conditions" in the legislative rule to mandate a specific condition); Pearson v. Shalala, 164 

F.3d 650, 660-61 (D.C. Cir. 1999) (invalidating a FDA rule because it lacked adequate definitional 

content); Mission Group Kansas, Inc. v. Riley, 146 F.3d 775 (10th Cir. 1998) (finding that the 

Secretary of Education’s interpretation of "entirely unrestricted" regulation was improper).] In Ethyl 

Corp. v. EPA, the Court held that EPA did not meet its statutory obligation to establish regulations 

when the Agency simply established a framework for "case- by-case" approvals after "private 

proceedings with each manufacturer."[FN16: Ethyl Corp., 306 F.3d at 1146 (holding that instead of 

promulgating regulations explaining how to determine whether carriers met the safety fitness 

requirements, the agency simply required the carrier to "demonstrate that it has adequate controls in 

place" to ensure compliance with the substantive requirements and developed a "safety fitness rating 

methodology" that was not the product of informal rulemaking). The court distinguished between 

(1) vaguely articulated test procedures, which are reviewed deferentially; and (2) procedures for later 

development of tests, which are invalid. Id. Here, the EPA appears to be engaging in the latter by 

requiring consultation with the Agency to develop protocols and tests.] Here, the proposed 

requirements are equally vague as those in the Ethyl case and similarly will achieve concrete form 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Legal Issues Section (30) Page 333 

only through future case-by-case interpretations.[FN17: Paralyzed Veterans of America v. D.C. 

Arena L.P., 117 F.3d 579, 584 (D.C. Cir. 1997) ("a substantive regulation must have sufficient 

content and definitiveness as to be a meaningful exercise in agency lawmaking.").] 

Response: See response 30.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27010 

Comment Code: 30000 

Comment: To meet the mandate of FIFRA 3(h), EPA must promulgate the data requirements for 

antimicrobials based on antimicrobial product types and use patterns. It is necessary and appropriate 

for EPA to consider the conventional pesticide rule in developing the antimicrobial regulation. 

However, if the same requirements are to be imposed, an explanation of why they also are 

appropriate for antimicrobials is needed. Similarly, if EPA imposes different requirements, it must 

explain the reasons for the differences. In either case, EPA should address the manner in which data 

requirements for antimicrobials address the considerations in FIFRA 3(h). 

Response: See response 1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27031 

Comment Code: 30000 

Comment: A. The Proposal Does Not Recognize that Environmental and Occupational Exposures 

to Antimicrobials Is Significantly Reduced Due to the Manner in Which They are Regulated under 

Other Statutes 

EPA fails to take in account the extent to which both human and environmental exposures from 

antimicrobial uses are regulated under other environmental statutes. For example, as explained 

above, industrial, institutional, and commercial users generally are subject to requirements pursuant 

to the Clean Water Act, which requires pretreatment and compliance with permits if a direct 

discharge to water occurs.[FN61: CWA section 307. Categorical pretreatment standards for 

discharges to POTWs are found at 40 CFR sec. 403.6 and Parts 405-471. For Prohibited discharge 

standards, see 40 CFR sec. 403.5.] 

Given the applicability of the CWA, it is unclear why the Proposal requires activated sludge, ready 

biodegradability, modified activated sludge, Tier II aquatic plant growth, and acute avian and fish 

and invertebrate toxicity studies for industrial recirculating water systems. Many recirculating 

systems are regulated under the Clean Water Act as zero discharge.[FN62: See the discussion of an 

EPA survey on the occurrence of zero discharge in recirculating water systems and growing reuse of 

water in the preamble to EPA’s Proposed Rule on NPDES - Regulations Addressing Cooling Water 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Legal Issues Section (30) Page 334 

Intake Structures at New Facilities, 65 Fed. Reg. 49060, 49087 ff. (Aug. 10, 2000).] Yet there is no 

recognition of this fundamental fact in the data requirement regulation. 

Response: See response 30.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27033 

Comment Code: 30000 

Comment: Antimicrobial uses and discharges to the environment are regulated under a range of 

other statutes: 

* Discharges to POTWs are subject to strict state, local and regional requirements and pretreatment 

regulations.[FN63: 40 CFR Part 403.] 

* The use and discharge of ballast water is regulated by the U.S. Coast Guard.[FN64: 33 CFR Part 

151 Subparts C and D.] 

* Antimicrobials used in the disinfection of municipal drinking water are regulated with regard to 

both efficacy and disinfection by-products (DBPs) under the Safe Drinking Water Act by the EPA 

Office of Water.[FN65: 40 CFR Parts 141, 142 and 143.] The DBP regulations are comprehensive. 

The EPA Pesticide program cannot regulate residues of antimicrobials from drinking water. 

* Industrial antimicrobial uses are subject to the full range of regulations pursuant to the 

Occupational Safety and Health Act administered by the Occupational Safety and Health 

Administration (OSHA).[FN66: 29 CFR Parts 1900-1910.] 

The Proposal does not adequately consider these other regulatory programs and whether additional 

regulation under FIFRA is necessary or appropriate. LANXESS submits that, in many instances, the 

Proposal contains requirements that duplicate controls under other federal programs. EPA should 

re-propose these regulations after considering regulation under other programs and, where it decides 

to pursue additional regulation under FIFRA, it should explain why this additional burden is 

necessary. Moreover, the recognition of the impact of other regulatory programs on environmental 

exposures is essential if EPA is to effectively regulate antimicrobials’ potential to adversely affect 

endangered and threatened species. See Appendix K for a complete discussion. 

Response: See responses 2, 30.2 and 180.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27215 

Comment Code: 30000 
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Comments and Response References: 

Legal Issues Section (30) Page 335 

Comment: XIII. The Proposed Rule Does Not Comply with the Applicable Statutes and Executive 

Orders Governing Notice and Comment Rulemaking 

Given the shortcomings explained in these comments and section-by-section analysis, and as further 

explained in this section, the Proposal is not in compliance with the applicable statutes and executive 

orders governing notice and comment rulemaking procedures. Specifically, the proposed rule does 

not comply with (1) Executive Order 12866; (2) the Regulatory Flexibility Act; (3) the Paperwork 

Reduction Act; (4) Executive Order 12988; and (5) the Information Quality Act. 

Response: See Response 20.4 

Comment Code: 31000 Comments on EPA’s Authority 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25791 

Comment Code: 31000 

Comment: Tri-TAC also requests that U.S. EPA impose more stringent conditions on issuing 

waivers for aquatic toxicity testing in the data requirements rule. Tri-TAC has reviewed several 

Reregistration Eligibility Decisions in which U.S. EPA has reregistered pesticides without receiving 

aquatic toxicity testing data. Tri-TAC recommends U.S. EPA withhold registration decisions until 

required testing is submitted and evaluated. By registering pesticides without required aquatic 

toxicity testing data, U.S. EPA cannot ensure that the pesticide does not pose an unreasonable risk 

to the environment. 

Response: See responses 20.2 and 30.12 

Commenter Name: William C. Balek 

Commenter Organization: ISSA 

Letter ID: 0074 

Comment ID: 25864 

Comment Code: 31000 

Comment: [In particular, ISSA supports the following aspects of the ACC Biocides Panel 

Comments:] * The proposal does not recognize the division ofjurisdiction between EPA and FDA; 

Response: See responses 30.6, 30.26, and 110.1 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25888 

Comment Code: 31000 
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Comments and Response References: 

Legal Issues Section (30) Page 336 

Comment: CASA also requests that U.S. EPA impose more stringent conditions on issuing waivers 

for aquatic toxicity testing in the data requirements rule. CASA recommends U.S. EPA withhold 

registration decisions until required testing is submitted and evaluated. By registering pesticides 

without required aquatic toxicity testing data, U.S. EPA cannot ensure that the pesticide does not 

pose an unreasonable risk to the environment. 

Response: See responses 20.2 and 30.12 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25911 

Comment Code: 31000 

Comment: [In the Panel's comments, 12 major discussion points are presented as follows:] * The 

proposal fails to clarify EPA authority to regulate antimicrobial food uses 

Response: See responses 30.6, 30.26, and 110.1 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26113 

Comment Code: 31000 

Comment: The Districts also request that U.S. EPA impose more stringent conditions on issuing 

waivers for aquatic toxicity testing in the data requirements rule. The Districts have reviewed several 

Reregistration Eligibility Decisions in which U.S. EPA has reregistered pesticides without receiving 

aquatic toxicity testing data. The Districts recommend U.S. EPA withhold registration decisions 

until required testing is submitted and evaluated. By registering pesticides without required aquatic 

toxicity testing data, U.S. EPA cannot ensure that the pesticide does not pose an unreasonable risk 

to the environment. 

Response: See responses 20.2 and 30.12 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26208 

Comment Code: 31000 

Comment: B. Pesticide Disposal Is Not Regulated Under FIFRA 

Disposal of pesticides is not regulated under FIFRA but rather is regulated by EPA’s Office of Solid 

Waste. Moreover, federal, state, and local laws address what can be discharged to POTWs or to U.S. 

waters under the Clear Water Act (e.g., with NPDES permits). State and local laws identify what can 

or cannot be disposed to sanitary sewers, and whether and what pretreatment requirements apply. A 
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Comments and Response References: 

Legal Issues Section (30) Page 337 

decision made under FIFRA cannot go beyond the statutory authority of that law, which addresses 

sale, distribution, and use of pesticides. The Agency has acknowledged this [FN#6:See for example, 

http://www.epa.gov/pesticides/regulating/storage.htm] and requires pesticide labeling to address 

disposal only to the extent that it must be done so in accordance with the appropriate federal, state, 

and local laws. As such, there is no need for data or information on such areas for a pesticide 

regulatory decision. The Agency must clearly explain and justify where it needs to evaluate under 

FIFRA potential environmental exposures and revise the proposed rule to reflect only those areas 

for antimicrobial pesticides. 

Response: See response 30.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26243 

Comment Code: 31000 

Comment: The Panel recognizes that there will be occasions when consultation between the 

applicant and the Agency are necessary to address scientific or technical issues unique to particular 

tests. Nonetheless, the Panel is concerned that this regulation requires individual agency 

consultations to address at least thirty seven identified regulatory situations, and in 8 Id. at [Section] 

158.2230(e) (21). 9 Id. at [Section] 158.2230(e)(32). 10 Id. at [Section] 158.2240(f)(10). 11 Id. at 

[Section] 158.2270(b). 12 Id. at [Section] 158.2290(f)(23). 10 almost all of these instances EPA is left 

with the sole discretion to determine whether data are needed. This raises legal, policy and practical 

concerns. 

Response: See responses 3 and 30.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26358 

Comment Code: 31000 

Comment: V. The Proposal Does Not Recognize the Division of Jurisdiction between EPA and 

FDA 

Another concerning aspect of the Proposal is the manner in which EPA addresses the intersection 

of EPA’s jurisdiction under FFDCA with FDA’s. Under FFDCA, some food uses of antimicrobials 

are subject to regulation by FDA as food additives pursuant to FFDCA section 409, while others are 

regulated as pesticide chemicals by EPA pursuant to FFDCA section 408. The proposed Part 158W 

does not contain a clear articulation of EPA’s view of this jurisdictional boundary, but appears to 

assert EPA’s jurisdiction under FIFRA over some antimicrobial food uses where, in the Panel’s 

view, the statutory scheme provides exclusive jurisdiction to FDA. The following comments identify 

portions of the preamble where clarification is needed on the regulation of food-use antimicrobial 

pesticides. In addition, the comments at Appendix B provide proposed revisions to use patterns, 

data tables and test notes to ensure conformance to statutory provisions. 
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Comments and Response References: 

Legal Issues Section (30) Page 338 

Response: See responses 30.6, 30.26, and 110.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26360 

Comment Code: 31000 

Comment: A. EPA’s Jurisdiction over Food Uses of Antimicrobials Is Limited by the Terms of the 

FFDCA 

Section 201(q) of FFDCA establishes the division of jurisdiction over antimicrobials between EPA 

and FDA by identifying which antimicrobial uses meet the statutory definition of "pesticide 

chemical" pursuant to FFDCA and those uses that are excluded from such definition. In pertinent 

part, "pesticide chemical" is defined at FFDCA Section 201(q)(1) as follows: 

(A) Except as provided in clause (B), the term "pesticide chemical" means any substance that is a 

pesticide within the meaning of the Federal Insecticide, Fungicide, and Rodenticide Act [7 U.S.C. 

136 et seq.], including all active and inert ingredients of such pesticide. . . 

However, this section goes on to exclude certain substances from the definition of "Pesticide 

chemical," including: 

* if the substance is applied for such use on food, or the substance is included for such use in water 

that comes into contact with the food, in the preparing, packing, or holding of the food for 

commercial purposes. 

* if the substance is a food contact substance as defined in section 348(h)(6) of this title, and any of 

the following circumstances exist: The substance is included for such use in an object that has a 

food contact surface but is not intended to have an ongoing effect on any portion of the object; the 

substance is included for such use in an object that has a food contact surface and is intended to 

have an ongoing effect on a portion of the object but not on the food contact surface; or the 

substance is included for such use in or is applied for such use on food packaging (without regard to 

whether the substance is intended to have an ongoing effect on any portion of the packaging). 

FFDCA Section 201(q)(1) can be summarized as follows: 

* No provision of FFDCA 201(q) impacts the scope of antimicrobial uses regulated as pesticides 

under FIFRA. 

*Antimicrobials with uses that may result in residues on food may be regulated as pesticide 

chemicals (subject to FFDCA section 408, administered by EPA) or as food additives (subject to 

FFDCA section 409, administered by FDA). 

* Antimicrobials with uses that may result in residues on food regulated as pesticide chemicals 

(subject to EPA jurisdiction under FFDCA section 408) include the following: 
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Comments and Response References: 

Legal Issues Section (30) Page 339 

* Antimicrobials applied to raw agricultural commodities (RACs) or to water applied to RACs in the 

field, during transportation, or in facilities where no other processing of RACs occurs (typically 

packing houses); 

* Antimicrobials applied to surfaces other than food packaging, e.g., a sanitizer or disinfectant; and 

* Antimicrobials included in objects or articles and intended to have an ongoing effect on the food 

contact surface, i.e., an article or object that is required to be registered because it claims pesticidal 

effects. 

* Antimicrobials with food uses regulated as food additives (subject to FFDCA section 409, 

administered by FDA) include the following: 

* Antimicrobials applied to food (including RACs) or in water applied to food in facilities where 

further processing occurs; and 

*Antimicrobials included in objects or articles where no ongoing effect on the food contact surface 

is intended, i.e., material preservatives. 

The distinction between what is and what is not a pesticide chemical within the meaning of FFDCA 

is critical to understanding the scope of EPA’s jurisdiction over food uses of antimicrobial 

pesticides. EPA is required to issue a tolerance or exemption from tolerance for an antimicrobial use 

within the scope of FFDCA section 408. Among other things, this requires that EPA evaluate the 

toxicity of and exposure to the pesticide chemical residue and publish a regulation setting the terms 

of its approval under FFDCA (i.e., a tolerance or exemption). This requirement to establish a 

regulation is in addition to, but in conjunction with, EPA’s pesticide registration decision under 

FIFRA. The decision regarding the tolerance or exemption for such food use must be made 

consistent with the risk assessment criteria of FFDCA 408, as amended by FQPA. 

Contrast that scenario with one involving registration of an antimicrobial pesticide with uses that 

may result in residues on food subject to FFDCA section 409. In such case, FDA has the 

responsibility to make a regulatory decision based on its evaluation of the toxicity of and exposure to 

the antimicrobial involved in the use that could result in the presence of the compound in food, i.e., 

a food additive. Based on its review, FDA establishes a food additive regulation, issues an effective 

Food Contact Substance (FCS) Notification, or issues an exemption under its Threshold of 

Regulation (21 CFR 170.39). EPA’s responsibility for such use is to evaluate whether the 

antimicrobial meets the standard for registration under FIFRA, taking into account FDA’s existing 

regulatory finding. The FDA finding must be consistent with the provisions of FFDCA 409, which 

includes an outright prohibition on any substances suspected of having carcinogenic properties, i.e., 

the "Delaney clause". EPA does not have the authority under either FIFRA or FFDCA to review or 

change the terms of the FDA approval. In fact, EPA has recently changed its regulations to 

eliminate any reference to FFDCA 409, acknowledging that FDA has "the sole authority under 

Section 409 to regulate food additives."[FN#48:73 Fed. Reg. 75592 (December 12, 2008).] 

Response: See responses 30.6, 30.26, and 110.1 
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Comments and Response References: 

Legal Issues Section (30) Page 340 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26367 

Comment Code: 31000 

Comment: As stated previously, disposal of pesticides is not regulated under FIFRA but rather is 

regulated under EPA’s Office of Solid and Hazardous Wastes. Further, federal, state, and local laws 

address what can be discharged to POTWs and/or to U.S. waters under the Clear Water Act (i.e., 

with NPDES permits). State and local laws identify what can or cannot be disposed of in sanitary 

sewers and whether and what pretreatment requirements apply. EPA’s activities under FIFRA 

should consider the interfaces with these other programs, and the Agency should limit its regulation 

under FIFRA to those areas not adequately covered by them. The Agency should clearly explain and 

justify where it needs to evaluate under FIFRA potential ecological effects resulting from 

environmental exposures, and revise the proposed rule to reflect only those areas for antimicrobial 

pesticides. 

Response: See response 30.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26369 

Comment Code: 31000 

Comment: B. The Proposal Does Not Reflect the Statutory Division of Authority between FIFRA 

and FFDCA 

FIFRA section 2(bb) defines "unreasonable adverse effects on the environment," in part, as: "a 

human dietary risk from residues that result from the use of a pesticide in or on any food 

inconsistent with the standard under section 408 of [FFDCA]." EPA’s long-standing position on the 

scope of FIFRA section 2(bb) is that the provision "does not apply to a registration decision when a 

tolerance is not required because use of the pesticide does not result in residues in or on the 

food."[FN#49:EPA’s Threshold of Regulation Policy, http://www.epa.gov/fedrgstr/EPAPEST/1999/October/Day-27/6042.pdf ) at page 12.] This is an entirely logical approach, given that 

EPA does not have the authority to regulate the presence of food additives (direct or indirect), 

which are by definition not residues from pesticide use. These fall solely within the purview of FDA 

under FFDCA 409. 

However, in the preamble to the proposed 158W, EPA asserts that it can invoke 2(bb) and require 

antimicrobial pesticides with only FFDCA 409 food uses to meet the requirements of FFDCA 408. 

For example, EPA asserts that "additional studies are needed even for the lower exposures for 

which FDA historically would not have required data."[FN#50:73 Fed. Reg. at 59394. This sentence 

is somewhat misleading because EPA, in fact, is asserting its ability to require "additional studies" 

for antimicrobial pesticide uses not only where FDA "would not have" required data, but also for 

the exact same uses where FDA has published a regulation or FCS Notification and has not required 

such additional data.] 
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Comments and Response References: 

Legal Issues Section (30) Page 341 

Response: See responses 30.6, 30.26, and 110.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26371 

Comment Code: 31000 

Comment: EPA’s expansive reinterpretation of its authority with regard to antimicrobial pesticides 

without any explanation also becomes apparent in comparing the preamble to the conventional 

pesticide data requirements with the current Proposal. 

Response: See responses 30.26 and 110.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26373 

Comment Code: 31000 

Comment: In the preamble to the conventional pesticide proposal, EPA appropriately limits its 

discussion of the coordination of FIFRA 2(bb) to registration actions where a tolerance or 

exemption is required. 

Unless EPA is able to establish or maintain a needed tolerance or exemption under FFDCA, a 

pesticide cannot be registered under FIFRA for a food/feed use. FQPA created a specific linkage 

(FIFRA sec. 2(bb)) between the "unreasonable adverse effects" finding under FIFRA and the 

determination of pesticide residue safety of ‘reasonable certainty of no harm" under FFDCA. In 

essence, a pesticide that is inconsistent with, or does not meet, the FFDCA sec. 408 safety standard 

poses an unreasonable adverse effect that precludes new or continued registration. Thus, both 

FIFRA and FFDCA standards must be met for pesticides intended to be registered in the United 

States for food or feed uses. 

Given this linkage between registration and tolerances, it makes sense for EPA to define data 

requirements for both purposes: the data required to support a determination of "reasonable 

certainty of no harm" under FFDCA are an integral part of the data needed for an "unreasonable 

adverse effects" determination under FIFRA. Consequently, when promulgated, these proposed 

data requirements would encompass the basic data requirements for both registration and tolerancesetting determinations. EPA will retain its authority to require additional data on a case-by-case 

basis. 

70 Fed. Reg., March 11, 2005 at 12279 (emphasis added). 

Response: See responses 30.26 and 110.1 

Commenter Name: Hasmukh C. Shah 
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Comments and Response References: 

Legal Issues Section (30) Page 342 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26381 

Comment Code: 31000 

Comment: However, the preamble to the antimicrobial data requirement Proposal eliminated any 

reference to the requirement for a tolerance or exemption or indeed any reference to food or feed 

uses, while adopting the text of second paragraph of the above quotation verbatim. 

Under FIFRA section 2(bb), a pesticide that is inconsistent with, or does not meet, the FFDCA 

section 408 safety standard poses an unreasonable adverse effect that precludes new or continued 

registration. Given this linkage between registration and tolerances, it makes sense for EPA to define 

data requirements for both purposes: the data required to support a determination of "reasonable 

certainty of no harm" under FFDCA are an integral part of the data needed for an "unreasonable 

adverse effects" determination under FIFRA. Consequently, when promulgated, these proposed 

data requirements would encompass the basic data requirements for both registration and tolerancesetting determinations. EPA will retain its authority to require additional data on a case-by-case 

basis. 

73 Fed. Reg. at 59394. EPA further states, without distinction as to whether uses under FFDCA 

section 408 are applicable, 'It is the applicant’s obligation under FIFRA to demonstrate that an 

individual product meets the standard under FIFRA and that of FFDCA."[FN#51:73 Fed. Reg. at 

59386.] 

Response: See responses 30.26 and 110.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26383 

Comment Code: 31000 

Comment: In effect, EPA is asserting that the reach of 2(bb) and the consequent scope of FFDCA 

408 is to all antimicrobial pesticides. This position is contrary to EPA policies and practices 

regarding conventional pesticides and biopesticides, and EPA has failed to provide any basis for its 

new position. Under this interpretation of 2(bb), EPA will re-review and approve the same 

chemicals for the same uses that FDA already has cleared, require extensive additional data for its 

reviews, and subject all uses of pesticides to the FFDCA safety standard regardless of whether any 

food uses subject to Section 408 exist. This creates a host of practical problems, including waste of 

government resources, potential for inconsistent decisions, waste of regulated parties’ resources, and 

deterrence of applications for new generation products. None of these is even referred to, much less 

discussed in the Proposal. EPA has not provided any meaningful opportunity to comment on its 

expansive view of its jurisdiction. 

Response: See responses 30.26 and 110.1 

Commenter Name: Hasmukh C. Shah 
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Comments and Response References: 

Legal Issues Section (30) Page 343 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26385 

Comment Code: 31000 

Comment: The scope of FIFRA section 2(bb) is clear, consistent with EPA’s recent regulatory 

revisions to strip most references to FFDCA 409 from its regulations.[FN#52:In EPA’s technical 

amendment to its regulations, the Agency provided: As part of the FQPA, Congress combined 

EPA’s authority to regulate all pesticide chemical residues in food under section 408 of the FFDCA 

(leaving the Food and Drug Administration the sole authority under section 409 to regulate food 

additives). As it no longer has any regulatory authority under section 409, EPA is eliminating most 

references to FFDCA section 409 from its regulations. 73 Fed. Reg. 75592 (December 12, 2008). 

Pesticide Regulations; Technical Amendments.] FDA has sole authority for the antimicrobial food 

contact uses subject to regulation of food additives pursuant to FFDCA 409. EPA has sole authority 

for regulating pesticide chemicals under FFDCA 408. Where there are antimicrobial food uses that 

fall under FFDCA 408, EPA is required to conduct a risk assessment consistent with that statutory 

provision. Where there are no antimicrobial uses subject to FFDCA 408, FIFRA 2(bb) does not 

apply and no FFDCA 408 risk assessment is mandated or appropriate. 

Response: See responses 30.26 and 110.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26395 

Comment Code: 31000 

Comment: For example, any release from a once-through water treatment system is a point- source 

discharge regulated under the Clean Water Act.[FN#56:Clean Water Act, sections 301 et seq., 

creates standards and permit obligations for point source discharges. It is illegal to discharge any 

pollutant from a point source without a permit. The National Pollutant Discharge Elimination 

System (NPDES) permit program controls point source discharges. EPA defines point source 

discharges as "discrete conveyances such as pipes or man-made ditches." Industrial, municipal, and 

other facilities must obtain NPDES permits if their discharges go directly to surface waters. See 40 

CFR Parts 100-135 for NPDES and related regulations; see also 40 CFR 400-471 for industryspecific effluent guidelines and standards, which cover the vast majority of industrial and 

institutional users of antimicrobials, e.g., pulp, paper and paperboard mills (40 CFR Part 430) and 

painting formulators (40 CFR Part 446).] This is in direct contrast to the extensive non-point source 

discharges of conventional pesticides.[FN#57:In contrast to the extensive regulation of point source 

discharges, non-point source discharges are regulated under CWA sections 208 and 319. These 

sections require states to develop watershed management plans to impede non-point source 

discharges and to identify waters damaged or threatened by runoff. There are no equivalent permit 

requirements or regulations to effectively control environmental exposures for the vast majority of 

non-point source discharges.] The ability to regulate and control point source discharges is far more 

comprehensive than any to control non-point source discharges and the regulatory requirements are 

concomitantly more comprehensive. 
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Comments and Response References: 

Legal Issues Section (30) Page 344 

Response: See responses 30.2 and 30.25 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26430 

Comment Code: 31000 

Comment: A statutory grant of legislative rulemaking authority does not give agencies the power to 

promulgate regulations retroactively unless that power is expressly conveyed by 

Congress.[FN#73:Bowen v. Georgetown Univ. Hosp., 488 U.S. 204, 216 (1988).] FIFRA confers no 

such authority.[FN#74:The APA and common law do not permit retroactive legal consequences for 

informal rulemaking. The text of the APA defines a "rule" as a "whole or a part of an agency 

statement of general or particular applicability and future effect designed to implement, interpret, or 

prescribe law or policy or describing the organization, procedure, or practice requirements of an 

agency . . . ."5 U.S.C. [Section] 551(4) (emphasis added). As Justice Scalia explained, "[t]he only 

plausible reading of [future effect] is that rules have legal consequences only for the future." Id. 

(Scalia, J. concurring).] A retroactive rule can "alter[ ] future regulation in a manner that makes 

worthless substantial past investment incurred in reliance upon the prior rule-- may for that reason 

be ‘arbitrary’ or ‘capricious,’ . . . and thus invalid."[FN#75:Id. at 220 (citing General Telephone Co. 

of Southwest v. United States, 449 F.2d 846, 863 (5th Cir. 1971); Nat’l Assn. of Independent 

Television Producers and Distributors v. FCC, 502 F.2d 249, 255 (2d Cir. 1974). EPA’s actions in 

promulgating Subpart 158W may be set aside if found to be "arbitrary, capricious, an abuse of 

discretion, or otherwise not in accordance with the law." 5 U.S.C. [Section] 706(2)(A); see Citizens to 

Preserve Overton Park v. Volpe, 401 U.S. 402, 414 (1971).] 

Response: See response 30.15 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26706 

Comment Code: 31000 

Comment: The Panel points out that disposal of pesticides is not regulated under FIFRA but rather 

is regulated under EPA’s Office of Solid and Hazardous Wastes. Further, federal, state, and local 

laws address what may be discharged to POTWs and/or to U.S. waters under the Clear Water Act 

(i.e., with NPDES permits). State and local laws identify what may or may not be disposed of in 

sanitary sewers and whether and what pretreatment requirements apply. EPA’s activities under 

FIFRA should consider the interfaces with these other programs, and the Agency should limit its 

regulation under FIFRA to those areas not adequately covered by them. FIFRA regulates sale, 

distribution, and use of pesticides, and EPA should not try to use it to accomplish goals in other 

areas. The Agency has clearly and consistently acknowledged this and requires pesticide labeling to 

address disposal only to the extent that it must be done so in accordance with the appropriate 

federal, state, and local laws. As such, there is no need for data or information on such areas for a 

pesticide regulatory decision. The Agency should clearly explain and justify where it needs to 
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Comments and Response References: 

Legal Issues Section (30) Page 345 

evaluate under FIFRA potential ecological effects resulting from environmental exposures, and 

revise the proposed rule to reflect only those areas for antimicrobial pesticides. 

Response: See response 30.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26765 

Comment Code: 31000 

Comment: LANXESS recognizes that there will be occasions when consultation between the 

applicant and the Agency are necessary to address scientific or technical issues unique to particular 

tests. Nonetheless, LANXESS is very concerned that this regulation requires individual agency 

consultations to address at least thirty seven identified regulatory situations. This raises legal, policy 

and practical concerns. 

Response: See responses 3 and 30.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26891 

Comment Code: 31000 

Comment: V. The Proposal Does Not Recognize the Division of Jurisdiction between EPA and 

FDA 

Another concerning aspect of the Proposal is the manner in which EPA addresses the intersection 

of EPA’s jurisdiction under FFDCA with FDA’s. Under FFDCA, some food uses of antimicrobials 

are subject to regulation by FDA as food additives pursuant to FFDCA section 409, while others are 

regulated as pesticide chemicals by EPA pursuant to FFDCA section 408. The proposed Part 158W 

does not contain a clear articulation of EPA’s view of this jurisdictional boundary, but appears to 

assert EPA’s jurisdiction under FIFRA over some antimicrobial food uses where, in LANXESS’s 

view, the statutory scheme provides exclusive jurisdiction to FDA. The following comments identify 

portions of the preamble where clarification is needed on the regulation of food-use antimicrobial 

pesticides. In addition, the comments at Appendix B provide proposed revisions to use patterns, 

data tables and test notes to ensure conformance to statutory provisions. 

A. EPA’s Jurisdiction over Food Uses of Antimicrobials Is Limited by the Terms of the FFDCA 

Section 201(q) of FFDCA establishes the division of jurisdiction over antimicrobials between EPA 

and FDA by identifying which antimicrobial uses meet the statutory definition of "pesticide 

chemical" pursuant to FFDCA and those uses that are excluded from such definition. In pertinent 

part, "pesticide chemical" is defined at FFDCA Section 201(q)(1) as follows: 
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Comments and Response References: 

Legal Issues Section (30) Page 346 

(A) Except as provided in clause (B), the term "pesticide chemical" means any substance that is a 

pesticide within the meaning of the Federal Insecticide, Fungicide, and Rodenticide Act [7 U.S.C. 

136 et seq.], including all active and inert ingredients of such pesticide... 

However, this section goes on to exclude certain substances from the definition of "Pesticide 

chemical," including: 

* if the substance is applied for such use on food, or the substance is included for such use in water 

that comes into contact with the food, in the preparing, packing, or holding of the food for 

commercial purposes. 

* if the substance is a food contact substance as defined in section 348(h)(6) of this title, and any of 

the following circumstances exist: The substance is included for such use in an object that has a 

food contact surface but is not intended to have an ongoing effect on any portion of the object; the 

substance is included for such use in an object that has a food contact surface and is intended to 

have an ongoing effect on a portion of the object but not on the food contact surface; or the 

substance is included for such use in or is applied for such use on food packaging (without regard to 

whether the substance is intended to have an ongoing effect on any portion of the packaging). 

FFDCA Section 201(q)(1) can be summarized as follows: 

* No provision of FFDCA impacts the scope of antimicrobial uses regulated as pesticides under 

FIFRA. 

* Antimicrobials with food uses may be regulated as pesticide chemicals (subject to FFDCA section 

408, administered by EPA) or as food additives (subject to FFDCA section 409, administered by 

FDA). 

* Antimicrobials with food uses regulated as pesticide chemicals (subject to EPA jurisdiction under 

FFDCA section 408) include the following: 

** Antimicrobials applied to raw agricultural commodities (RACs) or to water applied to RACs in 

the field, during transportation, or in facilities where no other processing of RACs occurs (typically 

packing houses); 

** Antimicrobials applied to surfaces other than food packaging, e.g., a sanitizer or disinfectant; and 

** Antimicrobials included in objects or articles and intended to have an ongoing effect on the food 

contact surface, i.e., an article or object that is required to be registered because it claims pesticidal 

effects. 

* Antimicrobials with food uses regulated as food additives (subject to FFDCA section 409, 

administered by FDA) include the following: 

** Antimicrobials applied to food or in water applied to food in facilities where further processing 

occurs; and 
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Comments and Response References: 

Legal Issues Section (30) Page 347 

** Antimicrobials included in objects or articles where no ongoing effect on the food contact 

surface is intended, i.e., material preservatives. 

The distinction between what is and what is not a pesticide chemical within the meaning of FFDCA 

is critical to understanding the scope of EPA’s jurisdiction over food uses of antimicrobial 

pesticides. EPA is required to issue a tolerance or exemption from tolerance for an antimicrobial use 

within the scope of FFDCA section 408. Among other things, this requires that EPA evaluate the 

toxicity of and exposure to the pesticide chemical residue and publish a regulation setting the terms 

of its approval under FFDCA (i.e., a tolerance or exemption). This requirement to establish a 

regulation is in addition to, but in conjunction with, EPA’s pesticide registration decision under 

FIFRA. The decision regarding the tolerance or exemption for such food use must be made 

consistent with the risk assessment criteria of FFDCA 408, as amended by FQPA. 

Contrast that scenario with one involving registration of an antimicrobial pesticide with food uses 

subject to FFDCA section 409. In such case, FDA has the responsibility to make a regulatory 

decision based on its evaluation of the toxicity of and exposure to the antimicrobial involved in the 

use that could result in the presence of the compound in food, i.e., a food additive. Based on its 

review, FDA establishes a food additive regulation, issues an effective Food Contact Substance 

(FCS) Notification, or issues an exemption under its Threshold of Regulation (21 CFR 170.39). 

EPA’s responsibility for such use is to evaluate whether the antimicrobial meets the standard for 

registration under FIFRA, taking into account FDA’s existing regulatory finding. The FDA finding 

must be consistent with the provisions of FFDCA 409, which includes an outright prohibition on 

any substances suspected of having carcinogenic properties, i.e., the "Delaney clause". EPA does not 

have the authority under either FIFRA or FFDCA to review or change the terms of the FDA 

approval. In fact, EPA has recently changed its regulations to eliminate any reference to FFDCA 

409, acknowledging that FDA has "the sole authority under Section 409 to regulate food 

additives."[FN48: 73 Fed. Reg. 75592 (December 12, 2008).] 

B. The Proposal Does Not Reflect the Statutory Division of Authority between FIFRA and FFDCA 

FIFRA section 2(bb) defines "unreasonable adverse effects on the environment," in part, as: "a 

human dietary risk from residues that result from the use of a pesticide in or on any food 

inconsistent with the standard under section 408 of [FFDCA]." EPA’s long-standing position on the 

scope of FIFRA section 2(bb) is that the provision "does not apply to a registration decision when a 

tolerance is not required because use of the pesticide does not result in residues in or on the 

food."[FN49: EPA’s Threshold of Regulation Policy, http://www.epa.gov/fedrgstr/EPAPEST/1999/October/Day-27/6042.pdf) at page 12.] This is an entirely logical approach, given that 

EPA does not have the authority to regulate the presence of food additives (direct or indirect), 

which are by definition not residues from pesticide use. These fall solely within the purview of FDA 

under FFDCA 409. 

However, in the preamble to the proposed 158W, EPA asserts that it can invoke 2(bb) and require 

antimicrobial pesticides with only FFDCA 409 food uses to meet the requirements of FFDCA 408. 

For example, EPA asserts that "additional studies are needed even for the lower exposures for 

which FDA historically would not have required data."[FN50: 73 Fed. Reg. at 59394. This sentence 

is somewhat misleading because EPA, in fact, is asserting its ability to require "additional studies" 

for antimicrobial pesticide uses not only where FDA "would not have" required data, but also for 
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Comments and Response References: 

Legal Issues Section (30) Page 348 

the exact same uses where FDA has published a regulation or FCS Notification and has not required 

such additional data.] 

Response: See responses 30.6, 30.26, and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26893 

Comment Code: 31000 

Comment: EPA’s expansive reinterpretation of its authority with regard to antimicrobial pesticides 

without any explanation also becomes apparent in comparing the preamble to the conventional 

pesticide data requirements with the current Proposal. 

Response: See responses 30.26 and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26901 

Comment Code: 31000 

Comment: In the preamble to the conventional pesticide proposal, EPA appropriately limits its 

discussion of the coordination of FIFRA 2(bb) to registration actions where a tolerance or 

exemption is required. 

"Unless EPA is able to establish or maintain a needed tolerance or exemption under FFDCA, a 

pesticide cannot be registered under FIFRA for a food/feed use. FQPA created a specific linkage 

(FIFRA sec. 2(bb)) between the "unreasonable adverse effects" finding under FIFRA and the 

determination of pesticide residue safety of ‘reasonable certainty of no harm" under FFDCA. In 

essence, a pesticide that is inconsistent with, or does not meet, the FFDCA sec. 408 safety standard 

poses an unreasonable adverse effect that precludes new or continued registration. Thus, both 

FIFRA and FFDCA standards must be met for pesticides intended to be registered in the United 

States for food or feed uses. 

Given this linkage between registration and tolerances, it makes sense for EPA to define data 

requirements for both purposes: the data required to support a determination of "reasonable 

certainty of no harm" under FFDCA are an integral part of the data needed for an "unreasonable 

adverse effects" determination under FIFRA. Consequently, when promulgated, these proposed 

data requirements would encompass the basic data requirements for both registration and tolerancesetting determinations. EPA will retain its authority to require additional data on a case-by-case 

basis." 70 Fed. Reg., March 11, 2005 at 12279 (emphasis added). 

Response: See responses 30.26 and 110.1 

Commenter Name: Stanley Oslosky 
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Comments and Response References: 

Legal Issues Section (30) Page 349 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26903 

Comment Code: 31000 

Comment: However, the preamble to the antimicrobial data requirement Proposal eliminated any 

reference to the requirement for a tolerance or exemption or indeed any reference to food or feed 

uses, while adopting the second paragraph of the above quotation verbatim. 

 "Under FIFRA section 2(bb), a pesticide that is inconsistent with, or does not meet, the FFDCA 

section 408 safety standard poses an unreasonable adverse effect that precludes new or continued 

registration. Given this linkage between registration and tolerances, it makes sense for EPA to define 

data requirements for both purposes: the data required to support a determination of "reasonable 

certainty of no harm" under FFDCA are an integral part of the data needed for an "unreasonable 

adverse effects" determination under FIFRA. Consequently, when promulgated, these proposed 

data requirements would encompass the basic data requirements for both registration and tolerancesetting determinations. EPA will retain its authority to require additional data on a case-by-case 

basis." 

73 Fed. Reg. at 59394. EPA further states, without distinction as to whether uses under FFDCA 

section 408 are applicable, "It is the applicant’s obligation under FIFRA to demonstrate that an 

individual product meets the standard under FIFRA and that of FFDCA."[FN51: 73 Fed. Reg. at 

59386.] 

Response: See responses 30.26 and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26905 

Comment Code: 31000 

Comment: In effect, EPA is asserting that the reach of 2(bb) and the consequent scope of FFDCA 

408 is to all antimicrobial pesticides. This position is contrary to EPA policies and practices 

regarding conventional pesticides and biopesticides, and EPA has failed to provide any basis for its 

new position. Under this interpretation of 2(bb), EPA will re-review and approve the same 

chemicals for the same uses that FDA already has cleared, require extensive additional data for its 

reviews, and subject all uses of pesticides to the FFDCA safety standard regardless of whether any 

food uses subject to Section 408 exist. This creates a host of practical problems, including waste of 

government resources, potential for inconsistent decisions, waste of regulated parties’ resources, and 

deterrence of applications for new generation products. None of these is even referred to, much less 

discussed in the Proposal. EPA has not provided any meaningful opportunity to comment on its 

expansive view of its jurisdiction. 

Response: See responses 30.26, and 110.1 

Commenter Name: Stanley Oslosky 
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Comments and Response References: 

Legal Issues Section (30) Page 350 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26955 

Comment Code: 31000 

Comment: The scope of FIFRA section 2(bb) is clear, consistent with EPA’s recent regulatory 

revisions to strip most references to FFDCA 409 from its regulations.[FN52: In EPA’s technical 

amendment to its regulations, the Agency provided: As part of the FQPA, Congress combined 

EPA’s authority to regulate all pesticide chemical residues in food under section 408 of the FFDCA 

(leaving the Food and Drug Administration the sole authority under section 409 to regulate food 

additives). As it no longer has any regulatory authority under section 409, EPA is eliminating most 

references to FFDCA section 409 from its regulations. 73 Fed. Reg. 75592 (December 12, 2008). 

Pesticide Regulations; Technical Amendments.] FDA has sole authority for the antimicrobial food 

contact uses subject to regulation of food additives pursuant to FFDCA 409. EPA has sole authority 

for regulating pesticide chemicals under FFDCA 408. Where there are antimicrobial food uses that 

fall under FFDCA 408, EPA is required to conduct a risk assessment consistent with that statutory 

provision. Where there are no antimicrobial uses subject to FFDCA 408, FIFRA 2(bb) does not 

apply and no FFDCA 408 risk assessment is mandated or appropriate. 

Response: See responses 30.26 and 110.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27001 

Comment Code: 31000 

Comment: B. Pesticide Disposal Is Not Regulated Under FIFRA 

Disposal of pesticides is not regulated under FIFRA but rather is regulated by EPA’s Office of Solid 

Waste. Moreover, federal, state, and local laws address what can be discharged to POTWs or to U.S. 

waters under the Clean Water Act (e.g., with NPDES permits). State and local laws identify what can 

or cannot be disposed to sanitary sewers, and whether and what pretreatment requirements apply. A 

decision made under FIFRA cannot go beyond the statutory authority of that law, which addresses 

sale, distribution, and use of pesticides. The Agency has acknowledged this [FN#3:See for example, 

http://www.epa.gov/pesticides/regulating/storage.htm] and requires pesticide labeling to address 

disposal only to the extent that it must be done so in accordance with the appropriate federal, state, 

and local laws. As such, there is no need for data or information on such areas for a pesticide 

regulatory decision. The Agency must clearly explain and justify where it needs to evaluate under 

FIFRA potential environmental exposures and revise the proposed rule to reflect only those areas 

for antimicrobial pesticides. (See Panel’s General Comments at Section VI for a more complete 

discussion of other statutes and regulations that limit the potential for antimicrobial exposures.) 

Response: See response 30.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
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Comments and Response References: 

Legal Issues Section (30) Page 351 

Letter ID: 0064 

Comment ID: 27391 

Comment Code: 31000 

Comment: LANXESS points out that disposal of pesticides is not regulated under FIFRA but 

rather is regulated under EPA’s Office of Solid and Hazardous Wastes. Further, federal, state, and 

local laws address what may be discharged to POTWs and/or to U.S. waters under the Clear Water 

Act (i.e., with NPDES permits). State and local laws identify what may or may not be disposed of in 

sanitary sewers and whether and what pretreatment requirements apply. EPA’s activities under 

FIFRA should consider the interfaces with these other programs, and the Agency should limit its 

regulation under FIFRA to those areas not adequately covered by them. FIFRA regulates sale, 

distribution, and use of pesticides, and EPA should not try to use it to accomplish goals in other 

areas. The Agency has clearly and consistently acknowledged this and requires pesticide labeling to 

address disposal only to the extent that it must be done so in accordance with the appropriate 

federal, state, and local laws. As such, there is no need for data or information on such areas for a 

pesticide regulatory decision. The Agency should clearly explain and justify where it needs to 

evaluate under FIFRA potential ecological effects resulting from environmental exposures, and 

revise the proposed rule to reflect only those areas for antimicrobial pesticides. 

Response: See responses 30.2, 30.26, and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27503 

Comment Code: 31000 

Comment: B. Pesticide Disposal Is Not Regulated Under FIFRA 

Disposal of pesticides is not regulated under FIFRA but rather is regulated by EPA’s Office of Solid 

Waste. Moreover, federal, state, and local laws address what can be discharged to POTWs or to U.S. 

waters under the Clear Water Act (e.g., with NPDES permits). State and local laws identify what can 

or cannot be disposed to sanitary sewers, and whether and what pretreatment requirements apply. A 

decision made under FIFRA cannot go beyond the statutory authority of that law, which addresses 

sale, distribution, and use of pesticides. The Agency has acknowledged this [FN#3:See for example, 

http://www.epa.gov/pesticides/regulating/storage.htm] and requires pesticide labeling to address 

disposal only to the extent that it must be done so in accordance with the appropriate federal, state, 

and local laws. As such, there is no need for data or information on such areas for a pesticide 

regulatory decision. The Agency must clearly explain and justify where it needs to evaluate under 

FIFRA potential environmental exposures and revise the proposed rule to reflect only those areas 

for antimicrobial pesticides. (See Panel’s General Comments at Section VI for a more complete 

discussion of other statutes and regulations that limit the potential for antimicrobial exposures.) 

Response: See responses 2 and 30.2 
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Comments and Response References: 

Legal Issues Section (30) Page 352 

Comment Code: 32000 Harmonization with the Pesticide Management Regulatory Agency of 

Canada (PMRA) 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25561 

Comment Code: 32000 

Comment: General Agency Comments 

General Considerations: 

*The PMRA outlines data requirements according to specific Use-Site Categories (USC), as listed in 

the PMRA’s data code (DACO) tables ( http://www.hc-sc.gc.ca/cps-spc/pest/registranttitulaire/prod/_daco-codo/index- eng.php). In contrast, CFR 158W proposes that a combination of 

how/where the product will be used (e.g. food vs. non-food, aquatic vs. non-aquatic, occupational 

vs. residential, indoor vs. outdoor), and the level of exposure (e.g. high vs. low toxicology and/or 

environmental exposure) be used as determining factors for data requirements for the various 

science disciplines. These differences present challenges with respect to comparing data 

requirements, and how/when they will be invoked, between the EPA and PMRA in several of the 

scientific disciplines. 

Response: See response 30.13 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25563 

Comment Code: 32000 

Comment: *The wording regarding required ("R") vs. conditionally required ("CR") data in the 

CFR 158W proposal document is not always clear in its intent. For example, it is not clear whether 

data listed as "R" must always be addressed by the applicant, whether through submission of an 

actual study or through the submission of a scientifically valid waiver request. In the CFR 158 

proposal, the text appears to indicate that in some cases, required data elements might not need to 

be addressed (see examples below). If this is the case, it could result in a lack of harmonization in 

data received by the USEPA and PMRA. 

E.g.: The use of R does not necessarily indicate that a study is always required, but that it is more 

likely to be required than not (p. 59386). 

Thus, NR, R, and CR are used for convenience to make the table format feasible, but serve only as a 

general indication of the applicability of a data requirement (p. 59386). 

Response: See response 30.13 
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Comments and Response References: 

Legal Issues Section (30) Page 353 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25574 

Comment Code: 32000 

Comment: Section Number IV. 

Title I . Use Patterns in Subpart W 

Paragraph p. 59388 

Excerpt from Federal Register General comment 

HC Comment The PMRA categorizes pesticides into use site categories (USC). The comparison of 

the EPA use patterns and PMRA use site category crosswalk appears in Table 1. The EPA use 

pattern 6, Human Drinking Water Systems, does not correspond to any PMRA use site category at 

this time. In Canada, registration of antimicrobial products to be used in human drinking water 

systems, as defined by the EPA use pattern, falls under the jurisdiction of the Healthy Environments 

and Consumer Safety Branch of Health Canada. 

[See Table 1: Crosswalk of EPA and PMRA uses, PDF Docket ID EPA-HQ- OPP-2008-0110-

0085.2.pdf] 

 Human Health 

Note: Tables comparing data requirements for toxicology, occupational exposure, and dietary 

exposure disciplines were prepared by the PMRA. However, because of the differences in the way 

data requirements are outlined between the PMRA and the EPA (as discussed above in the General 

Agency comments), the comparisons were not always straightforward. These tables can be made 

available to the EPA if it is thought that they would be useful. 

Response: See response 30.13 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25602 

Comment Code: 32000 

Comment: Environment 

General Considerations: 

*Apart from the proposed use of modelling data, the proposed CFR 158W data will result in a 

significantly greater degree of harmonization of data requirements between the EPA and the PMRA, 
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Comments and Response References: 

Legal Issues Section (30) Page 354 

with respect to environmental fate and environmental toxicology, for the respective USC’s when 

compared to the current EPA practice. 

Response: See response 30.13 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25610 

Comment Code: 32000 

Comment: Section Number XII. Section Number XIII. Section Number XIV. 

Title Environmental Fate Data Requirements Title Nontarget Organisms Data Requirements Title 

Plant Protection Data Requirements 

Paragraph p. 59406 Paragraph p. 59412 Paragraph p. 59415 

Excerpt from Federal Register General comment 

HC Comment An overview of the PMRA and proposed EPA antimicrobial environmental data 

requirements is presented in Table 3 (below). Although the data requirements are not completely 

harmonized, it is encouraging to see that there are significantly more common elements between the 

two agencies than in the past. Response: See response 30.13 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25611 

Comment Code: 32000 

Comment: The remaining differences in data requirements between the two agencies are: 

*The PMRA requirement for analytical methodologies for soil, sediment, water, and biota. These 

data are required for compliance/enforcement purposes and for post-registration monitoring. The 

remaining differences in data requirements between the two agencies are: *The inclusion of acute 

earthworm, salinity challenge, chronic toxicity to estuarine/marine organisms studies, and a toxicity 

study on predators and parasites by the PMRA for certain USCs. 

Response: See response 30.13 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25633 

Comment Code: 32000 
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Comments and Response References: 

Legal Issues Section (30) Page 355 

Comment: The remaining differences in data requirements between the two agencies are: 

*Regarding the low environmental exposure pesticides, the EPA’s planned use of the Down-TheDrain and STPWIN models, and their new data requirements for activated sludge sorption isotherm, 

ready biodegradability, modified activated sludge, respiration inhibition, and porous pot studies. 

Response: See response 30.13 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25634 

Comment Code: 32000 

Comment: The remaining differences in data requirements between the two agencies are: For 

complete details on the data requirements and the associated data notes/comments, please refer to 

the proposed CFR 158W rule for the EPA requirements, and to http://www.hc-sc.gc.ca/cpsspc/pest/registranttitulaire/ prod/_daco-codo/index- eng.php for the PMRA requirements. 

Response: See response 30.13 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25636 

Comment Code: 32000 

Comment: [See Table 2: Crosswalk of uses indicating where environmental data are required by the 

PMRA. PDF docket ID EPA-HQ-OPP-2008-0110-0085.2.pdf] 

 [See Table 3: Overview of PMRA and EPA antimicrobial environmental data requirements. PDF 

docket ID EPA-HQ-OPP-2008-0110-0085.2.pdf] 

* EPA data requirement is for once-through only. ** the Low Environmental Exposure group 

includes recirculating industrial processes and water systems (part of the industrial process fluids and 

water systems use pattern) *** either an adsorption/desorption study or soil column leaching study 

is required 

# this data requirement is described as an aquatic (sediment) field dissipation study by the EPA ## 

an acute inhalation (LD50) study and not acute oral toxicity study is CR 

For PMRA USC 5 and 6 only, there is a requirement for a hydrolysis, analytical methodology for soil 

and an aerobic soil biotransformation study. The remaining data requirements are CR, with 

conditions based on potential exposure and the results of "lower tier" studies. 

R = required CR = conditionally required NR = not required 

 cross-hatched cells indicate no data requirement 
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Comments and Response References: 

Legal Issues Section (30) Page 356 

Response: See response 30.13 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25638 

Comment Code: 32000 

Comment: Future considerations: 

The PMRA will continue to collaborate with our counterparts in the EPA Antimicrobials Division 

(AD) on further harmonization, especially in the following areas: *The use and incorporation of 

integrated testing strategies for the assessment of antimicrobial pesticides, as well as development of 

framework for the use of other modelling tools (e.g. Down-the-Drain). *Defining/standardizing to 

the extent possible the criteria and terminology used to describe the level of human exposure 

associated with the antimicrobial pesticides. *Methods used to assess environmental risks associated 

with wood preservatives. 

Response: See response 30.13 

Comment Code: 33000 Effective date for antimicrobials regarding future registrations of 

antimicrobials 

Commenter Name: Lisa M. Amadio 

Commenter Organization: JohnsonDiversey, Inc. 

Letter ID: 0084 

Comment ID: 25692 

Comment Code: 33000 

Comment: The Final Rule Should Apply Only to Applications Submitted After the Effective Date 

EPA states in the preamble to the Proposed Rule that it intends to apply any final rule on 

antimicrobial data requirements to applications and other actions pending at the time the final rule is 

adopted. We are apprehensive about this statement, and strongly believe that it is not in EPA's best 

interest to implement the Proposed Rule in this manner. FIFRA does not grant EPA the authority 

to implement rules retroactively. Other laws (the Administrative Procedure Act, for example) 

specifically indicate that any final rules should apply to applications submitted after the effective date 

of the new rule. Pending applications should be processed based on the requirements in place at the 

time of submission. 

Response: See response 30.15 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25730 

Comment Code: 33000 
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Comments and Response References: 

Legal Issues Section (30) Page 357 

Comment: General Comments: 

Implementation of Part 158W EPA states in the preamble "Impact of this Proposal on Future and 

Existing Registrations" (IV. Introduction to Subpart W, G.) that the finalized 158 data requirements 

would apply to all new antimicrobial registration applications submitted after the effective date of 

the final rule. The new data requirements would also apply to applications of antimicrobial pesticides 

that are undergoing Agency review when the final regulation goes into effect. When the regulation is 

finalized, Ecolab concurs that all new antimicrobial applications which have not been submitted to 

EPA would be subject to the new data requirements. However, Ecolab strongly disagrees that any 

registration currently under review should have the new data requirements imposed. This would 

result in lengthy delays and renegotiation of PRIA costs/timelines. Imposing new data requirements 

on registrations submitted prior to the finalization of 158W would unfairly penalize those 

registrations in review. Product registration data generation fees are budgeted by companies on an 

annual basis. To implement new requirements on a pending registration review would trigger 

unbudgeted and substantial data generation costs and PRIA costs, resulting in registrants 

withdrawing applications due to the lack of funds in this challenging economic environment. Given 

the onslaught of public health crises such as MRSA, Clostridium diffici/e, hoof and mouth disease, 

Avian Influenza, and the critical Anthrax response to bioterrorism threats, the Agency must carefully 

weigh the benefit of new public health technologies against imposing additional data requirements 

for applications submitted prior to promulgation of a final rule. 

Response: EPA acknowledges Ecolab's agreement that all new antimicrobial applications which 

have not been submitted to EPA would be subject to the new data requirements. See also response 

30.15. 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25731 

Comment Code: 33000 

Comment: The Agency should be consistent with how the data requirements were implemented for 

conventional pesticides. In that instance, EPA did not impose new data requirements retroactively 

on pending conventional pesticide submissions. 

Response: See response 30.15 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25733 

Comment Code: 33000 

Comment: In addition, to comply with the Administrative Procedure Act (APA), any final 

rulemaking on the data requirements for antimicrobials must apply only to antimicrobial pesticide 

registration applications submitted after the 158W rule effective date. For registrations pending at 
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Comments and Response References: 

Legal Issues Section (30) Page 358 

the time of final rule publication, Ecolab suggests those pending applications be given conditional 

registration under Section 3(c)(7) of FIFRA and that implementation of the 158W data requirements 

occur at the time of Periodic Registration Review. As pointed out in the ACC comments, a statutory 

grant of legislative rulemaking does not give the Agency the power to promulgate registrations 

retroactively unless that power is expressly conveyed by Congress. 

Response: See response 30.15 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25914 

Comment Code: 33000 

Comment: [In the Panel's comments, 12 major discussion points are presented as follows:] * Final 

rule should only apply to applications submitted after the effective date 

Response: See response 30.15 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26424 

Comment Code: 33000 

Comment: VIII. The Final Rule Should Apply Only to Applications Submitted After the Effective 

Date 

In the preamble, EPA states that it intends to apply any final rule on antimicrobial data requirements 

to applications and other actions pending at the time the final rule is adopted.[FN#72:73 Fed. Reg. 

59,388 (Oct. 8, 2008).] This is of concern to the Panel from legal, policy and practical perspectives. 

The Panel strongly urges EPA to revise its Proposal and apply any final rule only to actions initiated 

after its effective date. 

Response: See response 30.15 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26429 

Comment Code: 33000 

Comment: To comply with the Administrative Procedure Act (APA), any final rulemaking on the 

data requirements for antimicrobials should apply only to applications submitted after the effective 

date. In the alternative, the Panel suggests that pending applications be processed based on the 

requirements in place at the time of submission, and given a conditional registration pursuant to 

Section 3(c)(7) of FIFRA. 
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Comments and Response References: 

Legal Issues Section (30) Page 359 

Response: See response 30.15 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26432 

Comment Code: 33000 

Comment: EPA would diminish the substantial past investment incurred by registrants in reliance 

upon the present regulations governing antimicrobials if the final regulations are applied to pending 

applications. Additional testing and fees would be required, incurring unforeseen monetary and 

durational costs in applications for either a new active ingredient or a new use of an existing active 

ingredient. Together, this additional testing and Pesticide Registration Improvement Act (PRIA) 

review periods will append an additional two to six years to the registration process, as well as the 

additional expenses incurred before any costs are recouped. 

A. Additional Data Would Be Required for Pending Applications 

Registrants with pending applications for a new active ingredient or a new use of an existing active 

ingredient would be faced with the need to generate more data to meet the newly imposed generic 

data requirements. These additional studies may take as long as four years if higher tiered studies are 

indeed promulgated as the Proposal sets forth. As a consequence, EPA likely would suspend review 

of applications within, for example, a 24-month PRIA review time until the applicant generates the 

additional data required by the Proposal, regardless of where the application was in the review 

process.[FN#76:EPA could suspend its review in one of two ways: (1) by issuing a do-not-grant 

letter, requiring the applicant to withdraw its application; or (2) requiring the applicant to 

"voluntarily" agree to an extension of the PRIA time frame.] 

Response: See response 30.15 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26434 

Comment Code: 33000 

Comment: B. Additional PRIA Registration Fees Would Be Required for Pending Applications 

In addition, applicants may incur additional PRIA registration fees. If a do- not-grant letter or other 

mechanism for withdrawing the application is used, the applicant would have to submit a new 

application for registration upon completion of the data to satisfy the newly imposed requirements. 

This would require the payment of another PRIA registration fee; and a new PRIA review time of as 

long as two years would be imposed. 

Response: See response 30.15 
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Comments and Response References: 

Legal Issues Section (30) Page 360 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26435 

Comment Code: 33000 

Comment: In short, if the Proposal applies to pending applications, the rulemaking would have 

consequences for actions taken in the past in reliance on antimicrobial regulations, making the 

regulation unreasonably retroactive, and in violation of the APA. Applicants complied with the data 

requirements and applications fees in anticipation of receiving registration. The Panel asserts that if 

an application to the EPA is pending at the time of the effective date, and it meets the requirements 

as set out in Part 161, then it should be registered in accordance with Section 3(c)(5) of 

FIFRA.[FN#77:7 U.S.C. [Section] 136a(c)(5).] 

Response: See response 30.15 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26733 

Comment Code: 33000 

Comment: [FN6: Another example of requiring this type of individual determination is 

experimental use permits ("EUP’s"). EPA states in the preamble that it plans to apply, "on a caseby-case" basis, the requirements for experimental use permits for conventional pesticides found at 

40 CFR [section] 158C. Proposed Rule at page 59,385. However, the Proposed Rule has not clearly 

identified the circumstances under which such a permit would be required for antimicrobials or what 

data requirements are applicable.] 

Response: See response 30.19 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27093 

Comment Code: 33000 

Comment: VIII. The Final Rule Should Apply Only to Applications Submitted After the Effective 

Date 

In the preamble, EPA states that it intends to apply any final rule on antimicrobial data requirements 

to applications and other actions pending at the time the final rule is adopted.[FN74: 73 Fed. Reg. 

59,388 (Oct. 8, 2008).] This is of great concern to LANXESS from legal, policy and practical 

perspectives. LANXESS strongly urges EPA to revise its Proposal and apply any final rule only to 

actions initiated after its effective date. 

Response: See response 30.15 
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Comments and Response References: 

Legal Issues Section (30) Page 361 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27101 

Comment Code: 33000 

Comment: To comply with the Administrative Procedure Act (APA), any final rulemaking on the 

data requirements for antimicrobials should apply only to applications submitted after the effective 

date. In the alternative, LANXESS suggests that pending applications be processed based on the 

requirements in place at the time of submission, and given a conditional registration pursuant to 

Section 3(c)(7) of FIFRA. 

Response: See response 30.15 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27103 

Comment Code: 33000 

Comment: A statutory grant of legislative rulemaking authority does not give agencies the power to 

promulgate regulations retroactively unless that power is expressly conveyed by Congress.[FN75: 

Bowen v. Georgetown Univ. Hosp., 488 U.S. 204, 216 (1988).] FIFRA confers no such 

authority.[FN76: The APA and common law do not permit retroactive legal consequences for 

informal rulemaking. The text of the APA defines a "rule" as a "whole or a part of an agency 

statement of general or particular applicability and future effect designed to implement, interpret, or 

prescribe law or policy or describing the organization, procedure, or practice requirements of an 

agency..."5 U.S.C. [section]551(4) (emphasis added). As Justice Scalia explained, "[t]he only plausible 

reading of [future effect] is that rules have legal consequences only for the future." Id. (Scalia, J. 

concurring).] A retroactive rule can "alter[ ] future regulation in a manner that makes worthless 

substantial past investment incurred in reliance upon the prior rule-may for that reason be ‘arbitrary’ 

or ‘capricious,’... and thus invalid."[FN77: Id. at 220 (citing General Telephone Co. of Southwest v. 

United States, 449 F.2d 846, 863 (5th Cir. 1971); Nat’l Assn. of Independent Television Producers 

and Distributors v. FCC, 502 F.2d 249, 255 (2d Cir. 1974). EPA’s actions in promulgating Subpart 

158W may be set aside if found to be "arbitrary, capricious, an abuse of discretion, or otherwise not 

in accordance with the law." 5 U.S.C. [section]706(2)(A); see Citizens to Preserve Overton Park v. 

Volpe, 401 U.S. 402, 414 (1971).] 

Response: See response 30.15 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27105 

Comment Code: 33000 
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Comments and Response References: 

Legal Issues Section (30) Page 362 

Comment: EPA would diminish the substantial past investment incurred by registrants in reliance 

upon the present regulations governing antimicrobials if the final regulations are applied to pending 

applications. Additional testing and fees would be required, incurring unforeseen monetary and 

durational costs in applications for either a new active ingredient or a new use of an existing active 

ingredient. Together, this additional testing and Pesticide Registration Improvement Act (PRIA) 

review periods will append an additional two to six years to the registration process, as well as the 

additional expenses incurred before any costs are recouped. 

A. Additional Data Would Be Required for Pending Applications 

Registrants with pending applications for a new active ingredient or a new use of an existing active 

ingredient would be faced with the need to generate more data to meet the newly imposed generic 

data requirements. These additional studies may take as long as four years if higher tiered studies are 

indeed promulgated as the Proposal sets forth. As a consequence, EPA likely would suspend review 

of applications within, for example, a 24-month PRIA review time until the applicant generates the 

additional data required by the Proposal, regardless of where the application was in the review 

process.[FN78: EPA could suspend its review in one of two ways: (1) by issuing a do-not- grant 

letter, requiring the applicant to withdraw its application; or (2) requiring the applicant to 

"voluntarily" agree to an extension of the PRIA time frame.] 

Response: See response 30.15 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27118 

Comment Code: 33000 

Comment: B. Additional PRIA Registration Fees Would Be Required for Pending Applications 

In addition, pending applications may incur additional PRIA registration fees. If a do-not-grant letter 

or other mechanism for withdrawing the application is used, the applicant would have to submit a 

new application for registration upon completion of the data to satisfy the newly imposed 

requirements. This would require the payment of another PRIA registration fee; and a new PRIA 

review time of as long as two years would be imposed. Applicants may avoid paying the second 

PRIA registration fee if the PRIA time frame is renegotiated, but these negotiations are not 

guaranteed. 

Response: See response 30.15 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27120 

Comment Code: 33000 
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Comments and Response References: 

Legal Issues Section (30) Page 363 

Comment: In short, if the Proposal applies to pending applications, the rulemaking would have 

consequences for actions taken in the past in reliance on antimicrobial regulations, making the 

regulation unreasonably retroactive, and in violation of the APA. Applicants complied with the data 

requirements and applications fees in anticipation of receiving registration. LANXESS asserts that if 

an application to the EPA is pending at the time of the effective date, and it meets the requirements 

as set out in Part 161, then it should be registered in accordance with Section 3(c)(5) of 

FIFRA.[FN79: 7 U.S.C. [section]136a(c)(5).] 

Response: See response 30.15 
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Comments and Response References: 

Economic Analysis Section (40) Page 364 

Economic Analysis (40) 

Verbatim Comments and Response References for the Economic Analysis 

Section 

Comment Code: 40000 Economic analysis 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25540 

Comment Code: 40000 

Comment: Just as Congress has reminded EPA that the risks, benefits and human and 

environmental exposures to antimicrobials are unique, CSPA wishes to remind EPA that its own 

economic impact assessment of Subpart W data requirements confirms that the antimicrobial 

industry is unique. "There are about 750 unique parent antimicrobial firms. Of these, based on the 

SBA definition of a small business and the Dun & Bradstreet company data, EPA estimates that 

500, or approximately 67 percent, are small businesses." (Economic Analysis at 16.) While some 

smaller businesses formulate products from registered antimicrobial active ingredients and, 

therefore, are exempt from more costly active ingredient data requirements, these smaller businesses 

will have to absorb the costs of testing active ingredients in the form of higher costs for the active 

ingredients. The very rationale of the formulator's exemption is based on the assumption that the 

price of the active technical or manufacturing use product purchased by the formulator will include 

the cost of testing the active ingredient. 

Response: No response is needed. 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25552 

Comment Code: 40000 

Comment: e. EPA’s Economic Analysis Fails To Consider the Costs of Registration Review 

EPA's economic analysis considers the cost of Subpart W for registering new active ingredients, new 

products and amending products. Importantly, it fails to consider the impact of Subpart W on 

existing registrants, even though the Agency could presently estimate the data gaps for existing 

antimicrobials arising out of Subpart W. (Economic Analysis at [paragraph[sic]] 2.5). This is a 

fundamental and fatal flaw in the Agency's Economic Analysis. Instead, EPA contends that 

"[s]takeholders and the public have opportunities for input, consultation and involvement 

concerning individual pesticide cases throughout the registration review process." Once EPA adopts 

final Subpart W data requirements, however, these requirements will serve as the benchmark for 

identifying data gaps during EPA's registration review, just as Part 158 served as the benchmark for 
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Comments and Response References: 

Economic Analysis Section (40) Page 365 

identifying data gaps during reregistration for conventional chemicals. The real cost and impact of 

Subpart W will be felt by the industry during registration review, and EPA must evaluate and weigh 

these costs now, not later during registration review. 

Response: See response 40.6. 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25944 

Comment Code: 40000 

Comment: Troy Corporation is providing comments to the EPA Docket referenced above. Troy 

Corporation is a biocide manufacturer and registrant and this proposal will have dire consequences 

on our overall business. With the current economic climate and downturn this proposal could not 

come at a worse time. As a small to medium enterprise (SME), we have been challenged with 

supporting our products globally with regulations such as the EU Biocidal Products Directive 

(BPD), REACH, Globally Harmonized System (GHS) and now U.S. EPA revised requirements for 

registration. 

Response: See response 40.4 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25947 

Comment Code: 40000 

Comment: A. Unique Nature of Antimicrobials: The data requirements found in the 40 CFR Parts 

158 and 161 entitled "Data Requirements for Antimicrobial Pesticides; Proposed Rule," published 

on Wednesday, October 8,2008, are considerably more extensive and resource-intensive than 

present data requirements. This new proposal significantly increases the costs to maintain current 

registrations, as well as makes the registration of new products exceedingly difficult. It also does not 

take into consideration the unique nature of antimicrobial products which differ significantly from 

conventional and biochemical pesticides. Antimicrobials are not broadcast into the environment and 

are used at levels typically below one percent of the formula weight. The requirements, however, do 

not reflect these characteristics. In many cases the data requirements (ecotoxicity and environmental 

fate for example) are considerably more extensive than those found under the revised data 

requirements for conventional and biochemical pesticides. It is assumed that there is considerable 

environmental exposure necessitating extensive leaching studies from treated articles simply because 

the products are used outdoors. 

Response: See response 1 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 
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Comments and Response References: 

Economic Analysis Section (40) Page 366 

Comment ID: 26017 

Comment Code: 40000 

Comment: Thank you for this opportunity to comment on USEPA’s proposed revised data 

requirements for antimicrobial pesticides.[FN1:In this letter, the term "antimicrobials" includes (but 

is not limited to) biocides, disinfectants, sterilizers, preservatives, sanitizers, wood preservatives, and 

antifoulant coatings.] We appreciate the approach taken in this update because it will greatly improve 

USEPA’s capacity to prevent water quality problems from outdoor use of antimicrobial pesticides. 

The outdoor use of pesticide in urban areas has been linked to toxicity to organisms in urban creeks. 

Pesticide-related toxicity in surface waters receiving urban runoff creates regulatory burdens for 

many of our municipality members, including National Pollutant Discharge Elimination System 

(NPDES) stormwater permit requirements, and the threat of litigation under the citizen suit 

provisions of the Clean Water Act. 

Response: EPA acknowledges CASQA’s support for EPA’s approach for revised data requirements 

for antimicrobials. 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26020 

Comment Code: 40000 

Comment: Cost savings estimates are provided to document our assessment that adopting the 

updated rule will avoid significant water quality management costs to municipalities, states, and 

USEPA Office of Water-perhaps as much as $100 million nationwide over the next 20 years. 

Response: EPA acknowledges receipt of this information. CASQA provided information on the 

cost of correcting pesticide-related water quality problems. EPA will consider this information. 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26058 

Comment Code: 40000 

Comment: The cost of these additional and restructured tests would be very small compared to the 

costs that may be incurred without these data (see below). 

Response: EPA acknowledges receipt of this information. CASQA provided information on the 

cost of correcting pesticide-related water quality problems. EPA will consider this information. 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26059 

Comment Code: 40000 
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Comments and Response References: 

Economic Analysis Section (40) Page 367 

Comment: Significant Government Cost Savings 

Improving data requirements for antimicrobial pesticides will create significant cost savings for 

USEPA’s Office of Water, state water quality regulatory agencies, and municipalities. The additional 

costs of $35,000-70,000 per chemical incurred by registrants are small compared to the public cost 

savings and environmental benefits of the proposed new requirements. We note that the proposed 

rule is designed with tiered data requirements such that data necessary to identify water quality 

threats is obtained, but more expensive data requirements are only incurred for those pesticides with 

the greatest potential to threaten water quality. Although only a relatively small number of pesticides 

have been linked to surface water quality problems (most commonly incidents of toxicity to aquatic 

organisms), when water quality problems occur, the remediation costs can be significant. On the 

basis of the cost of responding to past pesticide-related water quality problems associated with 

outdoor urban pesticide use patterns, we estimate that even if only a few pesticide-related water 

quality problems are prevented by the rule, nationwide water quality- related cost savings could easily 

exceed $100 million dollars. 

The $100 million nationwide savings estimate is based on the costs for the activities listed below, our 

experience that pesticide-related water quality problems associated with urban pesticide use patterns 

normally are found in multiple urban watersheds, and the recognition that there are thousands of 

water bodies across the nation that receive urban runoff. 

* Complete process for formal designation of a water body as impaired under Section 303(d) of the 

Clean Water Act. We understand this requires tens of hours of staff time, but do not have a formal 

estimate. (This cost may be incurred by either USEPA or a state). 

* Preparation of a Total Maximum Daily Load (TMDL) for each water body on the Clean Water Act 

Section 303(d) list. California estimates that its average cost for preparing a single TMDL is 

$600,000.[FN4:California State Water Resources Control Board (2001). Structure and Effectiveness 

of the State’s Water Quality Programs: Section 303(d) of the Federal Clean Water Act and Total 

Maximum Daily Loads (TMDLs), Report to the Legislature Pursuant to AB 982 of 1999, January. 

Available on the Internet: http://www.swrcb.ca.gov/tmdl/political.html] 

* TMDL implementation activities to end impairment of the Clean Water Act section 303(d) listed 

water body. These costs often run into the millions. For example, the California Regional Water 

Quality Control Board, San Francisco Bay Region estimated that the implementation cost for a 

pesticide-related TMDL for Bay Area urban creeks would be roughly $7 million 

annually.[FN5:Johnson, B. (2005). Diazinon and Pesticide-Related Toxicity in Bay Area Urban 

Creeks. Water Quality Attainment Strategy and Total Maximum Daily Load (TMDL). Final Staff 

Report. Prepared by the California Regional Water Quality Control Board, San Francisco Bay 

Region. November 9. Available on the Internet: http://tinyurl.com/cqw76j] 

* Special monitoring and response plans in response to incident of pesticide- related toxicity. It is 

common for NPDES permits to require increased monitoring, Toxicity Identification Evaluations 

(TIEs), and Toxicity Reduction Evaluations (TREs) [FN6:U.S. EPA. (1999). Toxicity Reduction 

Evaluation Guidance for Municipal Wastewater Treatment Plants. EPA/833B-99/002. Available on 

the Internet: http://tinyurl.com/cwe66w] when toxicity is identified in surface waters receiving 
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Comments and Response References: 

Economic Analysis Section (40) Page 368 

urban runoff. These special monitoring and site- specific response costs can exceed $100,000 

annually for a single municipality. For example, one of our members recently incurred expenditures 

of more than $200,000 for special monitoring, TIEs, and a TRE required in response to ongoing 

pesticide-related toxicity in its urbanized watersheds. This municipality anticipates ongoing costs of 

nearly $100,000 per year for monitoring and TRE implementation. These avoidable costs will 

continue until pesticide regulators implement changes to end the toxicity, which is caused by use 

patterns that cannot be regulated at the local level. 

Response: EPA acknowledges receipt of this information. CASQA provided information on the 

cost of correcting pesticide-related water quality problems. EPA will consider this information. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26179 

Comment Code: 40000 

Comment: The Panel also has had an independent economic impact analysis performed by NERA 

Economic Consulting, which is included as an appendix. 

Response: No response is needed. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26226 

Comment Code: 40000 

Comment: The Panel has numerous other comments on specific provisions of the Proposal, which 

are provided in its Section-by-Section Analysis. An independent Economic Impact Analysis, 

prepared for the Panel by NERA also is attached as Appendix J. It concludes that the actual cost 5 

Id. 8 of implementing the Proposal as a final regulation would be significantly greater than that 

estimated by EPA’s economic analysis. 

Response: See response 40.1. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26259 

Comment Code: 40000 

Comment: Perhaps because of the unpredictability, the burden associated with these consultations 

has not been considered in the economic impact analysis EPA provided with the Proposal. 

Response: See responses 3 and 40.6 
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Comments and Response References: 

Economic Analysis Section (40) Page 369 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26437 

Comment Code: 40000 

Comment: IX. EPA’s Economic Analysis Underestimates the Cost of the Regulation and Its 

Impact on Registrants and Users 

EPA’s economic analysis significantly underestimates the costs associated with this 

regulation.[FN#78:44 U.S.C. [Section] 3501 et seq.] The Panel has sponsored a more comprehensive 

economic analysis, prepared by NERA Economic Consulting. The NERA report is attached as 

Appendix J to these comments and is incorporated into these comments by reference. The NERA 

report differs from EPA’s analysis in several important ways. Going beyond EPA’s analysis, NERA 

estimates costs of applying the Proposal’s data requirements to Registration Review. NERA then 

calculates average costs/company that will be imposed through the new generic data requirements. 

Response: See response 40.6. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26441 

Comment Code: 40000 

Comment: In sum, a more comprehensive economic analysis found that the costs of the Proposal 

are likely to be far greater than estimates in the EPA Economic Study. These realistic compliance 

costs need to be balanced against any perceived benefits from the regulation to determine whether 

the course proposed by EPA is appropriate. 

Response: See responses 40.1 and 40.2. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26465 

Comment Code: 40000 

Comment: A. Executive Order 12866 

To begin, the EPA has not accurately stated the potential costs and benefits, as required by 

Executive Order 12866.[FN#86:Executive Order 12,866 [Section] 1(b) (6) (Oct. 4, 1993) ("Each 

agency shall assess both the costs and the benefits of the intended regulation and, recognizing that 

some costs and benefits are difficult to quantify, propose or adopt a regulation only upon a reasoned 

determination that the benefits of the intended regulation justify its costs.").] In its economic 

analysis, the EPA estimates the incremental costs at $3.2 million annually.[FN#87:See EPA, 
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Comments and Response References: 

Economic Analysis Section (40) Page 370 

Economic Analysis of the Proposed Change in Data Requirements for Antimicrobial Pesticides, at 

16.] 

Response: See reponse 40.6. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26468 

Comment Code: 40000 

Comment: B. The Regulatory Flexibility Act (as amended by the Small Business Regulatory 

Enforcement Fairness Act) 

Contrary to the Agency’s assertion in the Preamble,[FN#91:See Proposed Rule, 73 Fed. Reg. 

59,428.] the proposed rule would have a significant adverse economic impact on a substantial 

number of small entities. Thus, the proposed rule’s analysis is unreasonable in light of the Regulatory 

Flexibility Act (RFA), as amended by the Small Business Regulatory Enforcement Fairness Act 

(SBREFA).[FN#92:See 5 U.S.C.§§ 601-612; Small Business Regulatory Enforcement Fairness Act, 

Pub. L. No. 104-121, tit. II, 110 Stat. 857, 864-68 (1996).] These Acts dictate that if an agency’s 

proposed rule would significantly burden small businesses, the agency must prepare an initial 

regulatory flexibility analysis (IRFA) describing the effect of the proposed rule on small businesses 

and discussing alternatives that might minimize adverse economic consequences.[FN#93:See id. 

[Section] 603.] 

The proposed rule must state whether it is "likely to have a significant economic impact on a 

substantial number of small entities." [FN#94:Id. [Section] 602(a)(1).] Under the RFA, "small 

entities" mean (1) a small business as defined by the Small Business Administration’s (SBA) 

regulations, which is based on either the maximum number of employees or on the sales for small 

businesses in each industry sector, as defined by a 6-digit NAICS code; (2) a small organization that 

is any not-for-profit enterprise that is independently owned and operated, and is not dominant in its 

field; and (3) a small governmental jurisdiction that is a government of a city, county, town, school 

district or special district with a population of less than 50,000.[FN#95:Id. [Section] 601.] 

The EPA correctly states that the rulemaking does not impact small governmental jurisdictions and 

small organizations because these entities are rarely antimicrobial pesticide applicants or registrants; 

but the EPA incorrectly concludes that the rule will not have a significant adverse economic impact 

on a substantial number of small businesses. As NERA’s economic analysis explains, the EPA’s 

conclusion is erroneously based on estimates that the incremental cost of the regulation would 

account for more than one percent of revenue for only 22 small firms, or only 4.4 percent of the 500 

small pesticide registrants.[FN#96:See Appendix J, NERA Economic Consulting, Economic 

Analysis of Proposed U.S. EPA Biocide Data Requirements: Prepared for the American Chemistry 

Council, at 17 (Mar. 2009).] Under this calculation, only 25 small registrants would incur any 

additional costs under the proposed rule.[FN#97:Id.] 

Response: See response 40.4. 
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Comments and Response References: 

Economic Analysis Section (40) Page 371 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26480 

Comment Code: 40000 

Comment: Because the proposed rule would substantially burden many small businesses, the RFA 

requires the Agency to prepare an IFRA and consider alternatives to minimize the economic burden. 

Response: See response 40.4. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26696 

Comment Code: 40000 

Comment: The American Chemistry Council Biocide Panel (the Panel) also has had an independent 

economic impact analysis performed by NERA. This document is provided in the comments 

provided to the EPA by the Panel. Issues raised in the economic impact analysis are also discussed 

in these comments. 

Response: No response is needed. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26730 

Comment Code: 40000 

Comment: LANXESS has numerous other comments on specific provisions of the Proposal, 

which are provided in our Section-by-Section Analysis. An independent Economic Impact Analysis, 

prepared for the American Chemistry Council’s Biocide Panel in which LANXESS is a member 

company, is provided in the Panels comments. The economic impact analysis concludes that the 

actual cost of implementing the Proposal as a final regulation would be significantly greater than that 

estimated by EPA’s economic analysis. 

Response: See response 40.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27051 

Comment Code: 40000 

Comment: B. Antimicrobials Perform Essential Functions that Must Be Considered in this 

Proposal 
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Comments and Response References: 

Economic Analysis Section (40) Page 372 

LANXESS is concerned that the Proposal also does not include any consideration of the extensive 

benefits of antimicrobials and the risks that will result if new product development is halted[FN67: 

See FIFRA 3(h).] and existing products are withdrawn from the market because of the new data 

requirements. The absence of any benefit consideration is a shortcoming of not only the Proposal, 

but also the economic analysis that accompanies it. 

Microorganisms exist anywhere there is a food supply in the presence of moisture. Many are 

harmless, beneficial, or even essential. But others pose risks of disease and death to humans and 

animals, severe economic losses, increased resource needs, lost energy efficiency and numerous 

other forms of loss. Antimicrobials are essential to the control of pathogens in health care facilities, 

institutions, public spaces and homes and the prevention of the spread of infectious organisms. 

They are integral to the disinfection of public water supplies and are considered one of the greatest 

public health advances in human history. They are essential to the protection of animals from 

infectious diseases, such as foot and mouth disease and avian flu, which could cause devastating 

economic losses and, in the case of avian flu, have the potential to cause human illness. 

Antimicrobials were essential to the treatment of facilities contaminated with weaponized anthrax 

spores and are one of the first lines of defense to maintain biosecurity. Matrices that are water-based 

must be preserved in order to prevent deterioration caused by bacteria or fungi that otherwise would 

result in rapid decay. Without preservation, matrices could rapidly decay, contrary to the goal of 

resource conservation. Antimicrobials have made possible the conversion of many products from 

organic-based solvents to water-based systems, making VOC reductions possible. Many of the 

components of paints are excellent food sources for microbes, making water-based latex paints 

perfect environments for microbial growth. Untreated latex paints and other water-based products 

would deteriorate even before use and gases produced by the growing microbe populations can 

cause the explosive disruption of paint cans and other containers. Even the most common materials, 

e.g., paper and leather, are dependent on antimicrobials during production, in order to maintain 

quality and to extend their useful lifetimes. 

Similarly, all water-based industrial systems and water cooling systems must rely on antimicrobials to 

control the growth of microbes. Without them, fouling would occur that reduces energy efficiency, 

causes the pitting and destruction of equipment, spoilage or damage to production processes and 

materials, and other costly and damaging effects. Comfort cooling or air conditioning would not be 

possible without the use of antimicrobials to prevent fouling, equipment damage and excessive 

energy consumption. Similarly, antifoulants are essential to prevent the unrestrained growth of 

microorganisms on ship hulls and underwater structures. Fouled hulls slow ships and dramatically 

increase energy usage. Ballast water and fouled hulls also are responsible for the introduction of 

invasive harmful species to U.S. waters. Fouling of underwater structures, e.g., offshore drilling rigs, 

shorten the useful lifetime of the equipment. Antimicrobials are essential to food processing, 

handling, storage and service. Antimicrobial "sanitizing solutions"[FN68: The use of the term 

"sanitizing solution" is an artifact of FDA’s regulation of these products prior to enactment of 

FQPA in 1996 and ARTCA in 1997. As used by FDA, it referred to solutions that were applied to 

articles and surfaces and allowed to drip or air dry without any rinsing. This term is built into many 

state and local food codes. The term as used by FDA did not imply any specific performance level 

of antimicrobial activity. The use of the term has become somewhat confusing since EPA assumed 

authority to regulate this use, as EPA typically uses the term "sanitizer" as a level of antimicrobial 

activity. It is used here as it was used by FDA.] maintain cleanliness on food-contact surfaces and 
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Comments and Response References: 

Economic Analysis Section (40) Page 373 

equipment, and are essential to control transmission of food-borne illnesses. The need for microbial 

control has been recently demonstrated by the Salmonella contamination of peanut products that 

has resulted in literally thousands of food product recalls. 

Even the production of oil and gas rely on antimicrobials. Water injection is used for secondary and 

tertiary oil and gas production. The water must be treated to maintain well integrity and protection 

of equipment. Moreover, hydrogen sulfide gas is routinely generated in oil and gas wells. It is both 

highly explosive and lethal by inhalation. Antimicrobials are essential to prevent the growth of the 

microbes that generate this gas. 

Antimicrobials are necessary to maintain the integrity of water-based fluids used for metalworking. 

The "cutting oils" or metalworking fluids are essential to the production of metal items, including 

the largest equipment parts to the smallest metal fasteners. 

Likewise, antimicrobials are used to prevent the growth of mold and mildew stains on surfaces, 

which ultimately lead to damage and shortened useful lifetimes for many items. They also are used 

for the prevention of odors associated with microbial growth that enhance our comfort and quality 

of life. 

EPA must revise its Proposal on antimicrobial data requirements to recognize that uses of 

antimicrobials are profoundly different than the uses of conventional pesticides and provide unique 

benefits. These benefits should be considered in determining the degree and types of review, as 

mandated by section 3(h) of FIFRA. 

Response: See responses 1 and 40.2. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27121 

Comment Code: 40000 

Comment: IX. EPA’s Economic Analysis Underestimates the Cost of the Regulation and Its 

Impact on Registrants and Users 

EPA’s economic analysis significantly underestimates the costs associated with this 

regulation.[FN80: 44 U.S.C. [section]3501 et seq.] The Biocide Panel (LANXESS is a member 

company) has sponsored a more comprehensive economic analysis, prepared by NERA Economic 

Consulting. The NERA report is provided with the Biocide Panels comments. The NERA report 

differs from EPA’s analysis in several important ways. Going beyond EPA’s analysis, NERA 

estimates costs of applying the Proposal’s data requirements to Registration Review. NERA then 

calculates average costs/company that will be imposed through the new generic data requirements. 

Response: See responses 40.1 and 40.6 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
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Comments and Response References: 

Economic Analysis Section (40) Page 374 

Letter ID: 0064 

Comment ID: 27135 

Comment Code: 40000 

Comment: In sum, a more comprehensive economic analysis found that the costs of the Proposal 

are likely to be far greater than estimates in the EPA Economic Study. These realistic compliance 

costs need to be balanced against any perceived benefits from the regulation to determine whether 

the course proposed by EPA is appropriate. 

Response: See responses 40.1 and 40.2. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27216 

Comment Code: 40000 

Comment: A. Executive Order 12866 

To begin, the EPA has not accurately stated the potential costs and benefits, as required by 

Executive Order 12866.[FN88: Executive Order 12,866 [section]1(b)(6) (Oct. 4, 1993) ("Each 

agency shall assess both the costs and the benefits of the intended regulation and, recognizing that 

some costs and benefits are difficult to quantify, propose or adopt a regulation only upon a reasoned 

determination that the benefits of the intended regulation justify its costs.").] In its economic 

analysis, the EPA estimates the incremental costs at $3.2 million annually.[FN89: See EPA, 

Economic Analysis of the Proposed Change in Data Requirements for Antimicrobial Pesticides, at 

16.] 

Response: See response 40.6. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27219 

Comment Code: 40000 

Comment: B. The Regulatory Flexibility Act (as amended by the Small Business Regulatory 

Enforcement Fairness Act) 

Contrary to the Agency’s assertion in the Preamble,[FN93: See Proposed Rule, 73 Fed. Reg. 59,428.] 

the proposed rule would have a significant adverse economic impact on a substantial number of 

small entities. Thus, the proposed rule’s analysis is unreasonable in light of the Regulatory Flexibility 

Act (RFA), as amended by the Small Business Regulatory Enforcement Fairness Act 

(SBREFA).[FN94: See 5 U.S.C. [sections]601-612; Small Business Regulatory Enforcement Fairness 

Act, Pub. L. No. 104-121, tit. II, 110 Stat. 857, 864-68 (1996).] These Acts dictate that if an agency’s 

proposed rule would significantly burden small businesses, the agency must prepare an initial 

regulatory flexibility analysis (IRFA) describing the effect of the proposed rule on small businesses 
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and discussing alternatives that might minimize adverse economic consequences.[FN95: See id. 

[section]603.] 

The proposed rule must state whether it is "likely to have a significant economic impact on a 

substantial number of small entities."[FN96: Id. [section] 602(a)(1).] Under the RFA, "small entities" 

mean (1) a small business as defined by the Small Business Administration’s (SBA) regulations, 

which is based on either the maximum number of employees or on the sales for small businesses in 

each industry sector, as defined by a 6-digit NAICS code; (2) a small organization that is any not-forprofit enterprise that is independently owned and operated, and is not dominant in its field; and (3) a 

small governmental jurisdiction that is a government of a city, county, town, school district or 

special district with a population of less than 50,000.[FN97: Id. [section]601.] 

The EPA correctly states that the rulemaking does not impact small governmental jurisdictions and 

small organizations because these entities are rarely antimicrobial pesticide applicants or registrants; 

but the EPA incorrectly concludes that the rule will not have a significant adverse economic impact 

on a substantial number of small businesses. LANXESS has participated in an economic analysis 

done in conjunction with the American Chemical council’s Biocides Panel. As this economic analysis 

explains, the EPA’s conclusion is erroneously based on estimates that the incremental cost of the 

regulation would account for more than one percent of revenue for only 22 small firms, or only 4.4 

percent of the 500 small pesticide registrants. Under this calculation, only 25 small registrants would 

incur any additional costs under the proposed rule. 

Response: See responses 40.4 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27235 

Comment Code: 40000 

Comment: APPENDIX J 

March 2009 

Economic Analysis of Proposed U.S. EPA Biocide Data Requirements Prepared for The American 

Chemistry Council 

NERA Economic Consulting 

Project Team David Harrison, Jr., Ph.D., Project Director James Johndrow Mark LeBel David 

Nagler 

NERA Economic Consulting 200 Clarendon Street, 11th Floor Boston, Massachusetts 02116 Tel: 

+1 617 927 4500 Fax: +1 617 927 4501 www.nera.com 

Acknowledgements 
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This report was prepared by NERA Economic Consulting ("NERA") at the request of and with the 

sponsorship of the American Chemistry Council ("ACC"). NERA is an international firm of 

economists who provide economic analysis and advice to corporations, governments, law firms, 

regulatory agencies, trade associations, and international agencies. The global team of more than 600 

professionals operates in over 20 offices across North America, Europe, and Asia Pacific. Founded 

in 1961 as National Economic Research Associates, our more than 45 years of experience creating 

strategies, studies, reports, expert testimony, and policy recommendations reflects our specialization 

in industrial and financial economics. Because of our commitment to deliver unbiased findings, we 

are widely recognized for our independence. 

The NERA authors include Dr. David Harrison, who served as project director, James Johndrow, 

Mark LeBel and David Nagler. The authors are solely responsible for this report, including its 

conclusions and recommendations and any errors or omissions it may contain. 

About the Project Director . 

Dr. David Harrison is Senior Vice President and head of NERA’s global environment practice. Dr. 

Harrison has extensive experience over more than three decades evaluating the costs and benefits of 

environment, health and safety regulations. These studies have been performed for a large number 

of sectors, including chemicals, pesticides, cement, electricity, automobile, trucking, marine, 

chemical, iron and steel, petroleum, pulp and paper, small utility engines, small handheld equipment, 

construction equipment, and others. The results of these analyses have been presented to company 

officials, government agencies, and the media. 

Before joining NERA, Dr. Harrison was an Associate Professor at the John F. Kennedy School of 

Government at Harvard University, where he taught energy and environmental economics and 

policy, microeconomics, transportation, regional economic development, and other courses for 

more than a decade. He also served as a Senior Staff Economist on the U.S. government’s 

President’s Council of Economic Advisors, where he had responsibility for environment and energy 

policy issues. Dr. Harrison was a member of the Regulatory Council, a group with responsibility for 

developing procedures for regulatory analyses to be used by federal regulatory agencies, and the 

Regulatory Analysis Review Group. He is the author or co-author of two books on environmental 

policy and numerous articles on various topics in professional journals. 

Dr. Harrison received a Ph.D. in Economics from Harvard University, where he was a Graduate 

Prize Fellow. He holds a B.A. magna cum laude in Economics from Harvard College, where he was 

a member of Phi Beta Kappa, and a M.Sc. in Economics from the London School of Economics, 

where he was the Rees Jeffreys Scholar. 

 Contents 

List of Figures............................................................ vii 

List of Tables............................................................ viii 

Executive Summary.......................................................... E-1 
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A. Full Compliance Costs of Proposed Regulation ........................... E-1 

B. Other Impacts of Proposed Regulation.................................... E-2 

1. Impacts on Manufacturers................................................ E-2 

2. Impacts of the Possible Withdrawal of Antimicrobial Pesticides ......... E-3 

C. Implications for Regulatory Decisions .................................. E-3 

I. Introduction...............................................................1 

A. Background.................................................................1 

1. Proposed Regulation........................................................1 

2. EPA Economic Study.........................................................1 

3. Objectives of this Study...................................................2 

B. Organization of the Report.................................................3 

II. Direct Costs of Potential Antimicrobial Data Requirements ................4 

A. EPA Economic Studay........................................................4 

1. Overall Methodology........................................................4 

2. EPA Basic Cost Results.....................................................6 

3. EPA Options Analysis.......................................................7 

a. EPA Summary of the Costs of the Three Options..............................7 

b. EPA Summary of the Benefits of the Options.................................8 

4. EPA Discussion of Limitations in the Economic Analysis.....................9 

B. Additional Data to Update and Complete the Cost Analysis ..................9 

1.Unit Test Costs............................................................10 

2. Tests Likely Required for Registration Review.............................11 

a. Tests Relative to Various Baselines.......................................11 

b. High and Low Values.......................................................12 
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3. Summary of Updated and Expanded Data......................................12 

C. NERA Updated/Expanded Cost Estimates......................................12 

1. NERA Estimates of Costs for New Registrations and Major New 

Uses/Amendments................................................13 

2. NERA Estimates of Costs for Existing Registrants..........................13 

a. Compliance Costs for Existing Registrants.................................14 

b. Distribution of Costs for Existing Registrants............................14 

3. NERA Expanded/Complete Costs for Existing and New Biocides................15 

III. Additional Societal Impacts of Potential Antimicrobial Pesticide Data Requirements 

...................................17 

A. Impacts of Compliance Costs on Manufacturers..............................17 

1. EPA Economic Study Estimates of Manufacturer Impacts......................17 

a. EPA Estimate of Incremental Cost per Firm.................................17 

b. EPA’s Assessment of Small Business Impacts................................17 

c. Limitations of the EPA Estimates of Manufacturer Impacts .................18 

2.NERA Estimates of Manufacturer Impacts.....................................19 

B. Implications of Potential Antimicrobial Product Withdrawals due to Compliance 

Costs......................................................20 

1. Products and Services that Use Antimicrobial Pesticides...................20 

2. Conditions under Which Antimicrobial Pesticides Might be Withdrawn........21 

3. Experience Indicating Possibility of Antimicrobial Pesticide Withdrawal due to the Proposed 

Regulations.........................22 

a. 1988 Amendments to FIFRA..................................................22 

b. European Union Biocidal Products Directive................................23 

4. Societal Costs if Antimicrobial Pesticides are Withdrawal.................24 
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IV. Conclusions and Implications.............................................26 

A. Full Compliance Costs of Proposed Regulation..............................26 

B. Other Impacts of Proposed Regulation......................................26 

1. Impacts on Manufacturers..................................................26 

2. Impacts of the Possible Withdrawal of Antimicrobial Pesticides ...........27 

C. Implications forRegulatory Decisions......................................28 

ppendix A: Information on Unit Study Costs and Frequency of Data Required for Registration 

Review.....................................30 

A. Unit Test Costs...........................................................30 

B. Test/Study Frequencies....................................................30 

Appendix B: Illustration of Social Welfare Losses from Product Withdrawal under Alternative 

Cases...................................39 

A. Measuring Societal Benefits of Antimicrobial Pesticides ..................39 

B. Estimating Social Welfare Effects of Antimicrobial Pesticide Withdrawal...40 

1. Change in Cost, No Change in Quality......................................41 

2. Change in Quality, No Change in Cost......................................42 

3. Changes in Both Quality and Costs.........................................44 

 List of Figures 

Figure 1. Flowchart of the EPA Analysis...................................... 6 

Figure 2. Comparison of EPA and ACC Technical Consultant Unit Test Costs.... 11 

Figure 3. Distribution of Registration Review Costs, by Frequency of Existing Registrants 

......................... 15 

Figure B-1. Changes in Consumer Surplus and Producer Surplus for Final Good: Antimicrobial 

Substitutes More Expensive and Same Quality............. 41 

Figure B-2. Changes in Consumer Surplus for Final Good with Horizontal Supply Curve: 

Antimicrobial Substitutes More Expensive and Same Quality..... 42 
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Figure B-3. Changes in Consumer Surplus and Producer Surplus for Final Good: Antimicrobial 

Substitutes Lower Quality and Same Cost................. 43 

Figure B-4. Changes in Consumer Surplus for Final Good with Horizontal Supply Curve: 

Antimicrobial Substitutes Lower Quality and Same Cost................ 44 

Figure B-5. Changes in Consumer Surplus and Producer Surplus for Final Good: Antimicrobial 

Substitutes Lower Cost and Lower Quality................ 45 

Figure B-6. Changes in Consumer Surplus for Final Good with Constant arginal Cost: antimicrobial 

Substitutes Lower Cost and Lower Quality....... 46 

 

List of Tables 

Table 1. EPA Estimates of Total and Incremental Annual Costs for the Proposed Rule. 

...................................................... 7 

Table 2. Annual Costs for New Registrations................................. 13 

Table 3. Annual Costs for Existing Active Ingredients Related to Registration Review. 

............................................ 14 

Table 4. Total Compliance Costs for Registration Review and New Registrations or Major New 

Uses/Amendments.......................... 15 

Table 5. EPA Analysis of Impacts on Small Firms............................. 18 

Table 6. Estimates of Compliance Costs per Firm in Thousands................ 20 

Table 7. Status of Selected Biocide Products in the EU BPD.................. 24 

Table 8. Comparison of EPA Partial Cost Estimates and NERA/ACC Cost Estimates. 

................................................... 26 

Table 9. Comparison of Costs per Firm in Thousands.......................... 27 

Executive Summary 

The U.S. Environmental Protection Agency ("EPA") has proposed a regulation under the Federal 

Insecticide, Fungicide, and Rodenticide Act ("FIFRA") to impose additional data requirements on 

registration of antimicrobial pesticides, a class of substances that play essential roles in a wide range 

of health-related industrial, resource conservation, commercial, institutional and other activities. The 

new regulation would modify a variety of registration requirements, including requirements related 

to product and residue chemistry, toxicology, environmental fate, ecotoxicity, human exposure, and 

product performance. 
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The EPA has prepared an economic analysis (the "EPA Economic Study") of the proposed 

regulation. The EPA study has several important limitations. Although the proposed regulation 

would apply to both new registrations as well to antimicrobials during the Registration Review 

process, the EPA Economic Study provides compliance cost estimates that include costs only for 

new active ingredient applications and applications for new uses. Also, the EPA Economic Study 

considers only direct compliance costs, without evaluating other social costs of the regulations, 

including additional impacts on manufacturers and consumers. 

The principal objective of this study is to provide assessments of the full costs of the proposed 

regulation. Specifically, we first provide complete estimates of the direct compliance costs of the 

new regulation, including costs for both new and existing antimicrobial active ingredient 

registrations. Second, we evaluate other impacts of the proposed regulation on manufacturers and 

consumers, including revised estimates of the likely costs per manufacturer as well as assessments of 

the potential indirect effects of possible product withdrawal due to the data requirements. 

A. Full Compliance Costs of Proposed Regulation 

The full compliance costs of the proposed regulation are likely to be substantial, far greater than the 

partial estimates provided in the EPA Economic Study. Table E-1 summarizes the EPA estimates 

(based upon new ingredients and uses) and the complete estimates developed in this report (labeled 

"ACC" because they reflect updated or expanded information provided by technical consultants to 

the American Chemistry Council). In addition to including information on likely requirements for 

existing registrants, the ACC estimates reflect updated estimates of study costs developed by ACC 

technical consultants. (These values are the average of "low" and "high" estimates described in the 

main report.) 

[See table E-1. Comparison of EPA Partial Cost Estimates and NERA/ACC Cost Estimates, 

appendix J, PDF docket ID EPA-HQ-OPP-2008-0110-0088] 

Note: All costs in millions of dollars per year Source: EPA Economic Study and NERA calculations 

as explained in text. 

The updated/complete estimates are substantially greater than the partial cost estimates provided in 

the EPA Economic Study. The full total costs based upon ACC technical consultant information are 

about six times the EPA costs. The full costs incremental to the Baseline are about eleven times the 

EPA estimate, and the full costs incremental to Current Practice are about seven times the EPA 

estimate. 

B. Other Impacts of Proposed Regulation 

The regulation will have impacts beyond the overall compliance costs of undertaking the various 

studies. These impacts include effects on firm profitability and effects on the number of 

antimicrobial pesticides that will be available. Changes in the availability of antimicrobial pesticides 

could lead to various "unintended effects," including other producer and consumer welfare losses. 

1. Impacts on Manufacturers 
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The EPA Economic Study provides estimates of the average cost per manufacturer to meet the 

requirements and information on the likely impacts on small manufacturers, with impacts measured 

by annual compliance costs as a percentage of annual sales. Table E-2 summarizes the EPA 

estimates of per-manufacturer costs as well as estimates based upon the ACC technical consultant 

information. The ACC results also reflect the ACC consultant estimate of the number of firms likely 

to be affected that differs from the estimate in the EPA Economic Study. 

[See Table E-2. Comparison of Costs per Firm in Thousands, appendix J, PDF docket ID EPAHQ-OPP-2008-0110-0088] 

Source: EPA Economic Study and NERA calculations as explained in text. 

The updated and expanded compliance cost estimates lead to substantially greater potential cost per 

firm. Total costs per firm are nine times higher than the EPA estimate, costs incremental to the 

baseline are sixteen times higher and costs incremental to current practice are over ten times higher 

than the EPA estimate. 

The EPA Economic Study also discusses potential impacts on small manufacturers, presenting 

estimates that incremental costs relative to the baseline only exceed 3 percent of revenues for small 

manufacturers in a small number of cases (14 out a total of an estimated 500 small manufacturers 

who produce antimicrobial pesticides). We do not have the underlying data on small manufacturers 

that would allow us to re-evaluate these estimates. There are, however, reasons to expect that 

impacts on small manufacturers would be more substantial than the EPA Economic Study 

estimates. 

* Compliance costs would be greater based upon the updated unit study data developed by ACC 

technical consultants. 

* Costs related to existing registrations are not included in the EPA estimates and these added costs 

could increase compliance costs substantially for small manufacturers who are current registrants. 

* Costs would be a substantially greater fraction of a small manufacturer’s profit than of their sales, 

and the potential profit impact could be a better indicator of impacts than costs as a percentage of 

sales, particularly if small manufacturers have little ability to pass costs on to their customers. 

* No information is provided on the potential for high compliance costs to lead to product 

withdrawal, which would eliminate all of the profits that small manufacturers would obtain on the 

withdrawn antimicrobial pesticide. 

2. Impacts of the Possible Withdrawal of Antimicrobial Pesticides 

The proposed regulations could lead some manufacturers to withdraw antimicrobial pesticides rather 

than incur the testing costs (and other regulatory costs that might be involved). Withdrawal is most 

likely in the case of pesticides with relatively small production volumes, other large fixed costs, and 

demand and supply conditions that make it difficult to absorb the added costs. 
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Experience both in the U.S. and Europe suggests that testing and other registration requirements 

can affect the number of pesticide products available in a substantial way. The 1988 amendments to 

FIFRA-which increased testing costs and added various fees-appear to have resulted in substantial 

reductions in the number of active ingredients. By 1998, 62 percent of the products and 35 percent 

of active ingredients had been withdrawn from the market. In the case of the EU Biocidal Products 

Directive-which appears to have similar requirements to those in the proposed rule-only 38 percent 

of substances initially identified appear to be going forward to be evaluated. Although these two 

cases do not "prove" that regulations led to pesticide withdrawal-since there may have been other 

causes-this experience does suggest that there is a real possibility of substantial withdrawal due to 

registration requirements. 

If antimicrobial products were withdrawn from the market, the social costs would depend largely on 

the nature of the substitutes that would be available. The social costs could include greater costs or 

inferior quality for the goods and services that currently use antimicrobial pesticides, or some 

combination of these two effects. Although difficult to quantify, these effects should be taken into 

account in a full assessment of the likely costs of the proposed regulation and in considering ways in 

which the cost-effectiveness of the regulation could be improved. 

C. Implications for Regulatory Decisions The EPA Economic Study provides general assessments 

of the likely benefits of the proposed regulation, noting the possibility that data required under the 

new requirements would lead to increased understanding of the possibility of risks to human health 

and the environment. The EPA has not quantified these potential benefits and compared them in 

any quantitative way to the compliance costs, and, indeed, it would be difficult to do so. The 

benefits are difficult to quantify and, as discussed above, the costs could include other societal costs 

beyond the specific compliance costs. 

It is possible, however, to suggest how the EPA might use the updated and expanded information 

on compliance costs-as well as information on the potential for product withdrawals and 

substitutions-to search for situations in which the cost-effectiveness of the regulation could be 

improved. The EPA notes, for example, the possibility of flexibility on a case-by-case basis if 

screening data indicate a need for further data. This same screening approach could be used to 

eliminate requirements for some tests in situations where the existing tests suggest the additional 

information would be of little value relative to the further testing costs. 

The overall objectives are to ensure that society’s resource are focused on efforts to reduce risks to 

human health and the environment and to avoid adverse "unintended consequences" from data 

requirements for antimicrobial pesticides, including the possibility that unnecessarily costly 

requirements would lead to product substitutions that could increase risks to human health and the 

environment. 

I. Introduction 

Antimicrobial pesticides play an essential role in a wide range of health- related, industrial, resource 

conservation, commercial, institutional and other activities. For example, health-related applications 

of antimicrobial pesticides include disinfection, and sanitization in facilities including hospitals, 

clinics and dental offices, and meat and other food processors, as well as in drinking water 

treatment. Industrially, their applications include pulp and paper production, cooling tower and heat 
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exchange operation, paint, vinyl, plastic, and other material manufacturing, and fuel preservation. 

Antimicrobial pesticides facilitate industrial processes by preventing contamination and fouling 

caused by bacteria, fungi, and other microorganisms. These uses are essential to conserving energy 

resources and preventing capital equipment damage and replacement. 

A. Background 

The U.S. Environmental Protection Agency ("EPA") regulates antimicrobial pesticides under the 

authority granted it by the Federal Insecticide, Fungicide, and Rodenticide Act ("FIFRA"). As 

described in the Federal Register notice for the proposed rule (73 FR 59382), FIFRA requires that 

an applicant for a new registration or an existing registrant demonstrate to the EPA that, among 

other things, when used in accordance with commonly accepted practice, the pesticide product will 

not cause "unreasonable adverse effects" to humans or the environment. This safety determination 

requires the agency to weigh the risks of the use of the pesticide against any benefits. The EPA has 

promulgated data requirements for conventional pesticides and biopesticides that outline the types 

of data and related information needed to register these types of pesticides. 

1. Proposed Regulation 

The proposed regulation would impose additional data requirements on the registration process and 

heighten some existing requirements for antimicrobial pesticides. The new data requirements would 

apply to both new registrations as well as to antimicrobials during the Registration Review process. 

Potentially modified data requirements would include those related to product and residue 

chemistry, toxicology, environmental fate, ecotoxicity, human exposure, and product performance. 

EPA reviews the registration of all pesticide products on a 15-year cycle, pursuant to its Registration 

Review regulations, as mandated by FIFRA section 3(g). Thus, all antimicrobial active ingredients 

registered prior to the implementation of the proposed regulation will be required to meet the new 

standards during the registration review process. 

2. EPA Economic Study 

The EPA prepared an economic analysis of the proposed regulation ("Economic Analysis of the 

Proposed Change in Data Requirements for Antimicrobial Pesticides"), dated June 26, 2008 ("EPA 

Economic Study"). Although the regulations would apply to existing active ingredients and uses, the 

EPA Economic Study included only the additional costs for new active ingredient applications and 

applications for new uses. EPA used the cost information it developed to estimate the direct 

compliance costs of the proposed rule and two options, a low-cost option that would codify the 

EPA’s current practices and a high-cost option that would require the same tests for antimicrobial 

pesticides that are required for conventional pesticides. For each of these options, EPA reported the 

following information. 

* Incremental cost per regulatory action; * Industry-wide incremental cost; * Distribution of 

incremental cost per firm; and * Distribution of incremental cost per firm as a percentage of sales 

for small manufacturing entities. 
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EPA notes that it is likely that the higher registration costs from at least some of the options would 

result in fewer antimicrobial products being available, although it does not provide information on 

these potential effects or indicate the types of social costs that might be involved. 

Assessment of the full costs is important to a complete analysis of any proposed regulation. The full 

costs include the direct costs related to existing applications and uses as well as any other impacts 

that the regulations might have on manufacturers and customers. 

3. Objectives of this Study 

The principal objective of this economic study is to provide assessments of the full costs of the 

proposed regulation. The full costs include the direct costs, including the costs related to existing 

applications and uses as well as the costs for new applications and uses that EPA estimates. 

Moreover, the full costs include other impacts that the regulations might have on manufacturers and 

customers. Indeed, if the regulation were to result in discontinuation of some pesticides, the full 

costs would include the "unintended consequences" of the lack of availability of the pesticide and 

related products. 

 Our assessments of full costs thus include two major tasks: 

1. Assess the complete direct costs of the proposed regulation. We estimate the full testing (and 

related) costs of the proposed rule, including the costs for the existing registered antimicrobial active 

ingredients expected to undergo registration review in the first years of the program, as well as those 

for new active ingredients and new uses. 

2. Assess other potential impacts of the proposed regulation. We evaluate the other impacts of the 

proposed regulation, including potential impacts on manufacturers and customers. These impacts 

include qualitative considerations of the potential indirect effects of possible product withdrawal. 

The assessments provide a mix of quantitative and qualitative results. We develop quantitative 

estimates for direct costs building upon the structure and data developed by EPA supplemented by 

information from technical consultants to the American Chemistry Council ("ACC"). The analyses 

in the second task include some quantitative estimates of impacts on firms as well as other primarily 

qualitative assessments of potential impacts from product withdrawal due to increases in testing 

costs. 

 B. Organization of the Report 

The remainder of the report is organized as follows. 

Chapter 2 provides estimates of the direct costs of the proposed data requirements, including costs 

for both new and existing registrants. We consider the overall costs of the data requirements as well 

as the incremental costs relative to two alternative baselines. 

Chapter 3 discusses the additional impacts of the proposed data requirements, including impacts on 

manufacturers and customers and impacts of potential product withdrawals. 
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Chapter 4 provides conclusions regarding the costs of the regulation as well as the implications of 

these costs for an overall assessment of the desirability of the regulation and possible modifications 

to maximize its cost-effectiveness within the limits of the FIFRA statute. 

 II. Direct Costs of Potential Antimicrobial Data Requirements 

This chapter considers the direct costs of potential antimicrobial pesticide data requirements. We 

begin with a summary of the EPA Economic Study, which provides estimates of annual costs for 

new registrations. Building upon the EPA study-but using updated and expanded data on test costs 

and likely data requirements-we then develop alternative estimates of the full direct costs of the 

regulation, including updated costs for new registrations as well as estimates of the costs for existing 

registrations. Using this updated and expanded information, we then consider the incremental costs 

of the regulation relative to various baselines. 

A. EPA Economic Study 

EPA developed an economic analysis of the effects of the proposed data requirements. The 

economic analysis includes a calculation of costs of the proposed rule, as well as costs for two other 

scenarios-"baseline" and "current practice"-that are used to calculate the incremental effect of the 

proposed regulation. EPA also reports the costs of two alternatives to the proposed rule, a low-cost 

option and a high-cost option. 

1. Overall Methodology 

The basic costs for each scenario were developed in four steps, as depicted in Figure 1 

1. Unit test costs. EPA developed estimates of the cost per study for the various tests based upon 

information obtained from various laboratories. EPA developed a "high cost" and "low cost" 

protocol for each test/study and requested estimates for both. The test costs reported by EPA are 

the average of the estimates of the high and low cost protocols. 

2. Data requirements per registration action. EPA staff estimated the probability that each test/study 

would be required for a new registration in each of six possible use categories based upon the nature 

of the use and the level of exposure: (1) High Exposure Food; (2) High Exposure Indirect Food; (3) 

High Exposure Industrial and Other Uses; (4) High Exposure Wood Preservatives; (5) Low 

Exposure Antifoulants; and (6) Low Exposure Industrial Uses and Miscellaneous Low Exposure. 

The probabilities were estimated for three scenarios as follows: 

a. Current practices. EPA used a sample of registrations between 2000 and 2005 to estimate the 

frequency of testing requirements for new registrations and major new uses/amendments in the six 

use categories. This set of probabilities is referred to as "current practice." 

b. Baseline. The baseline is taken to be the same as the "current practice" probability if the 

test/study is included in CFR part 161 and zero otherwise. 

c. Proposed Rule. EPA staff estimated the probability that each test would be required under the 

proposed rule for new registrations and major new uses/amendments and, within those categories, 
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for high and low exposure uses. The changes include newly codified tests (i.e., tests not currently 

required even thought they may be required on a case-by-case basis), expansions in the uses that 

require specific tests, newly imposed testing requirements, and in the case of one test (chronic oral 

toxicity data for non-rodent) an elimination of a test that would thus lower costs. 

3. Incremental costs per registration action. Multiplying unit test/study costs by the probability that 

each test/study would be required in each of the three scenarios gives an estimate of costs per 

registration action. In particular, EPA calculated the incremental costs separately for new 

registrations and major new use amendments and, within each of these categories, for low exposure 

and high exposure uses. EPA considered incremental costs relative to either the "baseline" or 

"current practice" (that is, the difference between the costs for the "proposed rule" scenario and the 

costs for one of the other two scenarios) as the appropriate measure for the costs of the data 

requirements. 

4. Industry- wide impacts. EPA staff estimated the number of products that would be registered in a 

typical year separately for new registrations and major new uses/amendments and for high and low 

exposure uses. The estimated number of products in each category was multiplied by the average 

cost for each category and aggregated across categories to obtain total incremental costs per year. 

To characterize impacts on firms, EPA performed two additional steps in its analysis: 

5. Incremental costs per firm. EPA utilized data on the expected number of firms involved in new 

registrations/major new use amendments to calculate the annual incremental costs per firm. 

6. Annual costs relative to revenues. The Agency also used its profile of the industry and associated 

data on small firms to develop an estimate of the distribution of incremental costs per firm as a 

percentage of annual revenue. 

Figure 1 shows the flowchart of the EPA analysis. 

[See Figure 1. Flowchart of the EPA Analysis, Appendix J, PDF docket ID EPA-HQ- OPP-2008-

0110-0088] 

$61,000. (As discussed below, the EPA estimate of the number of firms affected appears to be 

overstated, causing the EPA estimate of per-firm costs to be understated.) 

[See Table 1, EPA Estimates of Total and Incremental Annual Costs for the Proposed Rule, 

Appendix J, PDF docket ID EPA-HQ- OPP-2008-0110-0088] 

Note: Dollar values are assumed to be in 2008 dollars. Source: EPA Economic Study Table 5-3. 

3. EPA Options Analysis The EPA Economic Study included assessments of the benefits and costs 

of the proposed regulation and two additional options. Thus, the three options EPA considered are 

the following. 

* Proposed rule; * Low-cost option, codification of current practices; and * High-cost option, 

conventional data requirement for antimicrobial pesticides. 
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The Agency provides brief summaries of the costs and benefits of these three options. 

a. EPA Summary of the Costs of the Three Options 

The following are the estimates of the incremental costs (i.e., costs beyond the current baseline) for 

the three options reported in the EPA Economic Study. 

* Proposed rule: $3.9 million per year. * Low-cost option: $0.6 million per year. * High-cost option: 

No specific estimate, although the range of average (not incremental) costs for conventional 

pesticide registrations was reported to be about $4.4 million to $12 per million, in contrast to the 

range under the proposed rule of $1 million to $4.5 million. 

b. EPA Summary of the Benefits of the Options 

EPA provides qualitative assessments of the likely benefits under the three options. The primary 

benefits expected by EPA can be summarized as follows: 

* Proposed rule. Data required under the proposed new requirements "are intended to lead to 

increased understanding of the potential for exposure as well as the chemical and toxicological 

properties of pesticides" and thus "enhance the EPA’s ability to make sound regulatory decisions." 

* Low-cost option. Although this option would have process advantages (e.g., making data 

requirements known in advance), it is not preferred "because this option does not impose the new 

data requirements and changes to existing data requirements that the Agency believes are necessary 

to understand and measure the potential risks to human health and the environment from exposure 

to antimicrobial pesticides." 

* High-cost option. Although this option "may reduce the adverse effects of pesticides even more 

than the proposed option," it is not preferred for several reasons: 

-"additional data required under this option are not likely to improve greatly the quality of the 

regulatory decision, because antimicrobial pesticides have different use patterns than conventional 

pesticides, which are used more extensively on crops than antimicrobial pesticides, and are more 

exposed to the environment"; - "if screening data indicate a need or further data to resolve issues 

raised by the screen, the Agency will require additional data on a case- by-case basis"; - "registrants 

would request waivers of many tests under this approach, resulting in inefficiency and uncertainty 

similar to that described under the case-by-case approach of the current practices"; and - "the higher 

registration cost would likely result in fewer antimicrobial products being available". 

Note that EPA’s discussion of the benefits of the various options suggests several additional costs 

that are not included in its compliance cost analysis. 

* Additional compliance costs (if screening indicated the need for additional tests); and * Costs 

related to fewer antimicrobial products being available. 
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We consider the potential effects of the second additional cost-the impacts of fewer antimicrobial 

products-in Chapter III of this report. 

4. EPA Discussion of Limitations in the Economic Analysis 

EPA identifies various uncertainties and limitations that potentially affect the results of their 

analysis. The following is a summary of the items EPA identifies. 

* Unit test costs. EPA notes several reasons that the test costs might be out- of-date or inaccurate 

(e.g., limited survey, surveys in some cases were several years ago). 

* Probability of a test being required. EPA developed its probabilities for the proposed rule based 

upon the scientific judgment of experienced EPA staff and made various assumptions regarding 

current practices (generally based upon 2000 to 2005 experience) and the baseline. 

* Number of future requested registration actions. Actual future new registrations may be different 

than the past six years, which was the basis for the EPA estimate. EPA notes that there was no 

apparent trend that could be used to forecast future requested registration action. As emphasized 

above, the EPA information relates to new registrations rather than existing registrations (an 

element not mentioned by EPA in this section but pointed out elsewhere in the EPA Economic 

Study). 

* Sales data. Sales data were based upon a sample of the firms with registrations and there was no 

way to determine the accuracy of the sample. 

* Structure activity relationship (SAR) assessments. The use of these assessments might lead to cost 

savings relative to the EPA estimates. 

* Use of surrogate data. The EPA is considering use of surrogate data, which could "greatly reduce 

the costs to applicants." 

* Cost incidence. This item relates to the incidence of costs among manufacturers (rather than 

between manufacturers and customers). EPA notes that sharing of the data costs among multiple 

registrants would lower the cost per firm (compared to EPA’s estimate) while accounting for cost 

averaging would tend to increase the cost per firm. 

As discussed below, we address some of these uncertainties and limitations in our empirical and 

qualitative assessments. In particular, our quantitative estimates use updated information on unit test 

costs as well as an expanded universe to develop updated and complete compliance cost 

information. 

B. Additional Data to Update and Complete the Cost Analysis 

Our calculation of direct costs follows the EPA methodology, with two main additions to the data: 

1. Modified/updated unit test costs, which were provided to us by ACC technical consultants; 
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2. Tests likely required for registration review. 

The following are brief descriptions of these two sets of data. 

1. Unit Test Costs 

Technical consultants to the ACC developed updated information on the costs of the various tests. 

These cost data are based on actual experience and quotes obtained from firms that offer the various 

services. The ACC technical consultants also developed estimates of the company overhead 

associated with managing these types of tests/studies, which should be included in the full resource 

cost for each of the studies. Appendix A provides these updated data. 

Figure 2 shows a plot comparing the EPA’s estimates with the ACC technical consultants’ cost 

estimates. The plot graphs cost estimates for identical tests/studies on the two axes. The diagonal 

line indicates that the costs are the same for EPA and ACC technical consultants. The markers show 

the actual test costs for EPA and the ACC technical consultants. Markers falling below the diagonal 

line indicate that EPA’s test cost is lower than that provided by the ACC technical consultants. 

Markers falling above the line indicate that EPA’s test cost is higher that provided by the ACC 

technical consultants. The graph is shown on a log scale to allow for visualization of the entire range 

of test costs (which can be as low as hundreds of dollars and as high as millions of dollars). 

These comparisons provide the basis for the following conclusions. 

* The EPA cost estimates are generally lower than the ACC technical consultant cost estimates. * 

There are, however, instances in which the ACC technical consultant cost estimate is less than the 

EPA estimate. * Some of the differences in costs are substantial (a feature obscured by the log scale). 

[See Figure 2. Comparison of EPA and ACC Technical Consultant Unit Test Costs., appendix J, 

EPA docket ID EPA-HQ-OPP-2008-0110-0088] 

We rely upon the ACC technical consultants’ updated estimates of unit costs. We do, however, 

provide results that show the implications of using the EPA unit cost data. 

2. Tests Likely Required for Registration Review 

ACC technical consultants also developed information on the likely data requirements for a sample 

of 29 active ingredients scheduled for registration review between 2008 and 2010. 

a. Tests Relative to Various Baselines 

This information is differentiated based on how long each of the tests has been "common practice" 

in registration review. The requirements were grouped into four categories: 

1. Common practice for more than seven years; 2. Common practice beginning 6-7 years ago; 3. 

Common practice in the past 2 years; and 4. Has not yet been commonly required and expected to 

be required under the proposed rule. 
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We have used this information to develop three sets of cost estimates related to the review of 

existing registrants, building upon the framework that EPA developed. 

1. Total direct compliance costs. This is the total cost of the data requirements. Alternatively, this 

can be seen as the costs incremental to a baseline where no data are required. 

2. Costs Incremental to "Current Practice." We develop a baseline that is the same as EPA’s "current 

practice" for new registrations and major new uses/amendments. For registration review, this 

baseline includes tests that are currently common practice. We then develop estimates of the costs 

of the proposed rule incremental to the costs of "Current Practice." 

3. Costs incremental to "Baseline." We develop a baseline that is the same as EPA’s "baseline" for 

new registrations and major new uses/amendments. For registration review, we include in the 

baseline test requirements that have been common practice for more than seven years. We then 

develop estimates of the costs of the proposed rule incremental to the costs in the "Baseline." 

b. High and Low Values 

ACC technical consultants indicated that, in some cases, data requirements are contingent on the 

outcome of preliminary tests. We have used this information to develop "low" and "high" estimates 

for each of the three cases for registration review. 

* The "low" estimate assumes that none of the contingent tests are required. * The "high" estimate 

assumes that all contingent tests are required. 

3. Summary of Updated and Expanded Data 

In summary, the ACC technical consultants have provided NERA with the following updated and 

expanded data. 

* Updated information on the unit costs of various tests. * Expanded information on the likelihood 

that various tests would be required for various antimicrobial pesticides undergoing regulatory 

review. * Updated and expanded information to develop estimates of the costs of the "Proposed 

Regulation," "Current Practice" and "Baseline" that allow us to develop more comprehensive 

estimates of the overall direct costs. 

C. NERA Updated/Expanded Cost Estimates 

We use the methodology described above to develop estimates of annual compliance costs for new 

ingredients and major new uses/amendments as well as for registration review. As noted above, we 

develop three sets of cost estimates, as well as "high" and "low" estimates for each of the three cases 

for registration review- related costs. 

1. NERA Estimates of Costs for New Registrations and Major New Uses/Amendments 

Table 2 summarizes our updated estimates of the annual costs of new registrations, along with 

estimates from the EPA Economic Study. We estimate the annual costs of the proposed rule for 
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new registrations to be $25.9 million, with incremental costs of $9.2 million per year relative to 

"Baseline" and $8.2 million per year relative to "Current Practice." 

 [See Table 2, Annual Costs for New Registrations, Appendix J, PDF docket ID EPA- HQ- OPP2008-0110-0088] 

Note: All costs in millions of dollars per year, assumed to be 2008 dollars. Source: EPA Economic 

Study, ACC technical consultant cost data, and NERA calculations as explained in text. 

Our compliance cost estimates are substantially larger than the EPA cost estimates. The total 

compliance costs for new registrants are higher by $11.0 million per year, and incremental annual 

costs relative to "Baseline" and "Current Practice" are higher by $5.3 and $5.0 million, respectively. 

These differences are due mainly to the greater average unit test cost estimates developed by the 

ACC technical consultants. 

2. NERA Estimates of Costs for Existing Registrants 

As noted, EPA has acknowledged that it does not include the costs for existing registrants in its 

Economic Analysis: 

EPA has not evaluated the potential burden of the proposed data requirements on registrants of 

existing chemicals in this proposal. However, EPA anticipates that there will be additional costs 

associated with the proposed studies under Registration Review. For each chemical, EPA will 

evaluate the specific need for additional data, including studies proposed today. Stakeholders and the 

public have opportunities for input, consultation and involvement concerning individual pesticide 

cases throughout the registration review process. Although EPA has identified the schedule for 

which chemicals will be reviewed over the next few years, the evaluation of data needs has not been 

done. Thus, the costs are unknown. (EPA Economic Study, p. 16). 

The lack of information related to registration review in the EPA Economic Study is a significant 

omission, since we understand that new registrations are relatively uncommon, whereas all 

antimicrobials currently registered are required to undergo the registration review process every 

fifteen years. Thus, not including costs related to registration review results in substantially 

understating the overall compliance costs. 

a. Compliance Costs for Existing Registrants 

Table 3 provides our estimates of the costs related to registration review, based upon the 

methodology outlined above. We also provide estimates developed using EPA’s unit test cost 

estimates. The total annual costs of data requirements are $56.9 million (low estimate) to $65.4 

million (high estimate). The ranges of annual costs incremental to Baseline and Current Practice are 

$31.7-$34.3 million and $13.4-$15.1 million, respectively. Estimated compliance costs are lower if 

EPA’s unit test costs are used in place of the unit cost data provided by the ACC technical 

consultants. 

[See Table 3. Annual Costs for Existing Active Ingredients Related to Registration Review, 

Appendix J, PDF docket ID EPA- HQ- OPP-2008-0110-0088] 
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Note: All costs in millions of dollars per year, assumed to be 2008 dollars. Source: EPA Economic 

Study, ACC technical consultant cost data, and NERA calculations as explained in text. 

b. Distribution of Costs for Existing Registrants 

The likely costs for existing registrants can be used to provide information on the range of possible 

costs for different active ingredients. Figure 3 shows the total costs for registration review for each 

of the sample of 29 active ingredients that were analyzed by the ACC technical consultants. The 

height of the bars is proportional to the number of active ingredients in each bin, while the bins on 

the horizontal axis indicate the range of costs for each bin. 

[See Figure 3. Distribution of Registration Review Costs, by Frequency of Existing Registrants, 

Appendix J, PDF docket ID EPA- HQ- OPP-2008-0110-0088] 

Note: Assumed to be 2008 dollars. Source: EPA Economic Study, ACC technical consultant data, 

and NERA calculations as explained in text. 

Costs vary widely for different existing registrants. Out of the total of 29 cases, nine are projected to 

incur costs of less than $2 million. In contrast, a total of five cases would incur costs greater than 

$10 million. This wide distribution of costs suggests that there is likely to be a wide diversity of 

potential manufacturer impacts. 

3. NERA Expanded/Complete Costs for Existing and New Biocides 

Table 4 summarizes the full compliance costs based upon the updated and expanded cost and 

frequency information provided by ACC technical consultants. The table includes the totals that 

would be obtained if the EPA unit cost estimates were used, to show the implications of different 

cost information. 

[See Table 4. Total Compliance Costs for Registration Review and New Registrations or Major New 

Uses/Amendments, Appendix J, PDF docket ID EPA- HQ- OPP-2008-0110-0088] 

Note: All costs in millions of dollars per year, assumed to be 2008 dollars. Source: Tables 2 and 3. 

Perhaps the most important conclusion is that all of these cost estimates are substantially greater 

than the values developed by EPA based upon only the costs for new registrations or major new 

uses/amendments. In contrast to EPA’s estimate that annual incremental compliance costs relative 

to the baseline would be $3.9 million, the costs in Table 4 range from $22.9 million to $43.5 million. 

Thus, compliance costs could be more than ten times the value calculated in the EPA Economic 

Study. 

The results also indicate that the use of the updated ACC technical consultant cost information leads 

to substantially greater compliance cost estimates. The compliance cost estimates are almost twice as 

large based on the increment relative to the baseline, with the multiple somewhat smaller for the 

total costs and somewhat greater for the incremental costs relative to current practice. 
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III. Additional Societal Impacts of Potential Antimicrobial Pesticide Data Requirements 

This section considers additional societal impacts of the potential antimicrobial pesticide data 

requirements. We begin with impacts on manufacturers due to the direct costs imposed by the data 

requirements, including a summary of the analyses in the EPA Economic Study. We then consider 

the additional potential effects of the possible withdrawal of ingredients and products due to the 

data requirements. 

A. Impacts of Compliance Costs on Manufacturers 

This section discusses possible impacts on manufacturers due to the new data requirements. We first 

discuss EPA’s treatment of these issues in the EPA Economic Study. We then provide our own 

analysis of these impacts based upon the updated and expanded information developed in the 

previous chapter. 

1. EPA Economic Study Estimates of Manufacturer Impacts 

The EPA Economic Study provides information on two types of manufacturer impacts: 

1. Incremental cost per firm; and 2. Small business impacts. 

a. EPA Estimate of Incremental Cost per Firm 

EPA used its estimates of the average annual compliance costs and information on the number of 

firms involved to develop an estimate of the average annual cost per firm. Based upon the estimate 

of $3.9 million per year in additional compliance costs and an estimate of 64 firms that would have 

experienced increased costs during the 2000-2005 period, EPA estimated that the annual cost per 

affected firm would be about $61,000. (As discussed below, information from ACC technical 

consultants indicate that EPA’s estimate of the number of firms affected is overstated, causing the 

per-firm cost estimate to be understated.) 

The total compliance costs also can be calculated based upon the EPA’s estimate of the total 

compliance cost of the proposed regulation (about $15.0 million). Using this value in conjunction 

with the EPA estimate of firms that would face increased costs (64) results in a cost per firm of 

about $234,000. 

b. EPA’s Assessment of Small Business Impacts 

EPA notes that the Small Business Regulatory Enforcement Fairness Act ("SBREFA") requires that 

special consideration be given to the effects of federal regulations on small business entities. EPA 

thus is required to make a determination as to whether its regulation will have a significant impact 

on a substantial number of small entities. 

EPA concludes that "the proposed rule will not have a significant impact on a substantial number of 

small antimicrobial pesticide registrants." This conclusion is based upon estimates that the 

incremental cost of the regulation would account for more than 1 percent of revenue for only 22 
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small firms, or only 4.4 percent of the 500 small pesticide registrants and, indeed, that only 25 small 

registrants would incur any additional costs under the proposed rule. 

The EPA information on compliance costs as a percentage of total company revenue is reported in 

table 7-1 of EPA’s Economic Study, which is reproduced below in Table 5. As noted, annual 

incremental costs greater than 3 percent of revenues are predicted for only 14 firms, although no 

information is provided as to how large the costs are relative to revenues for these 14 firms (only 

that they are greater than 3 percent of annual revenues). 

[See Table 5. EPA Analysis of Impacts on Small Firms., Appendix J, PDF docket ID EPA- HQOPP-2008-0110-0088] 

Source: EPA Economic Study, Table 7-1. 

The next sub-section discusses several limitations of the EPA estimates of manufacturer impacts. 

c. Limitations of the EPA Estimates of Manufacturer Impacts 

EPA’s assessments of the potential effects of the proposed regulations on manufacturers have 

several limitations as indications of the full extent of the likely impacts on manufacturers. 

* Per unit test costs appear to be understated (based upon comparisons with data provided by ACC 

technical consultants). 

* Costs for existing registrations are not developed and thus not included in compliance costs. 

* EPA appears to overstate the number of firms that would experience increased costs due to the 

regulation, thus understating the average cost per firm. 

* Information is not provided on some important potential impacts of the compliance costs, notably 

how they might affect manufacturer profits and the impact on manufacturers’ decisions to maintain 

product registration. 

* No information is provided on the potential for high compliance costs to lead to product 

withdrawal and what the implications of product withdrawal might be under different circumstances. 

2. NERA Estimates of Manufacturer Impacts In this section and the next we provide expanded 

information to address some of these limitations. In particular, 

* This section provides updated and expanded information on per-firm incremental compliance 

costs based on information provided by ACC technical consultants. 

* The following section provides qualitative assessments of the implications of product withdrawal, 

including impacts on manufacturers as well as the societal costs related to product withdrawal. 

As reported above, the EPA Economic Study estimates the average annual incremental cost per firm 

affected by the new data requirements to be about $61,000. This figure is based on EPA’s estimate 
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of annual incremental costs relative to the baseline (about $3.9 million per year). As noted, this 

estimate does not include the impacts of the new data requirements on registration review or the 

updated information on per- unit study costs. Including this additional information leads to 

substantially greater costs per firm. 

EPA’s per-firm cost figure is also based on the Agency’s estimate of the number of firms affected by 

the regulation. As discussed above, the Agency states that "64 firms would have experienced 

incremental costs" due to the proposed regulation, citing information from its Office of Pesticide 

Programs Information Network ("OPPIN") database. ACC technical consultants have reviewed this 

information and also developed information on the number of firms affected by costs related to 

registration of existing products. We understand that the estimate in the EPA Economic Study 

includes a variety of firms involved in the production of antimicrobial pesticide products, including 

pesticide manufacturers and formulators. Since the cost burden is likely to be borne in large part by 

the firms manufacturing the pesticide ingredients themselves, the ACC technical consultants have 

concluded that using this broad figure is inappropriate. The more appropriate number of firms that 

would bear these costs is ten, which is equal to the number of new active ingredient registrations for 

the years 2000-2005 (see Appendix A [FN#1:Appendix A contains eleven columns; we understand 

that two are duplicates, and that there are ten relevant unique registrations.] of the EPA Economic 

Analysis). ACC technical consultants estimated that 32 firms would be affected by the requirements 

for existing products in the relevant period. Thus, our estimates of the cost per firm are based upon 

a total of 42 firms incurring these additional costs. Note that this figure may overstate the number of 

relevant firms since some firms might register both new and existing products. 

Table 6 presents estimates of the incremental costs per firm for the scenarios analyzed in the 

previous chapter. These calculations include costs for both existing and new registrations; they also 

incorporate the revised estimate of the number of firms experiencing increased costs due to the 

regulation. 

[See Table 6. Estimates of Compliance Costs per Firm in Thousands., Appendix J, PDF docket ID 

EPA- HQ- OPP-2008-0110-0088] 

Note: Assumed to be 2008 dollars. Source: NERA calculations as explained in text. 

The updated average total cost per firm per year ranges from about $2.0 million to $2.2 million using 

the ACC technical consultant unit test cost estimates and from about $1.2 million to $1.4 million 

using the EPA unit cost estimates. The average cost per firm relative to the baseline would be 

around $1 million per firm using the ACC technical consultant unit cost estimates. The estimates of 

incremental costs per firm are thus about sixteen times higher than EPA’s estimate of $61,000. 

B. Implications of Potential Antimicrobial Product Withdrawals due to Compliance Costs 

Regulatory requirements can have "unintended consequences" that can be difficult to assess but 

nonetheless can affect the net societal benefits of the proposed regulation by increasing its costs or 

decreasing its environmental and public health benefits. In particular, as the EPA Economic Study 

acknowledged, higher registration costs can lead to fewer antimicrobial products being available. 

Withdrawal of antimicrobial products can lead to reductions in the various benefits these products 

provide, to increased costs for final products, or some combination. Indeed, a switch to other 
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products could result in increases in public health and environmental effects if the substitute leads to 

adverse effects. 

This section considers the products likely to be affected by potential withdrawal of antimicrobial 

pesticides, the conditions under which manufacturers would decide to withdraw antimicrobial 

pesticides, some evidence that such withdrawals could occur based upon prior experience, and a 

discussion of the potential societal impacts if antimicrobial pesticides were to be withdrawn. 

1. Products and Services that Use Antimicrobial Pesticides 

The EPA Economic Study indicates that antimicrobial pesticides are used in a wide range of uses. 

The EPA divides antimicrobial use patterns into the following twelve categories: 

* Agricultural premises and equipment; Food handling/storage establishments, premises and 

equipment; * Commercial, institutional, and industrial premises and equipment; * Residential and 

public access premises; * Medical premises and equipment; * Human drinking water systems; * 

Material preservatives; * Industrial processes and water systems; * Antifoulant paints and coatings; * 

Wood preservatives; * Swimming pools; and * Aquatic areas. 

We do not have information on the significance of antimicrobial pesticides to these various 

categories. But these categories do suggest the proposed regulation could affect products and 

services in a wide range of sectors. 

2. Conditions under Which Antimicrobial Pesticides Might be Withdrawn 

We do not have information that would allow us to estimate what specific antimicrobial products 

might be withdrawn from use. But it is possible to identify the factors that would influence a 

decision to withdraw a product from the market. 

The proposed regulation will lead to increases in the costs to register or re- register antimicrobial 

pesticides. Although regulatory benefit-cost analyses might focus on the incremental costs and the 

incremental benefits of the proposed regulation relative to the existing data requirements, a 

manufacturer deciding on whether to undertake production of a new product or to maintain 

production and sale of an existing pesticide product will consider the full costs of complying with 

the FIFRA testing requirements (as well as any other regulatory requirements). 

Thus, from the standpoint of determining whether manufacturers might withdraw certain 

antimicrobial pesticides as a result of this regulation, it would be appropriate to consider the full 

costs of testing requirements. These costs (and other costs related to bringing the product to 

market) would represent largely fixed costs (since they would not depend upon the level of 

production). The manufacturer would choose to initiate (or continue) production only if the 

expected profits from manufacturing and selling the pesticide were greater than these fixed costs. 

The general factors that would influence the likelihood of antimicrobial pesticide withdrawal are the 

following: 
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* Sales volumes. Larger sales will allow the manufacturer to spread the fixed costs of registration 

over more volumes. * Demand conditions. Antimicrobial pesticides facing relative inelastic (price 

insensitive) demand will have greater ability to pass costs on to consumers and thus will be less likely 

to discontinue production. The demand elasticity depends in large part on the availability, cost and 

quality of substitutes for antimicrobial pesticides, including the possibility of international 

competitors. * Supply/cost conditions. Antimicrobial pesticides with relatively elastic (constant) 

production costs are less likely to be able to absorb the additional testing costs. * Other fixed costs. 

The presence of other fixed costs (e.g., other regulatory costs) would tend to increase the likelihood 

that more expensive testing requirements will lead manufacturers to discontinue production (or not 

initiate production). 

These considerations suggest that small specialty pesticides with relatively small markets and many 

substitutes would be most vulnerable to increases in the testing costs due to the proposed 

regulation. 

3. Experience Indicating Possibility of Antimicrobial Pesticide Withdrawal due to the Proposed 

Regulations Regulations similar to the proposed regulations in this case have been proposed and 

their experience sheds light on the likelihood that some antimicrobial pesticides might be withdrawn 

in response to the proposed regulation. Two cases seem particularly relevant: (1) the 1988 

amendments to FIFRA; and (2) the Biocidal Products Directive ("BPD") promulgated by the 

European Union in 2000. In both of these cases, the implementation of the regulations has led to 

widespread product withdrawal. 

a. 1988 Amendments to FIFRA [FN#2:This section is based upon Fagerstone 1990 and Fagerstone 

1998.] 

The 1988 FIFRA amendments included several additional elements. First, they required new and 

more costly data requirements: 

* For indoor pesticides, non-food use pesticides, they required approximately 34 studies that cost 

approximately $53,000 in 1989 dollars. * For terrestrial pesticides and non-food use pesticides, they 

required approximately 57 studies that cost approximately $670,000 (1989 dollars). * For food use 

pesticides, they required studies that cost about $1 million (1989 dollars). 

In addition to these data requirements, the amendments required two separate types of fees: (1) a 

"re-registration" fee of between $75,000 and $150,000 (1989 dollars) per active ingredient, divided 

among registrants of a particular active ingredient on the basis of market share; and (2) a 

"maintenance" fee per "end- use registration". 

These requirements appear to have had an immediate impact on the number of registered products. 

At the beginning of 1989, there were over 44,000 federal registrations. By October of 1989, nearly 

19,300 registrations had been cancelled. Subsequently, an additional 8,000 registrations were 

cancelled. Of the 600 active ingredients contained in registered products, 124 were withdrawn from 

the market by 1990 and a total of 212 were withdrawn by 1998. Thus, 62 percent of products and 35 

percent of active ingredients were ultimately withdrawn from the market within 10 years of the 

promulgation of the new data requirements. Although these figures do not "prove" that these 

withdrawals were caused by the new requirements-since there may have been other factors at work- 
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the values certainly suggest that the additional data and other requirements led manufacturers to 

withdraw pesticides from the market. 

b. European Union Biocidal Products Directive [FN#3:This section relies upon the materials 

developed by the European Commission (Commission of the European Communities 2008) and the 

Biocidal Products Directive Web site.] 

The Biocidal Products Directive ("BPD") resulted from a desire of the European Union ("EU") to 

coordinate regulation of biocidal products across the Member States. The EU took responsibility for 

collectively approving active ingredients (or in this case "active substances"). Each Member State 

could approve end-use products that used EU-approved active ingredients. In the first phase, 

industry had to "identify" for the EU the active substances used in their products and then "notify" 

the EC that they wished to go ahead with an evaluation of the active substances in their products. 

The full list of data requirements in the EU is similar to the list of data requirements under FIFRA. 

It is therefore useful to consider the implications of the EU regulation on the number of ingredients 

and products. Of the approximately 960 active substances that were identified when the BPD was 

put in place, only 416 had notified the EU for evaluation as of late 2007. In addition, nearly 50 of 

those 416 products were withdrawn after the EU was notified. Thus only 38 percent of identified 

substances were going forward with evaluation at the time. 

The EU published a progress report on the Directive in October 2008. This report suggests that the 

reason for the withdrawal of a number of products was financial and not related to safety. 

"[F]or a number of substances, the criterion for not supporting their inclusion was evidently 

financial: the expected profits would never cover the cost of a dossier [compilation and filing of the 

data requirements]". 

Table 7 shows the number of active substances identified as candidates for the EU BPD and the 

number still in the process for three broad categories of biocides included in the EPA proposal. 

[See Table 7. Status of Selected Biocide Products in the EU BPD., Appendix J, PDF docket ID 

EPA- HQ- OPP-2008-0110-0088] 

Source: EU Progress Report 

Less than one half of the disinfectants and wood preservatives are still in the approval process and 

less than a quarter of the antifouling products are still in the process. 

Although the EU data requirements are similar to those (the full set) in EPA’s proposed rule, there 

are significant differences between the two sets of regulations. In the EU Directive, no active 

substance may be approved if another active substance of the same product type4 presents 

significantly less risk to health or the environment. In addition, several of the EU’s flexibility 

mechanisms apparently did not work or were applied unevenly by different Member States. These 

differences may mean that the direct cost of the data requirements was not the sole reason for the 

withdrawal of the various active substances. Nevertheless, the EU results certainly do support the 
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likelihood that the proposed regulations could lead to withdrawal of a substantial number of 

antimicrobial pesticides. 

4. Societal Costs if Antimicrobial Pesticides are Withdrawal 

Withdrawal of antimicrobial pesticides would lead to costs to society that are more difficult to assess 

than compliance costs (i.e., the costs of the studies and tests), but are equally important. Indeed, as 

noted, withdrawal of an antimicrobial pesticide could lead to adverse environmental and public 

health effects-due to effects of substitutes-that are greater than any risks avoided. Although these 

effects could be significant, we focus on the effects of pesticide withdrawal on the markets that use 

the pesticides. 

Antimicrobial pesticides are used as intermediate products-that is products used in the production of 

other goods and services such as food or drinking water-and thus the social costs of withdrawal 

depend upon the nature of the available substitutes. A given antimicrobial pesticide is used because 

it provides benefits to users relative to the substitutes when included in the final products. In other 

words, it allows for the production of goods and services with lower costs and/or higher quality 

(e.g., effectiveness in applications, safety)-or some combination of the two-than would be possible 

with substitutes. 

The social cost of withdrawing an antimicrobial product would be measured by the benefits to 

consumers and producers with the use of the antimicrobial pesticide, relative to the benefits if a 

substitute were used. (Appendix B provides a more formal explanation of the consumers and 

producers benefits.) One can identify two extreme cases-one in which "perfect" substitutes and one 

in which "no" substitutes exist-that serve to illustrate the nature of the social costs involved in 

pesticide withdrawal. 

In the extreme case where "perfect" substitutes are available, the social benefit of the antimicrobial 

pesticide would be zero. In this case, there would be no social cost if the pesticide were withdrawn. 

In the other extreme case, where no substitutes are available for a particular good or service, the 

final products would not be able to be produced and there would be a total loss of the societal 

benefits of the final product. Although both of these extreme cases are possible, realistic cases fall 

somewhere in between. 

It is useful to consider four cases related to substitutes that could be used to assess the likely societal 

costs of withdrawing a given antimicrobial pesticide. The cases relate to the effect on the product 

(e.g., food type) if a substitute were used. 

* Change in cost, no change in quality. In this case, antimicrobials make possible a less expensive 

good or service but the product quality is not affected. * Change in quality, no change in cost. In this 

case, antimicrobials provide a higher quality product, although the cost of the final good or service is 

not changed. * Changes in both quality and cost. This situation includes two basic cases: (a) 

antimicrobials provide higher quality for the final product, but the use of the antimicrobial pesticide 

leads to products or services that are more costly than with the lower-quality alternative; and (b) 

antimicrobial pesticides provide higher quality for the final good or service, at a lower cost than 

would be possible with a substitute. 
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Appendix B provides graphical illustrations of how the social costs of antimicrobial pesticide could 

be approximated in these various cases. There are some empirical studies that have developed 

estimates of the societal costs of pesticide withdrawal (e.g., Lichtenberg et al. 1998, Osteen and 

Kuchler 1987). Although these studies use the basic framework outlined above, they also take into 

account various additional complications. [FN#5:The complexities include taking into account the 

possibility that some manufacturers of the final products do not use the pesticide and the "general 

equilibrium" effects of changes in pesticide and product/service markets that could influence the net 

social costs.] 

The overarching conclusion from the conceptual background and the empirical studies is that the 

withdrawal of antimicrobial pesticides-due to data requirements such as those in the proposed 

regulations-could lead to societal costs that should be included in a full assessment of the likely costs 

of the proposed rulemaking. 

IV. Conclusions and Implications 

This chapter summarizes our conclusions regarding the likely direct costs and other potential 

impacts of the proposed regulation. We also discuss the implications of using this information to 

maximize the cost-effectiveness of data requirements, within the confines of FIFRA. 

A. Full Compliance Costs of Proposed Regulation 

The full compliance costs of the proposed regulation are likely to be substantial, far greater than the 

partial estimates provided in the EPA Economic Study. Table 8 summarizes the EPA estimates 

(based upon new ingredients and uses) and the estimates developed in this report. The ACC 

estimates reflect the updated estimates of study costs and the information on likely requirements for 

existing registrants developed by ACC technical consultants. (These values are the average of the 

low and high values in prior tables.) 

[See Table 8. Comparison of EPA Partial Cost Estimates and NERA/ACC Cost Estimates., 

Appendix J, PDF docket ID EPA- HQ- OPP-2008-0110-0088] 

Note: All costs in millions of dollars per year Source: EPA Economic Analysis and NERA 

calculations as explained in text. 

The updated/complete estimates are substantially greater than the partial cost estimates provided in 

the EPA Economic Study. The full total costs based upon ACC technical consultant information are 

about six times the EPA costs. The full costs incremental to Baseline are about eleven times the 

EPA estimate, and the full costs incremental to Current Practice are about seven times the EPA 

estimate. 

B. Other Impacts of Proposed Regulation 

The regulation will have impacts beyond the overall compliance costs of undertaking the various 

studies. These impacts include effects on firm profitability and effects on the number of 

antimicrobial pesticides that will be available. Changes in the availability of antimicrobial pesticides 

could lead to various "unintended effects," including other producer and consumer welfare losses. 
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1. Impacts on Manufacturers 

The EPA Economic Study produces an estimate of the average cost per manufacturer to meet the 

requirements and information on the likely impacts on small manufacturers, with impacts measured 

by annual compliance costs as a percentage of annual sales. Table 9 summarizes the EPA estimates 

of per manufacturer costs as well as estimates based upon the ACC technical consultant 

information. 

[See Table 9. Comparison of Costs per Firm in Thousands., Appendix J, PDF docket ID EPA- HQOPP-2008-0110-0088] 

Source: EPA Economic Study and NERA calculations as explained in text. 

The updated and expanded compliance cost estimates lead to substantially greater potential cost per 

firm. Total costs per firm are nine times higher than the EPA estimate, costs incremental to the 

baseline are sixteen times higher and costs incremental to current practice are over ten times higher 

than the EPA estimate. 

The EPA Economic Study also discusses potential impacts on small manufacturers, presenting 

estimates that incremental costs relative to the baseline only exceed 3 percent of revenues for small 

manufacturers in a small number of cases (14 out a total of an estimated 500 small manufacturers 

who produce antimicrobial pesticides). We do not have the underlying data on small manufacturers 

that would allow us to re-evaluate these estimates. There are, however, reasons to expect that 

impacts on small manufacturers would be more substantial than the EPA Economic Study 

estimates. 

* Compliance costs would be greater based upon the updated unit study data developed by ACC 

technical consultants. * Costs related to existing registrations are not included in the EPA estimates 

and these added costs could increase compliance costs substantially for small manufacturers who are 

current registrants. * Costs would be a substantially greater fraction of a small manufacturer’s profit 

than of their sales, and the potential profit impact could be a better indicator of impacts than costs 

as a percentage of sales, particularly if small manufacturers have little ability to pass costs on to their 

customers. * No information is provided on the potential for high compliance costs to lead to 

product withdrawal, which would eliminate all of the profits that small manufacturers would obtain 

on the withdrawn antimicrobial pesticide. 

2. Impacts of the Possible Withdrawal of Antimicrobial Pesticides 

The proposed regulations could lead some manufacturers to withdraw antimicrobial pesticides rather 

than incur the testing costs (and other regulatory costs that might be involved). Withdrawal is most 

likely in the case of pesticides with relatively small production volumes, other large fixed costs, and 

demand and supply conditions that make it difficult to absorb the added costs. 

Experience both in the U.S. and Europe suggests that testing and other registration requirements 

can affect the number of pesticide products in a substantial way. The 1988 amendments to FIFRAwhich increased testing costs and added various fees-appear to have resulted in substantial 
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reductions in the number of active ingredients. By 1998, 62 percent of the products and 35 percent 

of active ingredients had been withdrawn from the market. In the case of the EU Biocidal Products 

Directive-which appears to have similar requirements to those in the proposed rule-only 38 percent 

of substances initially identified appear to be going forward to be evaluated. Although these two 

cases do not "prove" that regulations led to pesticide withdrawal-since there may have been other 

causes-this experience does suggest that there is a real possibility of substantial withdrawal due to 

registration requirements. 

If antimicrobial products were withdrawn from the market, the social costs would depend largely on 

the nature of the substitutes that would be available. The social costs could include greater costs or 

inferior quality for the goods and services that currently use antimicrobial pesticides, or some 

combination of these two effects. Although difficult to quantify, these effects should be taken into 

account in a full assessment of the likely costs of the proposed regulation and in considering ways in 

which the cost-effectiveness of the regulation could be improved. 

C. Implications for Regulatory Decisions 

The EPA Economic Study provides general assessments of the likely benefits of the proposed 

regulation, noting the possibility that data required under the new requirements would lead to 

increased understanding of the possibility of risks to human health and the environment. The EPA 

has not quantified these potential benefits and compared them in any quantitative way to the 

compliance costs, and, indeed, it would be difficult to do so. The benefits are difficult to quantify 

and, as discussed above, the costs could include other societal costs beyond the specific compliance 

costs. 

It is possible, however, to suggest how the EPA might use the updated and expanded information 

on compliance costs-as well as information on the potential for product withdrawals and 

substitutions-to search for situations in which the cost-effectiveness of the regulation could be 

improved. The EPA notes, for example, the possibility of flexibility on a case-by-case basis if 

screening data indicate a need for further data. This same screening approach could be used to 

eliminate requirements for some tests in situations where the existing tests suggest the additional 

information would be of little value relative to the further testing costs. 

The overall objectives are to ensure that society’s resource are focused on efforts to reduce risks to 

human health and the environment and to avoid adverse "unintended consequences" from data 

requirements for antimicrobial pesticides, including the possibility that unnecessarily costly 

requirements would lead to product substitutions that could increase risks to human health and the 

environment. 

References 

Biocidal Products Directive, Directive 98/8/EC of the European Parliament and of the Council, 

February 16, 1998. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri= 

OJ:L:1998:123:0001:0063:EN:PDF. Accessed March 5, 2009. 

Commission of the European Communities. 2008. "Evaluation of the Implementation of Directive 

98/8/EC concerning the placing of Biocidal Products on the Market (Submitted in accordance with 
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Comments and Response References: 

Economic Analysis Section (40) Page 404 

Article 18(5) of the Directive) and Progress Report on the Work Programme Referred to in Article 

16(2) of the same Directive." Report from the Commission to the Council and European 

Parliament. October 8. http://ec.europa.eu/environment/biocides/pdf/progress_report.pdf. 

Accessed March 5, 2009. 

Fagerstone, Kathleen A., Roger W. Bullard, and Craig A. Ramey. 1990. "Politics and Economics of 

Maintaining Pesticide Registrations." Proceedings of the Fourteenth Vertebrate Pest Conference. 

http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1027&context=vpc14. Accessed March 

5, 2009. 

Fagerstone, Kathleen A., and Edward W. Schafer Jr. 1998. "Status of APHIS Vertebrate Pesticides 

and Drugs." Proceedings of the Eighteenth Vertebrate Pest Conference. 

http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1010&context=vpc18. Accessed March 

5, 2009. 

Hydrotox GmbH, Okopol GmbH and Risk & Policy Analysts Ltd. 2007. "Study on Impact of the 

Implementation of Directive 98/8/EC Concerning the Placing on the Market of Biocidal Products." 

Report for DG Environment, European Commission. October 10. 

http://circa.europa.eu/Public/irc/env/bio_reports/library?l= 

/study_implementation/report_101007pdf/_EN_1.0_&a=d. Accessed March 5, 2009. 

Lichtenberg, Erik, Douglas Parker, and David Zilberman. 1988. "Marginal Analysis of Welfare Costs 

of Environmental Policies: The Case of Pesticide Regulation." The American Journal of Agricultural 

Economics. November. 70(4): 867-74. 

National Research Council, Committee on Prototype Explicit Analyses for Pesticides. 1980. 

"Regulating Pesticides." National Academies Press, Washington D.C. 

http://www.nap.edu/openbook.php?isbn=0309029465, Accessed March 5, 2009. 

Osteen, Craig and Fred Kuchler. 1987. "Pesticide Regulatory Decisions: Production Efficiency, 

Equity, and Interdependence." Agribusiness. Fall. 3(3): 307-22. 

U.S. Environmental Protection Agency (EPA). 2008. "Data Requirements for Antimicrobial 

Pesticides; Proposed Rule." Federal Register 73, No. 196. October. 

U.S. Environmental Protection Agency (EPA). 2008a. "Economic Analysis of the Proposed Change 

in Data Requirements for Antimicrobial Pesticides." June 26. 

 Appendix A: Information on Unit Study Costs and Frequency of Data Required for Registration 

Review 

The tables in this appendix contain two sets of data: 

1. Unit study costs, including those developed by ACC technical consultants and those reported by 

EPA; and 
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2. Frequency of data requirements per registration review case, including information on the 

additional data requirements for the proposed rule relative to two baselines ("Baseline" and "Current 

Procedures"). 

The tests included in these tables are only those that were considered by the ACC technical 

consultants in projecting data requirements for registration review. EPA may have considered other 

tests/studies for new registrations and major new uses/amendments that are not included here 

because they were not deemed relevant to registration review, and thus we have no alternative cost 

information for them. Below we provide brief descriptions of how the information in this table was 

developed. 

A. Unit Test Costs 

The unit test costs in the column labeled "ACC (incl. Overhead)" were provided by the ACC 

technical consultants for use in this study. The costs are based on quotes from laboratories, actual 

experience, and professional judgment. The costs reported here have been multiplied by 1.3 to 

reflect ACC technical consultants’ assessment of the administrative costs a company would incur to 

oversee the studies. For comparison, we also provide EPA’s estimates of unit test costs for the tests 

in the table. 

B. Test/Study Frequencies 

The ACC technical consultants provided case-by-case projections of data requirements for 

registration review for 29 registration review cases scheduled between 2008 and 2010. Where 

available, these projections were based on registration review work plans. Where work plans were 

not available, the ACC technical consultants relied on expert judgment. The tables in this appendix 

provide the average number of tests per registration review case for each test/study considered by 

the ACC technical consultants. The tests per registration review case were calculated by counting the 

total number of times each test is required across the 29 active cases considered, and dividing this 

total by 29. Average costs per registration review case were calculated by multiplying the average 

tests/studies per case by the unit test/study costs. 

This appendix also provides estimates of average number of tests per registration review case 

incremental to the two baseline used in this study-"Baseline," and "Current Procedures." These 

estimates are based on information provided to us by the ACC technical consultants. This 

information included categorization of tests/studies by when each test/study became common 

practice for EPA in registration review cases. Tests that have been commonly required for more 

than seven years are part of "Baseline". Tests that have been common more recently are included in 

"Current Procedures", in addition to all of the tests in "Baseline." Thus, the tables also include an 

estimate of the average number of tests that would be required in the proposed rule above and 

beyond those required in each baseline. 

[See Table in Appendix A: Information on Unit Study Costs and Frequency of Data Required for 

Registration Review, Appendix J, PDF docket ID EPA- HQ- OPP-2008-0110-0088] 

Notes: (a) No guideline exists; assume this will be similar to a microcosm study and based cost on 

that assumption. (b) Estimate of full study cost based on identification and quantification of 
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degradates and metabolites. (c) Cost based on cost for all species required under guideline; EPA 

estimate appears to be for a single species. (d) Cost is based on guideline requirement to conduct 

field study at multiple locations pursuant to FIFRA GLP regulation. (e) There are numerous 

anticipated difficulties and complexities for many antimicrobial active ingredients, including 

reasonable assumption that radiolabeling will not be possible for most inorganic compounds. (f) 

Cost includes method development for all required residues of concern, GLP validation of methods, 

independent lab validation. Assumes method development and validation across all fractions and 

matrices, as required by guideline. (g) Biocides Panel estimate based on practical experience with 

conduct of GLP field study at multiple location; assumed five major crops; includes method 

validation and storage stability testing. (h) Assumes five major crops. (i) EPA estimate of $2,000 for 

acute inhalation testing appears to be in error. (j) Cost based on GLP field testing at multiple 

locations with required method validation and storage stability testing. 

Source: (aa) Biocides Panel cost estimates are based on input from multiple contract testing 

laboratories and the experience of Panel member companies in sponsoring the same or similar 

studies. The estimates include the costs incurred by registrants in conducting these studies, as well as 

other associated non- laboratory costs, e.g., quality assurance activities, technical consultants, and 

studies monitors with appropriate expertise. 

Appendix B: Illustration of Social Welfare Losses from Product Withdrawal under Alternative Cases 

This appendix provides conceptual information on the societal costs that could be incurred if testing 

costs under the proposed regulations lead antimicrobial pesticide manufacturers to forego 

development/production of a pesticide. After providing a conceptual overview, we develop 

conceptual overviews of the societal costs under different circumstances. The societal costs depend 

in large part on the nature of the substitutes that would be available if the antimicrobial pesticide 

were withdrawn. We consider four scenarios: (1) the substitute to the withdrawn pesticide is of 

greater cost but equal quality; (2) the substitute is of equal cost but inferior quality; and (3) the 

substitute is of higher cost and inferior quality; and (4) the substitute is of lower cost but inferior 

quality. 

A. Measuring Societal Benefits of Antimicrobial Pesticides 

Antimicrobial pesticides are used entirely as intermediate goods, that is, as products in the 

production of other goods and services used in agricultural, industrial, and consumer applications. 

This means that changes in the price or elimination of the use or sale of these products would have 

impacts both in their own markets and in those for these various "final" products or "downstream" 

markets. 

A given antimicrobial pesticide is used because it provides benefits to producers and consumers 

relative to substitutes when incorporated into final products. In other words, it allows for the 

production of products with lower costs or higher quality (e.g., effectiveness in applications, safety, 

benefits in environmental protection)-or some combination of the two-than would be possible with 

substitutes. 

The incremental societal costs if an antimicrobial pesticide were withdrawn would be equal to the 

decrease in consumer and producer surplus for the final good relative to the substitute. (Consumer 
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surplus refers to the value consumers place on the product relative to the price they pay; producer 

surplus refers to the revenue producers receive relative to the costs of production.) Therefore, an 

important factor that determines the magnitude of benefits from the microbial pesticide is the nature 

of the substitutes that would be used if one or more of these products were withdrawn from the 

market. The magnitude depends on both the availability of substitutes and also the degree of 

substitutability. One can identify two extreme cases-one in which "perfect" substitutes exist and the 

other in which "no" substitutes exist.[FN#6:A "perfect" substitute is one that is identical in 

performance and cost to the withdrawn antimicrobial pesticide.] 

In the extreme case where "perfect" substitutes are available, the societal cost of withdrawing the 

antimicrobial pesticide (relative to the perfect substitute) would be zero. Thus, there generally would 

be no loss of societal benefits if the antimicrobial pesticide were withdrawn from the market if a 

perfect substitute were available. In the other extreme case, where no substitutes are available, the 

final products would not be able to be produced and there would be a total loss of the societal 

benefits of the final product-the societal costs of withdrawal thus would be equal to the entire 

benefits of the downstream product. In theory, both of these extreme cases are possible. However, 

most realistic cases fall somewhere in between. In the following section, we discuss four possible 

characteristics of potential substitutes to antimicrobial pesticides. 

B. Estimating Social Welfare Effects of Antimicrobial Pesticide Withdrawal 

As noted, the consumer surplus and producer surplus loss from withdrawal of an antimicrobial 

pesticide would depend upon the nature of potential substitutes. The following are the major 

situations in which an intermediate product such as an antimicrobial active ingredient provides 

benefits relative to substitutes. 

1. Change in cost, no change in quality. Antimicrobials make possible a less expensive final product 

than would otherwise be possible, but the quality of the downstream product would not be affected. 

2. Change in quality, no change in cost. Antimicrobials provide higher quality for the final product 

than would otherwise be possible, but the cost of the final product would not be affected. 

3. Changes in both quality and cost. This situation involves two potential cases: (a) Antimicrobials 

provide higher quality for the final product than would otherwise be possible, but the antimicrobial 

active ingredients lead to products that are more costly than with the lower-quality alternatives; and 

(b) antimicrobial active ingredients provide higher quality for the final product than would otherwise 

be possible, at a lower cost than would otherwise be possible. 

The following sections describe these situations and provide graphical explanations of how changes 

in social welfare from market withdrawal of a given antimicrobial pesticide could be assessed. Note 

that for many industries, the marginal cost is likely to be constant (i.e., flat) over much of its range. 

For many manufactured goods, marginal cost, at least in the long run, exhibits neither economies 

nor diseconomies of scale, at least to any substantial degree.[FN#7:For many kinds of raw materials, 

a substantial increase in industry output would require the use of inputs (e.g., mineral ores, crude oil 

fields) that are more costly to process than those already in use, so supply curves (if they exist) for 

these industries would rise as outputs increase. For some products that are produced in small 

quantities, economies of scale in manufacturing can be realized (e.g., by switching to different 
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processing technologies, by eliminating minor bottlenecks in capacity).] A flat supply curve implies 

there is no long-run producer surplus over that range of sales. As discussed in the following 

examples, a flat supply curve also means that societal benefits from intermediate products such as 

antimicrobial pesticides represent consumer surplus rather than producer surplus. 

1. Change in Cost, No Change in Quality 

The first situation is one in which a given antimicrobial pesticide permits lower costs in 

manufacturing the downstream product or service, but with no change in the quality of the 

downstream product. In this case, a standard approach to calculating the change in consumer 

surplus and producer surplus in the downstream market can be used: 

* Estimate the increase in marginal cost as a result of the absence of a given antimicrobial pesticide; 

* Estimate the increase in price as a result of this increase in marginal cost; * Estimate the extent to 

which demand for the downstream product will fall as a result of the increase in price; and * 

Perform the standard calculations for changes in combined consumer surplus and producer surplus. 

Figure B-1 shows the basis for these calculations graphically. An increase in marginal costs will raise 

the supply curve in the downstream industry, depicted here as the shift from "Original Supply" to 

"New Supply." This upward shift in the supply curve will increase price, and the increase in price 

will reduce demand. The loss in consumer surplus plus producer surplus equals the shaded area 

below the demand curve and between the two supply curves. 

[See Figure B-1. Changes in Consumer Surplus and Producer Surplus for Final Good: Antimicrobial 

Substitutes More Expensive and Same Quality, Appendix B of Appendix J, PDF docket ID EPAHQ- OPP-2008-0110-0088] 

An important variation on this situation arises when the industry supply curve is horizontal: marginal 

costs are independent of output within the relevant output range. This situation is shown in Figure 

B-2. In this case, the supply curve is horizontal, so the switch from an antimicrobial product causes 

the price to shift upward by the full amount of the cost increase for the downstream product. Since 

the downstream cost increase is fully passed on to purchasers of the downstream product, there is 

no change in producer surplus for the downstream product, though consumer surplus is reduced. 

In this situation, the loss in consumer surplus from the unavailability of a product containing 

antimicrobials can be decomposed into two elements: a rectangle that equals the higher price to 

consumers for the downstream purchases they continue to make, and a triangle [FN#8:If the 

demand curve is not linear, this second element will be approximately a triangle.] that equals the 

foregone value of purchases that they no longer make because doing so is no longer cost- effective 

at the higher downstream price. 

[See Figure B-2. Changes in Consumer Surplus for Final Good with Horizontal Supply Curve: 

Antimicrobial Substitutes More Expensive and Same Quality, Appendix B of Appendix J, PDF 

docket ID EPA- HQ- OPP-2008-0110-0088] 

2. Change in Quality, No Change in Cost 
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One can use the same basic framework to consider the case in which the withdrawal of an 

antimicrobial pesticide would affect the quality of the product (e.g., safety, effectiveness) rather than 

the cost. In this case, the procedures for estimating the change in producer and consumer surplus 

would be somewhat different, as a shift in the demand curve, rather than the supply curve, will be 

observed. 

* The process of estimating this loss would involve the following steps: * Estimate the leftward (i.e., 

downward) shift in the demand curve as a result of the quality change, reflecting a reduced 

willingness to pay on the part of buyers of the downstream product; * Estimate the reduction in 

price as a result of this shift in demand; and * Perform the calculations for changes in combined 

consumer surplus and producer surplus. 

Figure B-3 depicts this scenario. The loss in consumer and producer surplus would equal the 

[See Figure B-3. Changes in Consumer Surplus and Producer Surplus for Final Good: Antimicrobial 

Substitutes Lower Quality and Same Cost, Appendix B of Appendix J, PDF docket ID EPA- HQOPP-2008-0110-0088] 

shaded area between the two demand curves and above the supply curve. 

Figure B-4, below, illustrates the special case of a horizontal supply curve in this situation. Producer 

surplus both before and after the switch away from a withdrawn antimicrobial pesticide is zero. The 

change in welfare is therefore only the loss in consumer surplus. The loss in consumer surplus has 

two components: a parallelogram (assuming a linear demand curve) that reflects consumers’ lower 

willingness to pay for the units they continue to purchase, and a triangle that equals the foregone 

value of purchases that are no longer cost- effective to make due to the reduction in product quality. 

[See Figure B-4. Changes in Consumer Surplus for Final Good with Horizontal Supply Curve: 

Antimicrobial Substitutes Lower Quality and Same Cost, Appendix B of Appendix J, PDF docket 

ID EPA- HQ- OPP-2008-0110-0088] 

3. Changes in Both Quality and Costs The situation when both quality and costs change is essentially 

a combination of the two previous situations. We first examine the situation in which an 

antimicrobial pesticide is replaced in a downstream product with an inferior but less expensive 

substitute. In this situation, the quality of the downstream product declines, but the price of the 

downstream product also falls. In this case, estimating the change in producer and consumer surplus 

involves looking at two counteracting effects: 

* Estimate the leftward (i.e., downward) shift in the demand curve as a result of the quality change; * 

Estimate the rightward (i.e., downward) shift in the supply curve as a result of the cost change; * 

Estimate the new equilibrium price as a result of these shifts; and * Perform the calculations for 

changes in combined consumer and producer surplus. 

Figure B-5 illustrates this scenario. The change in combined producer and consumer surplus in this 

case is equal to the difference between two areas: the area bounded by the two demand curves and 

the original supply curve (this is the welfare loss), and the area between the two supply curves and 

the new demand curve (this is the welfare gain). When the reduction in cost is exactly equal to the 
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decline in consumer willingness to pay for the product, the two areas are equal and there would be 

no net change in welfare.[FN#9:A situation in which the reduction in cost exceeds the decline in 

consumer willingness to pay is not meaningful. In such a situation, the substitute would not be used, 

since the benefits to consumers of the substitute would be outweighed by the added costs of using 

them.] 

[See Figure B-5. Changes in Consumer Surplus and Producer Surplus for Final Good: Antimicrobial 

Substitutes Lower Cost and Lower Quality, Appendix B of Appendix J, PDF docket ID EPA- HQOPP-2008-0110-0088] 

The welfare analysis is equivalent to the following: calculate the welfare loss due to the quality 

reduction that results from use of a substitute, but with no shift in the supply curve; and calculate 

the welfare gain from the shift in the supply curve from the use of the substitute but using the 

demand curve that reflects demand when that antimicrobial pesticide is not available. 

Figure B-6 illustrates the special case of a flat supply curve under this last scenario. The welfare 

change is once again just the change in consumer surplus, but this time the change in consumer 

surplus has two major components: a loss due to the reduced quality of the downstream product; 

and a partially offsetting gain from the lower price for the downstream product. Each of these two 

major components can be decomposed into two elements: a triangle for effects of foregone (or 

additional) consumption; and either a rectangle or a parallelogram for effects of quality (or price) on 

the number of units that would be purchased under the initial circumstances. 

[See Figure B-6. Changes in Consumer Surplus for Final Good with Constant Marginal Cost: 

antimicrobial Substitutes Lower Cost and Lower Quality, Appendix B of Appendix J, PDF docket 

ID EPA- HQ- OPP-2008-0110-0088] 

An important implication of Figure B-6 is that when the second-order welfare effects (i.e., the 

additional purchases gained or lost due to cost and quality changes) are ignored, the combined 

effects on consumer surplus of substituting inferior and less expensive products for some 

antimicrobials equals the number of downstream units purchased multiplied by the difference 

between the decrease in willingness to pay and the decrease in price. 

The same framework can be used to evaluate the situation in which antimicrobials are replaced in a 

downstream product with materials that are both inferior and more expensive. In this situation, the 

quality of the downstream product declines and the price of the downstream product increases. The 

derivation of the changes in consumer and producer surplus is essentially similar to the situation 

with a cost decline, except that it involves the sum of two areas (not the difference between them): 

the welfare loss from the reduced quality (using the original supply curve); and the welfare loss from 

the increased downstream production cost (using the new demand curve). 

NERA Economic Consulting 200 Clarendon Street, 11th Floor Boston, Massachusetts 02116 Tel: 

+1 617 927 4500 Fax: +1 617 927 4501 www.nera.com 

Response: see responses 40.1, 40.2, 40.4, 40.6, 40.8, and 40.12 

Commenter Name: Stanley Oslosky 
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Comments and Response References: 

Economic Analysis Section (40) Page 411 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27236 

Comment Code: 40000 

Comment: Because the proposed rule would substantially burden many small businesses, the RFA 

requires the Agency to prepare an IFRA and consider alternatives to minimize the economic burden. 

Response: See response 40.4. 

Comment Code: 41000 General comments 

Commenter Name: Abigail Trueblood 

Commenter Organization: Dow Chemical Company 

Letter ID: 0082 

Comment ID: 25477 

Comment Code: 41000 

Comment: Another area of concern is the ambiguity of the data requirements; the lack of guidance 

enabling registrants to identify the correct data requirements, resulting in "case by case" 

consultations with the Agency. While Dow commends the Agency for the willingness to be flexible 

in the matter of data requirements, the necessity of determining those requirements by consultation 

rather than by issuing clear guidance could result in some products having less than adequate data 

requirements, while others have burdensome requirements inappropriate to both substance and 

use(s). While there will always be occasion for registrant consultation with the Agency, this Proposal 

requires this for virtually all submissions. This will not only be an imposition on the regulated 

community in terms of time and cost, it will create an overwhelming drain of Agency resources. 

Response: See reponses 3 and 40.6 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25748 

Comment Code: 41000 

Comment: EPA's Economic Analysis - Cost of Registration and Impact to Registrants and Users 

On page 59428 of the Federal Register Notice, the Agency provided a total Antimicrobial Industry 

Cost Per Year. EPA based its cost estimate on antimicrobial pesticide registrations that occurred 

from 2000-2005. The ACC Biocides Panel sponsored a more comprehensive economic analysis 

which was prepared by NERA Economic Consulting. NERA is a global firm with 25 offices world 

wide of economic and financial experts. NERA's economists create strategies, studies, reports, 

expert testimony, and policy recommendations for government authorities and the world's leading 

law firms and corporations. 

NERA's economic analysis differs substantially from EPA's in several ways. 
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Comments and Response References: 

Economic Analysis Section (40) Page 412 

1. The costs based on registration submissions from 2000 - 2005, fails to consider the cost burden to 

registrants during periodic registration review of antimicrobial pesticides (mandatory 15 year cycle). 

2. The NERA costs are based on more detailed information such as specific data requirements set 

out by a particular Agency guideline (i.e. testing with a mandatory number of species, number of lots 

required for testing, GLP vs. Non- GLP study costs.) 

The NERA analysis demonstrates the cost to industry is far greater than the costs estimated by the 

Agency (by as much as 6 times). The NERA data also show that the updated average cost · per 

company per year ranges from about $2 million to $2.2 million. This is over thirty times the 

Agency's estimated annual costs per company of $61,000. These projected costs present a significant 

barrier to the development and registration of new and improved antimicrobials to combat the 

unending emergence of new and stronger pathogens. 

Response: See responses 40.1, 40.2, and 40.6. 

Commenter Name: William C. Balek 

Commenter Organization: ISSA 

Letter ID: 0074 

Comment ID: 25859 

Comment Code: 41000 

Comment: The proposed data requirements found in the proposed rule entitled "Data 

Requirements for Antimicrobial Pesticides; Proposed Rule" published on Wednesday, October 8, 

2008, are considerably more extensive and resource intensive than present data requirements. This 

new proposal significantly increases the costs to maintain current registrations as well as make the 

registration of new products exceedingly difficult. ISSA has significant concerns related to the 

impact this proposal will have on the many small to medium size companies that maintain 

antimicrobial registrations with EPA. 

ISSA is a non-profit trade association that represents the cleaning industry, Our membership 

consists of over 5,800 companies including manufacturers and distributors of cleaning products as 

well as providers of cleaning services. Included in our membership are over 300 companies engaged 

in the formulation of hard surface disinfectants and sanitizers that are registered with the EPA 

Office of Pesticide Programs, The majority of these formulators are small businesses. 

Response: See responses 40.2, 40.4, and 40.6. 

Commenter Name: William C. Balek 

Commenter Organization: ISSA 

Letter ID: 0074 

Comment ID: 25866 

Comment Code: 41000 
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Comments and Response References: 

Economic Analysis Section (40) Page 413 

Comment: [In particular, ISSA supports the following aspects of the ACC Biocides Panel 

Comments:] * EPA's economic analysis underestimates the cost of the proposal and its impact on 

registrants and the end user community; and 

Response: See response 40.1. 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25915 

Comment Code: 41000 

Comment: [In the Panel's comments, 12 major discussion points are presented as follows:] * EPA's 

economic analysis underestimates the cost of the regulation and its impact 

Response: See response 40.1. 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25952 

Comment Code: 41000 

Comment: B. Transparency: The current proposal is not transparent in any way. As a registrant 

preparing a regulatory budget and plan, it is difficult to virtually impossible to determine total testing 

costs and timing based on the draft proposal. In many cases test footnotes contain statements such 

as "as determined by the Agency" or "if residues are considered significant as determined by the 

Agency" which leaves the determination of a regulatory plan impossible. It also greatly increases the 

need for Agency resources, since registrants will constantly be forced to meet with Agency staff to 

determine test needs and conclusions drawn by the Agency based on prior submitted data. 

Response: See responses 3 and 40.8 

Comment Code: 42100 Cost of Regulation 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25802 

Comment Code: 42100 

Comment: POTWs Costs for Non-Compliance 

In addition to the adverse environmental impacts, non-compliance with Clean Water Act 

requirements can be extremely costly for POTWs. Costs are incurred for identifying the source of 

pollutants causing non-compliance, source control to reduce impacts of the pollutants, and 
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Comments and Response References: 

Economic Analysis Section (40) Page 414 

construction, operation, and maintenance costs to upgrade POTWs with advanced treatment to 

remove pollutants that cannot be adequately reduced with source control. Also, when surface water 

bodies become impaired by pesticides, POTWs discharging to the water bodies can be impacted 

through additional requirements established as part of Total Maximum Daily Loads (TMDLs) set for 

the water bodies by the California State Water Resources Control Board and the Regional Water 

Quality Control Boards (Regional Boards). The cost to POTWs to comply with TMDLs can be up 

to millions of dollars per water body per pollutant. 

POTWs in California are also subject to mandatory minimum penalties for NPDES permit 

exceedances. The California Clean Water Enforcement Act requires the Regional Boards to assess 

penalties for each NPDES permit exceedance, whether or not the POTW has the authority to 

prevent the violation. In addition, the Regional Boards are required to continue to assess penalties 

until the POTW is in compliance with its NPDES permit.[FN1: The Clean Water Enforcement Act 

states that mandatory minimum penalties shall not be assessed if the violations are caused by one or 

any combination of (1) an act of war, (2) an unanticipated, grave natural disaster or other natural 

phenomenon of an exceptional, inevitable, and irresistible character, the effects of which could not 

have been prevented or avoided by the exercise of due care or foresight, or (3) an intentional act of a 

third party, the effects of which could not have been prohibited or avoided by the exercise of due 

care or foresight, see California Water Code, Section 13385(j) for further details.] Since POTWs do 

not have the authority to regulate pesticides, if a pesticide causes an NPDES exceedance, the POTW 

would be fined until U.S. EPA, U.S. Food and Drug Administration, and/or the California 

Department of Pesticide Regulation regulates the pesticide. POTWs can also be subject to legal 

action for NPDES violations, thereby causing the POTW to pay legal fees, settlements, and/or 

judgments. During the period of accelerated testing and TIE testing detailed above, the POTW may 

be assessed permit mandated financial penalties and subject to secondary lawsuits for not meeting 

the Clean Water Act provisions of discharging "toxics in toxic amounts." 

Response: See response 40.12. 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25898 

Comment Code: 42100 

Comment: POTWs Costs for Non-Compliance 

In addition to the adverse environmental impacts, non-compliance with Clean Water Act 

requirements can be extremely costly for POTWs. Costs are incurred for identifying the source of 

pollutants causing non-compliance, source control to reduce impacts of the pollutants, and 

construction, operation, and maintenance costs to upgrade POTWs with advanced treatment to 

remove pollutants that cannot be adequately reduced with source control. Also, when surface water 

bodies become impaired by pesticides, POTWs discharging to the water bodies can be impacted 

through additional requirements established as part of Total Maximum Daily Loads (TMDLs) set for 

the water bodies by the California State Water Resources Control Board and the Regional Water 

Quality Control Boards (Regional Boards). The cost to POTWs to comply with TMDLs can be up 

to millions of dollars per water body per pollutant. 
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Comments and Response References: 

Economic Analysis Section (40) Page 415 

POTWs in California are also subject to mandatory minimum penalties for NPDES permit 

exceedances. The California Clean Water Enforcement Act requires the Regional Boards to assess 

penalties for each NPDES permit exceedance, whether or not the POTW has the authority to 

prevent the violation. In addition, the Regional Boards are required to continue to assess penalties 

until the POTW is in compliance with its NPDES permit.[FN1: The Clean Water Enforcement Act 

states that mandatory minimum penalties shall not be assessed if the violations are caused by one or 

any combination of (1) an act of war, (2) an unanticipated, grave natural disaster or other natural 

phenomenon of an exceptional, inevitable, and irresistible character, the effects of which could not 

have been prevented or avoided by the exercise of due care or foresight, or (3) an intentional act of a 

third party, the effects of which could not have been prohibited or avoided by the exercise of due 

care or foresight, see California Water Code, Section 13385(j) for further details.] Since POTWs do 

not have the authority to regulate pesticides, if a pesticide causes an NPDES exceedance, the POTW 

would be fined until U.S. EPA, U.S. Food and Drug Administration, and/or the California 

Department of Pesticide Regulation regulates the pesticide. POTWs can also be subject to legal 

action for NPDES violations, thereby causing the POTW to pay legal fees, settlements, and/or 

judgments. During the period of accelerated testing and TIE testing detailed above, the POTW may 

be assessed permit mandated financial penalties and subject to secondary lawsuits for not meeting 

the Clean Water Act provisions of discharging "toxics in toxic amounts." 

Response: See response 40.12. 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26123 

Comment Code: 42100 

Comment: POTWs Costs for Non-Compliance 

In addition to the adverse environmental impacts, non-compliance with Clean Water Act 

requirements can be extremely costly for POTWs. Costs are incurred for identifying the source of 

the pollutants causing noncompliance, source control to reduce impacts of the pollutants, and 

construction, operation, and maintenance costs to upgrade POTWs with advanced treatment to 

remove pollutants that cannot be adequately reduced with source control. Also, when surface water 

bodies become impaired by pesticides, POTWs discharging to the water bodies can be impacted 

through additional requirements established as part of Total Maximum Daily Loads (TMDLs) set for 

the water bodies by the California State Water Resources Control Board and the Regional Water 

Quality Control Boards (Regional Boards). The cost to POTWs to comply with TMDLs can be up 

to millions of dollars per water body per pollutant. 

POTWs in California are also subject to mandatory minimum penalties for NPDES permit 

exceedances. The California Clean Water Enforcement Act requires the Regional Boards to assess 

penalties for each NPDES permit exceedance, whether or not the POTW has the authority to 

prevent the violation. In addition, the Regional Boards are required to continue to assess penalties 

until the POTW is in compliance with its NPDES permit. [FN#1: The Clean Water Enforcement 

Act states that mandatory minimum penalties shall not be assessed if the violations are caused by 
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Comments and Response References: 

Economic Analysis Section (40) Page 416 

one or any combination of (I) an act of war, (2) an unanticipated, grave natural disaster or other 

natural phenomenon of an exceptional, inevitable, and irresistible character, the effects of which 

could not have been prevented or avoided by the exercise of due care or foresight, or (3) an 

intentional act of a third party, the effects of which could not have been prohibited or avoided by 

the exercise of due care or foresight, see California Water Code, Section 13385U) for further details.] 

Since POTWs do not have the authority to regulate the use of pesticides, if a pesticide causes an 

NPDES permit exceedance, the POTW would be fined until U.S. EPA, U.S. Food and Drug 

Administration, and/or the California Department of Pesticide Regulation regulates the pesticide. 

POTWs can also be subject to legal action for NPDES violations, thereby causing the POTW to pay 

legal fees, settlements, and/or judgments. During the period of accelerated testing and TIE testing 

detailed above, the POTW may be assessed permit mandated financial penalties and subject to 

secondary lawsuits for not meeting the Clean Water Act provision of discharging "toxics in toxic 

amounts." 

Response: See response 40.12 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26440 

Comment Code: 42100 

Comment: In addition, NERA considers the societal impact of the Proposal on registrants due to 

(1) the direct costs imposed by the data requirements, and (2) the potential effects of the possible 

withdrawal of ingredients and products due to the data requirements. The effects of withdrawn 

antimicrobial products, while difficult to quantify, are substantial, oftentimes resulting in the deletion 

of end uses. As NERA notes, additional data requirements in the past have lead to substantial 

reductions in the numbers of products available. This can become a serious issue where a withdrawal 

leaves users with fewer and perhaps inadequate products remaining. EPA’s analysis should estimate 

the number of products likely to be withdrawn, the availability of efficient and cost effective 

substitutes, and consequences in the likely event that substitutes are not as effective as the products 

they replace. 

Response: See response 40.2. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26775 

Comment Code: 42100 

Comment: There will be an increased disparity between registrants, and a more uneven playing 

field. This will create an even greater burden on resources within the Agency and the regulated 

community than the current system. Such a burden has not been considered in the economic impact 

analysis EPA provided with the Proposal. In addition, with so many individual negotiations taking 

place, the process will not be transparent, as the current EPA administration has articulated. 
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Comments and Response References: 

Economic Analysis Section (40) Page 417 

Response: See responses 3 and 40.4 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27123 

Comment Code: 42100 

Comment: In addition, NERA considers the societal impact of the Proposal on registrants due to 

(1) the direct costs imposed by the data requirements, and (2) the potential effects of the possible 

withdrawal of ingredients and products due to the data requirements. The effects of withdrawn 

antimicrobial products, while difficult to quantify, are substantial, oftentimes resulting in the deletion 

of end uses. As NERA notes, additional data requirements in the past have lead to substantial 

reductions in the numbers of products available. This can become a serious issue where a withdrawal 

leaves users with fewer and perhaps inadequate products remaining. EPA’s analysis should estimate 

the number of products likely to be withdrawn, the availability of efficient and cost effective 

substitutes, and consequences in the likely event that substitutes are not as effective as the products 

they replace. 

Response: See response 40.2 

Comment Code: 42200 Cost of Registration/Re-registration 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26438 

Comment Code: 42200 

Comment: A. EPA’s Economic Analysis Is Flawed because It Does Not Include Costs Incurred in 

Registration Review 

EPA based its cost estimate only on new registration actions from 2000 through 2006. This 

limitation is inappropriate, as the burden will fall on all registered products through the Registration 

Review process. EPA explicitly chose not to consider the Registration Review process and its 

"potential burden" on registrants of existing chemicals in its burden estimate, stating that registrants 

and the public will have opportunities for "input, consultation and involvement concerning 

individual pesticide cases throughout the registration review process."[FN#79:EPA, Economic 

Analysis of the Proposed Change in Data Requirements for Antimicrobial Pesticides, June 26, 2008, 

at section 2.5.] While it is true that registrants and the public will have opportunities for input during 

Registration Review, the Agency acknowledges that the new data requirements will be applied, and 

therefore it must include the associated costs in the economic analysis for this Proposal.[FN#80:In 

the Preamble, EPA states that it "anticipates there will be additional costs associated with the 

proposed studies under Registration Review." The Agency goes on to say that the burdens 

associated with individual active ingredients will be provided as part of the Information Collection 

Request (ICR) approvals submitted to OMB under the Paperwork Reduction Act. 73 Fed. Reg. at 
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Comments and Response References: 

Economic Analysis Section (40) Page 418 

59428. The Panel believes that this approach has resulted in a serious underestimate of the costs of 

the Proposal to both the industry and the Agency, and has deprived OMB of the opportunity to 

assess fully the burden of the Proposal.] 

Registration Review is a statutorily required process under which all registrations are reviewed by 

EPA on a mandatory 15 year cycle. The process is now underway. The Panel asked its consultant, 

NERA, to include the Registration Review in its analysis. NERA reviewed 28 of the first 

antimicrobial cases undergoing Registration Review, based on Panel’s best estimates of the 

incremental data that would be required if this regulation is promulgated as proposed. Clearly, EPA 

could have adopted this or a similar approach to make a good faith estimate of the annual costs of 

the Proposal, as required by the PRA. 

The Panel provided its best estimates of individual study costs to NERA for use in its analysis. The 

Panel based its estimates on all the specific requirements set out in a particular guideline, including 

testing with the mandatory number of species, where applicable, and on its members experience in 

sponsoring these tests over time. In those instances where there are no guidelines or existing 

guidelines are inapplicable to antimicrobials, best professional judgment was used. 

The full compliance costs of the Proposal are far greater than the costs estimated by EPA based 

only on new active ingredients and uses. When the compliance costs are calculated, including the 

costs that will be incurred by registrants of existing active ingredients in registration review, the full 

cost is about six times the EPA estimate. As discussed more fully in the NERA Report, the costs 

incremental to EPA’s baseline are about eleven times the EPA estimate, and the full costs 

incremental to current practice are about seven times the EPA estimate, which the Agency claims is 

based on current Agency practices. Moreover, NERA found that the updated average total cost per 

firm per year is about $2.0 million, over thirty times the EPA’s estimated average annual costs per 

firm of $61,000. 

Response: See responses 40.1 and 40.6. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26466 

Comment Code: 42200 

Comment: Yet the EPA has not taken into account incremental costs or the impact of the new data 

requirements on registration review, which greatly increase the costs per firm. Even using EPA’s 

estimate that only 64 firms would be affected, the average cost per firm relative to the baseline--if 

one includes incremental costs--is approximately $750,000, nearly twelve times higher than the 

EPA’s estimate of $61,000.[FN#88:See Appendix J, NERA Economic Consulting, Economic 

Analysis of Proposed U.S. EPA Biocide Data Requirements: Prepared for the American Chemistry 

Council, at 18 (Mar. 2009).] After considering that registration review would bring in a larger 

number of firms, the incremental cost is $450,000, still more than seven times EPA’s 

estimate.[FN#89:Id. at 19.] Altogether, the incremental costs to current practice are not $3.2 million, 

as the EPA has found, but rather approach $22.5 million.[FN#90:Id. at 25.] 
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Comments and Response References: 

Economic Analysis Section (40) Page 419 

Response: See response 40.6. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26479 

Comment Code: 42200 

Comment: Yet, as explained above, the EPA has not taken into account incremental costs or the 

impact of the new data requirements on registration review, which greatly increase the costs per 

firm. The incremental cost is $750,000 for EPA’s estimate of 64 firms, and $450,000 after taking 

into account the additional firms that would undergo registration review.[FN#98:Id. at 19.] These 

revised numbers indicate that the proposed rule would have a significant adverse economic impact 

on a substantial number of small entities. Indeed, the additional costs are a substantial share of gross 

revenues, meaning the rule has a significant economic impact.[FN#99:See Harlan Land Co. v. U.S. 

Dep’t of Agric., 186 F.Supp.2d 1076 (E.D. Cal. 2001) (holding that the agency’s economic analysis 

was flawed because the analysis focused on the impact of Argentine imports on the supply and 

prices of citrus fruit in the United States, and resulting costs and benefits to domestic growers, 

brokers, importer and consumers; but not the costs if Argentine plant pests were introduced into 

U.S. citrus orchards).] Also, approximately ten percent of small pesticide registrants are likely to 

experience some impact. Ten percent of small pesticide registrants, as opposed to the 4.4% 

estimated by EPA, would constitute a substantial number of small entities. 

Response: See responses 40.6 and 40.4. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26481 

Comment Code: 42200 

Comment: C. Paperwork Reduction Act 

The Agency similarly has used inaccurate information to calculate the provided burden estimates 

under the Paperwork Reduction Act (PRA).[FN#100:44 U.S.C. [Section] 3501 et seq.] EPA should 

include the paperwork burden costs for existing registrants, who are required to undergo the 

registration review process every fifteen years.[FN#101:See EPA, Economic Analysis of the 

Proposed Change in Data Requirements for Antimicrobial Pesticides, at 16 (acknowledging that the 

study does not include costs for existing registrants in its economic analysis).] The additional data 

and testing requirements in the proposed rule would increase the paperwork costs for each registrant 

undergoing a registration review. As such, the total registrant paperwork burden and costs for 

antimicrobial pesticide registrations would be much more than the stated 3,929 hours and 

$255,773.25.[FN#102:Proposed Rule, 73 Fed. Reg. 59429.] 

Response: See response 40.6. 

Commenter Name: Stanley Oslosky 
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Comments and Response References: 

Economic Analysis Section (40) Page 420 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26732 

Comment Code: 42200 

Comment: I. EPA’s Proposed Subpart 158W does Not Provide Adequate Guidance to the 

Regulated Community 

A. The Proposal Calls for Individual Consultation Rather than Establishing Applicable Regulatory 

Requirements 

One of the most serious concerns with the Proposal is that it leaves many decisions to a case-bycase determination by EPA, which will impose a burden on both the regulated community and the 

Agency. Thirty-seven specific examples of this are listed in Appendix J to these Comments. For 

example, to obtain a registration for a new product or a new use, the Proposal seems to require a 

registrant to consult with the Agency a number of times in the early stages of the application process 

to determine whether data are required. Depending on the new product or use, these necessary 

consultations may include the following, among others: 

Response: See response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27122 

Comment Code: 42200 

Comment: EPA based its cost estimate only on new registration actions from 2000 through 2006. 

This limitation is inappropriate, as the burden will fall on all registered products through the 

Registration Review process. EPA explicitly chose not to consider the Registration Review process 

and its "potential burden" on registrants of existing chemicals in its burden estimate, stating that 

registrants and the public will have opportunities for "input, consultation and involvement 

concerning individual pesticide cases throughout the registration review process."[FN81: EPA, 

Economic Analysis of the Proposed Change in Data Requirements for Antimicrobial Pesticides, 

June 26, 2008, at section 2.5.] While it is true that registrants and the public will have opportunities 

for input during Registration Review, the Agency acknowledges that the new data requirements will 

be applied, and therefore it must include the associated costs in the economic analysis for this 

Proposal.[FN82: In the Preamble, EPA states that it "anticipates there will be additional costs 

associated with the proposed studies under Registration Review." The Agency goes on to say that 

the burdens associated with individual active ingredients will be provided as part of the Information 

Collection Request (ICR) approvals submitted to OMB under the Paperwork Reduction Act. 73 

Fed. Reg. at 59428. LANXESSbelieves that this approach has resulted in a serious underestimate of 

the costs of the Proposal to both the industry and the Agency, and has deprived OMB of the 

opportunity to assess fully the burden of the Proposal.] 

Registration Review is a statutorily required process under which all registrations are reviewed by 

EPA on a mandatory 15 year cycle. The process is now underway. NERA reviewed 28 of the first 
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Comments and Response References: 

Economic Analysis Section (40) Page 421 

antimicrobial cases undergoing Registration Review, based on Panel’s best estimates of the 

incremental data that would be required if this regulation is promulgated as proposed. Clearly, EPA 

could have adopted this or a similar approach to make a good faith estimate of the annual costs of 

the Proposal, as required by the PRA. 

The Panel provided its best estimates of individual study costs to NERA for use in its analysis. In 

some instances, Panel estimates exceed those of the Agency, and in other cases, Agency estimates 

exceed those of the Panel. The Panel based its estimates on all the specific requirements set out in a 

particular guideline, including testing with the mandatory number of species, where applicable, and 

on its members experience in sponsoring these tests over time. In those instances where there are no 

guidelines or existing guidelines are inapplicable to antimicrobials, best professional judgment was 

used. 

The full compliance costs of the Proposal are far greater than the costs estimated by EPA based 

only on new active ingredients and uses. When the compliance costs are calculated, including the 

costs that will be incurred by registrants of existing active ingredients in registration review, the full 

cost is about six times the EPA estimate. As discussed more fully in the NERA Report, the costs 

incremental to EPA’s baseline are about eleven times the EPA estimate, and the full costs 

incremental to current practice are about seven times the EPA estimate, which the Agency claims is 

based on current Agency practices. Moreover, NERA found that the updated average total cost per 

firm per year ranges from about $2.0 million to $2.2 million, over thirty times the EPA’s estimated 

average annual costs per firm of $61,000. 

Response: See responses 40.1 and 40.6. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27217 

Comment Code: 42200 

Comment: Yet the EPA has not taken into account incremental costs or the impact of the new data 

requirements on registration review, which greatly increase the costs per firm. Even using EPA’s 

estimate that only 64 firms would be affected, the average cost per firm relative to the baseline-if 

one includes incremental costs-is approximately $750,000, nearly twelve times higher than the EPA’s 

estimate of $61,000.[FN90: See Appendix J, NERA Economic Consulting, Economic Analysis of 

Proposed U.S. EPA Biocide Data Requirements: Prepared for the American Chemistry Council, at 

18 (Mar. 2009).] After considering that registration review would bring in a larger number of firms, 

the incremental cost is $450,000, still more than seven times EPA’s estimate.[FN91: Id. at 19.] 

Altogether, the incremental costs to current practice are not $3.2 million, as the EPA has found, but 

rather approach $22.5 million.[FN92: Id. at 25.] 

Response: See response 40.6. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 
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Comments and Response References: 

Economic Analysis Section (40) Page 422 

Comment ID: 27220 

Comment Code: 42200 

Comment: Yet, as explained above, the EPA has not taken into account incremental costs or the 

impact of the new data requirements on registration review, which greatly increase the costs per 

firm. The incremental cost is $750,000 for EPA’s estimate of 64 firms, and $450,000 after taking 

into account the additional firms that would undergo registration review.[FN98: Id. at 19.] These 

revised numbers indicate that the proposed rule would have a significant adverse economic impact 

on a substantial number of small entities. Indeed, the additional costs are a substantial share of gross 

revenues, meaning the rule has a significant economic impact.[FN99: See Harlan Land Co. v. U.S. 

Dep’t of Agric., 186 F.Supp.2d 1076 (E.D. Cal. 2001) (holding that the agency’s economic analysis 

was flawed because the analysis focused on the impact of Argentine imports on the supply and 

prices of citrus fruit in the United States, and resulting costs and benefits to domestic growers, 

brokers, importer and consumers; but not the costs if Argentine plant pests were introduced into 

U.S. citrus orchards).] Also, approximately ten percent of small pesticide registrants are likely to 

experience some impact. Ten percent of small pesticide registrants, as opposed to the 4.4% 

estimated by EPA, would constitute a substantial number of small entities. 

Response: See responses 40.6 and 40.4. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27237 

Comment Code: 42200 

Comment: C. Paperwork Reduction Act 

The Agency similarly has used inaccurate information to calculate the provided burden estimates 

under the Paperwork Reduction Act (PRA).[FN100: 44 U.S.C. [section]3501 et seq.] The EPA 

should include the paperwork burden costs for existing registrants, who are required to undergo the 

registration review process every fifteen years.[FN101: See EPA, Economic Analysis of the 

Proposed Change in Data Requirements for Antimicrobial Pesticides, at 16 (acknowledging that the 

study does not include costs for existing registrants in its economic analysis).] The additional data 

and testing requirements in the proposed rule would increase the paperwork costs for each registrant 

undergoing a registration review. As such, the total registrant paperwork burden and costs for 

antimicrobial pesticide registrations would be much more than the stated 3,929 hours and 

$255,773.25.[FN102: Proposed Rule, 73 Fed. Reg. 59429.] 

Response: See response 40.6. 

Comment Code: 42300 Agency Burden 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 
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Comments and Response References: 

Economic Analysis Section (40) Page 423 

Comment ID: 26443 

Comment Code: 42300 

Comment: In addition, burden on EPA has been substantial, as Agency staff has been highly 

involved in the process of reviews, consultations, and presentations to the advisory committee 

charged with reviewing the scientific and ethical sufficiency of these studies. The Panel cannot 

estimate the magnitude of the burden on EPA, but the Agency can and should do so. 

Response: See responses 3 and 40.8 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26445 

Comment Code: 42300 

Comment: C. Agency Estimates of the Burdens on its Resources and its Planning to Meet Such 

Burdens Are Inadequate 

The Panel likewise has reservations about the adequacy of EPA’s estimate of the burden on the 

Agency associated with the Proposal, but does not have sufficient information to prepare a more 

reliable estimate of this burden. The scope of many of the requirements is unknown, their 

application to many products is uncertain based on the lack of well-articulated triggers for higher tier 

testing, and, in particular, the manner in which EPA will conduct risk assessments for many 

antimicrobials is simply unknown. It is not clear that EPA, in fact, has complied with the 

requirements of PRA Section 3506(c)(1)(vi), to create "a plan for the efficient and effective 

management and use of the nformation to be collected, including necessary resources." The 

Proposal does not contain information on the manner in which EPA will use the data it plans to 

require from registrants. Such information should be included in a reproposal of the regulation. 

Response: See responses 3 and 40.8 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27137 

Comment Code: 42300 

Comment: In addition, burden on EPA has been substantial, as Agency staff has been highly 

involved in the process of reviews, consultations, and presentations to the advisory committee 

charged with reviewing the scientific and ethical sufficiency of these studies. LANXESS cannot 

estimate the magnitude of the burden on EPA, but the Agency can and should do so. 

Response: See response 40.8. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
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Comments and Response References: 

Economic Analysis Section (40) Page 424 

Letter ID: 0064 

Comment ID: 27140 

Comment Code: 42300 

Comment: B. Agency Estimates on its Burden and its Planning to Meet Such Burdens are 

Inadequate 

LANXESS likewise has reservations about the adequacy of EPA’s estimate of the burden on the 

Agency associated with the Proposal, but does not have sufficient information to prepare a more 

reliable estimate of this burden. The scope of many of the requirements is unknown, their 

application to many products is uncertain based on the lack of well-articulated triggers for higher tier 

testing, and, in particular, the manner in which EPA will conduct risk assessments for many 

antimicrobials is simply unknown. It is not clear that EPA, in fact, has complied with the 

requirements of PRA Section 3506(c)(1)(vi), to create "a plan for the efficient and effective 

management and use of the information to be collected, including necessary resources." The 

Proposal does not contain information on the manner in which EPA will use the data it plans to 

require from registrants. Such information should be included in a reproposal of the regulation. 

Response: See responses 3 and 40.8 

Comment Code: 43000 Test costs analysis (including cost of consultations) 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26442 

Comment Code: 43000 

Comment: B. The Costs of the Many Consultations Required by the Proposal Are Not Considered 

As currently proposed, there are 11 different studies for which EPA either directs or requires 

applicants to consult before conducting testing, and there are 10 different studies for which protocol 

details must be obtained from EPA and/or must be approved by EPA before a study can be 

conducted.[FN#81:See Appendix K.] The Panel does not have sufficient information to estimate 

the annual burden from these necessary consultations, but the costs to both registrants and EPA will 

be substantial. 

Consultations on and protocol development for human exposure applicator testing (proposed 40 

CFR section 158.2260) that have occurred to date with regard to the testing program of the 

Antimicrobial Exposure Assessment Task Force II (AEATF II) are an example of the level of 

burden to both registrants and the Agency that will occur when human exposure monitoring data 

are required. To date, in the process of developing protocols and other associated required 

documentation, the effort has taken the registrant group more than three years and required more 

than $2 million in direct costs, and additional approximately $1 million in individual member 

company technical resources. These costs are associated only with the protocol development and 
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Comments and Response References: 

Economic Analysis Section (40) Page 425 

approval process for four applicator exposure studies. Similar costs also will be incurred for other 

applicator and post- application (40 CFR section 158.2270) studies. 

Response: See responses 3 and 40.6 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26444 

Comment Code: 43000 

Comment: Consultations described above have imposed very substantial burdens on registrants. In 

Appendix K, the Panel identifies 21 places in which the Proposal calls for consultation before 

conducting testing. The substantial burdens on applicants, registrants and EPA associated with these 

consultations must be considered by EPA, as they will substantially increase the cost of compliance 

with the Proposal. EPA should revise its Economic Impact Analysis to include the costs associated 

with many consultations required by the Proposal. 

Response: See responses 3 and 40.6 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26467 

Comment Code: 43000 

Comment: Moreover, these costs do not include any consideration of the costs of the many 

"consultations" EPA requires or recommends. These costs should be included in a revised 

assessment of the costs of the regulation if EPA is to comply with Executive Order 12866. 

Response: See responses 3 and 40.6 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27136 

Comment Code: 43000 

Comment: A. The Costs of the Many Consultations Required by the Proposal Are Not Considered 

As currently proposed, there are 11 different studies for which EPA either directs or requires 

applicants to consult before conducting testing, and there are 10 different studies for which protocol 

details must be obtained from EPA and/or must be approved by EPA before a study can be 

conducted.[FN83: See Appendix K.] LANXESS does not have sufficient information to estimate 

the annual burden from these necessary consultations, but the costs to both registrants and EPA will 

be substantial. 
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Comments and Response References: 

Economic Analysis Section (40) Page 426 

Consultations on and protocol development for human exposure applicator testing (proposed 40 

CFR section 158.2260) that have occurred to date with regard to the testing program of the 

Antimicrobial Exposure Assessment Task Force II (AEATF II) are an example of the level of 

burden to both registrants and the Agency that will occur when human exposure monitoring data 

are required. To date, in the process of developing protocols and other associated required 

documentation, the effort has taken the registrant group more than three years and required more 

than $2 million in direct costs, and additional approximately $1 million in individual member 

company technical resources. These costs are associated only with the protocol development and 

approval process for four applicator exposure studies. Similar costs also will be incurred for other 

applicator and post- application (40 CFR section 158.2270) studies. 

Response: See responses 3 and 40.6 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27138 

Comment Code: 43000 

Comment: Consultations described above have imposed very substantial burdens on registrants. In 

Appendix J, LANXESS identifies 21 places in which the Proposal calls for consultation before 

conducting testing. The substantial burdens on applicants, registrants and EPA associated with these 

consultations must be considered by EPA, as they will substantially increase the cost of compliance 

with the Proposal. EPA should revise its Economic Impact Analysis to include the costs associated 

with any consultations required by the Proposal. 

Response: See responses 3, 40.6, and 40.8 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27218 

Comment Code: 43000 

Comment: Moreover, these costs do not include any consideration of the costs of the many 

"consultations" EPA requires and recommends. These costs should be included in a revised 

assessment of the costs of the regulation if EPA is to comply with Executive Order 12866. 

Response: See responses 3 and 40.6 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 427 

Antimicrobial Use Patterns (50) 

Verbatim Comments and Response References for the Antimicrobial Use 

Patterns Section 

Comment Code: 50000 Antimicrobial use patterns 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25588 

Comment Code: 50000 

Comment: [Section] 158.2990 Residue Chemistry Specific Comments 

(a) General. - This section references the Antimicrobial Use Patters in § 158.2201. CSPA references 

and supports the comments proposed by the Biocides Panel in regard to relevant use patterns for 

antimicrobials and suggested revised footnotes in section f (test notes). Please see those specific 

comments in regards on how the table would be used. 

Response: EPA acknowledges CSPA's support for the Biocides Panel's comments in regard to 

relevant use patterns for antimicrobials. 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25812 

Comment Code: 50000 

Comment: * We do not have specific comments regarding the 12 use patterns that have been 

proposed; however, we question the default assumption that many of these use patterns will be 

associated with of "high human exposure," absent a data-driven determination to this effect. In 

addition to being needlessly arbitrary when empirical exposure data will be available, assigning 

chemicals a priori to the high-exposure category will severely limit the practical application of a 

tiered approach to testing. 

Response: see response 50.14 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25822 

Comment Code: 50000 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 428 

Comment: Secondly, we question what appears to be a default assumption by the Agency that 

many of the dozen proposed new use patterns will be associated with "high human exposure" absent 

a data-driven determination to this effect. In addition to being needlessly arbitrary when empirical 

exposure data will be available, we fear that assigning chemicals a priori to the highexposure category 

will severely limit the practical application of a tiered approach to testing, thereby nullifying any 

potential gains in efficiency. 

Response: see response 50.14 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26018 

Comment Code: 50000 

Comment: In this letter, in addition to indicating our support for many elements of the proposed 

rule, we recommend modifications to the proposed use pattern categorization to ensure USEPA will 

obtain necessary data to evaluate all releases of antimicrobial pesticides into urban runoff. 

Response: EPA acknowledges CASQA's support for many elements of the proposed rule. 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26039 

Comment Code: 50000 

Comment: Proposed Data Requirements - Use Patterns 

We greatly appreciate USEPA’s proposed redesign of its antimicrobials data requirements to clarify 

the nature of antimicrobial pesticide use patterns and to identify those use patterns that would have 

the greatest potential to release antimicrobials to surface water. By identifying such use patterns and 

requiring the data necessary to evaluate their impacts on surface water quality, USEPA will have the 

ability to identify and mitigate potential water quality impacts at the time that pesticides are initially 

registered and when their registrations are reviewed. 

Response: EPA acknowledges CASQA's support for requiring the data necessary to evaluate the 

impact of antimicrobials on surface water quality. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26194 

Comment Code: 50000 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 429 

Comment: The Panel believes that the Proposal’s approach to use categories and patterns for 

antimicrobial pesticides does not properly meet FIFRA’s requirement to "adequately address the 

unique applications, use patterns, and other factors germane to antimicrobial pesticides." 

Response: see response 50.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26195 

Comment Code: 50000 

Comment: In the detailed comments that follow, the Panel explains the reasons for its position and 

proposes an alternative approach that, in the Panel’s view, is more consistent with the goals of 

FIFRA and better suited to the uses of antimicrobials. 

The Panel also believes that the Proposal does not fully implement the directive in section 3(h) of 

FIFRA to "conform the degree and type of review to the risks and benefits presented by 4 Id. 7 

antimicrobial pesticides . . ."[FN#5:Id.] The Proposal includes numerous requirements that the 

Panel believes are not appropriate for particular antimicrobial uses. 

Response: See response 1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26496 

Comment Code: 50000 

Comment: APPENDIX B 

COMMENTS ON THE PROPOSED USE CATEGORIES AND PATTERNS FOR 

ANTIMICROBIAL PESTICIDES 

According to 40 CFR 158.1, the purpose of the data requirement regulation is to enable registrants 

to identify the types of information the Agency requires in order to make a registration decision on a 

particular product. Within the regulation, the use pattern should group requirements into easily 

understood categories which require very similar types of information without needing to specify 

data requirements individually for every possible type of pesticide product and specific use site. Use 

patterns also allow registrants to determine the likely relevant data requirements without specialized 

consultation with the Agency. Use patterns must relate to the type of data needed for the Agency to 

reach a regulatory decision, including the types of exposures likely to occur and the risks from such 

exposures. Use patterns and the associated data requirement tables must be clear so that an applicant 

can identify the general use pattern(s) that best fit the proposed labeled uses and then refer to the 

specific tables and notes to determine the applicable requirements (40 CFR 158.120). 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 430 

FIFRA section 3(h)(3)(A)(ii) requires EPA to "differentiate the types of review undertaken for 

antimicrobial pesticides, ...conform[ing] the degree and type of review to the risks and benefits 

presented..., considering the use patterns of the product, toxicity, expected exposure and product 

type." Because of the extraordinarily broad scope of antimicrobial uses and the specialized 

knowledge involved in determining potential exposures from a particular use, the regulation setting 

out antimicrobial data requirements must include a definitive discussion of antimicrobial use 

patterns. 

The Panel does not believe section 158.2201 of the Proposal sets forth appropriate and relevant use 

categories and patterns for antimicrobial pesticides. The purported use patterns identified in this 

proposed regulation are descriptions of product types rather than use categories or use patterns. 

They come out of a draft document [FN#1:Appendix B to the April 30, 1997 draft data 

requirements presented to the FIFRA SAP in June 1997, available in the docket as EPA-HQ-OPP0110-0043.] that EPA has been using as if were final since it was issued in 1997. Based on the 

experience of member companies over the past 12 years, considering these product types as use 

patterns has not been useful in defining data requirements. The use patterns currently identified for 

conventional pesticides and biopesticides in 40 CFR 158.100 are largely inapplicable to antimicrobial 

pesticides. For this reason, the Panel believes the Proposal should be reissued with an entirely new 

approach to use patterns. The Panel hopes that EPA will include in that reproposal the alternative 

approach to identification of use patterns set forth below. This approach is consistent with the goals 

of FIFRA and Part 158 data requirement regulations, and applicable to the uses of antimicrobials. 

I. Proposed Use Categories and General Use Patterns for Antimicrobial Pesticides 

In a manner consistent with that used for conventional, biochemical and microbial pesticides, 158W 

should identify general use categories, with any necessary further division into general use patterns 

that clearly relate to the data requirements. The general categories and patterns must be adequately 

descriptive to allow registrants to understand where a particular product or use will fall. 

Response: see responses 1, 2, and 50.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26499 

Comment Code: 50000 

Comment: A. Considerations for Identifying Use Categories and Patterns 

1. Location of Application of the Registered Pesticide 

The first consideration in developing meaningful use categories and patterns for antimicrobials is the 

general location at which the registered pesticide product is to be applied. The following can be 

considered as the general use categories for antimicrobials: 

1. Indoor Industrial 2. Indoor Residential, Institutional, and Commercial 3. Aquatic Areas 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 431 

The following definitions from 40 CFR 153.2 are applicable to the above residential and institutional 

use pattern components, although use of an antimicrobial pesticide on humans or animals is 

excluded from the definition of "pest" and thus from regulation under FIFRA: 

Response: EPA believes that the commenter is referring to the definitions in 40 CFR 152.3. See 

response 50.1. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26514 

Comment Code: 50000 

Comment: 2. Registered Pesticide Application versus Use of an Exempt Treated Article 

The second consideration in assigning use categories and patterns is whether a registered pesticide is 

applied or the final use is an article containing a material preservative, where the antimicrobial has 

been incorporated into an article that is itself exempt regulation under FIFRA (see 40 CFR 

152.25(a)). This has a significant bearing on the types of exposures of concern and the data 

requirements needed to assess those exposures. 

Response: see response 50.3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26545 

Comment Code: 50000 

Comment: II. Guidance Must be Developed to Allow Registrants to Associate Specific Use Sites 

with the Use Patterns Identified in the Regulations 

The Agency has stated in the preamble (73 Fed. Reg. at page 59390) and identified at proposed 

section 158.2201(b) (Id. at 59431) that it proposes to post guidance on its website to relate specific 

use sites to the general use patterns. The document proposed to be posted as guidance was 

developed in 1997 without public input. The Panel believes that the 1997 information is inadequate 

as guidance for such a critical purpose. The Panel further notes that the Use Site Index for 

conventional pesticides currently posted on the Agency’s website does not include some sites to 

which either conventional pesticides or antimicrobial pesticides would be applied (for example, 

carpets, floors, clothing, other textile products). Even a registrant for conventional pesticides would 

not be able to determine the appropriate use pattern for those sites. 

The 1997 document the Agency proposes to use contains numerous errors. For example, it 

identifies application of antimicrobials to horses, dairy cattle, goats and similar animals as an indoor 

food use. In fact, such applications are not even pesticidal, as identified in FIFRA Section 2(t) and at 

40 CFR 152.5(d). Such uses are not subject to regulation under FIFRA. The document the Agency 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 432 

proposes to post is replete with similar errors, as well as numerous incorrect assignments, 

misinterpretations, and inconsistencies. 

Because guidance is not part of a data requirement regulation, the Panel will not provide specific 

comments on it in this document. Rather, the Panel will provide input on how to associate specific 

use sites with appropriate use patterns separately and will engage in discussions with the Agency 

about an appropriate public process to develop and finalize useful and accurate guidance upon 

which registrants can rely to link specific use sites to relevant use patterns within a data requirement 

regulation. In the meantime, the Panel opposes the posting or use of the 1997 document identified 

by EPA. Proposed section 158.2201(b) should be revised and reproposed reflecting the approach 

described above. 

Response: see responses 2 and 50.2 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26607 

Comment Code: 50000 

Comment: A. Proposed Alternative Section 158.2250 Data Requirements for Non- target Plant 

Protection 

If antimicrobial use pattern categories are described elsewhere in the regulations besides Section 

158.100, specific reference to the identification and description must be incorporated into the 

following paragraph. P&G supports the Biocide Panel’s revisions to Section158.2240(a) as follows: 

(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the 

environmental chemistry data requirements for a particular pesticide product. Notes that apply to an 

individual test and include specific conditions, qualifications, or exceptions to the designated test are 

listed in paragraph (e) of this section 

The existing paragraphs (b) and (c) should be replaced with the following: (b) Use Patterns. (1) The 

general use patterns for antimicrobial nontarget organism data requirements are ‘Indoor 

Institutional, Residential, and Commercial,’ Aquatic, and Material Preservatives, where these are 

identified as follows: 

(a) Indoor institutional, residential and commercial includes the use of sanitizers, disinfectants, 

virucides and similar products for the following: on hard surfaces; on soft surfaces; in the air; as 

laundry disinfectants and sanitizers; as swimming pool disinfectants or algaecides (public or private, 

including pool, hot tubs, and spas); on medical equipment; use in any of the types of facilities that 

fall within these definitions. This use pattern is included only when the product is not a hazardous 

waste and when the label does not restrict against disposal or rinsing down a sanitary sewer for a use 

that could result in such an exposure. 

(b) Aquatic areas involve uses that result in the potential for direct exposure of natural bodies of 

water to antimicrobials, although the exposure likely is limited and is not a direct application to 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 433 

aquatic sites. These include once- through cooling systems (where no pretreatment of the treated 

discharge occurs), antifoulant coatings, and ballast water treatments. 

(c) Material Preservatives include wood preservatives as well as any other type of preservative where 

the final article is used outdoors on a significant basis and there is reliable evidence that the article, 

under anticipated conditions of use, will release the antimicrobial preservative in sufficient quantities 

to produce environmental exposures of concern. 

(2) Data are not required if the end-use product is a gas, a highly volatile liquid, a highly reactive 

solid, or a highly corrosive material. 

(c) Use of products as aquatic herbicides or agricultural fungicides are outside of the scope of these 

data requirements. Registrants of such uses should refer to Subpart G or to Section 158.2060 of this 

Part. 

Response: See responses 50.1 and 50.9 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26723 

Comment Code: 50000 

Comment: LANXESS believes that the Proposal’s approach to use categories and patterns for 

antimicrobial pesticides does not properly meet FIFRA’s requirement to "adequately address the 

unique applications, use patterns, and other factors germane to antimicrobial pesticides." 

Response: see response 50.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26752 

Comment Code: 50000 

Comment: APPENDIX K 

THE PROPOSED RULE 158W IS VAGUE IN THE FOLLOWING SUBSECTIONS 

1. Proposed Regulation # [Section] 158.2200(c) 

Text of the Proposed Regulation (emphasis added) Antimicrobial use patterns. "An applicant unsure 

of the correct use pattern(s) for his product should consult the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated what the correct use patterns for each product is, and also requires private consultation with 

the Agency. 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 434 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26888 

Comment Code: 50000 

Comment: B. Proposed Alternative Section 158.2250 Data Requirements for Nontarget Plant 

Protection 

If antimicrobial use pattern categories are described elsewhere in the regulations besides Section 

158.100, specific reference to the identification and description must be incorporated into the 

following paragraph. The Panel offers the following revisions to Section 158.2240(a). 

(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the 

environmental chemistry data requirements for a particular pesticide product. Notes that apply to an 

individual test and include specific conditions, qualifications, or exceptions to the designated test are 

listed in paragraph (e) of this section 

The existing paragraphs (b) and (c) should be replaced with the following: 

(b) Use Patterns. (1) The general use patterns for antimicrobial nontarget organism data 

requirements are ‘Indoor Institutional, Residential, and Commercial,’ Aquatic, and Material 

Preservatives, where these are identified as follows: 

(a) Indoor institutional, residential and commercial includes the use of sanitizers, disinfectants, 

virucides and similar products for the following: on hard surfaces; on soft surfaces; in the air; as 

laundry disinfectants and sanitizers; as swimming pool disinfectants or algaecides (public or private, 

including pool, hot tubs, and spas); on medical equipment; use in any of the types of facilities that 

fall within these definitions. This use pattern is included only when the product is not a hazardous 

waste and when the label does not restrict against disposal or rinsing down a sanitary sewer for a use 

that could result in such an exposure. 

(b) Aquatic areas involve uses that result in the potential for direct exposure of natural bodies of 

water to antimicrobials, although the exposure likely is limited and is not a direct application to 

aquatic sites. These include once- through cooling systems (where no pretreatment of the treated 

discharge occurs), antifoulant coatings, and ballast water treatments. 

(c) Material Preservatives include wood preservatives as well as any other type of preservative where 

the final article is used outdoors on a significant basis and there is reliable evidence that the article, 

under anticipated conditions of use, will release the antimicrobial preservative in sufficient quantities 

to produce environmental exposures of concern. 

(2) Data are not required if the end-use product is a gas, a highly volatile liquid, a highly reactive 

solid, or a highly corrosive material. 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 435 

(c) Use of products as aquatic herbicides or agricultural fungicides is outside of the scope of these 

data requirements. Registrants of such uses should refer to Subpart G or to Section 158.2060 of this 

Part. 

Response: See responses 50.1 and 50.9 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27213 

Comment Code: 50000 

Comment: The Panel elsewhere has proposed new Use Pattern categories that are relevant, clear 

and applicable to antimicrobial pesticides. This alternative proposal incorporates those new Use 

Pattern categories. Where a use is excluded from the definition of an antimicrobial pesticide or from 

the definition of a pesticide chemical, it should be excluded from data requirements for residue 

chemistry. For food uses which are pesticidal but not within the scope of the definition of 

antimicrobial pesticides, a reference should be to the appropriate sections of the data requirements 

for conventional or biochemical pesticides. 

Response: see response 50.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27248 

Comment Code: 50000 

Comment: APPENDIX B 

COMMENTS ON THE PROPOSED USE CATEGORIES AND PATTERNS FOR 

ANTIMICROBIAL PESTICIDES 

According to 40 CFR 158.1, the purpose of the data requirement regulation is to enable registrants 

to identify the types of information the Agency requires in order to make a registration decision on a 

particular product. Within the regulation, the use pattern should group requirements into easily 

understood categories which require very similar types of information without needing to specify 

data requirements individually for every possible type of pesticide product and specific use site. Use 

patterns also allow registrants to determine the likely relevant data requirements without specialized 

consultation with the Agency. Use patterns must relate to the type of data needed for the Agency to 

reach a regulatory decision, including the types of exposures likely to occur and the risks from such 

exposures. Use patterns and the associated data requirement tables must be clear so that an applicant 

can identify the general use pattern(s) that best fit the proposed labeled uses and then refer to the 

specific tables and notes to determine the applicable requirements (40 CFR 158.120). 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 436 

FIFRA section 3(h)(3)(A)(ii) requires EPA to "differentiate the types of review undertaken for 

antimicrobial pesticides,...conform[ing] the degree and type of review to the risks and benefits 

presented..., considering the use patterns of the product, toxicity, expected exposure and product 

type." Because of the extraordinarily broad scope of antimicrobial uses and the specialized 

knowledge involved in determining potential exposures from a particular use, the regulation setting 

out antimicrobial data requirements must include a definitive discussion of antimicrobial use 

patterns. 

LANXESS does not believe section 158.2201 of the Proposal sets forth appropriate and relevant use 

categories and patterns for antimicrobial pesticides. The purported use patterns identified in this 

proposed regulation are descriptions of product types rather than use categories or use patterns. 

They come out of a draft document[FN1: Appendix B to the April 30, 1997 draft data requirements 

presented to the FIFRA SAP in June 1997, available in the docket as EPA-HQ- OPP-0110-0043.] 

that EPA has been using as if it were final since it was issued in 1997. Considering these product 

types as use patterns has not been useful in defining data requirements. The use patterns currently 

identified for conventional pesticides and biopesticides in 40 CFR 158.100 are largely inapplicable to 

antimicrobial pesticides. For this reason, LANXESS believes the Proposal should be reissued with 

an entirely new approach to use patterns. LANXESS hopes that EPA will include in that re-proposal 

the alternative approach to identification of use patterns set forth below. This approach is consistent 

with the goals of FIFRA and Part 158 data requirement regulations, and applicable to the uses of 

antimicrobials. 

I. Proposed Use Categories and General Use Patterns for Antimicrobial Pesticides 

In a manner consistent with that used for conventional, biochemical, and microbial pesticides, 158W 

should identify general use categories, with any necessary further division into general use patterns 

that clearly relate to the data requirements. The general categories and patterns must be adequately 

descriptive to allow registrants to understand where a particular product or use will fall. 

Response: See responses 1, 2, and 50.1. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27250 

Comment Code: 50000 

Comment: A. Considerations for Identifying Use Categories and Patterns 

1. Location of Application of the Registered Pesticide 

The first consideration in developing meaningful use categories and patterns for antimicrobials is the 

general location at which the registered pesticide product is to be applied. The following can be 

considered as the general use categories for antimicrobials: 

1. Indoor Industrial 2. Indoor Residential, Institutional, and Commercial 3. Aquatic Areas 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 437 

The following definitions from 40 CFR 153.2 are applicable to the above residential and institutional 

use pattern components, although use of an antimicrobial pesticide on humans or animals is 

excluded from the definition of "pest" and thus from regulation under FIFRA: 

Response: EPA believes that the commenter is referring to the definitions in 40 CFR 152.3. See 

response 50.1. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27260 

Comment Code: 50000 

Comment: 2. Registered Pesticide Application Versus Use of an Exempt Treated Article 

The second consideration in assigning use categories and patterns is whether a registered pesticide is 

applied or the final use is an article containing a material preservative, where the antimicrobial has 

been incorporated into an article that is itself exempt regulation under FIFRA (see 40 CFR 

152.25(a)). This has a significant bearing on the types of exposures of concern and the data 

requirements needed to assess those exposures. 

Response: see response 50.3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27269 

Comment Code: 50000 

Comment: II. Guidance Must be Developed to Allow Registrants to Associate Specific Use Sites 

with the Use Patterns Identified in the Regulations 

The Agency has stated in the preamble (73 Fed. Reg. at page 59390) and identified at proposed 

section 158.2201(b) (Id. at 59431) that it proposes to post guidance on its website to relate specific 

use sites to the general use patterns. The document proposed to be posted as guidance was 

developed in 1997 without public input. LANXESS believes that the 1997 information is inadequate 

s guidance for such a critical purpose. LANXESS further notes that the Use Site Index for 

conventional pesticides currently posted on the Agency’s website does not include some sites to 

which either conventional pesticides or antimicrobial pesticides would be applied (for example, 

carpets, floors, clothing, other textile products). Even a registrant for conventional pesticides would 

not be able to determine the appropriate use pattern for those sites. 

The 1997 document the Agency proposes to use contains numerous errors. For example, it 

identifies application of antimicrobials to horses, dairy cattle, goats and similar animals as an indoor 

food use. In fact, such applications are not even pesticidal, as identified in FIFRA Section 2(t) and at 

40 CFR 152.5(d). Such uses are not subject to regulation under FIFRA. The document the Agency 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 438 

proposes to post is replete with similar errors, as well as numerous incorrect assignments, 

misinterpretations, and inconsistencies. 

LANXESS opposes the posting or use of the 1997 document identified by EPA. Proposed section 

158.2201(b) should be revised and re-proposed reflecting the approach described above. 

Response: See responses 2 and 50.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27543 

Comment Code: 50000 

Comment: B. Proposed Alternative Section 158.2250 Data Requirements for Nontarget Plant 

Protection 

If antimicrobial use pattern categories are described elsewhere in the regulations besides Section 

158.100, specific reference to the identification and description must be incorporated into the 

following paragraph. LANXESS offers the following revisions to Section 158.2240(a). 

(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the 

environmental chemistry data requirements for a particular pesticide product. Notes that apply to an 

individual test and include specific conditions, qualifications, or exceptions to the designated test are 

listed in paragraph (e) of this section 

The existing paragraphs (b) and (c) should be replaced with the following: 

(b) Use Patterns. (1) The general use patterns for antimicrobial nontarget organism data 

requirements are ‘Indoor Institutional, Residential, and Commercial,’ Aquatic, and Material 

Preservatives, where these are identified as follows: 

(a) Indoor institutional, residential and commercial includes the use of sanitizers, disinfectants, 

virucides and similar products for the following: on hard surfaces; on soft surfaces; in the air; as 

laundry disinfectants and sanitizers; as swimming pool disinfectants or algaecides (public or private, 

including pool, hot tubs, and spas); on medical equipment; use in any of the types of facilities that 

fall within these definitions. This use pattern is included only when the product is not a hazardous 

waste and when the label does not restrict against disposal or rinsing down a sanitary sewer for a use 

that could result in such an exposure. 

(b) Aquatic areas involve uses that result in the potential for direct exposure of natural bodies of 

water to antimicrobials, although the exposure likely is limited and is not a direct application to 

aquatic sites. These include once- through cooling systems (where no pretreatment of the treated 

discharge occurs), antifoulant coatings, and ballast water treatments. 

(c) Material Preservatives include wood preservatives as well as any other type of preservative where 

the final article is used outdoors on a significant basis and there is reliable evidence that the article, 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 439 

under anticipated conditions of use, will release the antimicrobial preservative in sufficient quantities 

to produce environmental exposures of concern. 

(2) Data are not required if the end-use product is a gas, a highly volatile liquid, a highly reactive 

solid, or a highly corrosive material. 

(c) Use of products as aquatic herbicides or agricultural fungicides is outside of the scope of these 

data requirements. Registrants of such uses should refer to Subpart G or to Section 158.2060 of this 

Part. 

Response: See responses 50.1 and 50.9 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27643 

Comment Code: 50000 

Comment: LANXESS elsewhere has proposed new Use Pattern categories that are relevant, clear 

and applicable to antimicrobial pesticides. This alternative proposal incorporates those new Use 

Pattern categories. Where a use is excluded from the definition of an antimicrobial pesticide or from 

the definition of a pesticide chemical, it should be excluded from data requirements for residue 

chemistry. For food uses which are pesticidal but not within the scope of the definition of 

antimicrobial pesticides, a reference should be to the appropriate sections of the data requirements 

for conventional or biochemical pesticides. 

Response: see response 50.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27662 

Comment Code: 50000 

Comment: APPENDIX J THE PROPOSED RULE 158W IS VAGUE IN THE FOLLOWING 

SUBSECTIONS 

 1. Proposed Regulation # [Section] 158.2200(c) 

Text of the Proposed Regulation (emphasis added) Antimicrobial use patterns. "An applicant unsure 

of the correct use pattern(s) for his product should consult the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated what the correct use patterns for each product is, and also requires private consultation with 

the Agency. 

Response: see response 3 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 440 

Comment Code: 51000 General comments on the 12 use patterns 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25605 

Comment Code: 51000 

Comment: Section Number IV. 

Title I . Use Patterns in Subpart W 

Paragraph p. 59388 

Excerpt from Federal Register General comment 

HC Comment Refer to Table 2 (below) for a comparison of the EPA use patterns and PMRA use 

site category crosswalk. The PMRA does not have environmental data requirements for USC 15, 19 

and 29 (Indoor Hard Surfaces; Other Indoor Surfaces, Water and Air; and Swimming Pools, 

respectively). The PMRA environmental data requirements for USC 5 and 6 (Greenhouse Food 

Crops and Non-Food Crops, respectively) pertain mainly to the application of agricultural pesticides 

to greenhouse crops. USC 5 has the following exclusion: For treatment of empty greenhouses and 

empty mushroom houses devoid of growth media. Under this definition, it is indicated that 

disinfection or sanitization of greenhouses or mushroom houses where a food crop is growing is 

subject to the Food and Drugs Act. USC 6 has the following similar exclusion: For treatment of 

empty greenhouses devoid of growth media. For antimicrobial use, the PMRA environmental data 

requirements for treatment of greenhouses are more similar to those for empty food storage areas 

than those for greenhouse crops. From an environmental perspective, PMRA USC 3 appears to be 

the best fit for the EPA use pattern 1 and 2. One or two uses in EPA use pattern 5 (Medical 

Premises and Equipment) correspond to PMRA USC 18 (Material). The PMRA and EPA 

definitions of use pattern 7 and USC 18 are very similar. The once-through treatment of industrial 

water systems for zebra mussel control falls under USC 2 (Aquatic Non-Food Sites) for the PMRA, 

but it is classified under Industrial Processes and Water Systems by the EPA. The PMRA has 

defined antifouling coatings and their use on underwater structures and materials such as boat hulls, 

fishing nets, intake pipe, lobster traps, etc. as USC 22 (Underwater Structures and Materials), 

however, antifoulant use on aquaculture pens and nets is classified as USC 1 (Aquaculture). USC 1 

is, however, not specific to antifoulants and includes the use of other pesticides, i.e., herbicides, 

insecticides and insect growth regulators in aquaculture. 

Response: EPA acknowleges that there are differences between EPA's use patterns and PMRA's 

use site categories. 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 441 

Comment ID: 26217 

Comment Code: 51000 

Comment: 4) For certain Use Patterns, including Indoor Industrial, discharges to the environment 

from the facility are regulated by Agencies or Offices other than Office of Pesticide Programs (e.g.; 

facility wastewater treatment, NPDES permits for effluent, RCRA for wastes, etc). For these Use 

Patterns, environmental fate and ecotoxicity data requirements should not be required for FIFRA 

registration. 

Response: see response 140.4 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 28941 

Comment Code: 51000 

Comment: To ensure that EPA has the capacity to assess the water quality impacts of outdoor 

antimicrobial pesticide use in all urban areas, SFE and the SFPUC request modification of these 

outdoor use patterns to either designate certain outdoor uses as both "low" and "high" 

environmental exposure-or, alternatively, to create a separate outdoor use pattern framework to 

ensure EPA obtains the data necessary to evaluate the impacts of outdoor antimicrobials uses 

wherever they occur. The affected use patterns are: swimming pools, recirculating cooling water 

system discharges, materials preservatives (like biocides in paints and awning fabric), human drinking 

water systems (irrigation overflows, fire flows, and system flushing discharges), and all other outdoor 

uses of antimicrobials (i.e., outdoor applications to residential and public access premises; 

commercial, institutional and industrial premises and equipment; food handling/storage 

establishments, premises, and equipment; agricultural premises and equipment; and medical 

premises and equipment). 

Response: see response 50.9 

Comment Code: 52000 Specific use patterns 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26321 

Comment Code: 52000 

Comment: First, based on the use pattern designations for antimicrobial products with only indoor 

uses, environmental fate and ecotoxicity data are required in a manner inconsistent with the 

regulation of indoor conventional pesticides, without comment or explanation. As discussed below, 

the use patterns in this Proposal should be more clearly defined to provide more precision on when 

data are required and why. Please see the Panel’s alternate proposal regarding use patterns at 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 442 

Appendix B. Only when this is done can the Panel and other interested parties provide meaningful 

comments or input. 

Response: see response 50.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26505 

Comment Code: 52000 

Comment: * Indoor Residential and Institutional use includes the use of sanitizers, disinfectants, 

virucides and similar products whether to hard surfaces, soft surfaces or in the air and laundry 

disinfectants and sanitizers, to swimming pools as disinfectants or algaecides (public or private, 

including pool, hot tubs, and spas), in medical premises and equipment, and when used in any of the 

types of facilities that fall within those definitions. 

Response: See response 50.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26841 

Comment Code: 52000 

Comment: First, the use pattern designations for antimicrobial products do not account for indoor 

uses in a manner consistent with that for conventional pesticides, without comment or explanation. 

As discussed below, the use patterns in this Proposal should be more clearly defined to clarify when 

data are required and why. Please see the LANXESS’s alternate proposal regarding use patterns at 

Appendix B. Only when this is done can LANXESS and other interested parties provide meaningful 

comments or input. 

Response: see response 50.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27256 

Comment Code: 52000 

Comment: * Indoor Residential and Institutional use includes the use of sanitizers, disinfectants, 

virucides and similar products whether to hard surfaces, soft surfaces or in the air and laundry 

disinfectants and sanitizers, to swimming pools as disinfectants or algaecides (public or private, 

including pool, hot tubs, and spas), in medical premises and equipment, and when used in any of the 

types of facilities that fall within those definitions. 

Response: See response 50.1 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 443 

Comment Code: 52100 Agricultural 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25576 

Comment Code: 52100 

Comment: Detailed Characteristics Section Number IV. 

Title Introduction to Subpart W 

Paragraph I. Use Patterns in Subpart W Paragraphs 6 to 22, pp. 59389 to 59390 

Excerpt from Federal Register 1. Agricultural premises and equipment. This use pattern includes 

many indirect food uses with mostly indoor use sites. [... to...] Also, the water could be used in crop 

and/or livestock production thus providing for additional human exposure. 

HC Comment In the descriptions of some, but not all, of the use patterns, the level of exposure (i.e. 

high vs. low) is noted. For sake of consistency, both between submissions at the USEPA and 

between the USEPA and PMRA, it would be useful to discuss the level of human exposure for each 

of the use patterns. As noted above, the PMRA is interested in collaborating with the EPA on 

further defining the factors/criteria used to determine the level of human exposure. 

Response: see response 50.6 

Comment Code: 52300 Commercial, institutional and industrial uses (such as metal working 

fluid/MWF) 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26503 

Comment Code: 52300 

Comment: * Institutional use means any application of a pesticide in or around any property or 

facility that functions to provide a service to the general public or to public or private organizations, 

including but not limited to: 

(1) Hospitals and nursing homes. (2) Schools other than preschools and day care facilities. (3) 

Museums and libraries. (4) Sports facilities. (5) Office buildings. The Panel proposes that the 

following new use category definitions be included as part of any regulation: 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 444 

* Commercial use means any application of a pesticide in or around any property or facility other 

than at industrial or at residential or institutional sites, including but not limited to: 1) agricultural 

outbuildings and 2) treatment stations for raw agricultural commodities. 

* Indoor industrial uses are those that occur in industrial and manufacturing facilities, including 

industrial process water treatment, cooling tower uses, manufacturing, incorporation into treated 

materials, and similar specialized applications. This also includes applications where the use is 

environmentally contained, such as oil field biocides. 

Response: see response 50.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27254 

Comment Code: 52300 

Comment: * Institutional use means any application of a pesticide in or around any property or 

facility that functions to provide a service to the general public or to public or private organizations, 

including but not limited to: (1) Hospitals and nursing homes. (2) Schools other than preschools and 

day care facilities. (3) Museums and libraries. (4) Sports facilities. (5) Office buildings. 

LANXESS proposes that the following new use category definitions be included as part of any 

regulation: 

* Commercial use means any application of a pesticide in or around any property or facility other 

than at industrial or at residential or institutional sites, including but not limited to: 1) agricultural 

outbuildings and 2) treatment stations for raw agricultural commodities. 

* Indoor industrial uses are those that occur in industrial and manufacturing facilities, including 

industrial process water treatment, cooling tower uses, manufacturing, incorporation into treated 

materials, and similar specialized applications. This also includes applications where the use is 

environmentally contained, such as oil field biocides. 

Response: see response 50.1 

Comment Code: 52400 Residential and public access 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26501 

Comment Code: 52400 

Comment: * Residential use means use of a pesticide directly: 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 445 

(1) On humans or pets, (2) In, on, or around any structure, vehicle, article, surface, or area associated 

with the household, including but not limited to areas such as non- agricultural outbuildings, noncommercial greenhouses, pleasure boats and recreational vehicles, or (3) In any preschool or day 

care facility. 

Response: see response 50.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27252 

Comment Code: 52400 

Comment: * Residential use means use of a pesticide directly: (1) On humans or pets, (2) In, on, or 

around any structure, vehicle, article, surface, or area associated with the household, including but 

not limited to areas such as non- agricultural outbuildings, non-commercial greenhouses, pleasure 

boats and recreational vehicles, or (3) In any preschool or day care facility. 

Response: see response 50.1 

Comment Code: 52700 Materials preservative 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26518 

Comment Code: 52700 

Comment: The material preservative category is one that requires special consideration in terms of 

identifying potential data requirements. The vast majority of material preservative applications occur 

indoors, in structures or facilities, with no application to environmental media. These fall under the 

general use category of "Indoor industrial." When the final article or material is exempt from 

regulation under FIFRA different considerations are relevant than when the end- user applies or 

uses a registered pesticide. Treated articles or materials containing a preservative may be used 

indoors, outdoors, or both. In order to determine whether outdoor use of the treated article will 

result in environmental exposure from the preservative, generally two issues must be considered. 

The first is whether there is a reasonable likelihood that use of the particular article or material is 

sufficient to produce significant potential environmental exposure. This factor will depend upon 

where the final article is to be used (e.g., aquatic environments, a highly protected outdoor 

environment, indoors, or other). The second is whether there is reliable evidence that the article 

under anticipated conditions of use will release the antimicrobial preservative in sufficient quantities 

to produce significant environmental exposure. Therefore, data requirements associated with the use 

of treated articles (whether the article is wood, plastic, paint, or any other type of material) must be 

based on reliable science regarding potential exposure. The Agency also needs to distinguish the 

applicable data requirements when the treated article is exempt from regulation under FIFRA from 

those when the Agency registers the final article. 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 446 

Response: see response 50.3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27264 

Comment Code: 52700 

Comment: The material preservative category is one that requires special consideration in terms of 

identifying potential data requirements. The vast majority of material preservative applications occur 

indoors, in structures or facilities, with no application to environmental media. These fall under the 

general use category of "Indoor industrial." When the final article or material is exempt from 

regulation under FIFRA different considerations are relevant than when the end- user applies or 

uses a registered pesticide. Treated articles or materials containing a preservative may be used 

indoors, outdoors, or both. In order to determine whether outdoor use of the treated article will 

result in environmental exposure from the preservative, generally two issues must be considered. 

The first is whether there is a reasonable likelihood that use of the particular article or material is 

sufficient to produce significant potential environmental exposure. This factor will depend upon 

where the final article is to be used (e.g., aquatic environments, a highly protected outdoor 

environment, indoors, or other). The second is whether there is reliable evidence that the article 

under anticipated conditions of use will release the antimicrobial preservative in sufficient quantities 

to produce significant environmental exposure. Therefore, data requirements associated with the use 

of treated articles (whether the article is wood, plastic, paint, or any other type of material) must be 

based on reliable science regarding potential exposure. The Agency also needs to distinguish the 

applicable data requirements when the treated article is exempt from regulation under FIFRA from 

those when the Agency registers the final article. 

Response: see response 50.3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 28939 

Comment Code: 52700 

Comment: Material preservatives are incorporated into numerous matrices to extend their useful 

life, and are not discharged into environmental media. Environmental fate or ecotoxicity data 

requirements should not be imposed for material preservatives unless it has been demonstrated that 

there is a likelihood of release from the preserved matrices under typical conditions of use. Any 

requirement for measuring such potential release must be tailored to address the use scenario. Such 

an approach is lacking in the Proposal. 

Response: see response 50.3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 447 

Letter ID: 0064 

Comment ID: 28940 

Comment Code: 52700 

Comment: Material preservatives are incorporated into numerous matrices to extend their useful 

life, and are not discharged into environmental media. Environmental fate or ecotoxicity data 

requirements should not be imposed for material preservatives unless it has been demonstrated that 

there is a likelihood of release from the preserved matrices under typical conditions of use. Any 

requirement for measuring such potential release must be tailored to address the use scenario. Such 

an approach is lacking in the Proposal. 

Response: see response 50.3 

Comment Code: 52800 Industrial processes and water systems 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25577 

Comment Code: 52800 

Comment: Section Number IV. 

Title Introduction to Subpart W 

Paragraph I. Use Patterns in Subpart W Paragraphs 14 to 17 p. 59389 

Excerpt from Federal Register 8. Industrial processes and water systems. Certain antimicrobial 

chemicals, known as microbiocides, are used to control the growth of bacteria, fungi, and algae in 

circulating water systems. [... to...] Because of the distinct differences between the once-through and 

recirculating water systems, the once- through water system will be grouped with those use patterns 

with potential for higher environmental exposures and the recirculating water system with those use 

patterns with the potential for lower environmental exposures. 

HC Comment In the description for Use pattern 12 (Aquatic areas; I. Use Patterns in Subpart W, 

Paragraph 22, p. 59390), concern for human exposure downstream of treatment sites is noted. It 

seems that similar concerns for possible human exposure would be present downstream of industrial 

process and water system effluents. The PMRA suggests adding text in this regard in this section. 

Response: see response 50.7 

Comment Code: 52910 Wood preservatives 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 448 

Letter ID: 0085 

Comment ID: 25579 

Comment Code: 52910 

Comment: Section Number VIII. 

Title Toxicology Data Requirements 

Paragraph C. Groupings for Antimicrobial Toxicology Requirements Paragraph 7 p. 59393 

Excerpt from Federal Register i. Wood preservatives. For wood preservatives, the Agency may 

require toxicity data on both the active ingredient which is incorporated into the wood and on 

transformation/degradation products which occur in the wood post-treatment. 

HC Comment The PMRA requests clarification regarding why this use pattern is singled out with 

regards to the presence of transformation/degradation products, as it seems that this issue would 

arise with other use patterns. For example, the PMRA encounters this situation with many use 

patterns, including swimming pool and industrial process fluid scenarios. 

Response: see response 80.73 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25700 

Comment Code: 52910 

Comment: Wood preservative data requirements 

EPA requested comments on the structure of data requirements for wood preservative products. 

We agree with the Agency’s assessment that wood intended for land-only use commonly comes in 

contact with water, because most treated wood is used outdoors, where it can not only be placed 

directly into water-but also can be exposed to standing or flowing water as an inadvertent 

consequence of use location. Given the relatively high toxicity of most wood preservatives, SFE and 

the SFPUC urge EPA to take a conservative approach that will ensure that it has access to all 

necessary data. 

Since these products are commonly used outdoors in urban areas, it is essential that EPA require all 

data necessary to estimate their losses in urban runoff. The leaching test required for aquatic uses 

may be adequate for this purpose. 

EPA’s struggle to evaluate the impacts of pentachlorophenol during its recent reregistration 

highlights the need for an additional data requirement for treated wood products-product use data to 

quantify the loss of treated wood particles (from wear and drilling) into the environment. As we 

noted in our letters to EPA regarding pentachlorophenol reregistration, much of the wear on the 

external surface of utility poles is due to human interactions with utility poles (see photographic 

documentation in our letter of May 31, 2005). Human interactions include drilling and cutting 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 449 

materials, which generates waste material (fine pieces of wood contaminated with the preservative) is 

typically left on site, where both human and environmental exposures may occur. 

Response: see response 50.4 

Comment Code: 52911 Swimming pools 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26061 

Comment Code: 52911 

Comment: Attachment - Detailed Comments 

Detailed Comments on Use Pattern Classifications 

Swimming Pools 

In support of our request that swimming pools be classified as both "high" and "low" environmental 

exposure, we have enclosed [See attachments in PDF docket ID EPA-HQ- OPP-2008-0110-0089] a 

compilation of examples of pool emptying patterns from around the nation. The compilation 

includes examples of ordinances both requiring and restricting discharges to both municipal 

wastewater treatment plants and storm drains. Swimming pool and spa discharges may contain 

antimicrobials like chlorine (or hypochlorite), bromine, copper, silver, and polyhexamethylene 

biguanadine (PHMB) at levels that are potentially hazardous to aquatic life or harmful to municipal 

wastewater treatment plant operations. The attachment [See attachments in PDF docket ID EPAHQ- OPP-2008-0110-0089] includes examples of attempts (some of which are ill- directed or 

impractical) to prevent water quality problems from the presence of these pollutants in swimming 

pool and spa discharges. 

Response: EPA appreciates receiving this useful information and notes that the terms high and low 

are no longer used as table headers to the data requirements tables. 

Comment Code: 52912 Aquatic uses (such as ballast water) 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25683 

Comment Code: 52912 

Comment: EPA’s proposed aquatic exposures classification scheme regrettably misses a set of use 

patterns involving transport of pesticides by rain water or direct discharge from outdoor locations to 

gutters, storm drains, and surface waters. These outdoor discharges may flow directly to surface 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 450 

water without any treatment, which is the common pattern in much of the U.S. However, San 

Francisco, like many of the older cities in the U.S., is served by a "combined" sewer system, where 

sanitary and industrial wastes combine in one set of pipes with urban runoff and stormwater flows. 

These combined flows are transported to our wastewater treatment plants, which provide significant 

protection to the local surface water through the treatment process.[FN3: Like municipal wastewater 

treatment plants in many large cities in the Eastern U.S., our city- owned wastewater treatment 

plants receive storm water runoff when it rains, in addition to indoor wastewater (sewage) 

discharges, which they receive year- round. San Francisco’s sewers convey both sanitary and 

industrial sewage and urban and storm water runoff to the wastewater treatment plants in the same 

pipes. This configuration is known as a "combined" sewer system, as compared to "separate" sewer 

systems that are commonly found in more recently developed urban areas (e.g., all other urbanized 

portions of the San Francisco Bay area and most of the U.S.) where sanitary and industrial sewage 

are conveyed in a separate set of pipes than storm water. Separate systems are designed to direct 

storm water runoff into a separate storm drain system, which usually flows directly into creeks, 

rivers, bays, and/or the ocean without any treatment. Our wastewater treatment plants are operated 

by the San Francisco Public Utilities Commission (SFPUC), a separate city department from SFE.] 

Urban runoff and stormwater flows into San Francisco’s combined sewer system can create a 

regulatory challenge with respect to the transport of outdoor pollutants, including antimicrobial 

pesticides, which enter our wastewater treatment plants in concentrations higher than those 

measured by wastewater treatment plants with separate sewer systems that do not treat urban runoff. 

(For example, in our city and probably most cities, the use of disinfectants to clean sidewalks and 

play areas is very common; in some areas this is done on a daily basis. The volume of such 

discharges is therefore likely to be high.) These pollutants have the potential to not only disrupt the 

secondary biological treatment process, but may also pass through the treatment process to surface 

waters. 

Response: see response 50.9 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25939 

Comment Code: 52912 

Comment: Ballast Water- Clorox believes that it is important for the Agency to adequately protect 

the aquatic environments into which ballast waters may be released. The current regulatory 

environment is confusing. We encourage the Agency to resolve the various issues that prevent clear 

understanding of the requirements registrants face in registering products for ballast water 

treatment. Ballast water represents a biological threat to endemic species and needs to be treated 

before released. In evaluation of ballast water treatments, the Agency should take into account the 

reactive nature of some actives, such as sodium hypochlorite. Such reactive species are not present 

upon release after treatment because they are reacted with the organics present in the ballast water. 

Therefore, exhaustive requirements for aquatic toxicity data are not necessary. 

Response: see responses 50.10 and 50.11 

Commenter Name: Hasmukh C. Shah 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 451 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26494 

Comment Code: 52912 

Comment: Similarly, FIFRA 2(mm) excludes aquatic herbicides from the definition of an 

antimicrobial pesticide. Nonetheless, this proposal includes in its definition of aquatic areas subject 

to this proposal, products "designated to kill . . . algae in lakes, ponds, streams, drainage ditches, and 

other bodies of water." 73 Fed.Reg. at 59390. While the Panel agrees that algaecides used in 

manmade structures, facilities and processes are antimicrobial pesticide uses, these sites of 

application are not aquatic area use sites. The Panel understands that the algaecidal uses described in 

the preamble are "aquatic herbicide" uses that are excluded from the definition of antimicrobial 

pesticide and, therefore, should be excluded from the scope of this regulation. Again, it is essential 

that a definition of antimicrobial aquatic area is provided that is consistent with FIFRA and with 

Agency practice. 

EPA also defines antimicrobial pesticide uses in "aquatic areas" as having the potential for high 

human exposure via drinking water if the intake pipe for a drinking water treatment plant is in a lake 

or downstream, or through recreational activities such as swimming. Also the product could be used 

in crop and/or livestock production thus providing for additional human exposure. 73 Fed. Reg. at 

59390. Antimicrobials used in sources of public drinking water are subject to regulation pursuant to 

the Safe Drinking Water Act (42 USC secs. 300f to 300j-28) and to regulation under the EPA Office 

of Water’s Disinfection By- Product rules. 40 CFR Parts 141 and 142. Therefore, any assertion by 

EPA that an antimicrobial pesticide is used in source water to a drinking water treatment plant needs 

to be consistent with the regulatory scheme administered by the Office of Water. Further, 

antimicrobial pesticide uses for recreational waters are limited to swimming pools and spas and 

similar contained structures. The Panel understands that uses in natural bodies of water, including 

those waters used for crops, livestock production, or recreation are regulated as aquatic herbicide 

uses and are excluded from the statutory definition of antimicrobial pesticide. 

As noted above, the characterizations of antimicrobial pesticide uses in the Preamble are sometimes 

inconsistent with the statutory definitions of "pest," "pesticide," and "antimicrobial pesticide." In 

addition, the characterization of antimicrobial pesticide uses in "aquatic areas" is inconsistent with 

the definition of "antimicrobial pesticide," EPA regulation of conventional pesticides and 

biopesticides, and raises issues with regard to consistent regulation of public drinking water sources 

pursuant to the Safe Drinking Water Act. The scope of the 158W regulation should be clarified to 

comply with the limitations and exclusions described above before this regulation is promulgated. 

Response: see response 50.8 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26507 

Comment Code: 52912 
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Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 452 

Comment: * Aquatic uses are those that result in the potential for direct exposure of natural bodies 

of water to antimicrobials, although the exposure likely is somewhat limited and is not a direct 

application to aquatic sites. These include once-through cooling systems (where no pretreatment of 

the treated discharge occurs), antifoulant coatings, and ballast water treatments. It is important to 

note that when a material with antimicrobial properties is applied to natural bodies of water to 

reduce algal or other organic growth, it is considered an aquatic herbicide and is subject to relevant 

regulations for a similar conventional or biochemical pesticide. Likewise, when a similar material is 

applied to growing crops, it is subject to the relevant regulations for a similar conventional or 

biochemical pesticide, for example, an agricultural fungicide or an herbicide. 

Response: see response 50.8 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27246 

Comment Code: 52912 

Comment: Similarly, FIFRA 2(mm) excludes aquatic herbicides from the definition of an 

antimicrobial pesticide. Nonetheless, this proposal includes in its definition of aquatic areas subject 

to this proposal, products "designated to kill . . . algae in lakes, ponds, streams, drainage ditches, and 

other bodies of water." 73 Fed.Reg. at 59390. While LANXESS agrees that algaecides used in 

manmade structures, facilities and processes are antimicrobial pesticide uses, these sites of 

application are not aquatic area use sites. LANXESS understands that the algaecidal uses described 

in the preamble are "aquatic herbicide" uses that are excluded from the definition of antimicrobial 

pesticide and, therefore, should be excluded from the scope of this regulation. Again, it is essential 

that a definition of antimicrobial aquatic area is provided that is consistent with FIFRA and with 

Agency practice. 

EPA also defines antimicrobial pesticide uses in "aquatic areas" as having the potential for high 

human exposure via drinking water if the intake pipe for a drinking water treatment plant is in a lake 

or downstream, or through recreational activities such as swimming. Also the product could be used 

in crop and/or livestock production thus providing for additional human exposure. 73 Fed. Reg. at 

59390. Antimicrobials used in sources of public drinking water are subject to regulation pursuant to 

the Safe Drinking Water Act (42 USC secs. 300f to 300j-28) and to regulation under the EPA Office 

of Water’s Disinfection By- Product rules. 40 CFR Parts 141 and 142. Therefore, any assertion by 

EPA that an antimicrobial pesticide is used in source water to a drinking water treatment plant needs 

to be consistent with the regulatory scheme administered by the Office of Water. LANXESS 

understands that uses in natural bodies of water, including those waters used for crops, livestock 

production, or recreation are regulated as aquatic herbicide uses and are excluded from the statutory 

definition of antimicrobial pesticide.. 

As noted above, the characterizations of antimicrobial pesticide uses in the Preamble are sometimes 

inconsistent with the statutory definitions of "pest," "pesticide," and "antimicrobial pesticide." In 

addition, the characterization of antimicrobial pesticide uses in "aquatic areas" is inconsistent with 

the definition of "antimicrobial pesticide," EPA regulation of conventional pesticides and 

biopesticides, and raises issues with regard to consistent regulation of public drinking water sources 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 453 

pursuant to the Safe Drinking Water Act. The scope of the 158W regulation should be clarified to 

comply with the limitations and exclusions described above before this regulation is promulgated. 

Response: see response 50.8 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27258 

Comment Code: 52912 

Comment: * Aquatic uses are those that result in the potential for direct exposure of natural bodies 

of water to antimicrobials, although the exposure likely is somewhat limited and is not a direct 

application to aquatic sites. These include once-through cooling systems (where no pretreatment of 

the treated discharge occurs), antifoulant coatings, and ballast water treatments. It is important to 

note that when a material with antimicrobial properties is applied to natural bodies of water to 

reduce algal or other organic growth, it is considered an aquatic herbicide and is subject to relevant 

regulations for a similar conventional or biochemical pesticide. Likewise, when a similar material is 

applied to growing crops, it is subject to the relevant regulations for a similar conventional or 

biochemical pesticide, for example, an agricultural fungicide or an herbicide. 

Response: see response 50.8 

Comment Code: 53000 Suggested additions, deletions or re-organization of use patterns 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25757 

Comment Code: 53000 

Comment: Ecolab does not agree with the ACC Biocides Panel proposed Food/Non-food use 

patterns for the toxicology data requirement, but proposes use patterns that more clearly define the 

actually uses of the product; similar to the patterns proposed for environmental fate. 

Response: see responses 80.22 and 80.64 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26040 

Comment Code: 53000 

Comment: While the use pattern classifications presented in the proposed rule are a great 

improvement, they do not fully reflect actual pathways by which antimicrobial pesticides are 

transported to surface waters. A large number of current and past pesticide water quality 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 454 

impairments have been linked to rain water, which washes pesticides from outdoor surfaces to 

gutters, storm drains, and surface waters (usually without any treatment). This "storm water runoff" 

creates a direct connection between an outdoor pesticide use site (e.g., treated wood, surface sprays, 

biocide-impregnated paint) and surface water. We request that the proposed use pattern 

classifications be adjusted to reflect the urban storm water runoff pathway, thus ensuring that 

USEPA receives data adequate to evaluate the inevitable direct transport of antimicrobials from 

outdoor surfaces to surface waters when it rains. 

Several antimicrobials use patterns can be reasonably expected to cause antimicrobial pesticides to 

reach both municipal wastewater treatment plants and storm drains, where they can flow directly to 

surface waters without any form of treatment. Under the structure of the proposed rule, the simplest 

method for addressing these dual discharge pathways is to classify the use patterns in both the "low" 

and "high" environmental exposure groupings. Each such use pattern is described below. 

* Swimming pools. As noted in the preamble (page 59390), discharges from pools and spas routinely 

flow to surface water: they can flow either to municipal wastewater treatment plants or directly to 

surface waters via storm drains. Discharges include routine discharges from filter system 

backwashing, seasonal lowering of water levels, and irregular emptying for repairs. USEPA’s 

understanding of swimming pool and spa discharges is not fully reflected in the design of the 

regulation, which needs to be modified to ensure receipt of data necessary to evaluate the direct 

discharge pathway, which is more sporadic than-but otherwise similar to-discharges from single-pass 

industrial cooling water systems. 

* Recirculating cooling water system discharges. Discharges from recirculating cooling water systems 

can be environmentally significant-and may be directed either to municipal wastewater treatment 

plants or directly to surface waters via storm drains. A dual classification will ensure that USEPA 

receives the data necessary to complete environmental risk assessments for both discharge locations. 

The attachment [See attachements in PDF docket ID EPA-HQ- OPP-2008-0110-0089] and our 

enclosures provide additional details to support our request for this modification of the proposed 

rule. 

* Materials preservatives. Materials preservatives-like biocides in paints and awning fabric-are 

commonly used outdoors as well as indoors. Discharges to both municipal wastewater treatment 

plants (e.g., from washing treated fabrics) and storm drains occur (e.g., from storm water runoff 

from treated roofing materials and walls coated with biocide-containing paints). We enclose [See 

attachments in PDF docket ID EPA-HQ- OPP-2008-0110-0089] a copy of a paper (Kaegi et al. 

2008) documenting the washoff of building paint ingredients into urban creeks as an example 

documenting the potential transport of paint preservatives directly to surface waters. 

* Human drinking water systems. Although intended primarily for indoor use, human drinking water 

(potable water) supplies are extensively used outdoors in urban areas for landscaping irrigation and 

fire control. In addition, maintenance of these systems often involves flushing which results high 

volume and high rate discharges of potable water to receiving waters. Despite efforts to prevent 

runoff of potable water from outdoor use locations, such runoff is common if not inevitable. These 

discharges have proven problematic. For example, discharges associated with potable water system 

flushing have caused fish kills in the San Francisco Bay area. Several recent incidents have been 

attributed to biocides in the water, such as chloramines. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 455 

* All other outdoor uses of antimicrobials. A number of use patterns ("Residential and public access 

premises," "Commercial, institutional and industrial premises and equipment," "Food 

handling/storage establishments, premises, and equipment," "Agricultural premises and equipment," 

and "Medical premises and equipment") include outdoor applications. Outdoor use of pesticides-no 

matter the location-creates the potential that the pesticide will be washed directly into surface water 

when it rains. USEPA should ensure it obtains data necessary to evaluate the impacts of outdoor 

antimicrobials uses wherever they occur. 

Response: see response 50.9 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26543 

Comment Code: 53000 

Comment: B. Proposed General Use Patterns 

Based on the above considerations, the Panel proposes that the use categories for antimicrobials be 

subdivided into the following six general use patterns: 

1. Indoor industrial (all nonfood) 2. Indoor residential/commercial/institutional nonfood 3. Indoor 

commercial/institutional food 4. Aquatic areas nonfood 5. Aquatic areas food 6. Material 

preservative for exempt treated article uses. 

The Panel proposes that the above use patterns, as well as the descriptions of those use patterns 

provided above be incorporated into any final regulation at 40 CFR 158.100 or to replace proposed 

158.2201. Within the data tables, general use patterns should be combined into single columns when 

the data requirements are the same for the combined uses. If there are no data requirements for a 

specific use, the column for that use is not included in the table. Further, where particular product 

types raises additional concerns, the test notes accompanying the data tables should identify where 

additional data are likely to be required in order to allow the Agency to appropriately assess the risks. 

The Panel believes that adopting this framework on antimicrobial use patterns will provide the 

necessary guidance for applicants to identify the data requirements for their products. However, the 

Panel also believes that any proposed framework for organizing data requirements must be available 

for full review and comment by the entire regulated community. The Panel recommends that EPA 

adopt the use pattern framework presented below and repropose this regulation to permit full public 

review and comment on the revised framework. 

Response: see response 50.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26659 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 456 

Comment Code: 53000 

Comment: III. Alternative Proposals for Toxicology Data Requirements 

The Panel elsewhere has proposed alternative Use Pattern categories for inclusion in a final 

regulation in lieu of those in the proposal. In the Panel’s view, its alternative Use Pattern categories 

should be adopted by EPA because they are relevant, clear and applicable to antimicrobial 

pesticides. The following alternative proposals for toxicology data incorporate those new Use 

Pattern categories. Where a use is excluded from the definition of an antimicrobial pesticide or from 

the definition of a pesticide chemical, it should be excluded from this section. For uses that are 

pesticidal but not within the scope of the definition of antimicrobial pesticide, a reference should be 

made to the appropriate sections of the data requirements for conventional or biochemical 

pesticides. The following are suggested revisions that are applicable regardless of the alternative 

approach to the data requirement tables. 

If antimicrobial use pattern categories are described in sections other than Section 158.100, specific 

reference to the identification and description must be incorporated into the following paragraph. 

158.2230(a) should be completely rewritten as follows: 

(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the 

environmental chemistry data requirements for a particular pesticide product. Notes that apply to an 

individual test and include specific conditions, qualifications, or exceptions to the designated test are 

listed in paragraph (e) of this section. 

Section 158.2230 (b) should be eliminated in its entirety and replaced with the following: 

(b) Use Patterns: 

(1) Antimicrobial food use patterns include products classified under the general antimicrobial use 

patterns of ‘aquatic areas food use’ and ‘commercial and institutional indoor food use.’ (2) 

Antimicrobial nonfood use patterns include products classified under the general antimicrobial use 

patterns of indoor industrial, indoor residential/institutional/commercial nonfood, aquatic areas 

nonfood, and material preservative for exempt treated article use. (3) Use of products as aquatic 

herbicides or agricultural fungicides is outside of the scope of these data requirements. Registrants of 

such uses should refer to Subpart F or to Section 158.2050 of this Part. 

The Panel agrees that the Agency needs certain information to make a regulatory judgment on 

proposed uses of antimicrobial pesticides under FIFRA and to determine the safety of the pesticide 

chemical residues under FFDCA Section 408. The Panel has developed two alternative proposals 

intended to provide clearer instructions to registrants taking into account the specific considerations 

and applicability of these types of requirements for antimicrobial pesticides and to incorporate 

appropriate tiering to avoid unnecessary testing and generation of redundant data. In addition, the 

Panel reiterates its strong recommendation that the Agency explicitly incorporate integrative 

approaches to testing, as well as to the development of appropriate guidance on tiering data 

requirements to estimated exposures in a scientifically defensible manner, including a threshold 

concept for toxicological concerns. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 457 

The first proposal attempts to fully incorporate the new science for determination of toxicology 

testing. The Panel recognizes that this proposal may go beyond where the Agency feels it currently 

can be in terms of a data requirement regulation, since many components may still be under 

scientific review and policies may still need to be developed to incorporate these into risk assessment 

procedures [FN#13:See Agency comments in proposed rule at page 59423]. Even so, the Panel 

asserts that the Agency has a unique opportunity to propose regulations that are consistent with 

current science and permit sufficient flexibility to continue to move the science forward. The Panel 

strongly recommends consideration be given to incorporating this first proposal. 

The Panel’s second alternative is, in the view of the industry experts who make up the Panel’s 

toxicology work group, a less preferred approach. It represents an interim solution that is an 

advance over the approach in EPA’s current proposal but does not go as far as the Panel’s preferred 

proposal in incorporating the best current science. The Panel offers this as a potentially viable 

approach that will represent real progress, although not to the extent the Panel believes is 

appropriate. 

In the Panel’s view, either of these alternatives represents a substantial improvement over the 

Proposal EPA has published for comment. The Panel urges EPA to adopt one of the following two 

proposals. 

Response: see responses 50.16, 80.22, 80.64,and 80.72 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27267 

Comment Code: 53000 

Comment: B. Proposed General Use Patterns 

Based on the above considerations, LANXESS proposes that the use categories for antimicrobials 

be subdivided into the following six general use patterns: 1. Indoor industrial (all nonfood) 2. Indoor 

residential/commercial/institutional nonfood 3. Indoor commercial/institutional food 4. Aquatic 

areas nonfood 5. Aquatic areas food 6. Material preservative for exempt treated article uses 

LANXESS proposes that the above use patterns, as well as the descriptions of those use patterns 

provided above be incorporated into any final regulation at 40 CFR 158.100 or to replace proposed 

158.2201. Within the data tables, general use patterns should be combined into single columns when 

the data requirements are the same for the combined uses. If there are no data requirements for a 

specific use, the column for that use is not included in the table. Further, where particular product 

types raises additional concerns, the test notes accompanying the data tables should identify where 

additional data are likely to be required in order to allow the Agency to appropriately assess the risks. 

LANXESS believes that adopting this framework on antimicrobial use patterns will provide the 

necessary guidance for applicants to identify the data requirements for their products. However, 

LANXESS also believes that any proposed framework for organizing data requirements must be 

available for full review and comment by the entire regulated community. LANXESS recommends 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 458 

that EPA adopt the use pattern framework presented below and re-propose this regulation to permit 

full public review and comment on the revised framework. 

Response: see response 50.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27349 

Comment Code: 53000 

Comment: III. Alternative Proposals for Toxicology Data Requirements 

LANXESS elsewhere has proposed alternative Use Pattern categories for inclusion in a final 

regulation in lieu of those in the proposal. In LANXESS’s view, its alternative Use Pattern categories 

should be adopted by EPA because they are relevant, clear and applicable to antimicrobial 

pesticides. The following alternative proposals for toxicology data incorporate those new Use 

Pattern categories. Where a use is excluded from the definition of an antimicrobial pesticide or from 

the definition of a pesticide chemical, it should be excluded from this section. For uses that are 

pesticidal but not within the scope of the definition of antimicrobial pesticide, a reference should be 

made to the appropriate sections of the data requirements for conventional or biochemical 

pesticides. The following are suggested revisions that are applicable regardless of the alternative 

approach to the data requirement tables. 

If antimicrobial use pattern categories are described in sections other than Section 158.100, specific 

reference to the identification and description must be incorporated into the following paragraph. 

158.2230(a) should be completely rewritten as follows 

(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the 

environmental chemistry data requirements for a particular pesticide product. Notes that apply to an 

individual test and include specific conditions, qualifications, or exceptions to the designated test are 

listed in paragraph (e) of this section. 

Section 158.2230 (b) should be eliminated in its entirety and replaced with the following: (b) Use 

Patterns: (1) Antimicrobial food use patterns include products classified under the general 

antimicrobial use patterns of ‘aquatic areas food use’ and ‘commercial and institutional indoor food 

use.’ (2) Antimicrobial nonfood use patterns include products classified under the general 

antimicrobial use patterns of indoor industrial, indoor residential/institutional/commercial nonfood, 

aquatic areas nonfood, and material preservative for exempt treated article use. (3) Use of products 

as aquatic herbicides or agricultural fungicides is outside of the scope of these data requirements. 

Registrants of such uses should refer to Subpart F or to Section 158.2050 of this Part. 

LANXESS agrees that the Agency needs certain information to make a regulatory judgment on 

proposed uses of antimicrobial pesticides under FIFRA and to determine the safety of the pesticide 

chemical residues under FFDCA Section 408. LANXESS has developed two alternative proposals 

intended to provide clearer instructions to registrants taking into account the specific considerations 

and applicability of these types of requirements for antimicrobial pesticides and to incorporate 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Antimicrobial Use Patterns Section (50) Page 459 

appropriate tiering to avoid unnecessary testing and generation of redundant data. In addition, 

LANXESS reiterates its strong recommendation that the Agency explicitly incorporate integrative 

approaches to testing, as well as to the development of appropriate guidance on tiering data 

requirements to estimated exposures in a scientifically defensible manner, including a threshold 

concept for toxicological concerns. 

The first proposal attempts to fully incorporate the new science for determination of toxicology 

testing. LANXESS recognizes that this proposal may go beyond where the Agency feels it currently 

can be in terms of a data requirement regulation, since many components may still be under 

scientific review and policies may still need to be developed to incorporate these into risk assessment 

procedures [FN#13:See Agency comments in proposed rule at page 59423]. Even so, LANXESS 

asserts that the Agency has a unique opportunity to propose regulations that are consistent with 

current science and permit sufficient flexibility to continue to move the science forward. LANXESS 

strongly recommends consideration be given to incorporating this first proposal. 

LANXESS’s second alternative is, in the view of the industry experts who make up LANXESS’s 

toxicology work group, a less preferred approach. It represents an interim solution that is an 

advance over the approach in EPA’s current proposal but does not go as far as LANXESS’s 

preferred proposal in incorporating the best current science. LANXESS offers this as a potentially 

viable approach that will represent real progress, although not to the extent LANXESS believes is 

appropriate. 

In LANXESS’s view, either of these alternatives represents a substantial improvement over the 

Proposal EPA has published for comment. LANXESS urges EPA to adopt one of the following 

two proposals. 

Response: see responses 50.16, 80.22, 80.64, and 80.72 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Product Chemistry Section (60) Page 460 

Product Chemistry (60) 

Verbatim Comments and Response References for the Product Chemistry 

Section 

Comment Code: 60000 Product chemistry 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25708 

Comment Code: 60000 

Comment: OTHER REQUIREMENTS 

Product chemistry data requirements 

SFE supports application of existing "conventional pesticides" product chemistry data requirements 

to antimicrobials. These essential chemistry data requirements include data identifying the basic 

identity and chemical and physical characteristics of a pesticide chemical. 

Response: EPA acknowledges SFE's support for application of the existing "conventional 

pesticides" product chemistry data requirements to antimicrobials. 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26070 

Comment Code: 60000 

Comment: * Application of existing "conventional pesticides" product chemistry data requirements 

to antimicrobials. These essential chemistry data requirements include data identifying the basic 

identity and chemical and physical characteristics of a pesticide chemical. 

Response: EPA acknowledges CASQA's support for application of the existing "conventional 

pesticides" product chemistry data requirements to antimicrobials. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26546 

Comment Code: 60000 

Comment: APPENDIX C 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Product Chemistry Section (60) Page 461 

COMMENTS ON THE PROPOSED DATA REQUIREMENTS FOR PRODUCT 

CHEMISTRY 

The Proposed Rule at 40 CFR 158.2210 (page 59432) states that the product chemistry data 

requirements previously promulgated for conventional pesticides (72 FR 60934, October 26, 2007) 

at 40 CFR 158 Subpart D will apply to antimicrobial pesticides without comment or change. The 

regulations for biochemical and microbial pesticides do not rely upon the product chemistry data 

requirements for conventional pesticides but instead identify the relevant requirements for those 

types of compounds, including appropriate footnotes for each data requirement (see 40 CFR 158 

Part U and Part V). While product chemistry data requirements may not be dependent upon the use 

pattern of the pesticide, there are considerations which differ among the types of pesticide products. 

The Agency has not explained why the product chemistry data requirements at 40 CFR Subpart D 

for conventional pesticides are fully applicable to antimicrobial pesticides. 

Antimicrobial pesticides include chemistries that differ significantly from those of conventional 

pesticides. EPA should have developed the product chemistry requirements for antimicrobials with 

those differences in mind. For example, antimicrobial pesticides include compounds which are 

highly reactive, which may be generated only in-situ, or which are metals or other elements. The 

product chemistry data requirements for conventional pesticides were not developed with such 

compounds in mind. Failure to address the unique nature of antimicrobial pesticides may result 

either in generation of irrelevant information or in a need to provide other types of information. In 

either case, the simple adoption of the data requirements for conventional pesticides does not 

provide the applicant with a reasonable understanding of the types of data that will be needed for 

antimicrobials. 

Response: See responses 1 and 60.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26554 

Comment Code: 60000 

Comment: The Panel notes that the proposed rule identifying the data requirements for 

conventional pesticides was designated as only applicable to those pesticides (70 FR 12276, March 

11, 2005). As such, antimicrobial registrants were not put on notice that they should have reviewed 

and provided comments on the proposed requirements. While the Panel did submit comments on 

the conventional pesticides data requirements, the Agency identified certain comments as outside of 

the scope of the regulation and noted they might be considered at the time of further revisions (72 

FR 60934, October 26, 2007, at page 60939). The Panel believes that the substance of the 

conventional pesticide data requirements should be reconsidered before proposing to apply them to 

antimicrobials. 

Response: See response 60.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 
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Comments and Response References: 

Product Chemistry Section (60) Page 462 

Letter ID: 0088 

Comment ID: 26555 

Comment Code: 60000 

Comment: The Panel believes that there are issues associated with the data requirements 

"Discussion of the formation of Impurities" and "Preliminary Analysis" in the table at 40 CFR 

158.130. Under the columns for "test substance to support," the table indicates that testing of an EP 

may be required to address impurities and/or preliminary analysis of the MP. The use of the phrase 

"and possibly" is too imprecise to be used in a meaningful regulation. It should be removed from 

the table. The test notes should adequately identify any conditions where additional data are required 

or when the requirement is not applicable. The footnotes are not adequately descriptive. 

The data requirement at 40 CFR 158.130 for "Particle size, fiber length, and diameter distribution" 

also is of concern. The rationale for this new requirement included that these data, which clearly are 

applicable only under certain circumstances, are "needed in the environmental fate assessment to 

estimate potential drift to nontarget areas." In its response to comments on the conventional 

pesticides rule (EPA-HQ-OPP-2004-0387-0178 at page 15), EPA further identified that "this data 

requirement may also contribute to determinations of inhalation toxicity." The Panel requests that 

the Agency provide a detailed explanation of how such data will be used. It is impossible for the 

Panel to comment on the appropriateness of the data requirement without that explanation. In the 

case of antimicrobial pesticides, there are no proposed data requirements for spray drift; however, 

there is the possibility that such assessments could be conducted. Both of the proposed uses of 

these data are of concern. The possibility of evaluation using an end product is of particular concern, 

since no explanation of the potential application of the information has been provided. Until such 

explanation has been provided and the scientific and technical use has been opened to public 

comment, the Panel requests that the Agency remove this requirement. 

Footnote 23 for the table at 40 CFR 158.130 for "Particle size, fiber length, and diameter 

distribution" is unclear. The Panel suggests that the "and" be changed to "or" to more clearly 

identify that substances meeting either criteria must address the requirement. As it is written, it 

suggests that both criteria must be met before the requirement is applicable. 

The data requirement at 40 CFR 158.130 for "Water Solubility" does not clearly explain that the 

Agency historically has been interested in data on solubility in other solvents. The suggested testing 

guidelines do not include reference to other solvents. If the Agency intends to require data on 

solubility in solvents other than water (as was indicated by the Agency in verbal discussions with an 

industry group in February 2004 and as indicated in the Agency’s Standard Operating Procedures for 

Product Properties, January 8, 2003), the data requirement itself should be revised to say "Solubility 

in water and organic solvents" to accurately identify the actual data requirement. If appropriate, the 

Agency could suggest a preferred testing guideline. However, if the Agency is only interested in 

water solubility information, then that should be made clear. 

The Panel generally concurs with the proposal to amend 40 CFR 158.1(c)(4) to identify that the 

product chemistry data requirements at 40 CFR 158 Subpart D are applicable to antimicrobial 

pesticides. However, the Panel requests that the Agency specifically address the deficiencies above 

and provide adequate justification for applying the existing requirements to antimicrobials without 

consideration of the highly dissimilar chemistries and inapplicability of many of the requirements. 
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Comments and Response References: 

Product Chemistry Section (60) Page 463 

Response: See responses 60.1, 60.3, 60.4, 60.5, and 60.6 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27270 

Comment Code: 60000 

Comment: APPENDIX C 

COMMENTS ON THE PROPOSED DATA REQUIREMENTS FOR PRODUCT 

CHEMISTRY 

The Proposed Rule at 40 CFR 158.2210 (page 59432) states that the product chemistry data 

requirements previously promulgated for conventional pesticides (72 FR 60934, October 26, 2007) 

at 40 CFR 158 Subpart D will apply to antimicrobial pesticides without comment or change. The 

regulations for biochemical and microbial pesticides do not rely upon the product chemistry data 

requirements for conventional pesticides but instead identify the relevant requirements for those 

types of compounds, including appropriate footnotes for each data requirement (see 40 CFR 158 

Part U and Part V). While product chemistry data requirements may not be dependent upon the use 

pattern of the pesticide, there are considerations which differ among the types of pesticide products. 

The Agency has not explained why the product chemistry data requirements at 40 CFR Subpart D 

for conventional pesticides are fully applicable to antimicrobial pesticides. 

Antimicrobial pesticides include chemistries that differ significantly from those of conventional 

pesticides. EPA should have developed the product chemistry requirements for antimicrobials with 

those differences in mind. For example, antimicrobial pesticides include compounds which are 

highly reactive, which may be generated only in-situ, or which are metals or other elements. The 

product chemistry data requirements for conventional pesticides were not developed with such 

compounds in mind. Failure to address the unique nature of antimicrobial pesticides may result 

either in generation of irrelevant information or in a need to provide other types of information. In 

either case, the simple adoption of the data requirements for conventional pesticides does not 

provide the applicant with a reasonable understanding of the types of data that will be needed for 

antimicrobials. 

Response: See responses 1 and 60.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27272 

Comment Code: 60000 

Comment: LANXESS notes that the proposed rule identifying the data requirements for 

conventional pesticides was designated as only applicable to those pesticides (70 FR 12276, March 

11, 2005). As such, antimicrobial registrants were not put on notice that they should have reviewed 
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Comments and Response References: 

Product Chemistry Section (60) Page 464 

and provided comments on the proposed requirements. While the ACC Biocide Panel did submit 

comments on the conventional pesticides data requirements, the Agency identified certain 

comments as outside of the scope of the regulation and noted they might be considered at the time 

of further revisions (72 FR 60934, October 26, 2007, at page 60939). LANXESS believes that the 

substance of the conventional pesticide data requirements should be reconsidered before proposing 

to apply them to antimicrobials. 

Response: See response 60.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27273 

Comment Code: 60000 

Comment: LANXESS believes that there are issues associated with the data requirements 

"Discussion of the formation of Impurities" and "Preliminary Analysis" in the able at 40 CFR 

158.130. Under the columns for "test substance to support," the table indicates that testing of an EP 

may be required to address impurities and/or preliminary analysis of the MP. The use of the phrase 

"and possibly" is too imprecise to be used in a meaningful regulation. It should be removed from 

the table. The test notes should adequately identify any conditions where additional data are required 

or when the requirement is not applicable. The footnotes are not adequately descriptive. 

The data requirement at 40 CFR 158.130 for "Particle size, fiber length, and diameter distribution" 

also is of concern. The rationale for this new requirement included that these data, which clearly are 

applicable only under certain circumstances, are "needed in the environmental fate assessment to 

estimate potential drift to nontarget areas." In its response to comments on the conventional 

pesticides rule (EPA-HQ-OPP-2004-0387-0178 at page 15), EPA further identified that "this data 

requirement may also contribute to determinations of inhalation toxicity." LANXESS requests that 

the Agency provide a detailed explanation of how such data will be used. It is impossible for 

LANXESS to comment on the appropriateness of the data requirement without that explanation. In 

the case of antimicrobial pesticides, there are no proposed data requirements for spray drift; 

however, there is the possibility that such assessments could be conducted. Both of the proposed 

uses of these data are of concern. The possibility of evaluation using an end product is of particular 

concern, since no explanation of the potential application of the information has been provided. 

Until such explanation has been provided and the scientific and technical use has been opened to 

public comment, LANXESS requests that the Agency remove this requirement. 

Footnote 23 for the table at 40 CFR 158.130 for "Particle size, fiber length, and diameter 

distribution" is unclear. LANXESS suggests that the "and" be changed to "or" to more clearly 

identify that substances meeting either criteria must address the requirement. As it is written, it 

suggests that both criteria must be met before the requirement is applicable. 

The data requirement at 40 CFR 158.130 for "Water Solubility" does not clearly explain that the 

Agency historically has been interested in data on solubility in other solvents. The suggested testing 

guidelines do not include reference to other solvents. If the Agency intends to require data on 

solubility in solvents other than water (as was indicated by the Agency in verbal discussions with an 
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Comments and Response References: 

Product Chemistry Section (60) Page 465 

industry group in February 2004 and as indicated in the Agency’s Standard Operating Procedures for 

Product Properties, January 8, 2003), the data requirement itself should be revised to say "Solubility 

in water and organic solvents" to accurately identify the actual data requirement. If appropriate, the 

Agency could suggest a preferred testing guideline. However, if the Agency is only interested in 

water solubility information, then that should be made clear. 

LANXESS generally concurs with the proposal to amend 40 CFR 158.1(c)(4) to identify that the 

product chemistry data requirements at 40 CFR 158 Subpart D are applicable to antimicrobial 

pesticides. LANXESS requests that the Agency specifically address the deficiencies above and 

provide adequate justification for applying the existing requirements to antimicrobials without 

consideration of the highly dissimilar chemistries and inapplicability of many of the requirements. 

Response: See responses 60.1, 60.3, 60.4, 60.5, and 60.6 
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Comments and Response References: 

Product Performance Section (70) Page 466 

Product Performance (70) 

Verbatim Comments and Response References for the Product Performance 

Section 

Comment Code: 70000 Product performance 

Commenter Name: Kelly K. Naujock 

Commenter Organization: S.C. Johnson & Son, Inc. 

Letter ID: 0063 

Comment ID: 25423 

Comment Code: 70000 

Comment: An area of special concern to us is the efficacy guidelines appearing on page 59432 in 

the table entitled "Table - Antimicrobial Product Performance Data Requirements". This table 

references the 91 guidelines for generation of efficacy data. The 91 guidelines, published in draft in 

1982, were never deemed final. Further, they are not currently publicly available. The Agency has 

been working on the 810 guidelines for several years and we have been reassured several times that 

these guidelines are near completion. In fact, they should be published with a 60-day comment 

period during the first quarter of this year. Given these considerations, the referenced data 

requirements table should be amended to reference the appropriate 810 guidelines and this rule 

should be finalized after the 810 guidelines are published. 

Response: see responses 70.1, 70.2 and 191.1 

Commenter Name: Patrick H. Quinn 

Commenter Organization: Innovation and Reform Group (IRG) 

Letter ID: 0080 

Comment ID: 25497 

Comment Code: 70000 

Comment: Emerging Pathogens and Disinfection Hierarchy 

The Proposed Rule should include a clear explanation of OPP’s existing Emerging Pathogen 

expedited review mechanism and its use of the Disinfection Hierarchy in determining product 

efficacy under such circumstances. 

A several year effort by The IRG member companies--working in conjunction with the world’s 

leading microbiologists (Sattar, Rutala, etc.) and the Antimicrobial Division, led to EPA adoption of 

the well established science underlying the Hierarchy of Resistant Organisms ("Disinfection 

Hierarchy") on July 25, 2007. "Implementation of the Emerging Pathogens and Disinfection 

Hierarchy for Antimicrobial Products: Notice of Availability. Federal Register Vol. 72 No. 142 

[EPA-HQ-OPP-2007-0086]. Attached here. 
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Comments and Response References: 

Product Performance Section (70) Page 467 

This EPA Guidance is intended to deal specifically with situations involving "emerging" or "reemerging" pathogens. Its premise--based upon the work of Spaulding, Kline, DeForrest, and others, 

is that bacterial and viral organisms can be accurately ranked within a hierarchy of resistance (i.e. the 

degree of difficulty associated with controlling the organism). 

Proper disinfection is crucial to interrupt the environmental spread of many emerging viruses, but 

during an outbreak these new organisms cannot be fully characterized and disinfection products 

cannot be tested against the organism or its surrogate. The EPA Guidance under the Disinfection 

Hierarchy allows the Agency and CDC to provide recommendations on efficacious products based 

upon that product’s demonstrated ability to have killed a virus of similar size, structure and 

resistance. 

The 2007 EPA policy includes a detailed plan for working with CDC which would "trigger" the use 

of the Emerging Pathogen policy through its initial characterization of the viral organism. This 

"Emerging Pathogen" policy then allows health authorities to provide timely advice on registered 

broad spectrum disinfectants as appropriate tools for pathogen control during the outbreak. The 

policy also requires that registrants test the actual or surrogate organism in an approved method 

when they become available. 

The Antimicrobial Division should be commended for its role in the collaborative effort which led 

to the 2007 Emerging Pathogens and Disinfection Hierarchy Policy. In fact, in many ways it 

demonstrates that OPP can responsibly take advantage of established science to make its own 

judgments regarding innovative approaches to toxicological and efficacy assessments--and do so far 

more promptly and effectively apart from the federal rulemaking process. This case study reinforces 

our convictions that Subpart 158W must be an agile system, adaptable to change and encourage 

OPP to seek out other such opportunities for toxicological innovation. 

A Subpart 158W Final rule should include a discussion and explanation of the EPA Emerging 

Pathogen policy, the Disinfection Hierarchy, and its existing guidance for registrants on the 

procedure which OPP has already adopted to evaluate product efficacy in expedited timeframes in 

emerging pathogen situations. 

Response: see response 70.5 

Commenter Name: Patrick H. Quinn 

Commenter Organization: Innovation and Reform Group (IRG) 

Letter ID: 0080 

Comment ID: 25500 

Comment Code: 70000 

Comment: We also strongly encourage the inclusion of EPA’s existing Guidance on Emerging 

Pathogens and the Disinfection Hierarchy. Its absence from the Proposal is puzzling. 

Response: see response 70.5 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 
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Comments and Response References: 

Product Performance Section (70) Page 468 

Letter ID: 0086 

Comment ID: 25553 

Comment Code: 70000 

Comment: II. Product Performance/Efficacy 

The expressed reason for the Agency proposing this rule in 40 CFR subpart W of part 158 is that 

"revisions are needed to reflect current scientific knowledge and current Agency regulatory 

practices." (Federal Register/Vol. 73, No. 196 Oct 8, 2008/Proposed Rules, p.59382.) It is also 

stated that "EPA agrees with HHS that both current antimicrobial pesticide registrants and 

applicants seeking an antimicrobial registration should understand the applicability of the proposed 

data requirements, once promulgated." (p.59426) 

Response: see responses 191.1 and 70.1 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25556 

Comment Code: 70000 

Comment: Under Product Performance §158.2220 (a) (1) it states that "The Agency may require, 

on a case-by-case basis submission of product performance data for any pesticide product registered 

or proposed for registration". Either under this section or as a footnote to the table, EPA should 

insert the portion of the footnote relevant to antimicrobial pesticides that is currently found at § 

158.640.1 [FN#1: [Section]158.640 footnote 1 states "The Agency has waived all requirements to 

submit efficacy data unless the pesticide product bears a claim to control pest microorganisms that 

pose a threat to human health, and whose presence, cannot readily be observed by the user including 

but not limited to microorganisms infectious to man in any area of the inanimate environment" 

However, each registrant must ensure through testing that the products are efficacious when used in 

accordance with label directions and commonly accepted pest control practices. The Agency 

reserves the right to require, on a case-by- case basis, submission of efficacy data for any pesticide 

product registered or proposed for registration.] 

Response: see response 70.17 

Commenter Name: Jay Feldman 

Commenter Organization: Beyond Pesticides 

Letter ID: 0067 

Comment ID: 25722 

Comment Code: 70000 

Comment: The widespread and indiscriminate use of antimicrobial agents can lead to the 

development of resistant bacteria. Several peer-reviewed studies have been previously submitted to 

the agency detailing this prospect. It has also been brought to the agency’s attention that cross 

resistance to antibiotics may also be a consequence of widespread antimicrobial use. While the EPA 

maintains that it continues to work with the Interagency Task Force on Antimicrobial Resistance 
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Comments and Response References: 

Product Performance Section (70) Page 469 

and will monitor the issue, we feel that this is inadequate given the gravity of the consequences that 

resistant bacteria can pose to human health, especially to vulnerable populations including infants 

and children, the elderly and the immuno- compromised. Knowing that for most antimicrobial 

substances the EPA oversees there is no efficacy data, and that most of these are ineffective and 

unnecessary, we believe the agency must find that for these substances, the risks far outweigh any 

perceived benefit. 

Response: see responses 70.15 and 70.16 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25747 

Comment Code: 70000 

Comment: 158W Needs to Address Procedures for Emerging Pathogens The proposed regulation 

does not address how EPA will proactively address emerging pathogens which pose a serious public 

health threat. With a significant rise of hospital acquired infections (HAls), there is an immediate 

need for a more efficient process to address public health threats. Over the past 10 years, there have 

been emerging pests such as MRSA, VRE, Clostridium difficile, Avian Flu, Anthrax and hoof and 

mouth disease. With each emerging pathogen, healthcare facilities are immediately demanding 

products to address pathogens. 

The process to address emerging pathogens such a Clostridium difficile spores was an extremely 

slow process. While the Agency wanted expedited removal of Clostridium difficile vegetative claims, 

it took over one year for the Antimicrobial Division to publish a guidance document for registrants 

to add the C. difficile spore claims to labels. In fact, as of the first of 2009, AD had registered only 

one product with a claim of effectiveness against C. difficile endospores. 

Ecolab supports the ACC proposal for incorporation into 158W to expeditiously address emerging 

pathogens which would include the following elements: 

* A trigger mechanism that will activate expedited review of products for control of emerging 

pathogens. The mechanism can be based on other federal agencies' actions, such as FDA, USDA, 

and CDC. 

* Once expedited review has been triggered: 

** A mechanism for expedited efficacy protocol development and approval, if appropriate, involving 

a workshop-type process; 

** A mechanism for ensuring prompt review of efficacy data; and 

** A mechanism for expedited review of new products with claims against emerging pathogens (this 

would be limited to emerging pathogen claims, other claims will be subject to usual review timelines. 
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Comments and Response References: 

Product Performance Section (70) Page 470 

Ecolab encourages EPA's Antimicrobial Division to work with ACC and CSPA to develop a more 

expedited program and test method development to address emerging pathogens as the Agency 

does not have an effective process to address emerging pathogens. 

Response: see response 70.5 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25755 

Comment Code: 70000 

Comment: The proposed 158W product performance guidelines address data requirements for 

public health products, but remains silent as to data requirements for non- public health 

antimicrobial pesticides. The lack of discussion of non-public health pesticides renders the proposed 

rule incomplete. While data for non- public health claims do not require submission to the Agency, 

the registrant is required to generate the necessary data and keep it on file for Agency inspection. 

EPA should revise this section to include those requirements. 

Response: see response 70.7 

Commenter Name: William C. Balek 

Commenter Organization: ISSA 

Letter ID: 0074 

Comment ID: 25867 

Comment Code: 70000 

Comment: [In particular, ISSA supports the following aspects of the ACC Biocides Panel 

Comments:] * Proposed 158W requirements should address procedures for addressing emerging 

pathogens. 

Response: see response 70.5 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25916 

Comment Code: 70000 

Comment: [In the Panel's comments, 12 major discussion points are presented as follows:] * 158 W 

should include procedures for addressing emerging pathogens 

Response: see response 70.5 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 
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Comments and Response References: 

Product Performance Section (70) Page 471 

Comment ID: 25929 

Comment Code: 70000 

Comment: Consumer Specialty Products Association Comments 

Efficacy Guidelines are not Finalized 

CSPA took the Industry lead on Product Performance-Efficacy Data Requirements. The comments 

provided by CSPA on Efficacy data represent the views of Clorox. In the absence of the 810 

guidelines, the proposed rule does not define the efficacy data requirements. A clear set of standards 

followed by both the Agency and registrants should be established to address antimicrobial data 

requirements. 

Additionally, the Agency has failed to incorporate a process to address public health emergencies or 

emerging pathogens. 

Response: see responses 191.1, 70.1, and 70.5 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26158 

Comment Code: 70000 

Comment: Product Efficacy: Final Guidelines Not Available The Agency has not requested 

comments on product efficacy "EPA seeks to avoid comment on the product performance data 

requirements in the Proposal by stating that the Agency "is not proposing to revise product 

performance data requirements ([section] 158.2220) at this time." 73 Fed. Reg. at 59391." However, 

it is incumbent upon the regulated community to point out the Efficacy Guidelines cited in the 

Proposal rely on outdated information and reference a set of unavailable, never published guidelines 

that the Agency is in the process of replacing. The 91 series guidelines referenced in the proposal 

were never published in either draft or final form and it is impossible for a registrant to obtain a 

copy of them, even when they are referenced in Agency correspondence. Further, the 91 series 

guidelines do not reflect current scientific knowledge and may or may not reflect current Agency 

regulatory practices. 

Response: see responses 70.1 and 70.2 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26160 

Comment Code: 70000 

Comment: Furthermore, Page 59386 IV A introduces data requirements for the proposed 

regulation; capturing public health but with no mention of non-public health. This omission on the 

part of the Agency is significant. While Agency policy does not require submission of non-public 
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Comments and Response References: 

Product Performance Section (70) Page 472 

health data, registrants are required to develop data to substantiate label claims. P&G believes the 

definition, data requirements and product labeling instructions are necessary for a non-public health 

claims (i.e. odor-causing bacteria). 

In the case of product performance, data requirements and guidance on meeting these requirements 

are inextricably joined. P&G submits that EPA must complete the process of developing efficacy 

guidelines and then repropose this package with the new guidelines available. The guideline revision 

process should be a high priority for the Agency. It should be completed through the public process 

EPA has established for issuing guidelines. P&G urges EPA to act expeditiously and to include in 

the revised guidelines a process that provides the Agency with improved ability to address the 

efficacy needs arising from public health emergencies, emerging pathogens and innovative 

technologies. Once these product performance guidelines are updated, the Agency should repropose 

this regulation. 

Response: See responses 70.7 and 70.3. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26447 

Comment Code: 70000 

Comment: X. 158 W Should Include Procedures for Addressing Emerging Pathogens 

The Panel supports EPA’s steps toward publishing a policy statement, but there is still a need for a 

formal regulatory practice of registering products to combat emerging pathogens. Over the past 

several years, there have been a number of emerging pests of both economic (e.g. avian flu, hoof 

and mouth disease) and public health (e.g. MRSA, Clostridium difficile) significance. In response, 

EPA has developed testing methods for pathogens, such as Anthrax and C. difficile, as well as a 

process for the rapid response to viral pathogens with the issuance of the Disinfection Hierarchy ( 

http://www.epa.gov/oppad001/disinfection_hier.htm). 

While the disinfection hierarchy policy provides a mechanism for off label claims for control of viral 

pathogens on environmental surfaces, the policy does not address other, non- viral emerging or reemerging pathogens. Similarly, the policy does not address development of testing methods to 

establish efficacy. The experience with Anthrax and C. difficile methods development is that the 

issuance of test methods took an inordinate amount of time, and in the case of Anthrax, the 

mechanism for obtaining a claim is so burdensome as to be rarely achievable. Any process adopted 

by the Agency should take into account the relative urgency of the need for methods, policies, and 

products to control pathogens. 

There remains a need for a formal process to enable EPA to evaluate and register products to 

combat emerging pathogens promptly and effectively. A process that involves broad-based 

stakeholder input would ensure there is fully transparent scientific and technical input. Such a 

process would enable EPA to respond more rapidly to real world needs. The Subpart W regulation 

should set forth a procedure for EPA to quickly evaluate new products, or new uses for existing 

products, to meet these emerging threats. The regulations should include the following elements: 
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Comments and Response References: 

Product Performance Section (70) Page 473 

* A trigger mechanism that will activate expedited review of products for control of emerging 

pathogens. The mechanism can be based on other federal agencies’ actions, for example, USDA and 

CDC. 

* Once expedited review has been triggered: 

- A mechanism for expedited efficacy protocol development and approval, if appropriate, involving 

a workshop-type process. 

- A mechanism for ensuring prompt review of efficacy data. 

- A mechanism for expedited review of new products with claims against emerging pathogens (this 

would be limited to the emerging pathogen claims, other claims will be subject to usual review time 

frame). 

These regulations will help ensure there is a clear path forward for registrants to develop, test, obtain 

approval of and market products that can be used to combat emerging pathogens. It will also 

provide an appropriate degree of transparency. 

Response: see response 70.5 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26556 

Comment Code: 70000 

Comment: APPENDIX D 

COMMENTS ON PROPOSED DATA REQUIREMENTS FOR PRODUCT PERFORMANCE 

EPA does not solicit comment on the product performance data requirements in the proposal, 

stating that the Agency "is not proposing to revise product performance data requirements ([section] 

158.2220) at this time." 73 Fed. Reg. at 59391. According to EPA: 

At this time there are nearly identical product performance data requirements for antimicrobial 

chemicals in both [sections] 158.400 and part 161. EPA proposes to transfer the contents of the 

existing product performance data requirements for antimicrobial into subpart W, specifically 

[section] 158.2220. 

Id. However the Panel believes that the data requirements in both places, and in the proposal, do 

not reflect current Agency practice, rely on outdated information and reference a set of unavailable, 

never published guidelines that the Agency is in the process of replacing. The 91 series guidelines 

referenced in the proposal were never published in either draft or final form and it is impossible for 

a registrant to obtain a copy of them, even when they are referenced in Agency correspondence. It 

would appear that they are still used as internal guidance, but are not available to applicants and 
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Comments and Response References: 

Product Performance Section (70) Page 474 

registrants. All but the most routine public health uses are subject to uncertainty and lengthy delays 

because of the absence of up-to-date, reliable, publicly available guidance and stable EPA 

requirements. 

Response: see responses 70.1 and 70.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26558 

Comment Code: 70000 

Comment: The Agency has been working on the development of guidelines to be included in the 

810 Series Pesticide Assessment Guidelines. The Consumer Specialties Product Association (CSPA) 

provided input to the Agency in the development of the following proposed guidelines: 

810.2000 - General Considerations 810.2100 - Sterilants 810.2200 - Disinfectants 810.2300 - 

Sanitizers 

The Biocides Panel has participated with CSPA in this process. The latest drafts of the above 

guidelines available to CSPA and the Panel are from early 2006. The Agency has stated that these 

referenced 810 guidelines will be published as draft for public comments in the first quarter of 2009 

with a 60-day comment period.[FN#1:EPA plans to publish the sterilant, disinfectant and sanitizer 

guidelines for public comment in 2009 and to continue work on the air, water, and textile materials. 

See Antimicrobial Division Work Plan for 2009, at pp. 10-11. 

www.epa.gov/oppad001/pdf_files/adworkplan2009.pdf] Publication has not occurred as of the 

date of these Comments. 

According to discussions with EPA, in contrast to the six categories proposed at 158.2220, EPA 

intends to publish guidance on the following categories. 

Guideline Number* Data Requirement(Based on Use-Site/Claim Desired) 

810.2000 General Considerations 810.2100 Sterilants 810.2200 Disinfectants 810.2300 Sanitizers 

810.2400 Textiles 810.2500 Air Sanitizers 810.2600 Waste 810.2700 Water 810. 

x Mold 810. 

x Biofilm 810. 

x Fruit/Vegetable Rinse 810. 

x HVAC 810. 

x Medical Waste 810. 

x Treated Articles (Public Health Claims) 810. 
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Comments and Response References: 

Product Performance Section (70) Page 475 

x Other 

*Numbering system may vary depending on publication of final EPA guidelines. 

In the absence of 810 guidelines, efficacy data requirements remain uncertain. There is no process to 

address public health emergencies or emerging pathogens. Until EPA issues final guidelines, the 

Panel and other parties cannot fully comment on the proposal. 

One of the problems with this proposal is demonstrated by the set of definitions proposed for 

158.2203. As EPA acknowledges, these definitions were taken verbatim from the Agency’s proposal 

on antimicrobial registration procedures and labeling, proposed in 1999, but never finalized.[FN#2: 

See Proposed Rule on Registration Requirements for Antimicrobial Pesticide Products and Other 

Pesticide Regulatory Changes, 64 Fed. Reg. 50726 (September 17, 1999). This rulemaking is required 

by FIFRA 3(h)(3), requiring rulemaking to establish regulations to "accelerate and improve the 

review of antimicrobial pesticide products. Because of the changes in registration procedures 

resulting from the enactment of section 33 of FIFRA, which established pesticide registration 

service fees, along with mandatory procedural requirements, this regulatory proposal would have to 

be rewritten before reproposal. The Panel is not aware of any current plans for publication of an 

updated proposal.] However, as part of the process to develop the 810.2000 series antimicrobial 

efficacy guidelines, these have been significantly revised from the 1999 proposal. Moreover, some of 

definitions are inconsistent with definitions in FIFRA section FIFRA [Section] 4(i)(4) (C)(i, ii, iii)). 

CSPA in its comments, which the Panel incorporates by reference, has provided the definitions as 

they appear in the most recent working draft of EPA guidance that is more than two years 

old.[FN#3:If, in fact, EPA intends to include the definitions proposed at 40 CFR 158.2203 in its 

final 810 Series Guidance documents, the Panel questions why such definitions are proposed for 

inclusion in this regulation. There does not appear to be a need for inclusion of these definitions in 

both regulation and guidance.] 

Response: see responses 191.1, 70.1, 70.5, 70.6, 70.9, and 70.10 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26565 

Comment Code: 70000 

Comment: EPA stated in the Preamble to this proposed regulation that it was intended to provide 

"revisions . . . needed to reflect current scientific knowledge and current Agency regulatory 

practices." 73 Fed. Reg. at 59382. Unfortunately, this portion of the proposal is not current. 

Moreover, it is not consistent with EPA’s statement that it "agrees with HHS that both current 

antimicrobial pesticide registrants and applicants seeking an antimicrobial registration should 

understand the applicability of the proposed data requirements, once promulgated." 73 Red. Reg. at 

.59426. Clearly, registrants and applicants will not be able to understand the applicability of the 

efficacy data requirements to important public health uses unless this Proposal is updated and the 

long- awaited Agency guidance on antimicrobial efficacy requirements is finalized. 
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Comments and Response References: 

Product Performance Section (70) Page 476 

Response: see responses 191.1 and 70.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26566 

Comment Code: 70000 

Comment: The critical need for science-based guidance on what EPA requires the efficacy of 

antimicrobial pesticides for public health purposes cannot be overemphasized. While EPA generally 

has committed to flexibility with regard to test methods relied upon to meet its data 

requirements,[FN#4:See, e.g., EPA’s statement at 59387: "[T]he applicant is not to required to use 

these [EPA] Guidelines, but may instead seek to fulfill the data requirement by other appropriate 

means."] applicants for antimicrobial public health uses, in fact, typically are required to use only test 

methods that have been explicitly approved by EPA or that meet with specificity methods that have 

been designated by EPA to support a particular claim. Despite EPA’s reliance on such specific test 

methods, some have not been validated, even after decades of use, and are recognized by EPA as 

highly variable.[FN#5:Numerous peer-reviewed scientific studies published in the 1980s (e.g., 

Rutala, WA and Cole, EC. 1987. Infection Control, 8(12): 501-506. Cole, EC; Rutala, WA; Samsa, 

GP. 1988. Journal of AOAC, 71(6): 1187-1194. Cole, EC; Rutala, WA; Carson, JL. 1987. Journal of 

AOAC, 70(5): 903-906) and funded under a cooperative agreement between EPA and researchers at 

the University of North Carolina demonstrated the extreme variability of the Use-Dilution Test 

Method (UDM). EPA requires the UDM to demonstrate the efficacy of antimicrobials that make 

hospital disinfectant efficacy claims (Efficacy Data Requirements, Disinfectants for Use on Hard 

Surfaces, EPA DIS/TSS-1 (January 22, 1982). Furthermore, in response to a request by the House 

Committee on Government Operations, the then US General Accounting Office (GAO) undertook 

a review of EPA’s regulation of disinfectant efficacy during an investigation from January through 

November 1989 (GAO. 1990. "Report to Congressional Requesters, Disinfectants, EPA Lacks 

Assurance They Work". GAO/RCED-90-139. August.). Among other conclusions, the GAO 

reported that disinfectant efficacy methods recommended by EPA have been widely criticized by 

industry, academia, and others for producing highly variable results.] Moreover, the essential role of 

the protocol review process with regard to efficacy data requirements is confirmed by the fact that 

two PRIA fee categories were added to the antimicrobial PRIA fees table with the 2008 PRIA 

reauthorization.[FN#6:PRIA category A521 is for an internal AD review of a public health efficacy 

protocol, with a 4 month review time and a fee of $2,100 in 2009. PRIA category A522 is for an 

external EPA expert panel review of a public health efficacy protocol, with a 15 month review time 

and a fee in 2009 of $10,500.] These fee categories were added to the PRIA- covered actions 

because of an interest by registrants in obtaining some predictability with regard to review time 

frames. Even with the creation of these fee categories, the process for obtaining protocol approval 

or even Agency guidance is a slow and uncertain process. 

Response: see response 70.8 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26568 
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Comments and Response References: 

Product Performance Section (70) Page 477 

Comment Code: 70000 

Comment: In the case of product performance for public health uses, data requirements and 

guidance on meeting these requirements are inextricably joined. The Panel submits that EPA must 

complete the process of developing guidelines for public health antimicrobial uses and then 

repropose this package with the new guidelines available. The guideline revision process should be a 

high priority for the Agency. It should be completed through the public process EPA has 

established for issuing guidelines. The Panel urges EPA to act expeditiously and to include in the 

revised guidelines a process that provides the Agency with improved ability to address the efficacy 

needs arising from public health emergencies, emerging pathogens and innovative technologies. 

Once these product performance guidelines are updated, the Agency should repropose this 

regulation. 

Response: see responses 191.1, 70.1, and 80.7 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26753 

Comment Code: 70000 

Comment: 2. Proposed Regulation # [Section] 158.2220(a)(1) 

Text of the Proposed Regulation (emphasis added) Product performance: Product performance 

requirement for all antimicrobial pesticides. "Each applicant must ensure through testing that his 

product is efficacious when used in accordance with label directions and commonly accepted pest 

control practices. The Agency may require, on a case-by-case basis, submission of product 

performance data for any pesticide product registered or proposed for registration." 

The Proposed Regulations Are Vague for the Following Reasons . The Agency has not adequately 

stated the criteria for determining whether product performance data for pesticide products 

registered or proposed for registration must be submitted. Such information requires private 

consultation with the Agency. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27153 

Comment Code: 70000 

Comment: X. 158 W Should Include Procedures for Addressing Emerging Pathogens 

LANXESS supports the EPA’s steps toward publishing a policy statement, but there is still a need 

for formal regulatory practice of registering products to combat emerging pathogens. Over the past 

several years, there have been a number of emerging pests of both economic (e.g. avian flu, hoof 
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Comments and Response References: 

Product Performance Section (70) Page 478 

and mouth disease) and public health (e.g. MRSA, Clostridium difficile) significance. In response, 

EPA has developed testing methods for pathogens, such as Anthrax and C. difficile, as well as a 

process for the rapid response to viral pathogens with the issuance of the Disinfection Hierarchy 

(http://www.epa.gov/oppad001/disinfection_hier.htm). 

While the disinfection hierarchy policy provides a mechanism for off label claims for control of viral 

pathogens on environmental surfaces, the policy does not address other, non-viral emerging or reemerging pathogens. Similarly, the policy does not address development of testing methods to 

establish efficacy. The experience with Anthrax and C. difficile methods development is that the 

issuance of test methods took an inordinate amount of time, and in the case of Anthrax, the 

mechanism for obtaining a claim is so burdensome as to be rarely achievable. Such conservatism on 

the part of the Agency seems to run counter to the relative urgency of the need for methods, 

policies, and products to control pathogens. 

There remains a need for a formal process to enable EPA to evaluate and register products to 

combat emerging pathogens promptly and effectively. A process that involves broad-based 

stakeholder input would ensure there is fully transparent scientific and technical input. Such a 

process would enable EPA to respond more rapidly to real world needs. The Subpart W regulation 

should set forth a procedure for EPA to quickly evaluate new products, or new uses for existing 

products, to meet these emerging threats. The regulations should include the following elements: 

* A trigger mechanism that will activate expedited review of products for control of emerging 

pathogens. The mechanism can be based on other federal agencies’ actions, for example, USDA and 

CDC. 

* Once expedited review has been triggered: 

** A mechanism for expedited efficacy protocol development and approval, if appropriate, involving 

a workshop-type process. 

** A mechanism for ensuring prompt review of efficacy data. 

** A mechanism for expedited review of new products with claims against emerging pathogens (this 

would be limited to the emerging pathogen claims, other claims will be subject to usual review time 

frame). 

These regulations will help ensure there is a clear path forward for registrants to develop, test, obtain 

approval of and market products that can be used to combat emerging pathogens. It will also 

provide an appropriate degree of transparency. 

Response: see response 70.5 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27274 

Comment Code: 70000 
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Comments and Response References: 

Product Performance Section (70) Page 479 

Comment: APPENDIX D 

COMMENTS ON PROPOSED DATA REQUIREMENTS FOR PRODUCT PERFORMANCE 

EPA seeks to avoid comment on the product performance data requirements in the Proposal by 

stating that the Agency "is not proposing to revise product performance data requirements ([section] 

158.2220) at this time." 73 Fed. Reg. at 59391. According to EPA 

"At this time there are nearly identical product performance data requirements for antimicrobial 

chemicals in both [sections] 158.400 and part 161. EPA proposes to transfer the contents of the 

existing product performance data requirements for antimicrobial into subpart W, specifically 

[section] 158.2220." 

Id. However these statements ignore that the data requirements in both places, and in the proposal, 

do not reflect current Agency practice, rely on outdated information and reference a set of 

unavailable, never published guidelines that the Agency is in the process of replacing. The 91 series 

guidelines referenced in the proposal were never published in either draft or final form and it is 

impossible for a registrant to obtain a copy of them, even when they are referenced in Agency 

correspondence. It would appear that they are still used as internal guidance, but are denied to 

applicants and registrants. This is an untenable situation that is all the more alarming because it 

directly and negatively impacts on the Agency’s ability to regulate antimicrobials with public health 

uses. All but the most routine public health uses are subject to uncertainty and lengthy delays 

because of the absence of up-to-date, reliable, publicly available guidance and mature, stable EPA 

requirements. 

Response: see responses 70.1 and 70.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27276 

Comment Code: 70000 

Comment: The Agency has been working on the development of guidelines to be included in the 

810 Series Pesticide Assessment Guidelines. The Chemical Specialties Product Association (CSPA) 

worked jointly with the Agency to develop the following proposed guidelines: 

810.2000 - General Considerations 

810.2100 - Sterilants 

810.2200 - Disinfectants 

810.2300 - Sanitizers 
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Comments and Response References: 

Product Performance Section (70) Page 480 

The Biocides Panel has participated with CSPA in this process. The last drafts of the above 

guidelines available to CSPA and the Panel are from early 2006. The Agency has stated that these 

referenced 810 guidelines will publish in draft in the first quarter of 2009 with a 60-day comment 

period.[FN1: 1 EPA plans to publish the sterilant, disinfectant and sanitizer guidelines for public 

comment in 2009 and to continue work on the air, water, and textile materials. See Antimicrobial 

Division Work Plan for 2009, at pp. 10-11. www.epa.gov/oppad001/pdf_files/adworkplan2009.pdf] 

Publication has not occurred as of the date of these Comments. 

According to discussions with EPA, in contrast to the six categories proposed at 158.2220, EPA 

intends to publish guidance on the following categories. 

Guideline Number (Note: Numbering system may vary depending on publication of final EPA 

guidelines.) and Data Requirement (Based on Use-Site/Claim Desired) 

810.2000- General Considerations 810.2100- Sterilants 810.2200- Disinfectants 810.2300- Sanitizers 

810.2400- Textiles 810.2500- Air Sanitizers 810.2600- Waste 810.2700- Water 810. 

x- Mold 810. 

x- Biofilm 810. 

x- Fruit/Vegetable Rinse 810. 

x- HVAC 810. 

x- Medical Waste 810. 

x- Treated Articles (Public Health Claims) 810. 

x- Other 

In the absence of 810 guidelines, efficacy data requirements remain roiled in controversy, delay, 

inconsistency and a program incapable of acting with agility to address urgent public health needs. 

There is no process to address public health emergencies or emerging pathogens. One of the major 

goals of EPA with the development of antimicrobial data requirements should be a robust set of 

guidance materials that will help both EPA and registrants meet important public health needs. 

Based on the contents of this proposal, it would appear that that goal remains elusive. 

One of the problems with this proposal is demonstrated by the set of definitions proposed for 

158.2203. As EPA acknowledges, these definitions were taken verbatim from the Agency’s proposal 

on antimicrobial registration procedures and labeling, proposed in 1999, but never finalized.[FN2: 

See Proposed Rule on Registration Requirements for Antimicrobial Pesticide Products and Other 

Pesticide Regulatory Changes, 64 Fed. Reg. 50726 (September 17, 1999). This rulemaking is required 

by FIFRA 3(h)(3), requiring rulemaking to establish regulations to "accelerate and improve the 

review of antimicrobial pesticide products. Because of the changes in registration procedures 

resulting from the enactment of section 33 of FIFRA, which established pesticide registration 

service fees, along with mandatory procedural requirements, this regulatory proposal would have to 
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Comments and Response References: 

Product Performance Section (70) Page 481 

be rewritten before reproposal. LANXESS is not aware of any current plans for publication of an 

updated proposal.] However, as part of the process to develop the 810.2000 series antimicrobial 

efficacy guidelines, these have been significantly revised from the 1999 proposal. Moreover, some of 

definitions are inconsistent with definitions in FIFRA section 4(i)(4)(C)(i, ii, iii)). CSPA in its 

comments, which LANXESS incorporates by reference, has provided the definitions as they appear 

in the most recent working draft of EPA guidance that is more than two years old.[FN3: If, in fact, 

EPA intends to include the definitions proposed at 40 CFR 158.2203 in its final 810 Series Guidance 

documents, LANXESS questions why such definitions are proposed for inclusion in this regulation. 

There does not appear to be a need for inclusion of these definitions in both regulation and 

guidance.] 

Response: See responses 70.1, 70.5, 70.6, 70.9, 70.10, and 191.1. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27277 

Comment Code: 70000 

Comment: EPA stated in the Preamble to this proposed regulation that it was intended to provide 

"revisions...needed to reflect current scientific knowledge and current Agency regulatory practices." 

73 Fed. Reg. at 59382. Unfortunately, this portion of the proposal is not current. Moreover, it is not 

consistent with EPA’s statement that it "agrees with HHS that both current antimicrobial pesticide 

registrants and applicants seeking an antimicrobial registration should understand the applicability of 

the proposed data requirements, once promulgated." 73 Red. Reg. at .59426. Clearly, registrants and 

applicants will not be able to understand the applicability of the efficacy data requirements to 

important public health uses unless this Proposal is updated and the long- promised Agency 

guidance on antimicrobial efficacy requirements is finalized. 

Response: see responses 191.1 and 70.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27278 

Comment Code: 70000 

Comment: The critical need for science-based guidance on what EPA requires the efficacy of 

antimicrobial pesticides for public health purposes cannot be overemphasized. While EPA generally 

has committed to flexibility with regard to test methods relied upon to meet its data 

requirements,[FN4: See, e.g., EPA’s statement at 59387: "[T]he applicant is not to required to use 

these [EPA] Guidelines, but may instead seek to fulfill the data requirement by other appropriate 

means."] applicants for antimicrobial public health uses, in fact, typically are required to use only test 

methods that have been explicitly approved by EPA or that meet with specificity methods that have 

been designated by EPA to support a particular claim. Despite EPA’s reliance on such specific test 

methods, some have not been validated, even after decades of use, and are recognized by EPA as 

highly variable.[FN5: Numerous peer-reviewed scientific studies published in the 1980s (e.g., Rutala, 
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Comments and Response References: 

Product Performance Section (70) Page 482 

WA and Cole, EC. 1987. Infection Control, 8(12): 501-506. Cole, EC; Rutala, WA; Samsa, GP. 1988. 

Journal of AOAC, 71(6): 1187-1194. Cole, EC; Rutala, WA; Carson, JL. 1987. Journal of AOAC, 

70(5): 903-906) and funded under a cooperative agreement between EPA and researchers at the 

University of North Carolina demonstrated the extreme variability of the Use-Dilution Test Method 

(UDM). EPA requires the UDM to demonstrate the efficacy of antimicrobials that make hospital 

disinfectant efficacy claims (Efficacy Data Requirements, Disinfectants for Use on Hard Surfaces, 

EPA DIS/TSS-1 (January 22, 1982). Furthermore, in response to a request by the House Committee 

on Government Operations, the then US General Accounting Office (GAO) undertook a review of 

EPA’s regulation of disinfectant efficacy during an investigation from January through November 

1989 (GAO. 1990. "Report to Congressional Requesters, Disinfectants, EPA Lacks Assurance They 

Work". GAO/RCED-90-139. August.). Among other conclusions, the GAO reported that 

disinfectant efficacy methods recommended by EPA have been widely criticized by industry, 

academia, and others for producing highly variable results.] Moreover, the essential role of the 

protocol review process with regard to efficacy data requirements is confirmed by the fact that two 

PRIA fee categories were added to the antimicrobial PRIA fees table with the 2008 PRIA 

reauthorization.[FN6: PRIA category A521 is for an internal AD review of a public health efficacy 

protocol, with a 4 month review time and a fee of $2,100 in 2009. PRIA category A522 is for an 

external EPA expert panel review of a public health efficacy protocol, with a 15 month review time 

and a fee in 2009 of $10,500.] These fee categories were added to the PRIA- covered actions 

because of an interest by registrants in obtaining some predictability with regard to review time 

frames. Even with the creation of these fee categories, the process for obtaining protocol approval 

or even Agency guidance is a slow and uncertain process. 

Response: see response 70.8 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27280 

Comment Code: 70000 

Comment: In the case of product performance for public health uses, data requirements and 

guidance on meeting these requirements are inextricably joined. LANXESS submits that EPA must 

complete the process of developing guidelines for public health antimicrobial uses and then 

repropose this package with the new guidelines available. The guideline revision process should be a 

high priority for the Agency. It should be completed through the public process EPA has 

established for issuing guidelines. LANXESS urges EPA to act expeditiously and to include in the 

revised guidelines a process that provides the Agency with improved ability to address the efficacy 

needs arising from public health emergencies, emerging pathogens and innovative technologies. 

Once these product performance guidelines are updated, the Agency should repropose this 

regulation. 

Response: See responses 2, 70.1, 70.5, and 191.1. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 
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Comments and Response References: 

Product Performance Section (70) Page 483 

Comment ID: 27663 

Comment Code: 70000 

Comment: 2. Proposed Regulation # [Section] 158.2220(a)(1) 

Text of the Proposed Regulation (emphasis added) Product performance: Product performance 

requirement for all antimicrobial pesticides. "Each applicant must ensure through testing that his 

product is efficacious when used in accordance with label directions and commonly accepted pest 

control practices. The Agency may require, on a case-by-case basis, submission of product 

performance data for any pesticide product registered or proposed for registration." 

The Proposed Regulations Are Vague for the Following Reasons . The Agency has not adequately 

stated the criteria for determining whether product performance data for pesticide products 

registered or proposed for registration must be submitted. Such information requires private 

consultation with the Agency. 

Response: see response 3 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 27776 

Comment Code: 70000 

Comment: EPA also states that the purpose of the new data requirements is to update and improve 

the scientific knowledge and current Agency practices. While this is appropriate with any data 

requirement rule, it is critical to ensure that all required guidance documents and protocols relative 

to those data requirements are finalized to help ensure registrants have appropriate information 

prior to data generation and to avoid registration delays. At this time, there are several relevant 

guidance documents which have not been finalized and published. For example, CSPA has worked 

extensively with EPA's Antimicrobial Division to develop 810 efficacy guidelines for 810.2000 

(General Considerations), 810.2100 (Sterilants), 810.2200 (Disinfectants) and 810.2300 (Sanitizers). 

The last Agency draft of these guidelines has been available since 2006. Previously, the Agency had 

projected that the 810 guidelines would be published in draft by 1 st quarter 2009 with a 60 day 

comment period. The Agency has recently reported that due to procedural changes there is not a 

projected date for the drafts to be published for public comment. In addition, there are several 810 

guidelines which are either in draft or have not yet been drafted. 

Response: see responses 191.1 and 70.1 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 27777 

Comment Code: 70000 
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Comments and Response References: 

Product Performance Section (70) Page 484 

Comment: Section 158.2220 - Product Performance Ecolab agrees with and supports the 

comments submitted by CSPA that 158W should not be finalized or implemented until all 810 

guidelines are finalized. The proposed rule refers to the 91 guidelines which were proposed in 1991 

and to date have not been published or finalized. The current 91 guidelines fall short of reflecting 

current scientific knowledge and current Agency practices. CSPA's Antimicrobial Efficacy Group 

(AEG) has worked closely with EPA's Antimicrobial Division to develop the 810.2000, 810.2100, 

810.2200, and 810.2300 efficacy guidelines which have yet to be published for comment. In addition 

there are several outstanding 810 guidelines which have not be published or even drafted. As stated 

previously, OMB comments to the 158W rule require EPA to finalize all guidelines prior to 

publication of 158W as a final rule. 

Response: see responses 191.1 and 70.1 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 27778 

Comment Code: 70000 

Comment: The Agency has been working on the development of guidelines to be included in the 

810 Series Pesticide Assessment Guidelines. The Chemical Specialties Product Association (CSPA) 

worked jointly with the Agency to develop the following proposed guidelines: 

810.2000 - General Considerations 810.2100 - Sterilants 810.2200 - Disinfectants 810.2300 - 

Sanitizers 

In addition, there are several outstanding 810 guidelines which are either in draft form and/or have 

not yet been drafted. P&G encourages the Agency to collaborate with Industry to develop these 

outstanding guidelines building upon the successful endeavor for the development of the 810.2000, 

2100, 2200 and 2300 guidelines. It is P&G’s position that this proposed 40 CFR Part 158 rule 

cannot be promulgated until all 810 guidelines are published and finalized. 

According to industry discussions with EPA, in contrast to the six categories proposed at 158.2220, 

EPA intends to publish guidance on the following categories. 

[See Table on page 3 in PDF docket ID EPA-HQ-OPP-2008-0110-0081.PDF] 

Response: see responses 191.1 and 70.1 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 27779 

Comment Code: 70000 

Comment: To that end, the members of CSPA strongly object to promulgation of 40 CFR Part 158 

subpart W in absentia of the finalized 810 guidelines. The antimicrobial product performance 
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Comments and Response References: 

Product Performance Section (70) Page 485 

requirements table provided on page 59432 of the Proposed Rule refers to the guidelines which 

were proposed in 1991 and to date have not been published and have never been finalized. The 91 

guidelines do not "reflect current scientific knowledge and current Agency regulatory practices." 

CSPA worked jointly with the Agency to develop the following proposed guidelines: 

 * 810.2000 - General Considerations * 810.2100 - Sterilants * 810.2200 - Disinfectants * 810.2300 - 

Sanitizers 

The last drafts of the above guidelines available to CSPA for consideration are from early 2006. The 

Agency has stated that these referenced 810 guidelines will publish in draft 1st quarter of 2009 with a 

60-day comment period. 

In addition, there are several outstanding 810 guidelines which are either in draft form and/or have 

not yet been drafted. CSPA encourages the Agency to collaborate with Industry to develop these 

outstanding guidelines building upon the successful endeavor for the development of the 810.2000, 

2100, 2200 and 2300 guidelines. It is CSPA's position that this proposed 40 CFR Part 158 rule 

cannot be promulgated until all 810 guidelines are published and finalized. 

Response: see responses 191.1 and 70.1 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 27780 

Comment Code: 70000 

Comment: d. Comments on Data Requirements/References 

The Antimicrobial Product Performance Data Requirements Table on page 59432 referencing the 

91 guidelines which have never been finalized and are not publically available. As noted previously in 

our comments, we do not believe that it is appropriate to move forward with Part 158W until all 810 

Guidelines are final. When the 810 Guidelines are complete CSPA recommends the table below, 

which references the 810 guidelines, replace the table currently in the Proposed Part 158W Rule. 

[See Table listing suggested data requirement guidelines on p. 11 PDF Docket ID EPA- HQ-OPP2008-0110-0086.pdf] 

 At this time, none of the 810 guidelines above are finalized and only 810.2000, 810.2100, 810.2200 

and 810.2300 are being prepared for publication for comment this fiscal year. In the absence of 810 

guidelines for each of the use- site/desired claim sets provided in the table, a non-level playing field 

is created. A most recent example is the registration of copper alloys with public health claims, but 

no guidance has been provided to registrants for how such claims can be achieved on treated 

articles. CSPA cannot support a proposed rule until there are finalized data guidelines in place for 

reference. 

Response: see responses 191.1 and 70.1 
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Comments and Response References: 

Product Performance Section (70) Page 486 

Comment Code: 77000 Re-proposed definitions 

Commenter Name: Eileen J. Moyer 

Commenter Organization: Reckitt Benckiser, Inc. 

Letter ID: 0076 

Comment ID: 25417 

Comment Code: 77000 

Comment: 1. THE SECTION 158.2203(b)(5) LANGUAGE DEFINING NON-SPECIFIC 

PUBLIC HEALTH CLAIMS SUCH AS "SANITARY" AS FIFRA PUBLIC HEALTH CLAIMS 

SHOULD BE ENACTED WITH MINOR MODIFICATIONS 

Proposed Section 158.2203(b)(5) provides that a product will be considered to make a public health 

claim if: 

"A non-specific claim is made that the pesticide will beneficially impact or affect public health at the 

site of use or in the environment in which applied (such as a 'sanitary' claim), and: 

(i) The pesticide product contains one or more ingredients that, under the criteria in 40 CFR 

153,125(a), is an active ingredient with respect to a public health microorganism if there is no other 

functional purpose for the ingredient in the product; or 

(ii) The pesticide product is similar in composition to a registered pesticide product that makes 

explicit antimicrobial health claims. 

Reckitt supports the inclusion of this provision in the final rule. As noted in comments previously 

submitted to EPA in June, 1997 and in January, 2000, we believe it is appropriate for EPA to change 

its long standing position to treat the use of the term "sanitary" with respect to non-registered 

cleaning products as simply a "cleanliness" claim rather than as a pesticidal claim. In our previous 

comments we provided EPA with additional information to support this change. We cited a 

February 16, 1993 decision of the National Advertising Review Board (''NARB''), and consumer 

research conducted by Reckitt in 1998 regarding consumer perceptions of the term sanitary. 

The NARB is an industry self-regulatory organization that, among other things, helps resolve 

disputes involving false marketing claims between competing products through arbitration. The 

NARB 1993 decision found that the message conveyed by the use of the term sanitary on an 

unregistered toilet bowl cleaner is that "consumers are being told the bowl is left germ free, not 

merely clean." Since the unregistered product did not perform this function, the NARB found that 

the sanitary claim was unsubstantiated, and a false and misleading implied claim. 

In doing so, the NARB considered EPA's previous position suggesting that the meaning of the term 

sanitary to consumers was simply a "cleanliness" claim. The NARB found no indication that EPA 

had considered the implied message of the claim. 

Reckitt (under the company's previous name of Reckitt & Colman) conducted market research in 

1998. The results of this research confirmed that a significant majority of respondents are shown to 
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Comments and Response References: 

Product Performance Section (70) Page 487 

believe that household cleaning products, which make the claim that they make household surfaces 

sanitary, do have germ killing properties. 

We further submit that EPA should consider other types of non-specific terms such as "hygienic" as 

antimicrobial claims as well. Reckitt conducted a survey in November, 2008 using the on-line 

service, Communispace Corporation(R) [FN#1:Communispace Corporation is a market research 

supplier service that provides companies a forum for conducting qualitative market research testing 

using established panels of respondents. Companies solicit panel members via an online portal to 

obtain information for market research purposes.] to determine if members believed that the word 

"hygienic" meant germ kill. Communispace panel members were asked the following open ended 

question: "If a new toilet bowl cleaner said it was "hygienic", what do you think would be its main 

actions/benefits?" Out of 78 people who responded, two thirds provided answers that related to 

killing germs/bacteria, disinfecting or sanitizing. The same individuals were asked a close ended 

question: "If a new toilet bowl cleaner said it was "hygienic", do you think it would kill germs. 

Almost ninety five percent of the 78 respondents said yes. 

In order to fully capture the relevant class of products Section 158.2203(b)(5) (ii) should be 

expanded to read: "The pesticide product is similar in composition or function to a registered 

pesticide product that makes explicit antimicrobial public health claims. This modification is 

necessary to fully capture the universe of non-FIFRA registered cleaning products which may seek 

to communicate implied claims of germ-killing activity through the use of non- specific terms, such 

as sanitary or hygienic. 

II. EPA SHOULD NOT REDEFINE THE TERMS DISINFECTANT AND SANITIZER TO 

ONLY APPLY TO PRODUCTS THAT MAKE PUBLIC HEALTH CLAIMS 

We are concerned that EPA is redefining the terms disinfectant and sanitizer so that only 

antimicrobial pesticide products that make public health claims may call themselves disinfectants or 

sanitizers. We do not agree with this position. This is a significant change in policy as these terms 

have historically been defined in association with the level of reduction of microorganisms, not 

whether the microorganisms are public health or non-public health. EPA has provided no support 

for this position other than stating that the proposal is consistent with the September 17, 1999 

proposed rule entitled "Registration Requirements for Antimicrobial Pesticide Products and Other 

Pesticide Regulatory Changes". The preamble indicates on page 59391 that comments were received 

on the previously proposed rule and considered in the current rulemaking. EPA has not disclosed 

nor discussed the comments previously received. If EPA is relying on comments received in 

connection with the previously proposed rule it should have discussed those comments in the 

current preamble and their relationship to the provisions included in the current proposal. The 

Agency provides no justification as to why they have determined that the terms disinfectant and 

sanitizer should be restricted only to products that are effective against public health organisms and 

how the Agency has determined it is appropriate to propose definitions that differ from FIFRA. 

This change in status for disinfectants and sanitizers is not necessary in order for EPA to issue 

product performance data. Product performance data is needed for both public health and 

nonpublic health antimicrobial pesticides. The difference is only in whether EPA reviews the data or 

not at the time of registration. What does EPA propose non-public health products be called? For 

example, what would be the new statement of identity for air sanitizers? These products are already 
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Comments and Response References: 

Product Performance Section (70) Page 488 

defined as non-public health antimicrobial pesticides and as such must include specific statements 

on their labels. We encourage EPA to use the definitions for disinfectant and sanitizer CSPA 

provided to EPA for use within efficacy performance guidelines. These definitions are: 

"Disinfectant means a substance, or mixture of substances, intended to destroy or irreversibly 

inactivate bacteria, fungi, or viruses on surfaces or inanimate objects (FIFRA § 4(i)(4)(C)(iii))." 

"Sanitizer means a substance, or mixture of substances, intended to reduce the number of 

microorganisms on inanimate surfaces, in water or air (FIFRA § 4(i)(4) (C)(i))." 

Response: EPA acknowledges Reckitt Benckiser's support for the proposed language in section 

158.2203(b)(5). Also see responses 70.13, 70.11, 70.7, 70.9, and 70.6. 

Commenter Name: Kelly K. Naujock 

Commenter Organization: S.C. Johnson & Son, Inc. 

Letter ID: 0063 

Comment ID: 25422 

Comment Code: 77000 

Comment: In addition to supporting the comments submitted by the referenced trade associations, 

we do not agree with the new definition for 'sanitary' in this proposed rule. On page 59432, in 

section 158.2203 (b) (5), the definition of a public health pesticide includes a 'sanitary' claim, as it is 

purported to be a nonspecific claim that implies a beneficial impact which affects public health. 

Historically, 'sanitary' has been defined as a statement of cleanliness and, as such, is out of the scope 

of a registered claim. 'Sanitary' is commonly used on cleaning products that do not mitigate pests 

and, therefore, are not registered pesticides. This proposed rule attempts to apply an artificial 

definition to 'sanitary' while giving no basis for making a change of this sort. We are opposed to the 

inclusion of this new definition in the proposed rule. 

Response: see response 70.6 

Commenter Name: Sally Hayes 

Commenter Organization: Scientific & Regulatory Consultants, Inc. (SRC) 

Letter ID: 0066 

Comment ID: 25457 

Comment Code: 77000 

Comment: In this proposed rule, EPA has changed the statutory definitions of disinfectant and 

sanitizer. This change in status for disinfectants and sanitizers is not necessary for EPA to issue 

product performance data. Instead it seems that EPA is inappropriately using this proposed rule to 

implement new policy without providing any justification for redefining these terms found in FIFRA 

that are the foundation of the Antimicrobial Division. 

Response: see response 70.6 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 
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Comments and Response References: 

Product Performance Section (70) Page 489 

Letter ID: 0086 

Comment ID: 25545 

Comment Code: 77000 

Comment: c. Data Rule Should Not Be Used for Policy Modifications 

The proposed rule is meant to communicate the data requirements necessary to obtain antimicrobial 

pesticide registration. However, EPA is proposing a number of policy changes that must not be 

included within the scope of the proposed regulation. These policy changes are incorporated 

primarily in the definitions subsection (§ 158.2203). The preamble states that these policy changes 

are necessary in order for the agency to determine the scope of antimicrobials claims that would be 

considered public health claims for the purpose of product performance data submission (see page 

59391, Preamble Section VI Product Performance Data Requirements). 

We are concerned that EPA is redefining the terms disinfectant and sanitizer so that only 

antimicrobial pesticide products that make public health claims may call themselves disinfectants or 

sanitizers. We do not agree with this position. This is a significant change in policy as these Page 4 

terms have historically been defined in association with the level of reduction of microorganisms, 

not whether the microorganisms are public health or non-public health. EPA has provided no 

support for this position other than stating that the proposal is consistent with the September 17, 

1999 proposed rule entitled "Registration Requirements for Antimicrobial Pesticide Products and 

Other Pesticide Regulatory Changes". The preamble indicates on page 59391 that comments were 

received on the previously proposed rule and considered in the current rulemaking. EPA has not 

disclosed nor discussed the comments previously received. If EPA is relying on comments received 

in connection with the previously proposed rule it should have discussed those comments in the 

current preamble and their relationship to the provisions included in the current proposal. The 

Agency provides no justification as to why they have determined that the terms disinfectant and 

sanitizer should be restricted only to products that are effective against public health organisms and 

how the Agency has determined it is appropriate to propose definitions that differ from FIFRA. 

Response: see response 70.11 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25546 

Comment Code: 77000 

Comment: This change in status for disinfectants and sanitizers is not necessary in order for EPA 

to issue product performance data. Product performance data are needed for both public health and 

non-public health antimicrobial pesticides. The difference is in whether EPA reviews the data or not 

at the time of registration. What does EPA propose non- public health products be called? For 

example, what would be the new statement of identity for air sanitizers? These products are already 

defined as non-public health antimicrobial pesticides and as such must include specific statements 

on their labels. 

Response: see response 70.11 
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Comments and Response References: 

Product Performance Section (70) Page 490 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25547 

Comment Code: 77000 

Comment: EPA makes further policy changes in [Section]158.2203 (b) which discusses criteria 

EPA will use to determine when a product is making a public health claim. The Agency seems to 

propose in [Section]158.2203 (b)(5)(i) that if a pesticide product contains one or more active 

ingredients that are effective against public health organisms then that product is considered to make 

a public health claim. If this is truly the intent, then EPA has misinterpreted 40 CFR 153.125(a) 

which clearly is written to apply to non-registered non-pesticidal products that include active 

ingredients effective against public health organism in other products in order to function as a 

pesticide without obtaining an EPA registration. 

Response: see response 70.11 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25549 

Comment Code: 77000 

Comment: EPA further expands the definition of a public health pesticide in [Section] 158.2203 

(b)(5)(ii) by stating that other pesticide products that may be similar in composition to a public 

health product will be considered a public health product. How will EPA define "similar in 

composition"? This language leaves room for arbitrary determinations that a currently non-FIFRA 

regulated product may now be considered a public health pesticide without taking into account the 

function of the product ingredients relating to the product application. Again, EPA does not address 

the comments that were received in regards to the 1999 regulatory proposal and why the Agency 

feels these policy decisions are necessary for inclusion in the current proposal. 

CSPA feels EPA should not include fundamental policy changes in a regulation that is meant to 

outline data requirements for registration. In particular, EPA should not change the long standing 

statutory definitions for disinfectant and sanitizer in order to classify any product containing those 

terms as public health pesticides. If EPA intends to modify statutory definitions and/or long 

standing policies, it should provide justification and specific information to support Page 5 the need 

to make such changes. EPA needs to include this justification when this rule is re-proposed. 

Response: see responses 3, 2, and 70.14 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25558 

Comment Code: 77000 
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Comments and Response References: 

Product Performance Section (70) Page 491 

Comment: a. Comments on Proposed Definitions: 

The definitions provided on page 59431 section 158.2203 are inconsistent with the FIFRA § 

4(i)(4)(C)(i, ii, iii)) and with the definitions that were provided in comments on the draft 810.2000 

guideline submitted by CSPA to the Agency in February of 2006. CSPA strongly recommends that 

the Agency avoid using different definitions of terms which are defined in the statute. 

Instead, CSPA recommends that the definitions provided in the Proposed Part 158W rule be 

replaced with the following comprehensive list of definitions. These definitions were previously 

provided to EPA in the draft 810.2000 guideline dated February 16, 2006. 

Algicide means any substance, or mixture of substances, intended to kill the number of algae in 

water. 

Algistat means any substance, or mixture of substances, intended to inhibit the increase of algal 

populations. (ASTM E35.15 Draft) 

Antibacterial means any substance, or mixture of substances, intended to destroy, eliminate, reduce, 

mitigate or control the growth or development of bacteria in the inanimate environment. 

Antifoulant means any substance, or mixture of substances, intended to prevent the biological 

fouling of underwater structures. 

Antimicrobial Pesticide means a pesticide [substance or mixture of substances] that is intended to 

disinfect, sanitize, reduce, or mitigate growth or development of microbiological organisms; or 

protect inanimate objects, industrial processes or systems, surfaces, water, or other chemical 

substances from contamination, fouling, or deterioration caused by bacteria, viruses, fungi, protozoa, 

algae, or slime (FIFRA § 2 (mm)). 

Antiseptic means a drug product applied topically to the skin to help prevent infection or to help 

prevent cross contamination (FDA Tentative Final Monograph for Healthcare Drug Products, 

1994). Antiseptic products are applied on or in the living body of man or other animals. Antiseptic 

products are not identified as pesticides and are regulated by the Food and Drug Administration. 

Aseptic means free of microbial contamination consistent with FDA 21 CFR 178 for commercial 

sterilants for aseptic food packaging. 

Bacteriostat means a substance, or mixture of substances, intended to inhibit the growth of bacteria 

in the presence of moisture. (FIFRA § 4(i)(4)(C)(ii)) 

Biofilm means a dynamic, self- organized accumulation of microorganisms and environmental byproducts immobilized on a substrate and embedded in an organic polymer mix (ASTM E35.15 

Draft). This organic polymer mix is also known by the term "glycocalyx". 
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Product Performance Section (70) Page 492 

Biocide means any substance, or mixture of substances, intended to reduce the number of living 

microorganisms (e.g., virucide-virus, mycobactericide- mycobacteria, algicide-algae; bactericidebacteria; fungicide-fungi; slimicide- slime-forming microorganisms). (see also "microbicide.") 

Confirmatory data means a reduced set of data which may be used to support an application or 

amendment for registration of a product, or a minor formulation change of a registered product. 

Deodorizer means a substance, or mixture of substances, that are of two basic types: (1) Those that 

intended to prevent, reduce, or delay the formation of odors by acting upon micro-organisms which 

produce them, and (2) those that intended to mask, chemically destroy, or neutralize odors. Products 

that claim deodorization by antimicrobial means are subject to registration as pesticides. 

Disinfectant means a substance, or mixture of substances, intended to destroy or irreversibly 

inactivate bacteria, fungi, or viruses on surfaces or inanimate objects (FIFRA [Section] 4(i)(4)(C)(iii)). 

Fungicide means a substance, or mixture of substances, intended to destroy fungi (including yeasts) 

and/or fungal spores. 

Fungistat means a substance, or mixture of substances, intended to inhibit the growth of fungi in the 

inanimate environment. 

Microbicide mean any substance, or mixture of substances, intended to reduce the number of living 

microorganisms (e.g., virucide-virus, mycobactericide- mycobacteria, algicide-algae; bactericidebacteria; fungicide-fungi; slimicide- slime-forming microorganisms). (See also "biocide.") 

Microbiological water purifier means any unit, water treatment product or system intended to 

remove, kill or inactivate disease- causing microorganisms from the water, including bacteria, viruses 

and protozoan cysts so as to render the treated water microbiologically safe for drinking. 

Microbistat means a substance, or mixture of substances, intended to control or temporarily prevent 

the growth of microorganisms (e.g., bacteriostat, fungistat, algistat). 

Mycobactericide means a substance, or mixture of substances, intended to destroy or irreversibly 

inactivate mycobacteria in the inanimate environment. 

One-Step Sanitizer/Disinfectant means a substance or mixture of substances intended to be 

effective in the presence of light to moderate soil without a preclean step in the use directions. 

Preservative means a substance, or mixture of substances, intended to inhibit the growth of 

microorganisms capable of causing biological deterioration of a substance(s)/material(s). 

Sanitizer means a substance, or mixture of substances, intended to reduce the number of 

microorganisms on inanimate surfaces, in water or air (FIFRA [Section] 4(i)(4)(C)(i)). 

Slime means a dynamic, self-organized accumulation of microorganisms and environmental byproducts immobilized on a substrate and embedded in an organic polymer mix (ASTM E35.15 

Draft). This organic polymer mix is also known by the term "glycocalyx". 
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Comments and Response References: 

Product Performance Section (70) Page 493 

Slimicide means a substance, or mixture of substances, intended to reduce the number of slimeforming microorganisms. 

Sterilant means a substance, or mixture of substances, intended to destroy or eliminate all forms of 

microbial life in the inanimate environment, including all forms of vegetative bacteria, bacterial 

spores, fungi, fungal spores, and viruses. 

Sporicide means a substance, or mixture of substances, intended to irreversibly inactivate bacterial 

spores in the inanimate environment. 

Tuberculocide means a substance, or mixture of substances that destroys or irreversibly inactivates 

tubercle bacilli (e.g. Mycobacterium) in the inanimate environment. 

Two-Step Sanitizer/Disinfectant means a substance or mixture of substances that has not been 

tested in the presence of soil. The sanitizer/disinfectant use directions must state the need to 

preclean surfaces prior to sanitizing/disinfecting. 

Virucide means a substance, or mixture of substances that destroys or irreversibly inactivates viruses 

in the inanimate environment. 

If all of the definitions provided above are not accepted 'as-is', CSPA requests that the use of the 

terms "sanitizer" and "disinfectant" provided on page 59431 be referenced in terms of efficacy level 

and not by target organism or intended application. This is consistent with section (2) on page 59431 

which states "a claim is made for the pesticide products as a sterilant, disinfectant, virucide, sanitizer, 

or tuberculocide regardless of the site of use of the product, and regardless of whether specific 

microorganisms are identified." 

b. EPA’s Proposal to Restrict the Term "Sanitizers" and "Disinfectants" to Public Health 

Antimicrobials is Inconsistent with FIFRA. 

CSPA recommends clarifying the term "sanitizer" and "disinfectant" to include both public health 

and non-public health antimicrobial pesticides. (Page 59431 Proposed 158.2203). 

With EPA proposing new definitions for the terms "disinfectant" and "sanitizer" (that are 

inconsistent with statute), the proposed part 158 advocates the view that the term "disinfectant" 

inherently implies public health uses and should not be used on non-public health antimicrobials. 

Page 10 A sanitizer or a disinfectant is defined in terms of killing microorganisms on the surface it is 

applied. It is not defined by the types of microorganisms that are killed. It is a level of efficacy 

independent from whether or not the targeted microorganism is public health or non-public health. 

Products shown to be effective against non-public health microorganisms with the level of efficacy 

used to define the term "sanitizer" or "disinfectant" cannot be called a "sanitizer" or "disinfectant" 

leaving such a product without proper identification. The current term being offered by EPA is 

"antimicrobial treatment". Using "antimicrobial" in this context conflicts with other EPA guidance, 

PR Notice 2000-1 states EPA believes the claim "antimicrobial," is inconsistent with the intent of 40 

CFR 152.25(a) if it is not properly qualified as to its intended non-public health use. 
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Comments and Response References: 

Product Performance Section (70) Page 494 

This is also problematic when registering antimicrobial pesticides in California. California has 

determined that the term "antimicrobial" suggests a higher level of efficacy that include both 

"disinfectant" and "sanitizer". Industry must be able to register their antimicrobial pesticides in the 

states in order to sell them. When EPA and California take an opposite position on a given issue, the 

situation for the registrants becomes untenable; therefore we need EPA to establish clear definitions. 

Response: see responses 70.6, 70.9, and 70.11 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25567 

Comment Code: 77000 

Comment: c. Products That Are Similar in Composition to a Registered Public Health 

Antimicrobial Do Not Meet the Criteria to be Classified as Antimicrobial. 

Part 158.2203(b) lists several criteria that the Agency will apply in determining if a product makes a 

public health claim. This includes products that are similar in composition to a registered pesticide 

product that makes explicit health claims. (158.2203(b)(5(ii)) There are several interpretations of this 

definition of public health claims. One interpretation is that a non- registered, non-pesticidal 

product that is similar in formulary composition to a public health pesticide is also a public health 

pesticide. The criteria for determining if a product must be registered are provided in 40 CFR 152.15 

and non-pesticidal products are not within OPP's jurisdiction. EPA must take into account the 

function of the product ingredients relating to the product application. This section should be 

clarified with "This does not apply to products that are not registered antimicrobials but use active 

ingredients that have been designated as having antimicrobial uses in the other registered products." 

Response: see response 70.14 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25741 

Comment Code: 77000 

Comment: Part 158 W is not the appropriate venue to establish regulatory policies for labeling § 

158.2003 Definitions (b)(5) states that "sanitary" implies a public health benefit. Part 158 W is a 

proposed data requirement rule and is inappropriate to communicate regulatory policies which 

impact labeling. The Agency failed to finalize the proposed 40 CFR 152 and 156 which were 

published in the Federal Register on September 17, 1999. That regulation would have been the 

correct mechanism to implement regulatory labeling policies. In that rule, EPA proposed to include 

the term "sanitary" as a pesticide claim. The draft rule of September 17, 1999 was never finalized. 

Therefore, any proposal to include this type of label policy into a data requirement rule is impractical 

and inappropriate. 
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Comments and Response References: 

Product Performance Section (70) Page 495 

As was pointed out to the Agency in industry comments to the 1999 draft rule, to re-classify 

"sanitary" as a pesticidal claim directly contradicts the Agency's former 1992 document which stated 

the term "sanitary" is identified as a state of cleanliness and does not carry connotation of pesticidal 

benefits to support reclassification. In addition, terms such as "sanitary sewer" have been in 

common parlance for a material extent of time. To assign additional regulatory meaning at this time 

is arbitrary and meaningless. The Agency has indicated there is consumer focus group data provided 

by one consumer product company. The Agency has not shared this data or any other evidence with 

the regulated community for review and comment as to the appropriateness of reclassification of 

"sanitary" as a pesticide claim. As stated in comments to the 1999 rule, to summarily classify 

"sanitary" as a pesticide claim, without opportunity for industry comment is an unfair practice. In 

addition, there is no consensus within industry as to the meaning of "sanitary". Therefore the 

proposed reclassification of "sanitary" as a pesticide claim must be removed from the draft Part 158 

W rule and addressed th rough the appropriate regulatory policy mechanism. 

The Agency proposes in the 158 W rule to disallow the terms "sanitizers" and "disinfectants" for 

non-public health organisms. The product performance section advocates that the term 

"disinfectant" implies public health uses and should not be applied to non-public health uses. This 

should be removed from the rule as it proposes to insert regulatory labeling policy into a data 

requirement rule. 

Response: see response 70.6 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25751 

Comment Code: 77000 

Comment: Section Specific Comments 

158.2203 - Definitions Ecolab also agrees with the CSPA comments regarding definitions on page 

59431 section 158.2203 are inconsistent with FIFRA § 4(i)(4) (C)(i,ii, iii) and with the definitions 

provided by the CSPA AEG for the draft 810.2000 guideline. The Agency should revise the 

proposed definitions replacing them with the definitions provided in the CSPA comments for the 

158W rule to be consistent with what has been recommended by the CSPA AEG. 

Response: see responses 70.1, 70.9, and 191.1 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25753 

Comment Code: 77000 

Comment: As previously stated, Ecolab strongly objects to the Agency proposing to reclassify 

"sanitary" as a pesticide claim. The industry has had no opportunity to review or comment on data 

previously provided to determine if such a reclassification is appropriate. Also Part 158W is a data 
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Comments and Response References: 

Product Performance Section (70) Page 496 

requirement rule and is not the appropriate venue to communicate regulatory label policy decisions. 

This should be removed from 158 W. 

Ecolab also supports the CSPA comments that it is inappropriate to disallow the term "sanitizers" 

and "disinfectants" for non-public health antimicrobials. The proposed part 158 advocates the view 

that the term "disinfectant" inherently implies public health uses and should not be used on nonpublic health pesticides. The Agency has not provided to industry any data or substantiation to 

support this assertion. Again, the Agency is attempting to insert regulatory label policies and product 

classifications through a data requirement ru le. This should be removed from the proposed 158W 

rule. 

158W is a new rule for antimicrobials and must be thorough in providing definitions for acronyms 

such as TGAI , TEP, MU, etc. In addition, the Agency should note that the terms Industrial Use 

Only and Commercial Use Only are being challenged by various state pesticide offices as requiring 

use by certified applicators only. The Agency needs to come to an agreement with the state offices 

as to the appropriate terms which can be used to indicate a product is not for household use but at 

the same time is not "Restricted Use" requiring use by certified applicators. 

Response: see responses 70.6, 70.11, and 50.17 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25937 

Comment Code: 77000 

Comment: The Clorox Company Comments Not Addressed by Other Groups 

Use of the term "sanitary" -In proposed SS 158.2203 (b) (5), there is a discussion regarding nonspecific claims that can be considered a public health claim and therefore are pesticidal. In this 

section, there is a parenthetical example using the term "sanitary". The term "sanitary" has 

historically been a non-pesticidal term. The word "sanitary" is often associated with cleaning and not 

meant to signify sanitization, which is a pesticidal term. We are concerned that the Agency may 

create regulatory confusion by making the word "sanitary" pesticidal. Also, we do not believe that 

parenthetical examples are the proper mechanism for Agency policy changes. In future versions of 

the proposal we would encourage the elimination of such words. We encourage the Agency to vet 

policy in more traditional and transparent ways. 

Response: see responses 70.6 and 2 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26161 

Comment Code: 77000 
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Comments and Response References: 

Product Performance Section (70) Page 497 

Comment: Definitions One of the problems with this proposal is demonstrated by the set of 

definitions proposed for 158.2203. As EPA acknowledges, these definitions were taken verbatim 

from the Agency’s proposal on antimicrobial registration procedures and labeling, proposed in 1999, 

but never finalized. However, as part of the process to develop the 810.2000 series antimicrobial 

efficacy guidelines, these have been significantly revised from the 1999 proposal. Moreover, some of 

definitions are inconsistent with definitions in FIFRA section FIFRA [Section] 4(i)(4)(C)(i, ii, iii)). 

CSPA and the Panel in its comments have provided the definitions as they appear in the most recent 

working draft of EPA guidance available to it. 

Further, P&G recommends clarifying the terms "sanitizer" and "disinfectant" to include both public 

health and non-public health antimicrobial pesticides. In proposing new definitions for the terms 

"disinfectant" and "sanitizer", the proposed part 158 advocates the view that the terms 

"disinfectant" and "sanitizer" inherently implies public health uses and should not be used on nonpublic health antimicrobials. 

A sanitizer or a disinfectant is defined in terms of killing microorganisms on the surface it is applied. 

It is not defined by the types of microorganisms that are killed. It is a level of efficacy independent 

from whether or not the targeted microorganism is public health or non-public health. 

Current policy indicates products shown to be effective against non-public health microorganisms 

with the level of efficacy used to define the term "sanitizer" or "disinfectant" cannot be called a 

"sanitizer" or "disinfectant" leaving such a product without proper identification. The current term 

being offered by EPA for such product is "antimicrobial treatment". Using "antimicrobial" in this 

context conflicts with other EPA guidance, PR Notice 2000-1 states EPA believes the claim 

"antimicrobial," is inconsistent with the intent of 40 CFR 152.25(a) if it is not properly qualified as 

to its intended non-public health use. Unfortunately, the current draft policy Labeling Guidelines for 

Pesticide Use Directions - Antimicrobial Products (Subdivision H) prohibits the use of broad terms 

as label claims, specifically "Levels of activity: General terms such as "antimicrobial" or 

"antibacterial" are too broad and are generally not acceptable. Label terminology should specifically 

identify the level of antimicrobial activity (e.g., sterilization, disinfection, sanitization, bacteriostasis)." 

Subdivision H goes on to specifically require that label claims for non-public health products must 

be "..." (For non-health related antimicrobial agents) such claims should be expressly qualified (e.g., 

‘disinfects odor-causing bacteria’ or ‘sanitizes slime-forming bacteria’) in order to remove 

implications of human health significance". This section of Subdivision H actually provides 

examples of non-public health disinfectants. 

This is also problematic when registering antimicrobial pesticides in California. California has 

determined that the term "antimicrobial" suggests a higher level of efficacy that includes both 

"disinfectant" and "sanitizer". Industry must be able to register their antimicrobial pesticides in the 

states in order to sell them. When EPA and California take an opposite position on a given issue, the 

situation for the registrants becomes untenable; therefore we need EPA to establish clear definitions. 

Response: see responses 70.6 and 70.11 
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Comments and Response References: 

Toxicology Section (80) Page 498 

Toxicology (80) 

Verbatim Comments and Response References for the Toxicology Section 

Comment Code: 80000 Toxicology 

Commenter Name: Ray S. McAlister 

Commenter Organization: CropLife America 

Letter ID: 0079 

Comment ID: 25468 

Comment Code: 80000 

Comment: CLA also supports the work initiated jointly by the Panel and the International Life 

Sciences Institute to explore a threshold concept of assessing human risk for antimicrobials. Such a 

concept could be beneficial for regulation of all pesticides, in better fitting data requirements and 

risk assessment procedures to known and biologically relevant endpoints of concern, in addition to 

pesticide use patterns and potential for exposure. 

Response: see response 80.3 

Commenter Name: Patrick H. Quinn 

Commenter Organization: Innovation and Reform Group (IRG) 

Letter ID: 0080 

Comment ID: 25493 

Comment Code: 80000 

Comment: Since the IRG’s mission has--and will continue to be focused on innovation 

opportunities and value --added reform, we find it to be critical that OPP design a Subpart 158W 

Rule which properly anticipates and quickly recognizes the toxicological innovations which are 

anticipated over the next 10-20 years. A Final Rule which does not have these characteristics--but 

instead relies on the federal rulemaking process to update each science advancement--will not 

succeed in achieving the NAS/EPA Vision of Toxicity Testing in the 21st Century or EPA’s 

Strategic Plan for Evaluating the Toxicity of Chemicals. 

Response: see response 4 

Commenter Name: Patrick H. Quinn 

Commenter Organization: Innovation and Reform Group (IRG) 

Letter ID: 0080 

Comment ID: 25498 

Comment Code: 80000 

Comment: Conclusion 
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Comments and Response References: 

Toxicology Section (80) Page 499 

Since the IRG’s focus remains process innovation and reform, our comments contained here are 

limited to our recommended changes to the Proposed Rule (i.e. elimination of specific assay 

mandates within the Rule and their placement in the Test Guidelines) to allow timely EPA adoption 

of 21st Century Toxicology alternatives (in vitro, computational, SAR, etc.) and to promote their 

actual integration into the body of the Rule. 

Response: see response 4 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25578 

Comment Code: 80000 

Comment: Section Number IV. 

Title Introduction to Subpart W 

Paragraph I. Use Patterns in Subpart W Paragraph 18 p. 59390 

Excerpt from Federal Register 9. Antifoulant paints and coatings. Antifoulants are coatings and 

paints applied to boat hulls and bottoms, crab and lobster pots, and underwater structures or 

equipment to control the growth of freshwater or marine fouling organisms. Antifoulant coatings 

have the potential for high environmental exposure most particularly for marine (both freshwater 

and saltwater) environments. 

HC Comment The PMRA considers that antifouling paints could have the potential for significant 

human exposure. This would be the case for antifoulant treatments involving large vessels in a 

commercial setting. For this reason, a comprehensive toxicology data set is required to adequately 

characterize associated human health hazards. The potential for significant human exposure in such 

scenarios is consistent with "high human exposure uses" according to the proposed EPA approach. 

The PMRA suggests revising the text to indicate this. 

Response: see response 80.78 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25580 

Comment Code: 80000 

Comment: Section Number VIII. 

Title Toxicology Data Requirements 

Paragraph C. Groupings for Antimicrobial Toxicology Requirements Paragraph 8 p. 59393 
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Comments and Response References: 

Toxicology Section (80) Page 500 

Excerpt from Federal Register ii. Metal working fluids (MWFs). While both "open" and "closed" 

MWF systems are high human exposure uses, under the appropriate circumstances, the Agency 

distinguishes between "open" and "closed" systems. Fewer toxicity data may be required for a 

"closed" system... 

HC Comment The PMRA considers there to be additional uses beyond MWFs that could have 

‘closed’ systems (e.g. other industrial process fluids), and requests clarification concerning why the 

MWF uses are singled out in this regard. Would the EPA consider other use patterns that could 

have "closed" systems that might, for example, require fewer toxicity studies? 

Response: see response 80.79 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25674 

Comment Code: 80000 

Comment: The specifics of the proposed toxicity testing data requirements fall far short of what is 

needed, because evaluations of long-term effects are generally only required for the active 

ingredient-and not the end-use product. One of the major shortcomings in the current system is the 

fact that "other" ingredients and "active" ingredients are reviewed separately and unequally, with a 

default assumption that "other" ingredients are benign. SFE suggests that EPA begin requiring 

parallel testing of active ingredients and formulated products to the extent necessary to ensure that 

"other" ingredients will not cause additional adverse effects. 

Response: see response 80.8 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25675 

Comment Code: 80000 

Comment: It is our view that EPA should take the precautionary approach of assuming cumulative 

risk exists when exposure to more than one substance that affects the same organ system is likely. 

EPA should add a requirement of full testing of all active ingredient mixtures that EPA allows to be 

co-formulated into products. Cumulative risk must be assessed unless EPA can present a valid 

scientific argument as to why the combined toxicity does not increase risk. 

Response: see response 80.100 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25680 

Comment Code: 80000 
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Comments and Response References: 

Toxicology Section (80) Page 501 

Comment: Endocrine system effects 

It is well known that certain chemicals, including pesticides, can affect the endocrine system, with 

potentially serious results. The proposed rule does not include a process to identify chemicals with 

such potential nor does it call in the data necessary to assess risks to the endocrine system. SFE 

recognizes that developing protocols to screen endocrine disruptors in pesticide products has taken 

more time than initially expected and that required testing cannot yet be specified. However, given 

the importance of this issue and the fact that the Agency does already to some extent consider 

available endocrine effects data in the scientific literature during reregistration, we feel that EPA 

should take advantage of the opportunity provided by this rule to state the importance of assessing 

endocrine system effects and to make it clear that relevant testing will at some point be required. 

Response: see response 80.9 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25924 

Comment Code: 80000 

Comment: Of interest specific to Clorox are the following: 

* The proposed rule does not provide sufficient guidance when assessing corrosive antimicrobial 

products, leading to an increase in unwarranted animal studies and an excessive financial burden on 

the registrant. 

Response: see response 80.4 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25927 

Comment Code: 80000 

Comment: * We support the Panels' recommendation to use alternative proposal 1 over alternative 

proposal 2 as it addresses our specific interest and better assesses the exposure and risk. 

Response: EPA acknowledges Chlorox's support for the Panel's alternative toxicology concept 1. 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26427 

Comment Code: 80000 
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Comments and Response References: 

Toxicology Section (80) Page 502 

Comment: Inconsistency With Other Pesticide Regulations The approach this proposal takes 

results in inconsistency in data requirements between conventional chemical pesticides and 

antimicrobial pesticides with more stringent data requirements for antimicrobials. The test notes in 

the Proposal provide for numerous determinations at the sole discretion of EPA. This is not the 

case with the conventionals, where the criteria are fact-based. For example, test note 7 in the 

Proposal’s Toxicology Data Table provides that "the 90-day dermal toxicity study or the 90-day 

inhalation toxicity study may be substituted for the 90-day oral toxicity study if the Agency 

determines that dermal or inhalation exposure is a major route of exposure." Language similar to the 

emphasized phrase is repeated throughout the Proposal test notes, allowing for numerous ad hoc 

determinations at the sole discretion of EPA. 

 EPA has imposed a more rigorous standard on antimicrobials by expanding the exposures under 

which certain studies could be required. For conventionals, the criteria for triggering a data 

requirement are based on "repeated human exposure over a considerable portion of the human 

lifespan."[FN#2: Final regulation on data requirements for conventional pesticides at 40 CFR 

158.500, Guideline 870.4100, test note 17.] In the antimicrobial Proposal, however, EPA predicates 

such a requirement on "repeated human exposure over a limited portion of the human lifespan, as 

determined by the Agency."[FN#3: Proposed regulation on data requirements for antimicrobial 

pesticides at 40 CFR 158.2230, Guideline 870.4100, test note 20 (73 Fed. Reg. at 59434-35).] Thus, 

for antimicrobials, certain data requirements are imposed based on "limited" exposure, while 

conventional requirements are based on "considerable" exposure. The Agency provides no 

explanation as to why the duration of concern is "limited" for antimicrobials but "significant" for 

conventional chemicals. As these terms are also very vague, the Agency should also explain what 

these terms mean. 

Response: see responses 1, 2, and 80.16 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26571 

Comment Code: 80000 

Comment: Data requirements for toxicology should be imposed only as needed to make regulatory 

decisions under FIFRA, or, where relevant, for regulation of pesticide chemical residues under 

FFDCA Section 408. Any proposed requirement for toxicology data for antimicrobial pesticides 

must clearly explain to what uses the requirement applies and the reasons the data requested are 

necessary to make a regulatory decision under FIFRA or FFDCA. In setting data requirements, EPA 

is subject to the mandate of FIFRA Section 3(h)(3)(A)(ii), which directs EPA to "differentiate the 

types of review undertaken for antimicrobial pesticides, . . . conform[ing] the degree and type of 

review to the risks and benefits presented, . . . considering the use patterns of the product, toxicity, 

expected exposure and product type." 

Response: see response 1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 
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Comments and Response References: 

Toxicology Section (80) Page 503 

Letter ID: 0088 

Comment ID: 26576 

Comment Code: 80000 

Comment: In 1997, the SAP recognized the problems of applying normal assessment and tolerance 

requirements to antimicrobial pesticides that may result in residues on food and the need for a 

different approach in evaluating the risk of such antimicrobial pesticides. Specifically, the SAP 

recommended that EPA identify procedures similar to those established by the FDA to approve 

uses of these types of food contact antimicrobial pesticides under exemptions from tolerance rather 

than establishing numerical tolerances. Although the SAP’s recommendations were made during the 

period when EPA had jurisdiction over antimicrobials that prior to enactment of the FQPA in 1996, 

and currently, following enactment of the Antimicrobial Reform Technical Corrections Act 

(ARTCA) are within the jurisdiction of FDA, the logic of its recommendation remains intact. 

Risk is a function of toxicity and exposure. Recognizing the low exposure to most indirect food 

additives, FDA developed an approach to the assessment of heir dietary risk in which thresholds of 

toxicological concern (TTCs) have been established in association with worst-case estimates of 

dietary exposure to address broad and not easily quantifiable exposure scenarios. This approach is 

equally applicable to antimicrobials used in situations where some residue on food is possible. 

Where exposure remains low, the thresholds of toxicological concern minimize the need to conduct 

extensive toxicological evaluations to adequately assess the potential risk. When exposure exceeds a 

certain level, however, more extensive toxicological data are required to assess the potential risk. 

While the FDA approach has focused only on dietary exposure, the underlying premise is applicable 

to low exposures via any route. 

The Panel is sponsoring a collaborative project with EPA through ILSI-RF to determine whether a 

threshold of toxicological concern-type approach could be developed for regulatory decision-making 

on antimicrobial pesticides. This project will not be limited to dietary exposures. The project is 

underway and is scheduled to be completed within the next 12 months. It is anticipated that the 

recommendations from that project will lead to a meaningful TTC type approach for antimicrobials. 

The Panel believes EPA should include this work in a reproposal of Part 158W. 

The Panel also is concerned that the Proposal does not include a policy or guidance to address the 

methods of assessing products which do not result in systemic toxicity but which are corrosive or 

severe irritants at the point of dosing. If a corrosive effect of the chemical precludes determination 

of systemic toxicity from repeated exposure prior to the corrosive effect, no further toxicology 

studies would be necessary. For the majority of chemicals that are the subject of repeated dose 

toxicity studies, a measure of systemic toxicity can be assessed by increasing the dose, consistent 

with the guidelines of the maximum tolerated dose, to the point that target organ damage is 

observed. For compounds that are corrosive to the skin from dermal exposure, corrosive to the 

respiratory tract from inhalation exposure, or corrosive to the gastrointestinal tract from oral 

exposure, it may be difficult or unfeasible to determine the potential for damage to organs that are 

outside the scope of the initial site of contact. The proposed rule fails to distinguish the data 

requirements on the basis of this important characteristic, yet this is a critical issue in designing 

testing programs and making relevant risk decisions. PMRA (1997)[FN#3:Memorandum from D. 

Grant, PMRA to N. Cook, US EPA. December 1, 2007. Reproductive toxicity testing in proposed 

40 CFR 158W. Available in the docket as EPA-HQ-OPP-2008-0110-0015] specifically identified this 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 504 

issue as one which needed to be addressed. Further, the large number of antimicrobial pesticides 

that is inorganic needs to be appropriately addressed. 

Response: see responses 80.3 and 80.4 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26585 

Comment Code: 80000 

Comment: A. Exposure Considerations: 

1. Wood preservatives are listed throughout the preamble as a generic category but it is never 

defined. There are industrial uses, commercial uses and do it yourself use. The Agency should 

address each of these uses and explain how it views human and environmental, applicator and post 

applicator exposure to each. 

2. The EPA addresses "open" versus "closed" systems for metal working fluids (MWF) yet indicates 

"while both open and closed MWF are high exposure uses, under the appropriate circumstances, the 

Agency distinguishes between open and closed systems". This contradicts the overall limited 

exposure for closed system use. As in many places in the Proposal, EPA provides no explanation as 

to what "appropriate" might be. There is no way for registrants to know other than via ad hoc 

consultations with the Agency. 

3. The EPA does not explain why it has proposed the level of 200 ppb to differentiate between low 

and high exposure among food uses. If it decides to retain that dividing line, EPA should provide its 

reasoning in a reproposal, so that it can receive meaningful comment. 

4. The EPA uses the term "repeated human exposure over a limited portion of the human lifespan" 

in footnotes 11 and 20, yet never explains what that means. In the Panel’s view, it can mean two 

exposures in a lifetime, making virtually all antimicrobials subject to the complete set of data 

requirements. If it keeps this term, EPA should clarify what it means in a reproposal, so that it can 

receive meaningful comments. 

5. The Agency does not define "considerable" in the phrase "high human exposure is defined as that 

resulting over a considerable portion of human lifespan." [FN#4:Page 59392.] This should be 

addressed in a reproposal. 

6. EPA considers applicator exposures high for swimming pool use pattern, although this is not 

supported in the Proposal and, in the Panel’s view, cannot be. Applicator exposure for swimming 

pool chemicals can be low or nonexistent, depending upon the application method. 

7. The Agency should define what is meant by a "closed" system in the regulations, and whether this 

approach is acceptable for use patterns in addition to MWF, 

Response: See responses 50.4, 80.79, 3, 80.60, 80.22, 2, 80.80, and testnotes 80.11 and 80.20 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 505 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26613 

Comment Code: 80000 

Comment: Comments for Specific Footnotes 

Under footnotes 3 and 5, dermal sensitization is "Not required if test material is corrosive to skin or 

has pH less than 2 or greater than 11.5" and "Data are required if repeated dermal exposure is likely 

to occur under conditions of use". These two requirements can, in many situations, be contradictory. 

Under footnote 6, for low exposure uses, data are required if the neurotoxicity screen in the 90-day 

oral rodent study or other data indicate neurotoxicity." Yet the neurotoxicity screen in the 90-day 

oral study and acute neurotoxicity study are conditionally required for high exposure use patterns. 

The Agency should address this contradiction. 

Response: see responses 80.5 and 80.6, and testnotes 80.3, 80.5, and 80.6 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26658 

Comment Code: 80000 

Other EPA Comment Codes and Descriptions: 89140 Protocols on animal testing and animal 

testing alternatives 

Comment: K. Overall Comments 

As proposed, the toxicology data requirements for antimicrobial pesticides raise many issues and are 

too vague to permit a registrant to determine the kinds of data and information necessary. (See 

Panel’s General Comments at Section I.) The Panel urges EPA to repropose these requirements 

based upon these comments and other input received during the process. 

Response: see responses 2 and 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27283 

Comment Code: 80000 

Comment: Data requirements for toxicology should be imposed only as needed to make regulatory 

decisions under FIFRA, or, where relevant, for regulation of pesticide chemical residues under 

FFDCA Section 408. Any proposed requirement for toxicology data for antimicrobial pesticides 

must clearly explain to what uses the requirement applies and the reasons the data requested are 

necessary to make a regulatory decision under FIFRA or FFDCA. In setting data requirements, EPA 
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Comments and Response References: 

Toxicology Section (80) Page 506 

is subject to the mandate of FIFRA Section 3(h)(3)(A)(ii), which directs EPA to "differentiate the 

types of review undertaken for antimicrobial pesticides,..conform[ing] the degree and type of review 

to the risks and benefits presented,...considering the use patterns of the product, toxicity, expected 

exposure and product type." 

Response: see response 1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27288 

Comment Code: 80000 

Comment: In 1997, the SAP recognized the problems of applying normal assessment and tolerance 

requirements to antimicrobial pesticides that may result in residues on food and the need for a 

different approach in evaluating the risk of such antimicrobial pesticides. Specifically, the SAP 

recommended that EPA identify procedures similar to those established by the FDA to approve 

uses of these types of food contact antimicrobial pesticides under exemptions from tolerance rather 

than establishing numerical tolerances. Although the SAP’s recommendations were made during the 

period when EPA had jurisdiction over antimicrobials that prior to enactment of the FQPA in 1996, 

and currently, following enactment of the Antimicrobial Reform Technical Corrections Act 

(ARTCA) are within the jurisdiction of FDA, the logic of its recommendation remains intact. 

Risk is a function of toxicity and exposure. Recognizing the low exposure to most indirect food 

additives, FDA developed an approach to the assessment of their dietary risk in which thresholds of 

toxicological concern (TTCs) have been established in association with worst-case estimates of 

dietary exposure to address broad and not easily quantifiable exposure scenarios. This approach is 

equally applicable to antimicrobials used in situations where some residue on food is possible. 

Where exposure remains low, the thresholds of toxicological concern minimize the need to conduct 

extensive toxicological evaluations to adequately assess the potential risk. When exposure exceeds a 

certain level, however, more extensive toxicological data are required to assess the potential risk. 

While the FDA approach has focused only on dietary exposure, the underlying premise is applicable 

to low exposures via any route. 

The ACC Biocide Panel, of which LANXESS is a member, is sponsoring a collaborative project 

with EPA through ILSI-RF to determine whether a threshold of toxicological concern-type 

approach could be developed for regulatory decision-making on antimicrobial pesticides. This 

project will not be limited to dietary exposures. The project is underway and is scheduled to be 

completed within the next 12 months. It is anticipated that the recommendations from that project 

will lead to a meaningful TTC type approach for antimicrobials. LANXESS believes EPA should 

include this work in a re-proposal of Part 158W. 

LANXESS also is concerned that the Proposal does not include a policy or guidance to address the 

methods of assessing products which do not result in systemic toxicity but which are corrosive or 

severe irritants at the point of dosing. If a corrosive effect of the chemical precludes determination 

of systemic toxicity from repeated exposure prior to the corrosive effect, no further toxicology 

studies would be necessary. For the majority of chemicals that are the subject of repeated dose 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 507 

toxicity studies, a measure of systemic toxicity can be assessed by increasing the dose, consistent 

with the guidelines of the maximum tolerated dose, to the point that target organ damage is 

observed. For compounds that are corrosive to the skin from dermal exposure, corrosive to the 

respiratory tract from inhalation exposure, or corrosive to the gastrointestinal tract from oral 

exposure, it may be difficult or unfeasible to determine the potential for damage to organs that are 

outside the scope of the initial site of contact. The proposed rule fails to distinguish the data 

requirements on the basis of this important characteristic, yet this is a critical issue in designing 

testing programs and making relevant risk decisions. PMRA (1997)[FN3: Memorandum from D. 

Grant, PMRA to N. Cook, US EPA. December 1, 2007. Reproductive toxicity testing in proposed 

40 CFR 158W. Available in the docket as EPA-HQ-OPP-2008-0110-0015] specifically identified this 

issue as one which needed to be addressed. Further, the large number of antimicrobial pesticides 

that is inorganic needs to be appropriately addressed. 

Response: see responses 80.3 and 80.4 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27291 

Comment Code: 80000 

Comment: A. Exposure Considerations: 

1. Wood preservatives are listed throughout the preamble as a generic category but it is never 

defined. There are industrial uses, commercial uses and do it yourself use. The Agency should 

address each of these uses and explain how it views human and environmental, applicator and post 

applicator exposure to each. 

2. The EPA addresses "open" versus "closed" systems for metal working fluids (MWF) yet indicates 

"while both open and closed MWF are high exposure uses, under the appropriate circumstances, the 

Agency distinguishes between open and closed systems". This contradicts the overall limited 

exposure for closed system use. As in many places in the Proposal, EPA provides no explanation as 

to what "appropriate" might be. There is no way for registrants to know other than via ad hoc 

consultations with the Agency. 

3. The EPA does not explain why it has proposed the level of 200 ppb to differentiate between low 

and high exposure among food uses. If it decides to retain that dividing line, EPA should provide its 

reasoning in a re-proposal, so that it can receive meaningful comment. 

4. The EPA uses the term "repeated human exposure over a limited portion of the human lifespan" 

in footnotes 11 and 20, yet never explains what that means. In LANXESS’s view, it can mean two 

exposures in a lifetime, making virtually all antimicrobials subject to the complete set of data 

requirements. If it keeps this term, EPA should clarify what it means in a re-proposal, so that it can 

receive meaningful comments. 

5. The Agency does not define "considerable" in the phrase "high human exposure is defined as that 

resulting over a considerable portion of human lifespan."[FN4: Page 59392.] This should be 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 508 

addressed in a re-proposal. As is, the term "considerable" is too vague, does not account for 

concentration of concern, or frequency. 

6. EPA considers applicator exposures high for swimming pool use pattern, although this is not 

supported in the Proposal and, in LANXESS’s view, cannot be. Applicator exposure for swimming 

pool chemicals can be low or nonexistent, depending upon the application method. 

7. The Agency should define what is meant by a "closed" system in the regulations, and whether this 

approach is acceptable for use patterns in addition to MWF, 

Response: See responses 50.4, 80.79, 3, 80.60, 80.22, 2, 80.80, and testnotes 80.11 and 80.20 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27307 

Comment Code: 80000 

Comment: Comments for Specific Footnotes 

Under footnotes 3 and 5, dermal sensitization is "Not required if test material is corrosive to skin or 

has pH less than 2 or greater than 11.5" and "Data are required if repeated dermal exposure is likely 

to occur under conditions of use". These two requirements can, in many situations, be contradictory. 

Under footnote 6, for low exposure uses, data are required if the neurotoxicity screen in the 90-day 

oral rodent study or other data indicate neurotoxicity." Yet the neurotoxicity screen in the 90-day 

oral study and acute neurotoxicity study are conditionally required for high exposure use patterns. 

The Agency should address this contradiction. 

Response: see responses 80.5 and 80.6, and testnotes 80.3, 80.5, and 80.6 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27348 

Comment Code: 80000 

Comment: K. Overall Comments 

As proposed, the toxicology data requirements for antimicrobial pesticides raise many issues and are 

too vague to permit a registrant to determine the kinds of data and information necessary. (See 

LANXESS’s General Comments at Section I.) LANXESS urges EPA to repropose these 

requirements based upon these comments and other input received during the process. 

Response: see response 2 
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Comments and Response References: 

Toxicology Section (80) Page 509 

Comment Code: 81000 Acute toxicity studies 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25631 

Comment Code: 81000 

Comment: 2. In the Label Review Manual (Chapter 7, Section IVA), the Agency allows for 

extrapolation of acute systemic toxicology data on product concentrates to use- dilutions. This 

guidance should be referenced as an alternative to requiring additional animal testing for usesolutions. The guidance will need to be updated to reflect adoption of the Up/Down test for acute 

oral toxicity. The Agency will also need to work with some states (e.g. California) to obtain their 

acceptance of this approach before this is enacted. Again, we would like to reiterate that the industry 

must be able to register their pesticides in the states in order to sell them. When EPA and California 

take opposite positions on a given issue, the situation for the registrants becomes untenable. 

3. Test note # 2 does not currently apply to acute inhalation studies. It is not clear whether the 

omission is an oversight by the Agency or was an intentional exclusion. CSPA believes that 

registrants must have the opportunity to assess the inhalation toxicity potential of use-dilutions in 

order accurately label concentrated products. 

Response: see responses 80.11 and 80.12, testnote 80.2 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25672 

Comment Code: 81000 

Comment: Requiring data on toxicity of formulated products 

SFE supports the inclusion of acute toxicity testing for both active ingredients and end-use products 

as a way to gain data on the effects of inert ingredients. 

Response: EPA acknowledges SF Environment's support for requiring acute toxicity testing for 

both the TGAI and the EP. 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26168 

Comment Code: 81000 

Comment: In the preamble to the proposed rule, the EPA indicates that it may require the testing 

of the most concentrated use-dilution for biocide concentrates. Testing may be required if the 

Agency believes that the use dilution may result in "significant exposure." Test note #2, however, 
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Comments and Response References: 

Toxicology Section (80) Page 510 

indicates that usedilution testing is optional and at the discretion of the registrant. The Agency needs 

to reconcile its guidance on this matter. Alternatively, the Agency needs to clearly define "significant 

exposure" and rewrite test note #2 to provide clear guidance to registrants. P&G recommends that 

testing of the use-dilution of biocide concentrates remain at the discretion of the registrant. In the 

Label Review Manual, at Chapter 7, Section IVA, the Agency allows for extrapolation of acute 

systemic toxicology data on product concentrates to use-dilutions. This guidance should be 

referenced as an alternative to requiring additional animal testing for use-dilution solutions. 

Response: see response 80.11 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26588 

Comment Code: 81000 

Comment: B. Comments on Acute Toxicity Requirements 

1. In general, the overall acute toxicity data requirements are consistent with current Agency 

practices. 

2. Acute Toxicology Studies on Use-dilutions a. Requirement for Use-dilution testing: 

b. In the preamble to the proposed rule, the EPA indicates that it may require the testing of the 

most concentrated use- dilution for biocide concentrates. Testing may be required if the Agency 

believes that the use dilution may result in "significant exposure." Test note #2, however, indicates 

that use-dilution testing is optional and at the discretion of the registrant. The Agency needs to 

reconcile its guidance on this matter. Alternatively, the Agency needs to clearly define "significant 

exposure" and rewrite test note #2 to provide clear guidance to registrants. The Panel recommends 

that testing of the use-dilution of biocide concentrates remain at the discretion of the registrant. 

Precautionary labeling is currently based on the outcome of toxicity studies conducted on the 

concentrated product. Use-dilution testing would result in a near doubling of acute study costs for 

registrants. The current price for six acute studies generally required is approximately $35,000-

$70,000 and requires 70-100 test animals. The additional cost for the use-dilution studies is estimated 

at $20,000-30,000 and could require additional 30-40 test animals to complete. The only study that 

would not need to be repeated is the delayed contact hypersensitivity study since its design allows 

coverage of both the product concentrate and any use-dilutions. 

Response: see response 80.11 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26590 

Comment Code: 81000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 511 

Comment: In the Label Review Manual, at Chapter 7, Section IVA, the Agency allows for 

extrapolation of acute systemic toxicology data on product concentrates to use- dilutions. This 

guidance should be referenced as an alternative to requiring additional animal testing for usedilution solutions. The guidance will need to be updated to reflect adoption of the Up/Down test 

for acute oral toxicity. The Agency will also need to work with some states, for example, California, 

to obtain their acceptance of this approach. 

Response: see response 80.11 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26592 

Comment Code: 81000 

Comment: Test note # 2 does not currently apply to acute inhalation studies. The Panel believes 

that registrants must have the opportunity to assess the inhalation toxicity potential of use-dilutions 

in order to justify accurate labeling for concentrated products. 

Many biocidal products are corrosive concentrates that are intended to be diluted prior to use. 

Current Agency practice requires inhalation toxicity testing on the concentrate. If classified in 

Toxicity Category I or II for inhalation toxicity, significant precautionary labeling and protective 

equipment, for example, respiratory protection, is required. Once diluted, however, these products 

can have a much different toxicity profile. In some segments, concentrates are diluted up to 1:1024. 

The labeling and PPE requirements for the concentrate can be inappropriate for the use-dilution. 

The PPE requirements for many concentrates are also inconsistent with common practice. For 

example, it is not practical to train janitorial staff to use respiratory protection when handling diluted 

sanitizers or disinfectants in schools or healthcare facilities. In this situation, EPA should give 

registrants the discretion to test the inhalation toxicity of the use-dilution to justify appropriate 

precautionary labeling and PPE requirements for the use- solution. 

c. Test product as formulated for sale and distribution Test note #2 specifies that the "six acute 

toxicity studies conducted with the end- use product . . . must be conducted with the product 

formulated for sale and distribution." While the Panel essentially agrees with the Agency position on 

this issue, it recommends the following clarifications: 

i. The current wording of test note #2 may be perceived as prohibiting proper conduct of studies 

for dermal sensitization. These protocols require dilution of the test product to identify doses that 

distinguish between irritation and allergy. The irritating or corrosive nature of many antimicrobial 

formulations precludes testing the "product as formulated for sale and distribution" in these studies. 

Response: see response 80.12 and testnote 80.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26593 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 512 

Comment Code: 81000 

Comment: ii. Secondly, there are instances where it may not be possible to test the formulated 

product in a humane manner. The wording of test note #2 should provide flexibility to account for 

this well known property of many antimicrobials. 

For example, in the dermal toxicity test, corrosive materials can cause significant skin injury during 

the 24 hours of exposure required by the study. While the study can be waived, in the absence of 

data, the Agency will classify the product in Toxicity Category I, require skull and crossbones and 

mandate the statement "Fatal if absorbed through skin." For corrosive materials, with no significant 

systemic toxicity, this approach can result in inaccurate labeling. In these instances it may be 

desirable to dilute the product to reduce the amount of irritation while maintaining the same overall 

dose of the test material. For example, the test product could be diluted by 50% and dosed at 10 

g/kg vs. 5 g/kg. In some cases, this approach can allow the study to go forward while reducing 

unnecessary stress to the test animals. 

Therefore, the Panel recommends that Test note #2 be modified to read as follows: "For the six 

acute toxicity studies conducted with the end-use product, the test must be conducted using the 

product as formulated for sale and distribution except as required by study protocols or unless a 

variance is granted after consultation with the Agency". 

Response: see response 80.4 and testnote 80.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26601 

Comment Code: 81000 

Comment: 3. Consultation In both the preamble and in test note #2, the Agency states that 

"[c]onsultation with the Agency is highly suggested to assure that the appropriate product and any 

appropriate dilutions are tested." The Panel asserts that consultation should not be needed prior to 

conducting routine acute studies and that the Agency needs to clarify under what circumstances 

consultation is needed. Neither the Agency nor registrants have adequate resources to devote to 

consultation about these types of studies. 

An Agency review requirement for routine acute studies will impose a time and resource burden on 

both the registrant and the Agency to review and approve routine submissions prior to conducting 

the studies. The resource burden could be extensive given the numbers of these studies conducted 

and submitted. The Panel notes that EPA has not even attempted to estimate this burden. Under 

the current system, routine acute testing of end-use products does not require Agency pre-review. 

Pre-review by the Agency should always be an option for unique products or use- patterns. 

However, the Panel does not recommend that routine consultation be either required or 

recommended by EPA most acute study packages. 

Response: see response 3 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 513 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26603 

Comment Code: 81000 

Comment: 4. Bridging and Study Waivers It is in the interest of both registrants and the Agency to 

reduce the need for unnecessary animal testing. The increased use of bridging and study waivers can 

significantly reduce the number of toxicity studies that are needed to support antimicrobial 

registrations. Unnecessary toxicity testing imposes a significant financial and resource burden on 

both the registrants and the Agency. Registrants shoulder the direct cost to pay for the studies. The 

Agency has to dedicate resources to review the studies promptly after submission. (The Panel notes 

that some studies required by "time limited" registrations were submitted years ago, but have not 

been reviewed, so the time limited registrations continue.) Also, these studies require the use of a 

significant number of experimental animals; one "six-pack" can require 70-100 test animals. 

Response: see response 80.65 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26661 

Comment Code: 81000 

Comment: 1. Tier I 

Acute Toxicity The acute toxicity package of oral, dermal, inhalation exposure, skin and eye 

irritation, and skin sensitization is designed to assess the effects of single exposures. Acute oral and 

dermal exposure studies would not be necessary if physical characteristics (gas or highly volatile 

liquid) preclude conduct of the study. 

Evaluation of the toxicological profile of a chemical would always proceed beyond the level of acute 

toxicity except for the case of corrosive substances. If a corrosive effect of the chemical precludes 

determination of systemic toxicity from repeated exposure prior to the corrosive effect, no further 

toxicology studies would be necessary. For the majority of chemicals evaluated in repeated dose 

toxicity studies, a measure of systemic toxicity can be assessed by increasing the dose, consistent 

with the guidelines of the maximum tolerated dose, to the point that target organ damage is 

observed. However, for some chemicals, e.g. those that are corrosive to the skin from dermal 

exposure, corrosive to the respiratory tract from inhalation exposure, or corrosive to the 

gastrointestinal tract from oral exposure, it may be difficult if not impossible to determine the 

potential for damage to organs that are outside the scope of the initial site of contact. 

In the case of inhalation, oral, and dermal exposure, indirect or secondary effects can occur as a 

result of a corrosive effect at the site of contact. It is important to emphasize that direct irritation 

and/or corrosivity is dependent upon concentration at the site(s) of contact in contrast to systemic 

toxicity, which is driven by the overall body burden of a chemical. Inhalation of corrosive chemicals 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 514 

may cause burns only in the upper respiratory tract, but if not corrosive to the lungs, the chemical 

can produce irritation and inflammation to pulmonary tissue which, over time, can compromise lung 

function and set up sequelae adversely affecting other organs. Corrosive effects to the 

gastrointestinal tract can produce anemia with dose-related decreases in erythrocytes, haemoglobin, 

and hematocrit. The regenerative response to the anemia can produce changes to red cell 

morphology consistent with immature erythrocytes and splenic extramedullary hematopoiesis. This 

is in addition to inflammation, hyperkeratosis, and hyperplasia that typically occur in the stomach. 

Severe to moderate irritation to the skin from dermal exposure has been shown to adversely affect 

haematological and clinical chemistry variables (Hermansky et al., 1995). These investigators 

evaluated a series of repeated dose cutaneous application studies and noted a decrease in 

hemoglobin concentration, hematocrit, erythrocyte count and serum concentrations of calcium, 

potassium, inorganic phosphorus and creatinine. Increases were observed in total leukocyte and 

neutrophil count. Based on a consistent direction of change in these variables following dermal 

application of chemically distinct irritants, the above changes are considered secondary to cutaneous 

irritation and not a reflection of direct systemic toxicity. 

Secondary systemic effects from inhalation and oral exposure compared to dermal exposure are 

more easily understood because the irritating or corrosive substance makes contact with internal 

tissues of the body. However, even without significant dermal penetration of a substance into the 

systemic circulation, the work by Hermansky et al. (1995) demonstrates that severe dermal irritation 

can compromise the internal integrity of the mammalian system and the viability of the animal. 

Thus, substantial tissue damage, even without entry of the chemical into the systemic circulation, can 

compromise the health of the animal and place it in a moribund condition. Also, reduction of the 

integrity of the skin to act as a barrier to the external environment can allow invasion of 

opportunistic pathogenic organisms into the systemic circulation and produce septicemia with its 

potential attendant sequelae. A corrosive effect to the skin, with or without entry of the chemical 

into the systemic circulation, is self-limiting and represents a terminal toxicological finding. If the 

chemical does not enter the body in sufficient quantities to produce damage to internal organs, the 

only effects observed in a repeated dose dermal toxicity study will occur to the skin such as necrosis, 

ulceration, and sloughing of the skin. Of course, these effects can lead to sequelae that may 

compromise the health of the treated animals even without absorption of sufficient amounts of the 

chemical to produce internal target organ damage. But conduct of a study according to animal 

welfare guidelines would preclude an animal ever reaching such a debilitative state. 

The scientific support and EPA guidance and policy are clear that corrosivity is a recognized 

terminal toxicological endpoint in studies conducted orally, dermally, and via inhalation. 

It is scientifically indefensible to pursue a course of toxicological testing to produce systemic toxicity 

if corrosivity is observed in a study prior to and in absence of systemic toxicity. The potential for 

corrosivity can be adequately determined in acute toxicity studies, which would obviate the need for 

further study. 

Response: EPA agrees that the physical state of the pesticide chemical is a factor that should be 

considered in determining the testing plan. Also, see response 80.4 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 515 

Letter ID: 0064 

Comment ID: 27293 

Comment Code: 81000 

Comment: B. Comments on Acute Toxicity Requirements 

1. In general, the overall acute toxicity data requirements are consistent with current Agency 

practices. 

2. Acute Toxicology Studies on Use-dilutions 

a. Requirement for Use-dilution testing: 

b. In the preamble to the proposed rule, the EPA indicates that it may require the testing of the 

most concentrated use-dilution for biocide concentrates. Testing may be required if the Agency 

believes that the use dilution may result in "significant exposure." Test note #2, however, indicates 

that use-dilution testing is optional and at the discretion of the registrant. The Agency needs to 

reconcile its guidance on this matter. Alternatively, the Agency needs to clearly define "significant 

exposure" and rewrite test note #2 to provide clear guidance to registrants. LANXESS recommends 

that testing of the use-dilution of biocide concentrates remain at the discretion of the registrant. 

Precautionary labeling is currently based on the outcome of toxicity studies conducted on the 

concentrated product. Use-dilution testing would result in a near doubling of acute study costs for 

registrants. The current price for six acute studies generally required is approximately $35,000-

$70,000 and requires 70-100 test animals. The additional cost for the use-dilution studies is estimated 

at $20,000-30,000 and could require additional 30-40 test animals to complete. The only study that 

would not need to be repeated is the delayed contact hypersensitivity study since its design allows 

coverage of both the product concentrate and any use-dilutions. 

Response: see response 80.11 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27296 

Comment Code: 81000 

Comment: In the Label Review Manual, at Chapter 7, Section IVA, the Agency allows for 

extrapolation of acute systemic toxicology data on product concentrates to use- dilutions. This 

guidance should be referenced as an alternative to requiring additional animal testing for use-dilution 

solutions. The guidance will need to be updated to reflect adoption of the Up/Down test for acute 

oral toxicity. The Agency will also need to work with some states, for example, California, to obtain 

their acceptance of this approach. 

Response: see response 80.11 

Commenter Name: Stanley Oslosky 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 516 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27298 

Comment Code: 81000 

Comment: Test note # 2 does not currently apply to acute inhalation studies. LANXESS believes 

that registrants must have the opportunity to assess the inhalation toxicity potential of use-dilutions 

in order to justify accurate labeling for concentrated products. 

Many biocidal products are corrosive concentrates that are intended to be diluted prior to use. 

Current Agency practice requires inhalation toxicity testing on the concentrate. If classified in 

Toxicity Category I or II for inhalation toxicity, significant precautionary labeling and protective 

equipment, for example, respiratory protection, is required. Once diluted, however, these products 

can have a much different toxicity profile. In some segments, concentrates are diluted up to 1:1024. 

The labeling and PPE requirements for the concentrate can be inappropriate for the use-dilution. 

The PPE requirements for many concentrates are also inconsistent with common practice. For 

example, it is not practical to train janitorial staff to use respiratory protection when handling diluted 

sanitizers or disinfectants in schools or healthcare facilities. In this situation, EPA should give 

registrants the discretion to test the inhalation toxicity of the use-dilution to justify appropriate 

precautionary labeling and PPE requirements for the use-solution. 

c. Test product as formulated for sale and distribution 

Test note #2 specifies that the "six acute toxicity studies conducted with the end-use product . . . 

must be conducted with the product formulated for sale and distribution." While LANXESS 

essentially agrees with the Agency position on this issue, it recommends the following clarifications: 

i. The current wording of test note #2 may be perceived as prohibiting proper conduct of studies 

for dermal sensitization. These protocols require dilution of the test product to identify doses that 

distinguish between irritation and allergy. The irritating or corrosive nature of many antimicrobial 

formulations precludes testing the "product as formulated for sale and distribution" in these studies. 

Response: see responses 80.12 and 80.13, and testnote 80.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27299 

Comment Code: 81000 

Comment: ii. Secondly, there are instances where it may not be possible to test the formulated 

product in a humane manner. The wording of test note #2 should provide flexibility to account for 

this well known property of many antimicrobials. 

For example, in the dermal toxicity test, corrosive materials can cause significant skin injury during 

the 24 hours of exposure required by the study. While the study can be waived, in the absence of 

data, the Agency will classify the product in Toxicity Category I, require skull and crossbones and 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 517 

mandate the statement "Fatal if absorbed through skin." For corrosive materials, with no significant 

systemic toxicity, this approach can result in inaccurate labeling. In these instances it may be 

desirable to dilute the product to reduce the amount of irritation while maintaining the same overall 

dose of the test material. For example, the test product could be diluted by 50% and dosed at 10 

g/kg vs. 5 g/kg. In some cases, this approach can allow the study to go forward while reducing 

unnecessary stress to the test animals. 

Therefore, LANXESS recommends that Test note #2 be modified to read as follows: 

"For the six acute toxicity studies conducted with the end-use product, the test must be conducted 

using the product as formulated for sale and distribution except as required by study protocols or 

unless a variance is granted after consultation with the Agency". 

Response: see response 80.4 and testnote 80.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27301 

Comment Code: 81000 

Comment: 3. Consultation 

In both the preamble and in test note #2, the Agency states that "[c]onsultation with the Agency is 

highly suggested to assure that the appropriate product and any appropriate dilutions are tested." 

LANXESS asserts that consultation should not be needed prior to conducting routine acute studies 

and that the Agency needs to clarify under what circumstances consultation is needed. Neither the 

Agency nor registrants have adequate resources to devote to consultation about these types of 

studies. 

An Agency review requirement for routine acute studies will impose a time and resource burden on 

both the registrant and the Agency to review and approve routine submissions prior to conducting 

the studies. The resource burden could be extensive given the numbers of these studies conducted 

and submitted. LANXESS notes that EPA has not even attempted to estimate this burden. Under 

the current system, routine acute testing of end-use products does not require Agency pre- review. 

Pre-review by the Agency should always be an option for unique products or use- patterns. 

However, LANXESS does not recommend that routine consultation be either required or 

recommended by EPA most acute study packages. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27304 

Comment Code: 81000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 518 

Comment: 4. Bridging and Study Waivers 

It is in the interest of both registrants and the Agency to reduce the need for unnecessary animal 

testing. The increased use of bridging and study waivers can significantly reduce the number of 

toxicity studies that are needed to support antimicrobial registrations. Unnecessary toxicity testing 

imposes a significant financial and resource burden on both the registrants and the Agency. 

Registrants shoulder the direct cost to pay for the studies. The Agency has to dedicate resources to 

review the studies promptly after submission. (LANXESS notes that some studies required by "time 

limited" registrations were submitted years ago, but have not been reviewed, so the time limited 

registrations continue.) Also, these studies require the use of a significant number of experimental 

animals; one "six-pack" can require 70-100 test animals. 

Response: see response 80.65 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27351 

Comment Code: 81000 

Comment: 1. Tier I 

Acute Toxicity 

The acute toxicity package of oral, dermal, inhalation exposure, skin and eye irritation, and skin 

sensitization is designed to assess the effects of single exposures. Acute oral and dermal exposure 

studies would not be necessary if physical characteristics (gas or highly volatile liquid) preclude 

conduct of the study. 

Evaluation of the toxicological profile of a chemical would always proceed beyond the level of acute 

toxicity except for the case of corrosive substances. If a corrosive effect of the chemical precludes 

determination of systemic toxicity from repeated exposure prior to the corrosive effect, no further 

toxicology studies would be necessary. For the majority of chemicals evaluated in repeated dose 

toxicity studies, a measure of systemic toxicity can be assessed by increasing the dose, consistent 

with the guidelines of the maximum tolerated dose, to the point that target organ damage is 

observed. However, for some chemicals, e.g. those that are corrosive to the skin from dermal 

exposure, corrosive to the respiratory tract from inhalation exposure, or corrosive to the 

gastrointestinal tract from oral exposure, it may be difficult if not impossible to determine the 

potential for damage to organs that are outside the scope of the initial site of contact. 

In the case of inhalation, oral, and dermal exposure, indirect or secondary effects can occur as a 

result of a corrosive effect at the site of contact. It is important to emphasize that direct irritation 

and/or corrosivity is dependent upon concentration at the site(s) of contact in contrast to systemic 

toxicity, which is driven by the overall body burden of a chemical. Inhalation of corrosive chemicals 

may cause burns only in the upper respiratory tract, but if not corrosive to the lungs, the chemical 

can produce irritation and inflammation to pulmonary tissue which, over time, can compromise lung 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 519 

function and set up sequelae adversely affecting other organs. Corrosive effects to the 

gastrointestinal tract can produce anemia with dose-related decreases in erythrocytes, haemoglobin, 

and hematocrit. The regenerative response to the anemia can produce changes to red cell 

morphology consistent with immature erythrocytes and splenic extramedullary hematopoiesis. This 

is in addition to inflammation, hyperkeratosis, and hyperplasia that typically occur in the stomach. 

Severe to moderate irritation to the skin from dermal exposure has been shown to adversely affect 

haematological and clinical chemistry variables (Hermansky et al., 1995). These investigators 

evaluated a series of repeated dose cutaneous application studies and noted a decrease in 

hemoglobin concentration, hematocrit, erythrocyte count and serum concentrations of calcium, 

potassium, inorganic phosphorus and creatinine. Increases were observed in total leukocyte and 

neutrophil count. Based on a consistent direction of change in these variables following dermal 

application of chemically distinct irritants, the above changes are considered secondary to cutaneous 

irritation and not a reflection of direct systemic toxicity. 

Secondary systemic effects from inhalation and oral exposure compared to dermal exposure are 

more easily understood because the irritating or corrosive substance makes contact with internal 

tissues of the body. However, even without significant dermal penetration of a substance into the 

systemic circulation, the work by Hermansky et al. (1995) demonstrates that severe dermal irritation 

can compromise the internal integrity of the mammalian system and the viability of the animal. 

Thus, substantial tissue damage, even without entry of the chemical into the systemic circulation, can 

compromise the health of the animal and place it in a moribund condition. Also, reduction of the 

integrity of the skin to act as a barrier to the external environment can allow invasion of 

opportunistic pathogenic organisms into the systemic circulation and produce septicemia with its 

potential attendant sequelae. A corrosive effect to the skin, with or without entry of the chemical 

into the systemic circulation, is self-limiting and represents a terminal toxicological finding. If the 

chemical does not enter the body in sufficient quantities to produce damage to internal organs, the 

only effects observed in a repeated dose dermal toxicity study will occur to the skin such as necrosis, 

ulceration, and sloughing of the skin. Of course, these effects can lead to sequelae that may 

compromise the health of the treated animals even without absorption of sufficient amounts of the 

chemical to produce internal target organ damage. But conduct of a study according to animal 

welfare guidelines would preclude an animal ever reaching such a debilitative state. 

The scientific support and EPA guidance and policy are clear that corrosivity is a recognized 

terminal toxicological endpoint in studies conducted orally, dermally, and via inhalation. 

It is scientifically indefensible to pursue a course of toxicological testing to produce systemic toxicity 

if corrosivity is observed in a study prior to and in absence of systemic toxicity. The potential for 

corrosivity can be adequately determined in acute toxicity studies, which would obviate the need for 

further study. 

Response: EPA agrees that the physical state of the pesticide chemical is a factor that should be 

considered in determining the testing plan. Also, see response 80.4 

Comment Code: 82000 Subchronic studies 

Commenter Name: Marion Law 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 520 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25581 

Comment Code: 82000 

Comment: Section Number VIII. 

Title Toxicology Data Requirements 

Paragraph F. 90-Day Oral Studies Paragraph 2, p. 59395 

Excerpt from Federal Register Often, range-finding studies of at least 90 days are needed to select 

the appropriate dose levels for the mouse carcinogenicity study. Thus, 90- day studies are often 

performed routinely by most investigators prior to the initiation of the carcinogenicity study. Often 

the range-finding studies have been submitted to the Agency for review. Because of their utility in 

determining the dose levels in the mouse carcinogenicity study, in the test notes, the Agency 

encourages the use of range-finding studies in the mouse. 

HC Comment The PMRA seeks clarification regarding the intent of this paragraph. Is the Agency 

encouraging the applicant to submit the 90-day mouse range-finding study when it has been 

conducted? 

Response: see response 80.21 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25938 

Comment Code: 82000 

Comment: HVAC testing requirements - We applaud the Agency's emphasis on HVAC systems as 

a unique scenario that requires separate risk assessments for approval of products for such use. 

However, the toxicology data requirement noted in Footnote 15 in the table "Antimicrobial 

Toxicology Data Requirements" (two 90- day toxicity tests) appears to be excessive. We suggest that 

an indoor surface residue dissipation study (Guideline 875.2300) be conducted prior to a 

determination of additional toxicity studies beyond residue dissipation. This recommendation is 

being made because many products used for sanitizing of HVAC systems would lack longer term 

exposures. A more appropriate study would be acute in nature. 

Response: see response 80.75 and testnote 80.15 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25951 

Comment Code: 82000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 521 

Comment: If possible toxicological endpoints for studies such as immunotoxicity and neurotoxicity 

should be incorporated into other sub-chronic studies to enhance standard toxicity tests and provide 

substantive data to the Agency indicating the need to proceed to a full blown neurotoxicity or 

immunotoxicity study. In addition, simple leaching studies should be used where possible to 

determine the need for additional studies based on potential exposure. The use of more robust 

testing protocols and additional preliminary tests utilize company resources in a more efficient way. 

Response: see response 80.19 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26181 

Comment Code: 82000 

Comment: To address subchronic testing data requirements, the proposal requires a 90-day oral 

toxicity study in rodents for both "high" and "low" exposures, 90-day oral toxicity study in 

nonrodents for "high" exposure, 90-day neurotoxicity study in the rat, and immunotoxicity study. 

P&G recommends that a 90-day subchronic oral study in the rodent that is enhanced by including 

assessments for neurotoxicity and immunotoxicity. P&G considers the results from the proposed 

enhanced 90-day study in the rat sufficient to detect any effects to target organs including the 

potential to produce specific toxicity to the nervous system and the immune system. If the rodent 

90-day subchronic toxicity yields an inadequate margin of exposure, a 90-day non-rodent subchronic 

toxicity study, preferably in the dog, would be recommended. If any of the neurotoxicity endpoints 

in the 90-day subchronic rat study from Tier I indicate the potential for neurotoxicity, a 90- day 

subchronic neurotoxicity study in the rat would be recommended. If any of the immunotoxicity 

endpoints in the 90-day subchronic rat study from Tier I indicate the potential for immunotoxicity, a 

90-day subchronic immunotoxicity study in the rat would be recommended. If any of the 

neurotoxicity endpoints in the 90-day subchronic rat study from Tier I, or if the results 

(morphological and brain weight changes or functional or behavioral changes in the F1 offspring) 

from Tier I reproduction and developmental studies indicate the potential for neurotoxicity, a 90-

day subchronic developmental neurotoxicity study in the rat would be recommended. 

Response: see response 80.19 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26185 

Comment Code: 82000 

Comment: P&G further recommends in vitro dermal penetration data along with the data from 90-

day oral subchronic study be allowed to address the subchronic dermal toxicity data requirements 

when this study is triggered based on the results from the 90-day subchronic oral toxicity study and 

knowledge of the amount of the chemical that is absorbed dermally, considering the assumption that 

100% of the chemical is absorbed from oral administration. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 522 

Response: see responses 80.20 and 80.56 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26235 

Comment Code: 82000 

Comment: * The Agency has not identified the criteria used to determine if "the use of the 

pesticide is likely to result in repeated human exposure over a limited portion of the human 

lifespan." Instead, a registrant must consult with the Agency to determine if certain data are required 

for low human exposure uses.[FN#7:Proposed Rule at [Section] 158.2230(e)(11).] 

Response: see response 80.16 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26322 

Comment Code: 82000 

Comment: Second, the test notes in the Proposal provide for numerous determinations at the sole 

discretion of EPA. For example, test note 7 in the Proposal’s Toxicology Data Table provides that 

"the 90-day dermal toxicity study or the 90- day inhalation toxicity study may be substituted for the 

90-day oral toxicity study if the Agency determines that dermal or inhalation exposure is a major 

route of exposure" (emphasis added). Language similar to the emphasized phrase is repeated 

throughout the Proposal test notes, allowing for numerous ad hoc determinations at the sole 

discretion of EPA. 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26348 

Comment Code: 82000 

Comment: D. Toxicology Data Requirements 

For toxicology data requirements, a 90-day oral rat is required for all antimicrobials, while it is 

conditional for conventional pesticides - required only if oral exposure is expected to occur for 

conventional pesticides.[FN#44:Compare 40 CFR 158.500 with Proposed [Section] 158.2230.] 

Similarly, a 90-day non-rodent study is required for food use conventional pesticides and 

conditionally required for non-food use if oral exposure (e.g., drinking water) is expected. However, 

for low human exposure antimicrobials (which includes non-food use), the study is required based 

on EPA’s sole discretion if any of the following criteria are met: 
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Comments and Response References: 

Toxicology Section (80) Page 523 

i. The use of the pesticide is likely to result in repeated human exposure over a limited portion of the 

human lifespan, as determined by the Agency. 

ii. The use is an indirect food use (less than 200 ppb).[FN#45:Proposed Rule [Section] 158.2230 

n.11.] 

As noted above, the criteria for triggering a data requirement for conventional pesticides is based on 

"repeated human exposure over a considerable portion of the human lifespan." Thus, EPA has 

imposed a more rigorous standard on antimicrobials without providing any explanation as to why 

that is necessary or appropriate. The Panel submits this change is inappropriate and unwarranted. 

Review of this change by the FIFRA SAP should be conducted before implementing this Proposal. 

A 21/28 day dermal study is not required for nonfood use conventional pesticides, but it is 

conditionally required for all antimicrobials, based on Test Note 12: 

Data are required if the intended use of the antimicrobial pesticide product is expected to result in 

human exposure to the product and the three following conditions are met: 

i. Human exposure is via skin contact. 

ii. Expected human exposure is not purposeful and is over a limited portion of the human lifespan; 

however, as determined by EPA, the exposure is significant in terms of the frequency of exposure, 

magnitude of exposure, or the duration of exposure. 

iii. Data from a subchronic 90-day dermal toxicity study are not available and the 90-day dermal 

toxicity study has not been triggered. 

Test Note 12 again introduces, without any explanation, a conditional requirement for exposure 

over a "limited" portion of the lifespan, if EPA, in its sole discretion, deems the exposure significant. 

Response: see responses 3, 80.16, and 80.17, and testnote 80.12 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26614 

Comment Code: 82000 

Comment: C. Comments on Subchronic Toxicity Requirements 

1. The Agency has added reference to testing "if use of the pesticide is likely to result in repeated 

human exposure over a limited portion of the human lifespan, as determined by the Agency." As 

explained above, this can be interpreted to trigger testing for virtually all antimicrobials. EPA should 

clarify what it means and re-issue that for comment in a reproposal. 
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Comments and Response References: 

Toxicology Section (80) Page 524 

2. In the 90-Day non-rodent (dog) study, the requirement is based on bioaccumulation and slow 

elimination of pesticide for both conventional and antimicrobial pesticides. However, for 

antimicrobial pesticides the Agency has added a requirement for the study "if use of the pesticide is 

likely to result in repeated human exposure over a limited portion of the human lifespan, as 

determined by the Agency." No explanation is provided for this additional trigger. It also effectively 

gives EPA full discretion to require this animal- intensive study without clear basis. This language 

must be clarified and then reproposed. (See Panel’s General Comments at Section I.) 

3. For Conventional Pesticides there is no reference to HVAC systems. For AM Pesticides the 

Agency has added the requirement for a 90-day inhalation and 90- day dermal studies if the intended 

use of the antimicrobial pesticide is in HVAC systems. This requirement is of concern to the Panel 

in several respects. EPA and the Panel are working to develop an approach to labeling for 

antimicrobials used in HVAC systems, yet that work is not reflected in the Proposal. Similarly, the 

additional 90-day study requirements seem to be based on intuitive, but not empirical views on 

exposure. If EPA has evidence of inhalation and dermal exposure from antimicrobials used, in 

accordance with their labels, in HVAC systems, that information should be shared and available for 

comment. Without such information, there is no basis for a differential data requirement. In any 

event, EPA should explain the reasons behind these new requirements and make them available for 

comment. The Panel believes that the threshold of toxicological concern approach should be 

adopted for HVAC systems and other uses. If exposures are below the level of toxicological 

concern, there should be no requirement to conduct a study. Also, the Panel notes that the 

requirement for HVAC systems is inconsistent with the footnote for both Conventional Pesticides 

and AM Pesticides in which the Agency states that a 90-day inhalation study is "required if there is 

the likelihood of significant repeated inhalation exposure to the pesticide as a gas, vapor, or aerosol." 

4. The Panel asserts that the 90-Day neurotoxicity for the ‘High" exposure scenario should also be 

CR (conditionally required) as in the "Low" exposure scenarios, as stated in the Test Note 6. The 

trigger for the study should not be based on the arbitrarily established "Low" or "High" exposure 

but on the indications from the results of the 90-day oral or other required studies including SAR 

data. Generally the comprehensive clinical observations and routine histopathology are sufficient to 

assess the neurotoxic potential of a product. Similarly, the acute neurotoxicity study should be 

conditionally required. The trigger should be based on the indications from the acute, subchronic, 

and other available data including SAR information. However, the triggers for the neurotoxicity 

should not be based on the results seen at the high dose levels. For example, lethal or sub lethal 

doses in the acute studies, and maximum tolerated dose (MTD) or exceeding MTD doses in the 

subchronic studies provide a basis for determining the need for neurotoxicity studies. 

5. The Panel suggests that the 90-day oral toxicity study include enhanced endpoints to minimize the 

need for additional testing: The recommended enhanced endpoints for each area of testing are as 

follows: 

* Neurotoxicity 

o Changes in motor function (e.g. disturbances in gait, abnormal posture, or muscle tone), level of 

arousal (e.g. hyperactivity and lethargy), autonomic functions (salivation, lacrimation, urination, and 

defecation), psychological status (e.g. stereotypy, aggression, biting, licking, and self- mutilation), and 

pharmacological effects (e.g. sedation). In addition to the extensive functional assessment just 
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Comments and Response References: 

Toxicology Section (80) Page 525 

described, this study should also include a satellite group of animals for the evaluation of 

histopathological change to the central and peripheral nervous systems following fixation by 

perfusion. 

Response: see responses 80.16, 80.18, and 80.19 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26618 

Comment Code: 82000 

Comment: Comments for Specific Footnotes 

The Panel interprets footnote 9 as requiring a 90-day rat study but not a 90-day mouse study to 

characterize the hazard from subchronic exposure. However, if a rodent carcinogenicity evaluation is 

required in two species, the Agency encourages the applicant to conduct a dose-ranging-finding 

study in the mouse. The second species (rodent) study should only be conducted when long term 

chronic/carcinogenicity studies are triggered. 

In footnote 10, the Panel asserts that a 90-day dog study for either the high exposure (Required) or 

the low dose exposure (Conditionally Required) is not warranted and the following observations 

regarding the regulatory use of non- rodent studies should be considered when requiring this study: 

a. Since the 1-year non-rodent (dog) study has been eliminated under most circumstances as a 

required test to support conventional pesticide registrations, it would seem more appropriate to 

conduct all additional testing beyond 90 days in the rodent rather than the dog. The wording of 

footnote 10 is inconsistent with what is stated for the comparable footnote (footnote 36) for 

conventional pesticides.[FN#5:40 CFR 158.500] 

b. Thus, when a second species is required to be tested over 90 days, the mouse would be a more 

appropriate selection than the dog because of the limited sample size, statistical limitations, and 

flexibility available in a repeated dose dog study,. 

c. In test note 11, the Agency’s concern of human exposure due to repeated use and indirect food 

use of the antimicrobial pesticide are well covered by the data generated with the repeated dose 

studies in the rodent. The repeated dose studies in the rodent (90-day rat and other studies) provide 

sufficient information to define the hazard and end points for addressing the concerns of repeated 

use exposure and indirect food use of the product. 

As explained above, the Panel believes the Agency must modify its use of the term "repeated human 

exposure over a limited portion of the human lifespan" in footnote 11(i) and 12(ii). This is a vague 

phrase that would require Agency interpretation for a registrant to understand the requirement. (See 

Panel’s General Comments at Section I) 

Response: see response 80.16, and testnotes 80.9, 80.10, 80.11, and 80.36 
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Comments and Response References: 

Toxicology Section (80) Page 526 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26664 

Comment Code: 82000 

Comment: Regimen of Repeated Dosing to Evaluate the Endpoints of Systemic Toxicity 

The assessment of systemic toxicity is a key component in the overall assessment of a chemical’s 

potential to cause adverse effects on health. The objective of this assessment is to develop an 

approach that ensures evaluation of all relevant toxicity parameters, and identify a hierarchy of study 

types, endpoints and triggers that would be used in a tiered approach (Doe et al., 2006). A study that 

serves to predict systemic or target organ toxicity beyond acute exposure is one in which the selected 

animal species is administered the test chemical in a multiple doses regimen. It is important to 

recognize that a key aspect of such a study is to provide data that describe the shape of the doseresponse curve, rather than emphasizing effects that may occur only at high doses that are irrelevant 

to situations encountered by humans and other organisms in the environment from use of products 

that contain antimicrobial pesticides. 

The study of choice to achieve this objective is the 90-day subchronic oral toxicity study in the 

rodent with the rat as the preferred species. This study is designed to assess the toxicity to target 

organs. An evaluation of clinical conditions and observations, clinical chemistry, hematology, and 

histopathological change in the set of organs is conducted to answer this question. However, there 

are endpoints, e.g. neurotoxicity and immunotoxicity, which may not be covered adequately by a 

basic subchronic study. Therefore, we propose to enhance this study by including assessments for 

neurotoxicity and immunotoxicity. 

The 90-day study should include clinical observations (cage-side monitoring of animals, as well as 

during handling at the time of dosing or body weight determination), a functional observational 

battery, and motor activity assessment (Moser and MacPhail, 1990). Endpoints that should be 

evaluated include changes in motor function (e.g. disturbances in gait, abnormal posture, or muscle 

tone), level of arousal (e.g. hyperactivity and lethargy), autonomic functions (e.g. salivation, 

lacrimation, urination, and defecation), psychological status (e.g. stereotypy, aggression, biting, 

licking, and self- mutilation), and pharmacological effects (e.g. sedation). In addition to the extensive 

functional assessment just described, this study should also include a satellite group of animals for 

morphological evaluation of the central and peripheral nervous systems following fixation by 

perfusion. This study as proposed should be sufficient to detect any potential effects on the nervous 

system. 

Assessment of potential adverse effects on the immune system is an important component of the 

overall toxicity evaluation of chemicals. When appropriate endpoints are included in the study 

design, evidence of immunotoxicity can be observed in a subchronic rat study. Evidence of 

immunotoxicity should be evaluated as follows: 

* Full hematology - CBC including leukocyte differential and cell morphology; 
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Comments and Response References: 

Toxicology Section (80) Page 527 

* Assessment of immune system organ weights and histopathological change (e.g. hypocelluarity of 

immune system tissues such as the thymus, spleen, lymph nodes, and bone marrow); and 

* Measurement of serum globulin levels (IgA, IgG, IgM) 

* In addition, the lymphoid tissue that drains or contacts the site of chemical administration should 

be specifically examined (Basketter et al., 1995). The endpoints listed above are considered sufficient 

to detect any potential effects on the immune system. 

The Panel considers the results from the proposed 90-day study in the rat sufficient to detect any 

effects to target organs including the potential to produce specific toxicity to the nervous system and 

the immune system. 

Response: see response 80.19 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26671 

Comment Code: 82000 

Comment: Systemic Toxicity 

If the rodent 90-day subchronic toxicity yields an inadequate margin of exposure (<1000), a 90-day 

non-rodent subchronic toxicity study, preferably in the dog, would be recommended. A margin of 

exposure of 1000 was selected because if the dog is found to be more sensitive than the rat, this 

sensitivity typically does not exceed 10-fold. An analysis of the NOAEL from rat and dog 90-day 

studies of 28 pesticides (Doe et al., 2006) indicated that when the dog was more sensitive than the 

rat, this sensitivity was not more than 10-fold in all cases except one, if cholinesterase inhibitors 

were excluded. The lone example, in the chemical class of phenoxyacids, was 15 times more 

sensitive in the dog. But in this case the effects in the dog were to the liver and kidneys, and not in 

the organ systems involving neural or immune function. 

If any of the neurotoxicity endpoints in the 90-day subchronic rat study from Tier I indicate the 

potential for neurotoxicity, a 90-day subchronic neurotoxicity study in the rat would be 

recommended. 

If any of the immunotoxicity endpoints in the 90-day subchronic rat study from Tier I indicate the 

potential for immunotoxicity, a 90-day subchronic immunotoxicity study in the rat would be 

recommended. 

Reproductive and Developmental Toxicity 

If either of the two studies proposed in Tier I to assess reproductive and developmental toxicity 

indicate the potential for adverse effects to fetal developmental, a rodent, preferably in the rat, 

developmental toxicity study would be recommended. 
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Comments and Response References: 

Toxicology Section (80) Page 528 

The design of the one- generation reproduction would allow the option of continuing dosing one of 

the three subsets of F1 offspring and allowing them to mate to extend the one- generation study 

into a second generation (Cooper et al., 2006). The triggers for the extension of the study to a 

second generation are 1) an adverse effect on fertility or fecundity of the parental generation, 2) 

indications of abnormal sexual development of the F1 pups, or 3) deaths or evidence of toxicity to 

the F1 pups preweaning (Cooper et al., 2006). 

If any of the neurotoxicity endpoints in the 90-day subchronic rat study from Tier I, or if the results 

(morphological and brain weight changes or functional or behavioral changes in the F1 offspring) 

from Tier I reproduction and developmental studies indicate the potential for neurotoxicity, a 90-

day subchronic developmental neurotoxicity study in the rat would be recommended. 

Response: see response 80.19 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26746 

Comment Code: 82000 

Comment: * The Agency has not explained the criteria used to determine if "the use of the 

pesticide is likely to result in repeated human exposure over a limited portion of the human 

lifespan." Instead, a registrant must consult with the Agency to determine if certain data are required 

for low human exposure uses.[FN7: Proposed Rule at [section]158.2230(e)(11).] 

Response: see response 80.16 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26842 

Comment Code: 82000 

Comment: Second, the test notes in the Proposal provide for numerous determinations at the sole 

discretion of EPA. For example, test note 7 in the Proposal’s Toxicology Data Table provides that 

"the 90-day dermal toxicity study or the 90- day inhalation toxicity study may be substituted for the 

90-day oral toxicity study if the Agency determines that dermal or inhalation exposure is a major 

route of exposure" (emphasis added). Language similar to the emphasized phrase is repeated 

throughout the Proposal test notes, allowing for numerous ad hoc determinations at the sole 

discretion of EPA. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26874 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 529 

Comment Code: 82000 

Comment: D. Toxicology Data Requirements 

For toxicology data requirements, a 90-day oral rat is required for ALL antimicrobials, while it is 

conditional for conventional pesticides - required only if oral exposure is expected to occur for 

conventional pesticides.[FN44: Compare 40 CFR 158.500 with Proposed [section]158.2230.] 

Similarly, a 90-day non-rodent study is required for food use conventional pesticides and 

conditionally required for non-food use if oral exposure (e.g., drinking water) is expected. However, 

for low human exposure antimicrobials (which includes non-food use), the study is required based 

on EPA’s sole discretion if any of the following criteria are met: 

i. The use of the pesticide is likely to result in repeated human exposure over a limited portion of the 

human lifespan, as determined by the Agency. 

ii. The use is an indirect food use (less than 200 ppb).[FN45: Proposed Rule [section]158.2230 n.11.] 

As noted above, the criteria for triggering a data requirement for conventional pesticides is based on 

"repeated human exposure over a considerable portion of the human lifespan." Thus, EPA has 

imposed a more rigorous standard on antimicrobials without providing any explanation as to why 

that is necessary or appropriate. LANXESS submits this change is inappropriate and unwarranted. 

Review of this change by the FIFRA SAP should be conducted before implementing this Proposal. 

A 21/28 day dermal study is not required for nonfood use conventional pesticides, but it is 

conditionally required for all antimicrobials, based on Test Note 12: 

Data are required if the intended use of the antimicrobial pesticide product is expected to result in 

human exposure to the product and the three following conditions are met: 

i. Human exposure is via skin contact. 

ii. Expected human exposure is not purposeful and is over a limited portion of the human lifespan; 

however, as determined by EPA, the exposure is significant in terms of the frequency of exposure, 

magnitude of exposure, or the duration of exposure. 

iii. Data from a subchronic 90-day dermal toxicity study are not available and the 90-day dermal 

toxicity study has not been triggered. 

Test Note 12 again introduces, without any explanation, a conditional requirement for exposure 

over a "limited" portion of the lifespan, if EPA, in its sole discretion, deems the exposure significant. 

Response: see responses 3, 80.16 and 80.17, and testnote 80.12 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 530 

Comment ID: 26877 

Comment Code: 82000 

Comment: 8.Proposed Regulation # [Section] 158.2230(e)(12) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "Data are required 

if the intended use of the antimicrobial pesticide product is expected to result in human exposure to 

the product, and the following three conditions are met . . . (ii) Expected human exposure is not 

purposeful, and is over a limited portion of the human lifespan; however, as determined by EPA, 

the exposure is significant in terms of the frequency of exposure, magnitude of exposure, or the 

duration of exposure." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine if the exposure is significant in terms of the frequency of 

exposure, magnitude of exposure, or the duration of the exposure. 

9. Proposed Regulation # [Section] 158.2230(e)(17) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "Based on estimates 

of the magnitude and duration of human exposure, studies of shorter duration, e.g., 21- or 28-days, 

may be sufficient to satisfy this requirement. Applicants for registration may consult with the 

Agency to determine whether studies of shorter duration would meet this requirement." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether studies of shorter duration would meet the 

requirement. The Agency also requires private consultation with the Agency. 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26960 

Comment Code: 82000 

Comment: 12. Proposed Regulation # [Section] 158.2230(e)(22) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "If the requirements 

for carcinogenicity study in any species is modified or waived for any reason, then a subchronic 90-

day oral study in the same species may be required." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether a subchronic 90-day oral study in the same species may 

be required. 

Response: see response 3 
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Comments and Response References: 

Toxicology Section (80) Page 531 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27309 

Comment Code: 82000 

Comment: C. Comments on Subchronic Toxicity Requirements 

1. The Agency has added reference to testing "if use of the pesticide is likely to result in repeated 

human exposure over a limited portion of the human lifespan, as determined by the Agency." As 

explained above, this can be interpreted to trigger testing for virtually all antimicrobials. EPA should 

clarify what it means and re-issue that for comment in a reproposal. 

2. In the 90-Day non-rodent (dog) study, the requirement is based on bioaccumulation and slow 

elimination of pesticide for both conventional and antimicrobial pesticides. However, for 

antimicrobial pesticides the Agency has added a requirement for the study "if use of the pesticide is 

likely to result in repeated human exposure over a limited portion of the human lifespan, as 

determined by the Agency." No explanation is provided for this additional trigger. It also effectively 

gives EPA full discretion to require this animal- intensive study without clear basis. This language 

must be clarified and then re-proposed. (See LANXESS’s General Comments at Section I.) 

3. For Conventional Pesticides there is no reference to HVAC systems. For AM Pesticides the 

Agency has added the requirement for a 90-day inhalation and 90- day dermal studies if the intended 

use of the antimicrobial pesticide is in HVAC systems. This requirement is of concern to LANXESS 

in several respects. EPA and the Panel are working to develop an approach to labeling for 

antimicrobials used in HVAC systems, yet that work is not reflected in the Proposal. Similarly, the 

additional 90-day study requirements seem to be based on intuitive, but not empirical views on 

exposure. If EPA has evidence of inhalation and dermal exposure from antimicrobials used, in 

accordance with their labels, in HVAC systems, that information should be shared and available for 

comment. Without such information, there is no basis for a differential data requirement. In any 

event, EPA should explain the reasons behind these new requirements and make them available for 

comment. LANXESS believes that the threshold of toxicological concern approach should be 

adopted for HVAC systems and other uses. If exposures are below the level of toxicological 

concern, there should be no requirement to conduct a study. Also, LANXESS notes that the 

requirement for HVAC systems is inconsistent with the footnote for both Conventional Pesticides 

and AM Pesticides in which the Agency states that a 90-day inhalation study is "required if there is 

the likelihood of significant repeated inhalation exposure to the pesticide as a gas, vapor, or aerosol." 

4. LANXESS asserts that the 90-Day neurotoxicity for the ‘High" exposure scenario should also be 

CR (conditionally required) as in the "Low" exposure scenarios, as stated in the Test Note 6. The 

trigger for the study should not be based on the arbitrarily established "Low" or "High" exposure 

but on the indications from the results of the 90-day oral or other required studies including SAR 

data. Generally the comprehensive clinical observations and routine histopathology are sufficient to 

assess the neurotoxic potential of a product. Similarly, the acute neurotoxicity study should be 

conditionally required. The trigger should be based on the indications from the acute, subchronic, 

and other available data including SAR information. However, the triggers for the neurotoxicity 

should not be based on the results seen at the high dose levels. For example, lethal or sub lethal 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 532 

doses in the acute studies, and maximum tolerated dose (MTD) or exceeding MTD doses in the 

subchronic studies provide a basis for determining the need for neurotoxicity studies. 

5. LANXESS suggests that the 90-day oral toxicity study include enhanced endpoints to minimize 

the need for additional testing: The recommended enhanced endpoints for each area of testing are as 

follows: 

* Neurotoxicity 

** Changes in motor function (e.g. disturbances in gait, abnormal posture, or muscle tone), level of 

arousal (e.g. hyperactivity and lethargy), autonomic functions (salivation, lacrimation, urination, and 

defecation), psychological status (e.g. stereotypy, aggression, biting, licking, and self-mutilation), and 

pharmacological effects (e.g. sedation). In addition to the extensive functional assessment just 

described, this study should also include a satellite group of animals for the evaluation of 

histopathological change to the central and peripheral nervous systems following fixation by 

perfusion. 

* Immunotoxicity 

** Full hematology - CBC including leukocyte differential and cell morphology; 

** Assessment of immune system organ weights and histopathological change (e.g. hypocelluarity of 

immune system tissues such as the thymus, spleen, lymph nodes, Peyer’s patches, and bone 

marrow); and 

** Measurement of serum globulin levels (IgA, IgG, IgM) 

** In addition, the lymphoid tissue that drains or contacts the site of chemical administration should 

be specifically examined (Basketter et al., 1995). The endpoints listed above are considered sufficient 

to detect any potential effects on the immune system. 

Support for use of the above program to assess the potential for neurotoxicity and immunotoxicity 

is provided by Doe et al. (2006). 

* Doe, J. E., A. R. Boobis, A. Blacker, V. Dellarco, N. G. Doerrer, C. Franklin, J. I. Goodman, J. M. 

Kronenberg, R. Lewis, E. E. McConnell, T. Mercier, A. Moretto, C. Nolan, S. Padilla, W. Phang, R. 

Solecki. L. Tilbury, B. van Ravenzwaay, and D. C. Wolf. 2006. A Tiered Approach to Systemic 

Toxicity Testing for Agricultural Chemical Safety Assessment. Crit. Rev. Toxicol. 36: 37-68. 

Response: see responses 80.16, 80.18, and 80.19 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27311 

Comment Code: 82000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 533 

Comment: Comments for Specific Footnotes 

LANXESS interprets footnote 9 as requiring a 90-day rat study but not a 90-day mouse study to 

characterize the hazard from subchronic exposure. However, if a rodent carcinogenicity evaluation is 

required in two species, the Agency encourages the applicant to conduct a dose-ranging-finding 

study in the mouse. The second species (rodent) study should only be conducted when long term 

chronic/carcinogenicity studies are triggered. 

In footnote 10, LANXESS asserts that a 90-day dog study for either the high exposure (Required) or 

the low dose exposure (Conditionally Required) is not warranted and the following observations 

regarding the regulatory use of non- rodent studies should be considered when requiring this study: 

a. Since the 1-year non-rodent (dog) study has been eliminated under most circumstances as a 

required test to support conventional pesticide registrations, it would seem more appropriate to 

conduct all additional testing beyond 90 days in the rodent rather than the dog. The wording of 

footnote 10 is inconsistent with what is stated for the comparable footnote (footnote 36) for 

conventional pesticides.[FN5: 40 CFR 158.500] 

b. Thus, when a second species is required to be tested over 90 days, the mouse would be a more 

appropriate selection than the dog because of the limited sample size, statistical limitations, and 

flexibility available in a repeated dose dog study,. 

c. In test note 11, the Agency’s concern of human exposure due to repeated use and indirect food 

use of the antimicrobial pesticide are well covered by the data generated with the repeated dose 

studies in the rodent. The repeated dose studies in the rodent (90-day rat and other studies) provide 

sufficient information to define the hazard and end points for addressing the concerns of repeated 

use exposure and indirect food use of the product. 

As explained above, LANXESS believes the Agency must modify its use of the term "repeated 

human exposure over a limited portion of the human lifespan" in footnote 11(i) and 12(ii). This is a 

vague phrase that would require Agency interpretation for a registrant to understand the 

requirement. (See LANXESS’s General Comments at Section I) 

Response: see response 80.16, and testnotes 80.9, 80.10, 80.11, and 80.36 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27354 

Comment Code: 82000 

Comment: Regimen of Repeated Dosing to Evaluate the Endpoints of Systemic Toxicity 

The assessment of systemic toxicity is a key component in the overall assessment of a chemical’s 

potential to cause adverse effects on health. The objective of this assessment is to develop an 

approach that ensures evaluation of all relevant toxicity parameters, and identify a hierarchy of study 

types, endpoints and triggers that would be used in a tiered approach (Doe et al., 2006). A study that 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 534 

serves to predict systemic or target organ toxicity beyond acute exposure is one in which the selected 

animal species is administered the test chemical in a multiple doses regimen. It is important to 

recognize that a key aspect of such a study is to provide data that describe the shape of the doseresponse curve, rather than emphasizing effects that may occur only at high doses that are irrelevant 

to situations encountered by humans and other organisms in the environment from use of products 

that contain antimicrobial pesticides. 

The study of choice to achieve this objective is the 90-day subchronic oral toxicity study in the 

rodent with the rat as the preferred species. This study is designed to assess the toxicity to target 

organs. An evaluation of clinical conditions and observations, clinical chemistry, hematology, and 

histopathological change in the set of organs is conducted to answer this question. However, there 

are endpoints, e.g. neurotoxicity and immunotoxicity, which may not be covered adequately by a 

basic subchronic study. Therefore, we propose to enhance this study by including assessments for 

neurotoxicity and immunotoxicity. 

The 90-day study should include clinical observations (cage-side monitoring of animals, as well as 

during handling at the time of dosing or body weight determination), a functional observational 

battery, and motor activity assessment (Moser and MacPhail, 1990). Endpoints that should be 

evaluated include changes in motor function (e.g. disturbances in gait, abnormal posture, or muscle 

tone), level of arousal (e.g. hyperactivity and lethargy), autonomic functions (e.g. salivation, 

lacrimation, urination, and defecation), psychological status (e.g. stereotypy, aggression, biting, 

licking, and self- mutilation), and pharmacological effects (e.g. sedation). In addition to the extensive 

functional assessment just described, this study should also include a satellite group of animals for 

morphological evaluation of the central and peripheral nervous systems following fixation by 

perfusion. This study as proposed should be sufficient to detect any potential effects on the nervous 

system. 

Assessment of potential adverse effects on the immune system is an important component of the 

overall toxicity evaluation of chemicals. When appropriate endpoints are included in the study 

design, evidence of immunotoxicity can be observed in a subchronic rat study. Evidence of 

immunotoxicity should be evaluated as follows: 

* Full hematology - CBC including leukocyte differential and cell morphology; 

* Assessment of immune system organ weights and histopathological change (e.g. hypocelluarity of 

immune system tissues such as the thymus, spleen, lymph nodes, and bone marrow); and 

* Measurement of serum globulin levels (IgA, IgG, IgM) 

* In addition, the lymphoid tissue that drains or contacts the site of chemical administration should 

be specifically examined (Basketter et al., 1995). The endpoints listed above are considered sufficient 

to detect any potential effects on the immune system. 

LANXESS considers the results from the proposed 90-day study in the rat sufficient to detect any 

effects to target organs including the potential to produce specific toxicity to the nervous system and 

the immune system. 
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Comments and Response References: 

Toxicology Section (80) Page 535 

Response: see response 80.19 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27362 

Comment Code: 82000 

Comment: Systemic Toxicity 

If the rodent 90-day subchronic toxicity yields an inadequate margin of exposure (<1000), a 90-day 

non-rodent subchronic toxicity study, preferably in the dog, would be recommended. A margin of 

exposure of 1000 was selected because if the dog is found to be more sensitive than the rat, this 

sensitivity typically does not exceed 10-fold. An analysis of the NOAEL from rat and dog 90-day 

studies of 28 pesticides (Doe et al., 2006) indicated that when the dog was more sensitive than the 

rat, this sensitivity was not more than 10-fold in all cases except one, if cholinesterase inhibitors 

were excluded. The lone example, in the chemical class of phenoxyacids, was 15 times more 

sensitive in the dog. But in this case the effects in the dog were to the liver and kidneys, and not in 

the organ systems involving neural or immune function. 

If any of the neurotoxicity endpoints in the 90-day subchronic rat study from Tier I indicate the 

potential for neurotoxicity, a 90-day subchronic neurotoxicity study in the rat would be 

recommended. 

If any of the immunotoxicity endpoints in the 90-day subchronic rat study from Tier I indicate the 

potential for immunotoxicity, a 90-day subchronic immunotoxicity study in the rat would be 

recommended. 

Response: see response 80.19 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27671 

Comment Code: 82000 

Comment: 6. Proposed Regulation # [Section] 158.2230(e)(10) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "EPA may require 

the appropriate tier II metabolism and pharmacokinetic studies to evaluate more precisely 

bioavailability, half life, and steady state to determine if a longer duration dog toxicity study is 

needed." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria to determine if the Agency will require tier II metabolism and pharmacokinetic 

studies. 
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Comments and Response References: 

Toxicology Section (80) Page 536 

7. Proposed Regulation # [Section] 158.2230(e)(11) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "For low human 

exposure uses, data are required if any of the following criteria are met: (i) the use of the pesticide is 

likely to result in repeated human exposure over a limited portion of the human lifespan, as 

determined by the Agency . . ." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine if the use of the pesticide is likely to result in repeated human 

exposure over a limited portion of the human lifespan. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27672 

Comment Code: 82000 

Comment: 8.Proposed Regulation # [Section] 158.2230(e)(12) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "Data are required 

if the intended use of the antimicrobial pesticide product is expected to result in human exposure to 

the product, and the following three conditions are met . . . (ii) Expected human exposure is not 

purposeful, and is over a limited portion of the human lifespan; however, as determined by EPA, 

the exposure is significant in terms of the frequency of exposure, magnitude of exposure, or the 

duration of exposure." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine if the exposure is significant in terms of the frequency of 

exposure, magnitude of exposure, or the duration of the exposure. 

9. Proposed Regulation # [Section] 158.2230(e)(17) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "Based on estimates 

of the magnitude and duration of human exposure, studies of shorter duration, e.g., 21- or 28-days, 

may be sufficient to satisfy this requirement. Applicants for registration may consult with the 

Agency to determine whether studies of shorter duration would meet this requirement." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether studies of shorter duration would meet the 

requirement. The Agency also requires private consultation with the Agency. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
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Comments and Response References: 

Toxicology Section (80) Page 537 

Letter ID: 0064 

Comment ID: 27679 

Comment Code: 82000 

Comment: 12. Proposed Regulation # [Section] 158.2230(e)(22) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "If the requirements 

for carcinogenicity study in any species is modified or waived for any reason, then a subchronic 90-

day oral study in the same species may be required." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether a subchronic 90-day oral study in the same species may 

be required. 

Response: see response 3 

Comment Code: 83000 Chronic studies 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25551 

Comment Code: 83000 

Comment: d. EPA Should Require Higher-Tiered Testing Requirements Only If Exposure Data 

Justify Imposing Such Requirements 

When they become effective, EPA's Subpart W Data Requirements for antimicrobials will apply to 

three types of registration actions: 1) an application for registration of a new product that contains 

an antimicrobial active ingredient that is not included in any currently registered product; 2) an 

application for a new product that includes the addition of an antimicrobial use pattern that is not 

currently registered for one or more active ingredients contained in the product, and 3) an 

amendment of a registration of a product that includes the addition of a use pattern that is not 

currently registered for one or more active ingredients contained in the product. 

EPA's Subpart W data requirements propose 12 use patterns for antimicrobial pesticides. The 

Agency has stated that it will consider some uses as high human exposure when they result in 

significant repeated human exposure over a considerable portion of the human life span. As 

explained below, we urge EPA not to prejudge the exposure classification of any antimicrobial use 

except for classifying a use as a food use. When EPA implements the new Subpart W data 

requirements for a nonfood use of an antimicrobial, we urge EPA to impose the higher tiered data 

requirement only after reviewing exposure data on an antimicrobial and, together with the applicant 

or registrant, determining whether higher tired data are scientifically justified. 

Response: see response 80.22 
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Comments and Response References: 

Toxicology Section (80) Page 538 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25575 

Comment Code: 83000 

Comment: a. Toxicology 

General Considerations: 

*In the CFR 158W proposal, several uses are specifically designated as being of high exposure (i.e. 

those related to exposure from food, feed or drinking water, including fruit and vegetable rinses, egg 

washes, outdoor aquatic uses in lakes, rivers, or streams which have the potential to contaminate 

potable water, indirect food uses with residues [greater than or equal to] 200 ppb, any use that 

requires a tolerance or tolerance exemption [except for indirect food uses requiring a tolerance or 

tolerance exemption in which residues are [less than 200 ppb]; those related to non-food exposures, 

including wood preservatives, metal cutting fluids and swimming pools). Other uses appearing in the 

12 use patterns are not specifically designated as being of "high" or "low" human exposure. In these 

situations, the exposure designation appears to be subject to the Agency’s determination on a caseby-case basis, taking into consideration the "frequency, duration or magnitude of the exposure," 

factors which are not explicitly defined. The terms "significant," "minimal," and "negligible" are also 

occasionally used to qualify these factors. For example, the term "significant" is used when 

determining the requirement of carcinogenicity data for "low" exposure chemicals. In view of the 

importance of the exposure designation in determining toxicology data requirements, the PMRA 

considers collaboration with the EPA to further define the criteria used to determine the level of 

exposure to be a high priority. Specifically, the PMRA would like to discuss criteria for factors such 

as "frequency, magnitude and duration," as well as for the terms "significant," "minimal," and 

"negligible" as they apply to human exposure, with the goal of establishing a common (more 

concrete) definition of these terms. Ultimately, it is hoped that such discussions would enable 

greater consistency between the agencies with regard to the circumstances under which conditionally 

required data elements are triggered. 

Response: see response 80.22 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25594 

Comment Code: 83000 

Comment: Section Number Subpart W 

Title Antimicrobial Pesticide Data Requirements 

Paragraph [Section]158.2230 Toxicology data, (e) Test notes p. 59435 
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Comments and Response References: 

Toxicology Section (80) Page 539 

Excerpt from Federal Register 21. For low exposure, data are required if any of the following 

criteria, as determined by the Agency, are met: i. the use of the pesticide is likely to result in 

significant human exposure over a considerable portion of the human life span which is significant 

in terms of frequency time, duration and/or magnitude of exposure. 

HC Comment As noted above, the PMRA would like to collaborate with the EPA on further 

defining the term ‘significant’ as it relates to human exposure, in order to gain a common 

understanding/criteria of this term. 

 Section Number Subpart W 

Title Antimicrobial Pesticide Data Requirements 

Paragraph §158.2230 Toxicology data, (e) Test notes p. 59435 

Excerpt from Federal Register 22. If the requirement for a carcinogenicity study in any species is 

modified or waived for any reason, then a subchronic 90-day oral study in the same species may be 

required. 

HC Comment A 90-day oral rodent study is required for all uses, and is almost always conducted in 

the rat. Consequently, the PMRA seeks clarification regarding whether this note means that under 

the condition listed, a 90-day oral mouse study will be required in addition to the 90-day oral rat 

study? 

Response: see responses 80.21 and 80.29 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25625 

Comment Code: 83000 

Comment: EPA's 200 ppb Benchmark for Residues of Indirect Food Uses of Antimicrobials: EPA 

proposes to treat "[i]indirect food uses with residues equal to greater than 200 ppb" as "high' human 

exposure uses. CSPA concurs with the approach of using a particular value as a benchmark for 

separating first and second-tiered testing of antimicrobials, and believes that such an approach is 

consistent with EPA's "Threshold of Regulation Policy" (PR Notice 2002-2) and that it is supported 

by the FIFRA SAP Panel recommendations of June, 1997. 

While CSPA supports the use of a benchmark, we are uncertain if that value is 200 ppb and urge the 

Agency to adopt a scientifically sound benchmark that reflects FDA's approach to calculating an 

estimated daily intake (CEDI) value which is more than one-time "residue" value. Moreover, FDA's 

value of 200 ppb is based on its premise that biocides are "toxic" and that a 5x safety factor is 

justified. Any value should be based on real data and not assumed toxicity. See, "Guidance for 

Industry: Preparation of Food Contact Notifications and Food Additive and Food Additive 

Petitions for Food Contact Substances: Chemistry Recommendations." The CEDI is a cumulative 

daily exposure value, not a "residue". As noted below, CSPA recommends that EPA adopt a 
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Comments and Response References: 

Toxicology Section (80) Page 540 

food/nonfood criteria for separating first and second-tiered testing requirements instead of high and 

low exposure, in which case EPA would treat CEDI's of less than the benchmark as nonfood uses. 

Response: EPA acknowledges CSPA's support for a 2-tiered testing approach. See also response 

80.60. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26324 

Comment Code: 83000 

Comment: Third, EPA has imposed a more rigorous standard on antimicrobials by expanding the 

exposures under which certain studies could be required. For conventional pesticides, the criteria for 

triggering a data requirement are based on "repeated human exposure over a considerable portion of 

the human lifespan."[FN#38:Final regulation on data requirements for conventional pesticides at 40 

CFR 158.500, Guideline 870.4100, test note 17 (emphasis added).] In the antimicrobial Proposal, 

however, EPA predicates such a requirement on "repeated human exposure over a limited portion 

of the human lifespan."[FN#39:Proposed regulation on data requirements for antimicrobial 

pesticides at 40 CFR 158.2230, Guideline 870.4100, test note 20 (73 Fed. Reg. at 59434-35) 

(emphasis added).] Thus, for antimicrobials, certain data requirements are imposed based on 

"limited" exposure, while conventional requirements are based on "considerable" exposure. The 

Agency provides no explanation as to why the duration of concern is "limited" for antimicrobials 

but "considerable" (i.e., "significant") for conventional chemicals. Furthermore, the Agency fails to 

explain what these vague terms mean. 

Response: see response 80.16 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26332 

Comment Code: 83000 

Comment: EPA should acknowledge that this language has the potential to totally eliminate any 

tiering of testing. Instead, it turns studies subject to this note into required studies for almost all 

antimicrobial uses. Any compound with any human exposure can be found to involve "repeated 

exposure over a limited portion of a human lifespan." Applying a pesticide or coming into contact 

with an article preserved with it twice in a lifetime could be interpreted by some to meet the 

language EPA is proposing. Thus, this note effectively makes the data requirements applicable to all 

antimicrobials. If that is the result EPA intended, the Agency should make the data "required," and 

provide its justification for the requirement. If that is not the intended result, a more meaningful test 

note should be reproposed for comment. 

Response: see response 80.16 

Commenter Name: Hasmukh C. Shah 
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Comments and Response References: 

Toxicology Section (80) Page 541 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26349 

Comment Code: 83000 

Comment: A chronic oral toxicity rodent study is required for food use conventional pesticides and 

conditionally required for non-food uses.[FN#46:See supra note 20.] For antimicrobials, a chronic 

oral rodent study is required for uses termed to be "high" exposure, which, as explained above, is 

insufficiently defined to provide any certainty and could be interpreted to include virtually all 

antimicrobials. Similarly, the Proposal would conditionally require this study for low exposure uses, 

including non-food, subject to the 'repeated exposure over a limited portion of the lifespan" 

addressed above.[FN#47:See supra note 21.] The corresponding conventional test note (17.i.) 

requires the study only if exposure is likely over a considerable portion of the lifespan. 

Response: see response 80.22 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26623 

Comment Code: 83000 

Comment: D. Comments on Chronic Toxicity and Carcinogenicity Requirements 

In the Proposal, the Agency has artificially created two use groups-"high human exposure" and "low 

human exposure". Chronic and oncogenicity studies are required (R) for the high exposure grouping 

and conditionally required (CR) for the low exposure grouping. However, the delineation of these 

exposure groupings is ambiguous because the EPA has failed to provide explanations for the 

groupings. A registrant cannot determine when the longer term studies are either required or 

conditionally required given the particular use patterns. Also, even if exposures are frequent, or of a 

long duration there is little risk if the magnitude of exposure to a pesticide is well below the 

thresholds of toxicological concern. Next, the Agency has grouped a number of antimicrobial 

uses/applications, such as wood preservatives, metal working fluids, swimming pools, and outdoor 

aquatic uses, into the ‘high exposure’ without explanation. 

The Agency must define the "high exposure group" and the "low exposure group" in a rational 

manner and provide an opportunity for public comment on the definitions. Without these 

definitions, the absolute or conditional requirements for the chronic/oncogenicity studies in the test 

plans for antimicrobials are unclear. The Agency says as much on page 59393, "This list is not 

exhaustive. There may be other uses that the Agency would consider high human exposure uses 

based on their potential for human exposure. Low human exposure uses are defined as those that 

are not high human exposure uses". The agency should evaluate exposure scenarios based on actual 

data wherein the important exposure parameter is the magnitude of potential exposures. 

Additionally, the Agency should determine how these then relate to maximum use levels of specific 

antimicrobials. A tiered approach to toxicity studies should be proposed and the chronic 

toxicity/oncogenicity studies considered conditionally required (CR) based on characteristics, such 

as genotoxicity, based on a weight of evidence approach, cumulative neurotoxicity established in 
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Comments and Response References: 

Toxicology Section (80) Page 542 

multiple dose studies, and other morphologic changes indicative of long-term toxicity, as well as 

exposure. 

The Panel encourages the Agency to continue evaluating whether the mouse oncogenicity study 

should be required for pesticides. The mouse study does not add significant additional information 

for carcinogenicity from the 24-month assay in the male and female rat (Batterhill and Fielder, 1998; 

Cohen, 2004; Doe et al., 2006; Monro, 1993; Usui et al., 1996; Van Oosterhout et al., 1997), and 

therefore it no longer should be included as mandatory requirement. 

* Batterhill, J. M. and R. J. Fielder. 1998. Mouse-specific Carcinogens: An Assessment of Hazard 

and Significance for Validation of Short-Term Carcinogenicity Bioassays in Transgenic Mice. Hum. 

Exp. Toxicol. 17: 193-205. 

* Cohen, S. M. 2004. Human carcinogenic risk evaluation: An alternative approach to the two-year 

rodent bioassay. Toxicol. Sci. 80: 225-229. 

* Doe, J. E., A. R. Boobis, A. Blacker, V. Dellarco, N. G. Doerrer, C. Franklin, J. I. Goodman, J. M. 

Kronenberg, R. Lewis, E. E. McConnell, T. Mercier, A. Moretto, C. Nolan, S. Padilla, W. Phang, R. 

Solecki. L. Tilbury, B. van Ravenzwaay, and D. C. Wolf. 2006. A Tiered Approach to Systemic 

Toxicity Testing for Agricultural Chemical Safety Assessment. Crit. Rev. Toxicol. 36: 37-68. 

* Monro, A. 1993. How Useful are Chronic (Life-Span) Toxicology Studies in Rodents in Identifying 

Pharmaceuticals that Pose a Carcinogenic Risk to Humans? Adverse Drug React. Toxicol. Rev. 12: 

5-34. 

* Usui, T., S. A. Griffiths, and C. E. Lumley. 1996. Industry Viewpoint: The Utility of the Mouse for 

the Assessment of the Carcinogenic Potential of Pharmaceuticals. In: Proceedings, Third 

International Conference on Harmonisation, Yokohama, 1995. F. D’Arcy and D. W. G. Harron, 

eds., pp. 279-284. Greystone Books, Antrim, N. Ireland. 

* Van Oosterhout, J. P., J. W. Van der Laan, E. J. De Waal, K. Olejniczak, M. Hilgenfeld, V. 

Schmidt, and R. Bass. 1997. The Utility of Two rodent Species in Carcinogenic Risk Assessment of 

Pharmaceuticals in Europe. Regul. Toxicol. Pharmacol. 25: 6-17. 

Response: see responses 80.3, 80.22, 80.23, and 80.24 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26625 

Comment Code: 83000 

Comment: Specific Comments on Test Notes 

Test Footnote 18 
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Comments and Response References: 

Toxicology Section (80) Page 543 

Test Note Number 18 for Chronic oral toxicity (rodent) states "[b]ased on the positive results of the 

acute and/or 90-day neurotoxicity studies, or on other data indicating neurotoxicity, a 

chronic/neurotoxicity study (i.e. a chronic study with additional neurotoxicity evaluations) may be 

required to provide information about potential neurotoxic effects from long-term exposures". 

The use of "and/or" implies that findings in an acute neurotoxicity study alone could trigger a 

chronic neurotoxicity study. Yet chemicals that produce acute neurotoxicity effects alone do not 

produce cumulative type changes that need to be investigated in a chronic toxicity study. This test 

note should read as the same as it does with conventional pesticides: "Based on the results of the 

acute and subchronic neurotoxicity studies, or other available data, a combined chronic toxicity and 

neurotoxicity study may be required". 

In addition, to establish transparency in the test guidelines, the Agency should define or give other 

examples of what type of "other available data" would trigger the requirement for a chronic 

neurotoxicity study. 

Response: The commenter is correct. EPA will replace the "and/or" in proposed testnote 18 with 

"or", so that the testnote reads identical to that in 158.500. Also see testnote 80.18 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26627 

Comment Code: 83000 

Comment: Test Footnote 19 

The requirements for a chronic and oncogenicity study can be fulfilled in one study; however, as the 

agency has done for conventional pesticides, it should specify minimal acceptable duration times. 

This is especially important when investigating only a chronic toxicity issue in the rodent for a nonfood use wherein the Agency has established that twelve months is adequate to assess chronic 

toxicity.[FN#6:See 72 Fed. Reg. 60,977 (Oct. 26, 2007).] 

Test Footnote 20 

Test note 20 implies that a chronic study may be required if the use of the pesticide is likely to result 

in repeated human exposure over a limited portion of the human lifespan, as determined by the 

Agency. Yet the Agency needs to explain why a chronic study would be triggered if the antimicrobial 

was used only over a limited portion of the lifespan. The Agency also must define a "limited portion 

of the lifespan." 

Response: see response 80.16, and testnotes 80.19 and 80.20 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26629 
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Comments and Response References: 

Toxicology Section (80) Page 544 

Comment Code: 83000 

Comment: With respect to the requirement for a chronic study for an antimicrobial with a tolerance 

or tolerance exemption, a study could be waived based on the magnitude of potential residues for a 

specific antimicrobial based on what is known about the toxicity of a class (or family) of 

antimicrobials. This would eliminate the potential for substantial waste of animals and resources. 

Moreover, there is little more useful data gained from these studies. To this end, recent legislation 

from the EU provides guidance for waiver justifications in lieu of conducting animal 

studies.[FN#7:Guidance on Data Requirements for Active Substances and Biocidal Products, 

Technical guidance document in support of directive 98/8/EC concerning the placing of biocidal 

products on the market, dated October 2000, Reformatted, by ECB February 2008; ECHA, 

Guidance on information requirements and chemical safety assessment Chapter R.7a: Endpoint 

specific guidance, dated May 2008.] 

Response: see response 80.28 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26631 

Comment Code: 83000 

Comment: Test Footnote 21 

The Agency must clarify when studies are triggered. As the Panel has interpreted the proposed rule, 

the following criteria could trigger oncogenicity studies. 

i. The use of the pesticide is likely to result in significant human exposure over a considerable 

portion of the human life span which is significant in terms of frequency time, duration, and/or 

magnitude of exposure. ii. The use requires that a tolerance or a tolerance exemption be established. 

iii. The active ingredient, metabolite, degradate, or impurity 

A.is structurally related to a recognized carcinogen, B. causes mutagenic effects as demonstrated by 

in vitro or in vivo testing, or C. produces a morphologic effect in any organ (e.g., hyperplasia, 

metaplasia) in subchronic studies that may lead to a neoplastic change. 

Response: see testnote 80.21 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26633 

Comment Code: 83000 

Comment: In point (i) the Agency needs to define more clearly what is a "significant portion of the 

lifespan" (and how this relates to test note No. 20 wherein the phrase "limited portion of the 

lifespan" is used), and what frequency or duration would require these studies. The Agency must 
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Comments and Response References: 

Toxicology Section (80) Page 545 

clarify if frequency or duration alone would trigger these studies if the magnitude of exposure (dose) 

was minimal based on maximum use levels of a specific antimicrobial as well as its known toxicity. 

In point (iii)(A), more weight should be given to recognized carcinogens that are genotoxic and are 

known human carcinogens, based on structural alerts. Antimicrobials whose structures are related to 

chemicals that are non-genotoxic and produce neoplasia only at high doses in the rodent should 

receive much less weight, given their lack of relevance to human health. In (iii)(B) the Agency 7 

Guidance on Data Requirements for Active Substances and Biocidal Products, Technical guidance 

document in support of directive 98/8/EC concerning the placing of biocidal products on the 

market, dated October 2000, Reformatted, by ECB February 2008; ECHA, Guidance on 

information requirements and chemical safety assessment Chapter R.7a: Endpoint specific guidance, 

dated May 2008. should clarify whether positive findings in in vitro assays alone would trigger a need 

for oncogenicity studies. The decision as to whether a chemical is mutagenic or not should be based 

on a weight of evidence approach with respect to a battery of in vitro and in vivo assays, with greater 

weight applied to findings in the in vivo studies. In point (iii)(C), consideration should be given in 

evaluating morphological changes in subchronic studies to whether the biocide is genotoxic and 

whether the changes observed only occur at the high doses where metabolizing capacity is most 

likely compromised. 

Response: see responses 80.16 and 80.22 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26635 

Comment Code: 83000 

Comment: Similar to chronic requirements, fulfillment of oncogenicity requirements may not 

require actual studies, but could be waived based on the magnitude of potential exposure for a 

specific antimicrobial and/or be based on what is known about the toxicity of a class (or family) of 

antimicrobials. See above. 

Response: see response 80.27 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26639 

Comment Code: 83000 

Other EPA Comment Codes and Descriptions: 85000 Prenatal development studies 

Comment: 1. Prenatal Developmental Toxicity (2 species) 

a. The requirement (2 species in all cases) fails to take into account the advantages of the proposed 

approach to separate "high" and "low" exposure. b. Data for structural analogs, physical properties 

(e.g. corrosion), and potential exposure, can be used to eliminate the requirement for a second 

species. c. For example, testing a corrosive substance by gavage in rabbits often results in significant 

animal welfare issues which can be avoided if exposure to the substance is limited based on its 

corrosive properties and toxicity from other studies is taken into account. d. The EPA should 
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Comments and Response References: 

Toxicology Section (80) Page 546 

propose that a single species test be Required and the second species is Conditionally Required for 

Low Exposure.[FN#9:Cooper, R. L., J. C. Lamb, S. M. Barlow, K. Bentley, A. M. Brady, N. G. 

Doerrer, D. L. Eisenbrandt, P. A. Fenner-Crisp, R. N. Hines, L. F. H. Irvine, C. A. Kimmel, H. 

Koeter, A. A. Li, S. L. Makris, L. P. Sheets, G. J. A. Speijers, and K. E. Whitby. 2006. A Tiered 

Approach to Life Stages Testing for Agricultural Chemical Safety Assessment. Crit. Rev. Toxicol. 36: 

69-98.] e. The EPA should propose that a footnote be added to the Table as follows: "For low 

exposure uses, testing in a second species may be eliminated if there is no significant systemic 

toxicity observed in other studies, developmental effects are observed in the first species, or if 

exposure is limited by physical/chemical properties, such as irritation/corrosion." 

Response: see responses 80.4 and 80.33 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26756 

Comment Code: 83000 

Comment: 4. Proposed Regulation # [Section] 158.2230(e)(9) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "The 90-day study 

is required in the rodent for hazard characterization (possibly endpoint selection) and dose-setting 

for the chronic/carcinogenicity study. . . . The applicant is also encouraged to consult with the 

Agency on the results of the 90-day mouse study prior to conducting the carcinogenicity study." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria to determine whether the carcinogenicity study is necessary, and requires private 

consultation with the Agency. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26850 

Comment Code: 83000 

Comment: Third, EPA has imposed a more rigorous standard on antimicrobials by expanding the 

exposures under which certain studies could be required. For conventional pesticides, the criteria for 

triggering a data requirement are based on "repeated human exposure over a considerable portion of 

the human lifespan."[FN38: Final regulation on data requirements for conventional pesticides at 40 

CFR 158.500, Guideline 870.4100, test note 17 (emphasis added).] In the antimicrobial Proposal, 

however, EPA predicates such a requirement on "repeated human exposure over a limited portion 

of the human lifespan."[FN39: Proposed regulation on data requirements for antimicrobial 

pesticides at 40 CFR 158.2230, Guideline 870.4100, test note 20 (73 Fed. Reg. at 59434-

35)(emphasis added).] Thus, for antimicrobials, certain data requirements are imposed based on 

"limited" exposure, while conventional requirements are based on "considerable" exposure. The 
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Comments and Response References: 

Toxicology Section (80) Page 547 

Agency provides no explanation as to why the duration of concern is "limited" for antimicrobials 

but "considerable" (i.e., "significant") for conventional chemicals. Furthermore, the Agency fails to 

explain what these vague terms mean. 

Response: see response 80.16 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26851 

Comment Code: 83000 

Comment: EPA should acknowledge that this language has the potential to totally eliminate any 

tiering of testing. Instead, it turns studies subject to this note into required studies for almost all 

antimicrobial uses. Any compound with any human exposure can be found to involve "repeated 

exposure over a limited portion of a human lifespan." Applying a pesticide or coming into contact 

with an article preserved with it twice in a lifetime could be interpreted by some to meet the 

language EPA is proposing. Thus, this note effectively makes the data requirements applicable to all 

antimicrobials. If that is the result EPA intended, the Agency should make the data "required," and 

provide its justification for the requirement. If that is not the intended result, a more meaningful test 

note should be re-proposed for comment. 

Response: see response 80.16 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26876 

Comment Code: 83000 

Comment: A chronic oral toxicity rodent study is required for food use conventional pesticides and 

conditionally required for non-food uses.[FN46: See supra note 20.] For antimicrobials, a chronic 

oral rodent study is required for uses termed to be "high" exposure, which, as explained above, is 

insufficiently defined to provide any certainty and could be interpreted to include virtually all 

antimicrobials. Similarly, the Proposal would conditionally require this study for low exposure uses, 

including non-food, subject to the "repeated exposure over a limited portion of the lifespan" 

addressed above.[FN47: See supra note 21.] The corresponding conventional test note (17.i.) 

requires the study only if exposure is likely over a considerable portion of the lifespan. 

Response: see response 80.22 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26889 

Comment Code: 83000 
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Comments and Response References: 

Toxicology Section (80) Page 548 

Comment: In sum, EPA has significantly broadened the circumstances under which data will be 

required for many antimicrobial uses by imposing requirements based on "limited" rather than 

"considerable" exposure. However, there is no rationale provided as to why data requirements 

would be predicated based on limited exposures for antimicrobial products, nor is there any clarity 

regarding the term "limited". 

Response: see response 80.16 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27315 

Comment Code: 83000 

Comment: D. Comments on Chronic Toxicity and Carcinogenicity Requirements 

In the Proposal, the Agency has artificially created two use groups-"high human exposure" and "low 

human exposure". Chronic and oncogenicity studies are required (R) for the high exposure grouping 

and conditionally required (CR) for the low exposure grouping. However, the delineation of these 

exposure groupings is ambiguous because the EPA has failed to provide explanations for the 

groupings. A registrant cannot determine when the longer term studies are either required or 

conditionally required given the particular use patterns. Also, even if exposures are frequent, or of a 

long duration there is little risk if the magnitude of exposure to a pesticide is well below the 

thresholds of toxicological concern. Next, the Agency has grouped a number of antimicrobial 

uses/applications, such as wood preservatives, metal working fluids, swimming pools, and outdoor 

aquatic uses, into the ‘high exposure’ without explanation. 

The Agency must define the "high exposure group" and the "low exposure group" in a rational 

manner and provide an opportunity for public comment on the definitions. Without these 

definitions, the absolute or conditional requirements for the chronic/oncogenicity studies in the test 

plans for antimicrobials are unclear. The Agency says as much on page 59393, "This list is not 

exhaustive. There may be other uses that the Agency would consider high human exposure uses 

based on their potential for human exposure. Low human exposure uses are defined as those that 

are not high human exposure uses". The agency should evaluate exposure scenarios based on actual 

data wherein the important exposure parameter is the magnitude of potential exposures. 

Additionally, the Agency should determine how these then relate to maximum use levels of specific 

antimicrobials. A tiered approach to toxicity studies should be proposed and the chronic 

toxicity/oncogenicity studies considered conditionally required (CR) based on characteristics, such 

as genotoxicity, based on a weight of evidence approach, cumulative neurotoxicity established in 

multiple dose studies, and other morphologic changes indicative of long-term toxicity, as well as 

exposure. 

LANXESS encourages the Agency to continue evaluating whether the mouse oncogenicity study 

should be required for pesticides. The mouse study does not add significant additional information 

for carcinogenicity from the 24-month assay in the male and female rat (Batterhill and Fielder, 1998; 

Cohen, 2004; Doe et al., 2006; Monro, 1993; Usui et al., 1996; Van Oosterhout et al., 1997), and 

therefore it no longer should be included as mandatory requirement. 
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Comments and Response References: 

Toxicology Section (80) Page 549 

* Batterhill, J. M. and R. J. Fielder. 1998. Mouse-specific Carcinogens: An Assessment of Hazard 

and Significance for Validation of Short-Term Carcinogenicity Bioassays in Transgenic Mice. Hum. 

Exp. Toxicol. 17: 193-205. 

* Cohen, S. M. 2004. Human carcinogenic risk evaluation: An alternative approach to the two-year 

rodent bioassay. Toxicol. Sci. 80: 225-229. 

* Doe, J. E., A. R. Boobis, A. Blacker, V. Dellarco, N. G. Doerrer, C. Franklin, J. I. Goodman, J. M. 

Kronenberg, R. Lewis, E. E. McConnell, T. Mercier, A. Moretto, C. Nolan, S. Padilla, W. Phang, R. 

Solecki. L. Tilbury, B. van Ravenzwaay, and D. C. 

* Wolf. 2006. A Tiered Approach to Systemic Toxicity Testing for Agricultural Chemical Safety 

Assessment. Crit. Rev. Toxicol. 36: 37-68. 

* Monro, A. 1993. How Useful are Chronic (Life-Span) Toxicology Studies in Rodents in Identifying 

Pharmaceuticals that Pose a Carcinogenic Risk to Humans? Adverse Drug React. Toxicol. Rev. 12: 

5-34. 

* Usui, T., S. A. Griffiths, and C. E. Lumley. 1996. Industry Viewpoint: The Utility of the Mouse for 

the Assessment of the Carcinogenic Potential of Pharmaceuticals. In: Proceedings, Third 

International Conference on Harmonisation, Yokohama, 1995. F. D’Arcy and D. W. G. Harron, 

eds., pp. 279-284. Greystone Books, Antrim, N. Ireland. 

* Van Oosterhout, J. P., J. W. Van der Laan, E. J. De Waal, K. Olejniczak, M. Hilgenfeld, V. 

Schmidt, and R. Bass. 1997. The Utility of Two rodent Species in Carcinogenic Risk Assessment of 

Pharmaceuticals in Europe. Regul. Toxicol. Pharmacol. 25: 6-17. 

Response: see responses 80.3, 80.22, 80.23, and 80.24 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27317 

Comment Code: 83000 

Comment: Specific Comments on Test Notes 

Test Footnote 18 

Test Note Number 18 for Chronic oral toxicity (rodent) states "[b]ased on the positive results of the 

acute and/or 90-day neurotoxicity studies, or on other data indicating neurotoxicity, a 

chronic/neurotoxicity study (i.e. a chronic study with additional neurotoxicity evaluations) may be 

required to provide information about potential neurotoxic effects from long-term exposures". 

The use of "and/or" implies that findings in an acute neurotoxicity study alone could trigger a 

chronic neurotoxicity study. Yet chemicals that produce acute neurotoxicity effects alone do not 
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Comments and Response References: 

Toxicology Section (80) Page 550 

produce cumulative type changes that need to be investigated in a chronic toxicity study. This test 

note should read as the same as it does with conventional pesticides: "Based on the results of the 

acute and subchronic neurotoxicity studies, or other available data, a combined chronic toxicity and 

neurotoxicity study may be required". 

In addition, to establish transparency in the test guidelines, the Agency should define or give other 

examples of what type of "other available data" would trigger the requirement for a chronic 

neurotoxicity study. 

Response: The commenter is correct. EPA will replace the "and/or" in proposed testnote 18 with 

"or", so that the testnote reads identical to that in 158.500. Also see testnote 80.18 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27319 

Comment Code: 83000 

Comment: Test Footnote 19 

The requirements for a chronic and oncogenicity study can be fulfilled in one study; however, as the 

agency has done for conventional pesticides, it should specify minimal acceptable duration times. 

This is especially important when investigating only a chronic toxicity issue in the rodent for a nonfood use wherein the Agency has established that twelve months is adequate to assess chronic 

toxicity.[FN6: See 72 Fed. Reg. 60,977 (Oct. 26, 2007).] 

Test Footnote 20 

Test note 20 implies that a chronic study may be required if the use of the pesticide is likely to result 

in repeated human exposure over a limited portion of the human lifespan, as determined by the 

Agency. Yet the Agency needs to explain why a chronic study would be triggered if the antimicrobial 

was used only over a limited portion of the lifespan. The Agency also must define a "limited portion 

of the lifespan." 

Response: see response 80.16 and testnotes 80.19 and 80.20 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27322 

Comment Code: 83000 

Comment: With respect to the requirement for a chronic study for an antimicrobial with a tolerance 

or tolerance exemption, a study could be waived based on the magnitude of potential residues for a 

specific antimicrobial based on what is known about the toxicity of a class (or family) of 

antimicrobials. This would eliminate the potential for substantial waste of animals and resources. 

Moreover, there is little more useful data gained from these studies. To this end, recent legislation 
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Comments and Response References: 

Toxicology Section (80) Page 551 

from the EU provides guidance for waiver justifications in lieu of conducting animal studies.[FN7: 

Guidance on Data Requirements for Active Substances and Biocidal Products, Technical guidance 

document in support of directive 98/8/EC concerning the placing of biocidal products on the 

market, dated October 2000, Reformatted, by ECB February 2008; ECHA, Guidance on 

information requirements and chemical safety assessment Chapter R.7a: Endpoint specific guidance, 

dated May 2008.] 

Response: see response 80.28 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27323 

Comment Code: 83000 

Comment: Test Footnote 21 

The Agency must clarify when studies are triggered. As LANXESS has interpreted the proposed 

rule, the following criteria could trigger oncogenicity studies. 

i. The use of the pesticide is likely to result in significant human exposure over a considerable 

portion of the human life span which is significant in terms of frequency time, duration, and/or 

magnitude of exposure. 

ii. The use requires that a tolerance or a tolerance exemption be established. 

iii. The active ingredient, metabolite, degradate, or impurity 

A. is structurally related to a recognized carcinogen, 

B. causes mutagenic effects as demonstrated by in vitro or in vivo testing, or 

C. produces a morphologic effect in any organ (e.g., hyperplasia, metaplasia) in subchronic studies 

that may lead to a neoplastic change. 

Response: see testnote 80.21 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27326 

Comment Code: 83000 

Comment: In point (i) the Agency needs to define more clearly what is a "significant portion of the 

lifespan" (and how this relates to test note No. 20 wherein the phrase "limited portion of the 

lifespan" is used), and what frequency or duration would require these studies. The Agency must 

clarify if frequency or duration alone would trigger these studies if the magnitude of exposure (dose) 
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Comments and Response References: 

Toxicology Section (80) Page 552 

was minimal based on maximum use levels of a specific antimicrobial as well as its known toxicity. 

In point (iii)(A), more weight should be given to recognized carcinogens that are genotoxic and are 

known human carcinogens, based on structural alerts. Antimicrobials whose structures are related to 

chemicals that are non-genotoxic and produce neoplasia only at high doses in the rodent should 

receive much less weight, given their lack of relevance to human health. In (iii)(B) the Agency should 

clarify whether positive findings in in vitro assays alone would trigger a need for oncogenicity 

studies. The decision as to whether a chemical is mutagenic or not should be based on a weight of 

evidence approach with respect to a battery of in vitro and in vivo assays, with greater weight 

applied to findings in the in vivo studies. In point (iii)(C), consideration should be given in 

evaluating morphological changes in subchronic studies to whether the biocide is genotoxic and 

whether the changes observed only occur at the high doses where metabolizing capacity is most 

likely compromised. 

Response: see responses 80.16 and 80.22, and testnotes 80.20 and 80.21 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27327 

Comment Code: 83000 

Comment: Similar to chronic requirements, fulfillment of oncogenicity requirements may not 

require actual studies, but could be waived based on the magnitude of potential exposure for a 

specific antimicrobial and/or be based on what is known about the toxicity of a class (or family) of 

antimicrobials. See above. 

Response: see response 80.27 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27666 

Comment Code: 83000 

Comment: 4. Proposed Regulation # [Section] 158.2230(e)(9) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "The 90-day study 

is required in the rodent for hazard characterization (possibly endpoint selection) and dose-setting 

for the chronic/carcinogenicity study. . . . The applicant is also encouraged to consult with the 

Agency on the results of the 90-day mouse study prior to conducting the carcinogenicity study." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria to determine whether the carcinogenicity study is necessary, and requires private 

consultation with the Agency. 

Response: see response 3 
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Comments and Response References: 

Toxicology Section (80) Page 553 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27675 

Comment Code: 83000 

Comment: 10. Proposed Regulation # [Section] 158.2230(e)(20) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "For low exposure, 

data are required if either of the following criteria are met . . . (i) The use of the pesticide is likely to 

result in repeated human exposure over a limited portion of the human lifespan, as determined by 

the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine if the use of the pesticide is likely to result in repeated human 

exposure over a limited portion of the human lifespan. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27677 

Comment Code: 83000 

Comment: 11. Proposed Regulation # [Section] 158.2230(e)(21) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "For low exposure, 

data are required if any of the following criteria, as determined by the Agency are met . . ." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated how it will assess the criteria set out in this subsection. 

Response: see response 3 

Comment Code: 84000 Carcinogenicity 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25624 

Comment Code: 84000 

Comment: d. EPA’s Note 20 accompanying [Section] 158.500 (first of three criteria for requiring a 

mouse oncogenicity study for nonfood use conventional pesticide): 
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Comments and Response References: 

Toxicology Section (80) Page 554 

"The use of the pesticide is likely to result in significant human exposure over a considerable portion 

of the human life span which is significant in terms of frequency, duration, or magnitude of 

exposure." 

Not only is EPA's proposed definition of a high human exposure use for an antimicrobial missing 

the important and instructive qualifiers "repeated" and "significant" before "human exposure," but 

the "i.e." parenthetically following the Agency's definition of "high human exposure use" -- through 

its use of the disjunctive "or" -- incorrectly implies that EPA may classify an antimicrobial use as 

"high" and trigger second and third-tier toxicology testing on the basis of a single high exposure, 

rather than repeated and frequent exposure for additional subchronic studies and significant lifetime 

exposure for additional chronic studies. 

The second limitation of the Agency's high/low dichotomy is that, after attempting to define "high" 

exposure use, EPA then arbitrarily places certain uses of antimicrobials in the high category in the 

absence of any data demonstrating that exposures from these uses meet the criteria that divides first 

and second- tier testing -- whether an antimicrobial's use in fact is likely to result in repeated or 

lifetime exposure, even though the Agency's Part 158W proposed antimicrobial data requirements 

will require applicants and registrants to submit applicator ([Section] 158.2260), post-application 

([Section] 158.2270) and residue chemistry ([Section] 158.2290). 

n using this approach, the Agency has not adequately defined the basis for its determinations, has 

not adequately addressed the unique exposures associated with antimicrobial pesticides, and has not 

taken into account the requirements of FIFRA 3(h). CSPA submits that it is mistaken to require 

higher tier testing of antimicrobials without first determining that there is exposure such that further 

information is needed to determine whether the risk is acceptable. 

Response: see response 1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26673 

Comment Code: 84000 

Other EPA Comment Codes and Descriptions: 85000 Prenatal development studies 

Comment: Genetic Toxicity 

If the results from Tier I studies indicate the potential for genotoxicity, a mouse micronucleus assay 

in vivo would be recommended. 3. Tier III If the genetic toxicology testing package indicates the 

compound produces point mutations or clastogenicity, a rodent, preferably the rat, 

carcinogenicity/chronic toxicity study would be recommended. The mouse is considered not to add 

significant additional information for carcinogenicity over and above the use of the 24-month assay 

in the male and female rat (Batterhill and Fielder, 1998; Cohen, 2004; Monro, 1993; Usui et al., 1996; 

Van Oosterhout et al., 1997), and is, therefore, not recommended. The ACSA Systemic Toxicity 

Task Force supports this view that the 24-month rat carcinogenicity assay is adequate to detect 

carcinogens, including those which only cause carcinogenicity following prolonged perturbation of 

physiological mechanisms. The mouse is not well suited to evaluation of the risk of cancer in 

humans because this species has very high metabolic requirements compared to humans, and is 
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Comments and Response References: 

Toxicology Section (80) Page 555 

easily nudged into an abnormal (pathologic) proliferative state. In substantiation of the high 

metabolic requirements for the mouse, the difference in oxygen saturation between arterial and 

venous blood is dramatic. While the oxygen saturation in arterial blood is close to 100% in both the 

rat and mouse, the saturation in venous blood is approximately 25% in the mouse and 

approximately 70% in the rat (Criswell, unpublished data). The murine metabolic system is literally 

running in perpetual overdrive, a state that leaves the mouse vulnerable to perturbation of its normal 

cellular processes. 

Response: see response 80.24 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27796 

Comment Code: 84000 

Comment: 3. Tier III 

If the genetic toxicology testing package indicates the compound produces point mutations or 

clastogenicity, a rodent, preferably the rat, carcinogenicity/chronic toxicity study would be 

recommended. The mouse is considered not to add significant additional information for 

carcinogenicity over and above the use of the 24-month assay in the male and female rat (Batterhill 

and Fielder, 1998; Cohen, 2004; Monro, 1993; Usui et al., 1996; Van Oosterhout et al., 1997), and is, 

therefore, not recommended. The ACSA Systemic Toxicity Task Force supports this view that the 

24-month rat carcinogenicity assay is adequate to detect carcinogens, including those which only 

cause carcinogenicity following prolonged perturbation of physiological mechanisms. The mouse is 

not well suited to evaluation of the risk of cancer in humans because this species has very high 

metabolic requirements compared to humans, and is easily nudged into an abnormal (pathologic) 

proliferative state. In substantiation of the high metabolic requirements for the mouse, the 

difference in oxygen saturation between arterial and venous blood is dramatic. While the oxygen 

saturation in arterial blood is close to 100% in both the rat and mouse, the saturation in venous 

blood is approximately 25% in the mouse and approximately 70% in the rat (Criswell, unpublished 

data). The murine metabolic system is literally running in perpetual overdrive, a state that leaves the 

mouse vulnerable to perturbation of its normal cellular processes. 

Response: see response 80.24 

Comment Code: 85000 Prenatal development studies 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25677 

Comment Code: 85000 

Comment: Developmental neurotoxicity 
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Comments and Response References: 

Toxicology Section (80) Page 556 

SFE favors the inclusion of developmental neurotoxicity testing for pesticides and acknowledges the 

usefulness of the criteria listed in the proposed rules for identifying high-priority chemicals. 

However, we are concerned that, as the FIFRA Scientific Advisory Panel and EPA acknowledge, 

these criteria cannot identify every potential neurotoxicant. We would prefer that this test be a 

requirement for all pesticides used in and around homes, schools, parks, and daycare centers. SFE 

feels that criteria for triggering this test should include not only chemical-specific but also exposurespecific criteria. 

Response: The Agency acknowledges SF Environment's support for DNT testing. See response 

80.46 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26637 

Comment Code: 85000 

Comment: E. Comments on Developmental Toxicity and Reproduction Requirements 

In general, the requirements for the Prenatal Developmental and Reproduction and Fertility toxicity 

tests are clear. The Panel nonetheless proposes an alternative to the "Required" for two-species 

Developmental Toxicity and the 2- Generation study for "Low Exposure" antimicrobials. For the 

DNT, the "triggers" are consistent with Conventional Pesticides; however, it seems that these are 

poorly defined, and the Panel suggests providing a more structured approach to the "triggers." The 

inclusion of a developmental toxicity study in a 2- generation study is not advisable in most 

situations for a number of reasons (e.g. second breeding often adversely affects the offspring due to 

the older age of the mother; the dose route, diet vs. gavage, would usually be inconsistent with 

normal developmental toxicity studies; cost savings would be minimal, if any). 

The Panel also believes that the Agency has misinterpreted both the content and intent of PMRA’s 

analysis in its 1997 analysis [FN#8:Memorandum from D. Grant, PMRA to N. Cook, US EPA. 

December 1, 2007. Reproductive toxicity testing in proposed 40 CFR 158W. Available in the docket 

as EPA-HQ-OPP-2008-0110-0015]. PMRA analyzed 91 pesticides for which full toxicology 

databases were available to determine for which pesticides the pivotal endpoint for risk assessment 

was from the reproduction study or from developmental toxicity study. Their intent was to see 

whether the Tier 1 data requirements proposed by EPA in 1997 would have identified the 

reproduction concerns or would have triggered the need for additional testing, as a means of 

providing comments on the proposal. In other words, would an adequate margin of exposure 

(MOE) have existed even without a full database? PMRA commented that exposure level and the 

nature of the endpoint were important for acceptability of the proposed tier 1. They also concluded 

that "the issue of inherent toxicity versus route- specificity is important in considering approaches to 

address reproductive endpoints in tier 1 testing." They determined that since the proposed tier 1 did 

not include any oral exposure studies other than the developmental toxicity study, the 90-day dermal 

study in tier 1 was typically considered the most relevant for antimicrobials. 
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Comments and Response References: 

Toxicology Section (80) Page 557 

PMRA suggested several different approaches to addressing reproductive toxicity effects in Tier 1. 

One of those, based on their detailed analysis, was simply to apply an extra 10X safety factor to the 

NOAEL from the developmental toxicity study. Another was to require the 90-day study to be by 

the oral route and incorporate some additional parameters into the evaluation. PMRA evaluated 

both advantages and disadvantages to these and other options and suggested that the document 

could serve as a vehicle for further discussion. These options do not appear to have been 

considered. The Agency should provide a more complete discussion of the PMRA document and 

how it formed the basis for the Agency’s decision. 

Since the Agency is considering revisions to the approaches to determining reproductive and fertility 

effects, such as the use of an extended one- generation study, the Panel strongly encourages the 

incorporation of approaches that take advantage of new science and more integrative approaches 

and recommends that such flexibility be incorporated into this regulation. 

In the requirement for DNT studies, the EPA must define "weight of evidence." The EPA also 

must be more specific in how to interpret the eight criteria that trigger DNT. For example a 

criterion could be interpreted as a specific neurological effect when the effect could be due, for 

example, to narcosis and/or CNS depression similar to what would occur with some organic 

solvents or a local corrosive effect that could generate behavior that could be interpreted falsely as 

having a neurological component. For example, clinical signs of neurotoxicity and functional or 

behavioral effects need to be defined more specifically. Given the costs for a DNT, the EPA should 

provide more thorough criteria for registrants to assess the need to do this study. 

Response: see responses 4, 80.30, 80.31, and 80.32 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26639 

Comment Code: 85000 

Other EPA Comment Codes and Descriptions: 83000 Chronic studies 

Comment: 1. Prenatal Developmental Toxicity (2 species) 

a. The requirement (2 species in all cases) fails to take into account the advantages of the proposed 

approach to separate "high" and "low" exposure. b. Data for structural analogs, physical properties 

(e.g. corrosion), and potential exposure, can be used to eliminate the requirement for a second 

species. c. For example, testing a corrosive substance by gavage in rabbits often results in significant 

animal welfare issues which can be avoided if exposure to the substance is limited based on its 

corrosive properties and toxicity from other studies is taken into account. d. The EPA should 

propose that a single species test be Required and the second species is Conditionally Required for 

Low Exposure.[FN#9:Cooper, R. L., J. C. Lamb, S. M. Barlow, K. Bentley, A. M. Brady, N. G. 

Doerrer, D. L. Eisenbrandt, P. A. Fenner-Crisp, R. N. Hines, L. F. H. Irvine, C. A. Kimmel, H. 

Koeter, A. A. Li, S. L. Makris, L. P. Sheets, G. J. A. Speijers, and K. E. Whitby. 2006. A Tiered 

Approach to Life Stages Testing for Agricultural Chemical Safety Assessment. Crit. Rev. Toxicol. 36: 

69-98.] e. The EPA should propose that a footnote be added to the Table as follows: "For low 

exposure uses, testing in a second species may be eliminated if there is no significant systemic 
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Comments and Response References: 

Toxicology Section (80) Page 558 

toxicity observed in other studies, developmental effects are observed in the first species, or if 

exposure is limited by physical/chemical properties, such as irritation/corrosion." 

Response: see responses 80.4 and 80.33 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26666 

Comment Code: 85000 

Comment: Reproductive and Developmental Toxicity 

The studies in this section of Tier I testing are designed to ensure adequate coverage of all life 

stages, e.g. preconception, fetal development, and neonatal development (Cooper et al., 2006). Two 

studies are proposed to address these endpoints. They are a developmental toxicity study in the 

rabbit, and an F1- extended one-generation reproduction study in the rat. 

The proposed testing scheme for this section of Tier I testing does not provide for effects on 

prenatal development in the rodent. However, triggers for potential effects on fetal development in 

the rat will be identified by observations of pup death, pup weight, and gross structural anomalies 

(Cooper et al., 2006). An analysis of the sensitivity of the rat and rabbit to developmental toxicity 

demonstrates that no single species was capable of detecting more than 61% of developmental 

toxicants (Hurtt et al., 2003). This observation clearly supports the use of two species to assess 

developmental toxicity. However, this need not require the use of two conventional developmental 

toxicity studies (Cooper et al., 2006). The proposed testing package of a developmental toxicity 

study in the rabbit, and an assessment of developmental toxicity in the rat by examining pups in the 

F1-extended (to post- natal day 70) one-generation reproduction study will suffice to determine the 

potential for effects to reproduction and development. If neither test produces findings of concern 

regarding reproductive potential and fetal development, and if there is no more than a 10-fold 

difference in developmental lowest-observed- adverse-effect levels (LOAELs) between the two 

species using the same route of administration, and if there is a sufficient margin of exposure 

(>1000) for the lowest no-observed-adverse-effect level (NOAEL), then no further testing would be 

required in Tier II for reproduction and developmental toxicity. 

The F1- extended one-generation reproduction study proposed in this testing scheme has been 

evaluated by the ACSA Life Stages Task Force (Cooper et al., 2006) The conclusion of this Task 

Force is that such a study is sufficient to detect abnormalities of reproductive function and sexual 

development. The study design specifies that larger subsets (3/sex/litter) of F1 offspring be 

maintained and dosed postweaning. This allows an assessment of offspring maturation (including 

the timing of sexual development), along with limited evaluations of delayed or latent manifestations 

of some toxicities, and of additive effects may be related to the amount of time over which exposure 

has occurred. 

According to the ACSA Life Stages Task Force, a limitation of this one- generation design is that it 

would not detect transmissible germ-cell effects because it does not include an evaluation of 

reproduction in animals exposed both prenatally and postnatally. The example given at the 1987 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 559 

EPA workshop on latent effects was acrylamide (Shelby et al., 1987), a chemical that produced a 

high frequency of translocation carriers in the F1 male population when animals were conceived 7-

10 days after intraperitoneal dosing of parental mice for 5 days. However, in the overall testing 

paradigm, the potential for related effects of acrylamide should be detected, because it elicits 

mutagenicity, clastogenicity, male reproductive toxicity, prenatal lethality, and peripheral 

neurotoxicity (Tyl and Friedman, 2003). 

Although there is a perception that some compounds might exert an adverse effect only in a second 

generation, preliminary results (unpublished data provided by Makris, 2004) of a recent review of the 

EPA Office of Pesticide Programs Health Effects Division (HED) data set of approximately 350 

pesticide chemicals evaluated since 1996 (post-Food Quality Protection Act) indicate that, with two 

possible exceptions, adverse effects would have been detected from first generation results and 

other available toxicology data. 

Response: see response 80.34 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26668 

Comment Code: 85000 

Other EPA Comment Codes and Descriptions: 87000 Mutagenicity studies 

Comment: Genetic Toxicity 

The proposed testing for the evaluation of genetic toxicity in Tier I includes the 3 tests as follows: 

Mammalian cell mutation assay in either mouse lymphoma cells (L5178Y TK locus) or Chinese 

hamster ovary cells (CHO HGPRT locus) In vitro cytogenetic assay 

The Ames/Salmonella bacterial point mutation assay is not recommended because antimicrobial 

chemicals are designed to produce cytotoxicity to the test cells used in this assay. Therefore, the 

validity of the results is questionable, and the high probability of a false positive must be assumed. 

Response: see response 80.41 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26673 

Comment Code: 85000 

Other EPA Comment Codes and Descriptions: 84000 Carcinogenicity 

Comment: Genetic Toxicity 

If the results from Tier I studies indicate the potential for genotoxicity, a mouse micronucleus assay 

in vivo would be recommended. 3. Tier III If the genetic toxicology testing package indicates the 

compound produces point mutations or clastogenicity, a rodent, preferably the rat, 

carcinogenicity/chronic toxicity study would be recommended. The mouse is considered not to add 

significant additional information for carcinogenicity over and above the use of the 24-month assay 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 560 

in the male and female rat (Batterhill and Fielder, 1998; Cohen, 2004; Monro, 1993; Usui et al., 1996; 

Van Oosterhout et al., 1997), and is, therefore, not recommended. The ACSA Systemic Toxicity 

Task Force supports this view that the 24-month rat carcinogenicity assay is adequate to detect 

carcinogens, including those which only cause carcinogenicity following prolonged perturbation of 

physiological mechanisms. The mouse is not well suited to evaluation of the risk of cancer in 

humans because this species has very high metabolic requirements compared to humans, and is 

easily nudged into an abnormal (pathologic) proliferative state. In substantiation of the high 

metabolic requirements for the mouse, the difference in oxygen saturation between arterial and 

venous blood is dramatic. While the oxygen saturation in arterial blood is close to 100% in both the 

rat and mouse, the saturation in venous blood is approximately 25% in the mouse and 

approximately 70% in the rat (Criswell, unpublished data). The murine metabolic system is literally 

running in perpetual overdrive, a state that leaves the mouse vulnerable to perturbation of its normal 

cellular processes. 

Response: see response 80.24 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26961 

Comment Code: 85000 

Comment: 13. Proposed Regulation # [Section] 158.2230(e)(25) 

Text of the Proposed Regulation (emphasis added) "Additional testing by other routes of exposure 

may be required if the pesticide is determined to be a prenatal developmental toxicant after oral 

dosing." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated which other routes of exposure may be required or what criteria is used to determine if the 

routes of exposure are required, apart from the fact that the pesticide is determined to be a prenatal 

developmental toxicant after oral dosing. 

14. Proposed Regulation # [Section] 158.2230(e)(26) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "The developmental 

toxicity study in rodents may be combined with the two-generation reproduction study in rodents by 

using a second mating of the parental animals in either generation. Protocols must be approved by 

the Agency prior to the initiation of the study. Details for developing protocols are available from 

the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the requirements of the protocol, and the "details for developing the protocol" should be 

published as notice and comment rulemaking. These required private negotiations are a procedure 

for the development of later tests. 

15. Proposed Regulation # [Section] 158.2230(e)(28) 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 561 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "[Alternative 

proposed testing protocols] must be approved by the Agency prior to the initiation of the study. 

Details for developing protocols are available from the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria for developing alternative proposed testing protocols. These required private 

negotiations are a procedure for the development of later tests. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27330 

Comment Code: 85000 

Comment: E. Comments on Developmental Toxicity and Reproduction Requirements 

In general, the requirements for the Prenatal Developmental and Reproduction and Fertility toxicity 

tests are clear. LANXESS nonetheless proposes an alternative to the "Required" for two-species 

Developmental Toxicity and the 2-Generation study for "Low Exposure" antimicrobials. For the 

DNT, the "triggers" are consistent with Conventional Pesticides; however, it seems that these are 

poorly defined, and LANXESS suggests providing a more structured approach to the "triggers." The 

inclusion of a developmental toxicity study in a 2-generation study is not advisable in most situations 

for a number of reasons (e.g. second breeding often adversely affects the offspring due to the older 

age of the mother; the dose route, diet vs gavage, would usually be inconsistent with normal 

developmental toxicity studies; cost savings would be minimal, if any). 

LANXESS also believes that the Agency has misinterpreted both the content and intent of PMRA’s 

analysis in its 1997 analysis.[FN8: Memorandum from D. Grant, PMRA to N. Cook, US EPA. 

December 1, 2007. Reproductive toxicity testing in proposed 40 CFR 158W. Available in the docket 

as EPA-HQ-OPP-2008-0110-0015] PMRA analyzed 91 pesticides for which full toxicology 

databases were available to determine for which pesticides the pivotal endpoint for risk assessment 

was from the reproduction study or from developmental toxicity study. Their intent was to see 

whether the Tier 1 data requirements proposed by EPA in 1997 would have identified the 

reproduction concerns or would have triggered the need for additional testing, as a means of 

providing comments on the proposal. In other words, would an adequate margin of exposure 

(MOE) have existed even without a full database? PMRA commented that exposure level and the 

nature of the endpoint were important for acceptability of the proposed tier 1. They also concluded 

that "the issue of inherent toxicity versus route-specificity is important in considering approaches to 

address reproductive endpoints in tier 1 testing." They determined that since the proposed tier 1 did 

not include any oral exposure studies other than the developmental toxicity study, the 90-day dermal 

study in tier 1 was typically considered the most relevant for antimicrobials. 

PMRA suggested several different approaches to addressing reproductive toxicity effects in Tier 1. 

One of those, based on their detailed analysis, was simply to apply an extra 10X safety factor to the 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 562 

NOAEL from the developmental toxicity study. Another was to require the 90-day study to be by 

the oral route and incorporate some additional parameters into the evaluation. PMRA evaluated 

both advantages and disadvantages to these and other options and suggested that the document 

could serve as a vehicle for further discussion. These options do not appear to have been 

considered. The Agency should provide a more complete discussion of the PMRA document and 

how it formed the basis for the Agency’s decision. 

Since the Agency is considering revisions to the approaches to determining reproductive and fertility 

effects, such as the use of an extended one- generation study, LANXESS strongly encourages the 

incorporation of approaches that take advantage of new science and more integrative approaches 

and recommends that such flexibility be incorporated into this regulation. 

In the requirement for DNT studies, the EPA must define "weight of evidence." The EPA also 

must be more specific in how to interpret the eight criteria that trigger DNT. For example a 

criterion could be interpreted as a specific neurological effect when the effect could be due, for 

example, to narcosis and/or CNS depression similar to what would occur with some organic 

solvents or a local corrosive effect that could generate behavior that could be interpreted falsely as 

having a neurological component. For example, clinical signs of neurotoxicity and functional or 

behavioral effects need to be defined more specifically. Given the costs for a DNT, the EPA should 

provide more thorough criteria for registrants to assess the need to do this study. 

Response: see responses 4, 80.30, 80.31, and 80.32 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27332 

Comment Code: 85000 

Comment: 1. Prenatal Developmental Toxicity (2 species) 

a. The requirement (2 species in all cases) fails to take into account the advantages of the proposed 

approach to separate "high" and "low" exposure. 

b. Data for structural analogs, physical properties (e.g. corrosion), and potential exposure, can be 

used to eliminate the requirement for a second species. 

c. For example, testing a corrosive substance by gavage in rabbits often results in significant animal 

welfare issues which can be avoided if exposure to the substance is limited based on its corrosive 

properties and toxicity from other studies is taken into account. 

d. The EPA should propose that a single species test be Required and the second species is 

Conditionally Required for Low Exposure.[FN9: Cooper, R. L., J. C. Lamb, S. M. Barlow, K. 

Bentley, A. M. Brady, N. G. Doerrer, D. L. Eisenbrandt, P. A. Fenner-Crisp, R. N. Hines, L. F. H. 

Irvine, C. A. Kimmel, H. Koeter, A. A. Li, S. L. Makris, L. P. Sheets, G. J. A. Speijers, and K. E. 

Whitby. 2006. A Tiered Approach to Life Stages Testing for Agricultural Chemical Safety 

Assessment. Crit. Rev. Toxicol. 36: 69-98.] 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 563 

e. The EPA should propose that a footnote be added to the Table as follows: "For low exposure 

uses, testing in a second species may be eliminated if there is no significant systemic toxicity 

observed in other studies, developmental effects are observed in the first species, or if exposure is 

limited by physical/chemical properties, such as irritation/corrosion." 

Response: see responses 80.4 and 80.33 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27356 

Comment Code: 85000 

Comment: Reproductive and Developmental Toxicity 

The studies in this section of Tier I testing are designed to ensure adequate coverage of all life 

stages, e.g. preconception, fetal development, and neonatal development (Cooper et al., 2006). Two 

studies are proposed to address these endpoints. They are a developmental toxicity study in the 

rabbit, and an F1- extended one-generation reproduction study in the rat. 

The proposed testing scheme for this section of Tier I testing does not provide for effects on 

prenatal development in the rodent. However, triggers for potential effects on fetal development in 

the rat will be identified by observations of pup death, pup weight, and gross structural anomalies 

(Cooper et al., 2006). An analysis of the sensitivity of the rat and rabbit to developmental toxicity 

demonstrates that no single species was capable of detecting more than 61% of developmental 

toxicants (Hurtt et al., 2003). This observation clearly supports the use of two species to assess 

developmental toxicity. However, this need not require the use of two conventional developmental 

toxicity studies (Cooper et al., 2006). The proposed testing package of a developmental toxicity 

study in the rabbit, and an assessment of developmental toxicity in the rat by examining pups in the 

F1- extended (to post-natal day 70) one-generation reproduction study will suffice to determine the 

potential for effects to reproduction and development. If neither test produces findings of concern 

regarding reproductive potential and fetal development, and if there is no more than a 10-fold 

difference in developmental lowest-observed-adverse-effect levels (LOAELs) between the two 

species using the same route of administration, and if there is a sufficient margin of exposure (> 

1000) for the lowest no-observed-adverse-effect level (NOAEL), then no further testing would be 

required in Tier II for reproduction and developmental toxicity. 

The F1-extended one-generation reproduction study proposed in this testing scheme has been 

evaluated by the ACSA Life Stages Task Force (Cooper et al., 2006) The conclusion of this Task 

Force is that such a study is sufficient to detect abnormalities of reproductive function and sexual 

development. The study design specifies that larger subsets (3/sex/litter) of F1 offspring be 

maintained and dosed postweaning. This allows an assessment of offspring maturation (including 

the timing of sexual development), along with limited evaluations of delayed or latent manifestations 

of some toxicities, and of additive effects may be related to the amount of time over which exposure 

has occurred. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 564 

According to the ACSA Life Stages Task Force, a limitation of this one- generation design is that it 

would not detect transmissible germ-cell effects because it does not include an evaluation of 

reproduction in animals exposed both prenatally and postnatally. The example given at the 1987 

EPA workshop on latent effects was acrylamide (Shelby et al., 1987), a chemical that produced a 

high frequency of translocation carriers in the F1 male population when animals were conceived 7-

10 days after intraperitoneal dosing of parental mice for 5 days. However, in the overall testing 

paradigm, the potential for related effects of acrylamide should be detected, because it elicits 

mutagenicity, clastogenicity, male reproductive toxicity, prenatal lethality, and peripheral 

neurotoxicity (Tyl and Friedman, 2003). 

Although there is a perception that some compounds might exert an adverse effect only in a second 

generation, preliminary results (unpublished data provided by Makris, 2004) of a recent review of the 

EPA Office of Pesticide Programs Health Effects Division (HED) data set of approximately 350 

pesticide chemicals evaluated since 1996 (post-Food Quality Protection Act) indicate that, with two 

possible exceptions, adverse effects would have been detected from first generation results and 

other available toxicology data. 

Response: see response 80.34 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27358 

Comment Code: 85000 

Other EPA Comment Codes and Descriptions: 87000 Mutagenicity studies 

Comment: Genetic Toxicity 

The proposed testing for the evaluation of genetic toxicity in Tier I includes the 3 tests as follows: 

Mammalian cell mutation assay in either mouse lymphoma cells (L5178Y TK locus) or Chinese 

hamster ovary cells (CHO HGPRT locus) In vitro cytogenetic assay 

The Ames/Salmonella bacterial point mutation assay is not recommended because antimicrobial 

chemicals are designed to produce cytotoxicity to the test cells used in this assay. Therefore, the 

validity of the results is questionable, and the high probability of a false positive must be assumed. 

Response: see response 80.41 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27359 

Comment Code: 85000 

Other EPA Comment Codes and Descriptions: 89100 Dermal Penetration studies 

Comment: Dermal Penetration In Vitro 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 565 

This study, conducted using in vitro methodology, provides an assessment of the degree of dermal 

absorption, and allows determination of the risk from dermal exposure based on the results from 

the 90-day subchronic toxicity study and knowledge of the amount of the chemical that is absorbed 

dermally, considering the assumption that 100% of the chemical is absorbed from oral 

administration. In vitro methods have been validated, and have been demonstrated to provide an 

accurate prediction of the degree of dermal absorption compared to in vivo methods. 

Response: see responses 80.20 and 80.56 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27363 

Comment Code: 85000 

Comment: Reproductive and Developmental Toxicity 

If either of the two studies proposed in Tier I to assess reproductive and developmental toxicity 

indicate the potential for adverse effects to fetal developmental, a rodent, preferably in the rat, 

developmental toxicity study would be recommended. 

The design of the one- generation reproduction would allow the option of continuing dosing one of 

the three subsets of F1 offspring and allowing them to mate to extend the one- generation study 

into a second generation (Cooper et al., 2006). The triggers for the extension of the study to a 

second generation are 1) an adverse effect on fertility or fecundity of the parental generation, 2) 

indications of abnormal sexual development of the F1 pups, or 3) deaths or evidence of toxicity to 

the F1 pups preweaning (Cooper et al., 2006). 

If any of the neurotoxicity endpoints in the 90-day subchronic rat study from Tier I, or if the results 

(morphological and brain weight changes or functional or behavioral changes in the F1 offspring) 

from Tier I reproduction and developmental studies indicate the potential for neurotoxicity, a 90-

day subchronic developmental neurotoxicity study in the rat would be recommended. 

Response: See response 80.34. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27365 

Comment Code: 85000 

Other EPA Comment Codes and Descriptions: 87000 Mutagenicity studies 

Comment: Genetic Toxicity 

If the results from Tier I studies indicate the potential for genotoxicity, a mouse micronucleus assay 

in vivo would be recommended. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 566 

Response: The mouse lymphoma study is one of the studies that can fulfill the data requirement for 

an in vitro mammalian gene mutation study 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27680 

Comment Code: 85000 

Comment: 13. Proposed Regulation # [Section] 158.2230(e)(25) 

Text of the Proposed Regulation (emphasis added) "Additional testing by other routes of exposure 

may be required if the pesticide is determined to be a prenatal developmental toxicant after oral 

dosing." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated which other routes of exposure may be required or what criteria is used to determine if the 

routes of exposure are required, apart from the fact that the pesticide is determined to be a prenatal 

developmental toxicant after oral dosing. 

14. Proposed Regulation # [Section] 158.2230(e)(26) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "The developmental 

toxicity study in rodents may be combined with the two- generation reproduction study in rodents 

by using a second mating of the parental animals in either generation. Protocols must be approved 

by the Agency prior to the initiation of the study. Details for developing protocols are available from 

the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the requirements of the protocol, and the "details for developing the protocol" should be 

published as notice and comment rulemaking. These required private negotiations are a procedure 

for the development of later tests. 

15. Proposed Regulation # [Section] 158.2230(e)(28) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "[Alternative 

proposed testing protocols] must be approved by the Agency prior to the initiation of the study. 

Details for developing protocols are available from the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria for developing alternative proposed testing protocols. These required private 

negotiations are a procedure for the development of later tests. 

Response: see response 3 

Comment Code: 86000 Reproductive studies 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 567 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25595 

Comment Code: 86000 

Comment: Section Number Subpart W 

Title Antimicrobial Pesticide Data Requirements 

Paragraph [Section]158.2230 Toxicology data, (e) Test notes p. 59435 

Excerpt from Federal Register 28. An information-based approach to testing is preferred, which 

utilizes the best available knowledge on the chemical (hazard, pharmacokinetic, or mechanistic data) 

to determine whether a standard guideline study, an enhanced guideline study, or an alternative study 

should be conducted to assess potential hazard to the developing animal, or in some cases to 

support a waiver for such testing... 

HC Comment This test note is added to the reproductive toxicity and developmental neurotoxicity 

data elements. The PMRA seeks clarification regarding why the possibility of submitting waivers is 

mentioned for these two studies only. It seems to imply that these studies would be more likely to be 

waived than others. The PMRA seeks the EPA’s comment on this point, and suggests removing the 

reference to waivers in this test note. 

 Section Number Subpart W 

Title Antimicrobial Pesticide Data Requirements 

Paragraph §158.2230 Toxicology data, (e) Test notes p. 59435 

Excerpt from Federal Register 30. A DNT study is required using a weight of evidence approach 

when... 

HC Comment The triggers for requirement of a DNT study are very similar for the PMRA, with the 

exception that the PMRA also includes the criterion "if the compound is shown to be hormonally 

active in vivo." The PMRA suggests amending test note 30 to include this additional trigger. 

Response: see responses 80.38 and 80.39, and testnotes 80.28 and 80.39 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25678 

Comment Code: 86000 

Comment: Reproductive and prenatal developmental toxicity testing 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 568 

SFE supports the inclusion and enlargement of these studies. We believe studies on end-use 

products are also needed to identify effects caused by or enhanced by other ingredients. We are also 

concerned that the proposed testing would not identify or assess reproductive or developmental 

effects caused by exposure of the male parent. 

Response: see response 80.37 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26638 

Comment Code: 86000 

Comment: E. Comments on Developmental Toxicity and Reproduction Requirements 

In general, the requirements for the Prenatal Developmental and Reproduction and Fertility toxicity 

tests are clear. The Panel nonetheless proposes an alternative to the "Required" for two-species 

Developmental Toxicity and the 2- Generation study for "Low Exposure" antimicrobials. For the 

DNT, the "triggers" are consistent with Conventional Pesticides; however, it seems that these are 

poorly defined, and the Panel suggests providing a more structured approach to the "triggers." The 

inclusion of a developmental toxicity study in a 2- generation study is not advisable in most 

situations for a number of reasons (e.g. second breeding often adversely affects the offspring due to 

the older age of the mother; the dose route, diet vs. gavage, would usually be inconsistent with 

normal developmental toxicity studies; cost savings would be minimal, if any). 

The Panel also believes that the Agency has misinterpreted both the content and intent of PMRA’s 

analysis in its 1997 analysis [FN#8:Memorandum from D. Grant, PMRA to N. Cook, US EPA. 

December 1, 2007. Reproductive toxicity testing in proposed 40 CFR 158W. Available in the docket 

as EPA-HQ-OPP-2008-0110-0015]. PMRA analyzed 91 pesticides for which full toxicology 

databases were available to determine for which pesticides the pivotal endpoint for risk assessment 

was from the reproduction study or from developmental toxicity study. Their intent was to see 

whether the Tier 1 data requirements proposed by EPA in 1997 would have identified the 

reproduction concerns or would have triggered the need for additional testing, as a means of 

providing comments on the proposal. In other words, would an adequate margin of exposure 

(MOE) have existed even without a full database? PMRA commented that exposure level and the 

nature of the endpoint were important for acceptability of the proposed tier 1. They also concluded 

that "the issue of inherent toxicity versus route- specificity is important in considering approaches to 

address reproductive endpoints in tier 1 testing." They determined that since the proposed tier 1 did 

not include any oral exposure studies other than the developmental toxicity study, the 90-day dermal 

study in tier 1 was typically considered the most relevant for antimicrobials. 

PMRA suggested several different approaches to addressing reproductive toxicity effects in Tier 1. 

One of those, based on their detailed analysis, was simply to apply an extra 10X safety factor to the 

NOAEL from the developmental toxicity study. Another was to require the 90-day study to be by 

the oral route and incorporate some additional parameters into the evaluation. PMRA evaluated 

both advantages and disadvantages to these and other options and suggested that the document 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 569 

could serve as a vehicle for further discussion. These options do not appear to have been 

considered. The Agency should provide a more complete discussion of the PMRA document and 

how it formed the basis for the Agency’s decision. 

Since the Agency is considering revisions to the approaches to determining reproductive and fertility 

effects, such as the use of an extended one- generation study, the Panel strongly encourages the 

incorporation of approaches that take advantage of new science and more integrative approaches 

and recommends that such flexibility be incorporated into this regulation. 

In the requirement for DNT studies, the EPA must define "weight of evidence." The EPA also 

must be more specific in how to interpret the eight criteria that trigger DNT. For example a 

criterion could be interpreted as a specific neurological effect when the effect could be due, for 

example, to narcosis and/or CNS depression similar to what would occur with some organic 

solvents or a local corrosive effect that could generate behavior that could be interpreted falsely as 

having a neurological component. For example, clinical signs of neurotoxicity and functional or 

behavioral effects need to be defined more specifically. Given the costs for a DNT, the EPA should 

provide more thorough criteria for registrants to assess the need to do this study. 

Response: see response 80.30 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26641 

Comment Code: 86000 

Comment: 2. Reproduction and Fertility Effects 

a. The requirement (2-generation study in all cases) fails to take into account the advantages of the 

proposed approach to separate "high" and "low" exposure. b. Data for structural analogs, physical 

properties (e.g. corrosion), and potential exposure, can be used to reduce this requirement to a 

screening study if no effects are observed in such a screen. c. The EPA should propose that for 

"Low Exposure" the 2-Generation study is "CR". d. The EPA should propose that a footnote be 

added to the Table as follows: "For low exposure uses, a 2- Generation Study is required if there 

effects observed in a reproductive screening test or effects on reproductive organs are observed in 

acute or subchronic tests." e. The EPA should clarify footnote 28. 

Response: see responses 80.34, 80.38, and 80.36, and testnote 80.28 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26667 

Comment Code: 86000 

Comment: Reproductive and Developmental Toxicity 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 570 

The studies in this section of Tier I testing are designed to ensure adequate coverage of all life 

stages, e.g. preconception, fetal development, and neonatal development (Cooper et al., 2006). Two 

studies are proposed to address these endpoints. They are a developmental toxicity study in the 

rabbit, and an F1- extended one-generation reproduction study in the rat. 

The proposed testing scheme for this section of Tier I testing does not provide for effects on 

prenatal development in the rodent. However, triggers for potential effects on fetal development in 

the rat will be identified by observations of pup death, pup weight, and gross structural anomalies 

(Cooper et al., 2006). An analysis of the sensitivity of the rat and rabbit to developmental toxicity 

demonstrates that no single species was capable of detecting more than 61% of developmental 

toxicants (Hurtt et al., 2003). This observation clearly supports the use of two species to assess 

developmental toxicity. However, this need not require the use of two conventional developmental 

toxicity studies (Cooper et al., 2006). The proposed testing package of a developmental toxicity 

study in the rabbit, and an assessment of developmental toxicity in the rat by examining pups in the 

F1-extended (to post- natal day 70) one-generation reproduction study will suffice to determine the 

potential for effects to reproduction and development. If neither test produces findings of concern 

regarding reproductive potential and fetal development, and if there is no more than a 10-fold 

difference in developmental lowest-observed- adverse-effect levels (LOAELs) between the two 

species using the same route of administration, and if there is a sufficient margin of exposure 

(>1000) for the lowest no-observed-adverse-effect level (NOAEL), then no further testing would be 

required in Tier II for reproduction and developmental toxicity. 

The F1- extended one-generation reproduction study proposed in this testing scheme has been 

evaluated by the ACSA Life Stages Task Force (Cooper et al., 2006) The conclusion of this Task 

Force is that such a study is sufficient to detect abnormalities of reproductive function and sexual 

development. The study design specifies that larger subsets (3/sex/litter) of F1 offspring be 

maintained and dosed postweaning. This allows an assessment of offspring maturation (including 

the timing of sexual development), along with limited evaluations of delayed or latent manifestations 

of some toxicities, and of additive effects may be related to the amount of time over which exposure 

has occurred. 

According to the ACSA Life Stages Task Force, a limitation of this one- generation design is that it 

would not detect transmissible germ-cell effects because it does not include an evaluation of 

reproduction in animals exposed both prenatally and postnatally. The example given at the 1987 

EPA workshop on latent effects was acrylamide (Shelby et al., 1987), a chemical that produced a 

high frequency of translocation carriers in the F1 male population when animals were conceived 7-

10 days after intraperitoneal dosing of parental mice for 5 days. However, in the overall testing 

paradigm, the potential for related effects of acrylamide should be detected, because it elicits 

mutagenicity, clastogenicity, male reproductive toxicity, prenatal lethality, and peripheral 

neurotoxicity (Tyl and Friedman, 2003). 

Although there is a perception that some compounds might exert an adverse effect only in a second 

generation, preliminary results (unpublished data provided by Makris, 2004) of a recent review of the 

EPA Office of Pesticide Programs Health Effects Division (HED) data set of approximately 350 

pesticide chemicals evaluated since 1996 (post-Food Quality Protection Act) indicate that, with two 

possible exceptions, adverse effects would have been detected from first generation results and 

other available toxicology data. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 571 

Response: see response 80.34 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27329 

Comment Code: 86000 

Comment: E. Comments on Developmental Toxicity and Reproduction Requirements 

In general, the requirements for the Prenatal Developmental and Reproduction and Fertility toxicity 

tests are clear. LANXESS nonetheless proposes an alternative to the "Required" for two-species 

Developmental Toxicity and the 2-Generation study for "Low Exposure" antimicrobials. For the 

DNT, the "triggers" are consistent with Conventional Pesticides; however, it seems that these are 

poorly defined, and LANXESS suggests providing a more structured approach to the "triggers." The 

inclusion of a developmental toxicity study in a 2-generation study is not advisable in most situations 

for a number of reasons (e.g. second breeding often adversely affects the offspring due to the older 

age of the mother; the dose route, diet vs gavage, would usually be inconsistent with normal 

developmental toxicity studies; cost savings would be minimal, if any). 

LANXESS also believes that the Agency has misinterpreted both the content and intent of PMRA’s 

analysis in its 1997 analysis.[FN8: Memorandum from D. Grant, PMRA to N. Cook, US EPA. 

December 1, 2007. Reproductive toxicity testing in proposed 40 CFR 158W. Available in the docket 

as EPA-HQ-OPP-2008-0110-0015] PMRA analyzed 91 pesticides for which full toxicology 

databases were available to determine for which pesticides the pivotal endpoint for risk assessment 

was from the reproduction study or from developmental toxicity study. Their intent was to see 

whether the Tier 1 data requirements proposed by EPA in 1997 would have identified the 

reproduction concerns or would have triggered the need for additional testing, as a means of 

providing comments on the proposal. In other words, would an adequate margin of exposure 

(MOE) have existed even without a full database? PMRA commented that exposure level and the 

nature of the endpoint were important for acceptability of the proposed tier 1. They also concluded 

that "the issue of inherent toxicity versus route-specificity is important in considering approaches to 

address reproductive endpoints in tier 1 testing." They determined that since the proposed tier 1 did 

not include any oral exposure studies other than the developmental toxicity study, the 90-day dermal 

study in tier 1 was typically considered the most relevant for antimicrobials. 

PMRA suggested several different approaches to addressing reproductive toxicity effects in Tier 1. 

One of those, based on their detailed analysis, was simply to apply an extra 10X safety factor to the 

NOAEL from the developmental toxicity study. Another was to require the 90-day study to be by 

the oral route and incorporate some additional parameters into the evaluation. PMRA evaluated 

both advantages and disadvantages to these and other options and suggested that the document 

could serve as a vehicle for further discussion. These options do not appear to have been 

considered. The Agency should provide a more complete discussion of the PMRA document and 

how it formed the basis for the Agency’s decision. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 572 

Since the Agency is considering revisions to the approaches to determining reproductive and fertility 

effects, such as the use of an extended one- generation study, LANXESS strongly encourages the 

incorporation of approaches that take advantage of new science and more integrative approaches 

and recommends that such flexibility be incorporated into this regulation. 

In the requirement for DNT studies, the EPA must define "weight of evidence." The EPA also 

must be more specific in how to interpret the eight criteria that trigger DNT. For example a 

criterion could be interpreted as a specific neurological effect when the effect could be due, for 

example, to narcosis and/or CNS depression similar to what would occur with some organic 

solvents or a local corrosive effect that could generate behavior that could be interpreted falsely as 

having a neurological component. For example, clinical signs of neurotoxicity and functional or 

behavioral effects need to be defined more specifically. Given the costs for a DNT, the EPA should 

provide more thorough criteria for registrants to assess the need to do this study. 

Response: see responses 80.32, 80.30, 80.31, and 4 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27334 

Comment Code: 86000 

Comment: 2. Reproduction and Fertility Effects 

a. The requirement (2-generation study in all cases) fails to take into account the advantages of the 

proposed approach to separate "high" and "low" exposure. 

b. Data for structural analogs, physical properties (e.g. corrosion), and potential exposure, can be 

used to reduce this requirement to a screening study if no effects are observed in such a screen. 

c. The EPA should propose that for "Low Exposure" the 2-Generation study is "CR". 

d. The EPA should propose that a footnote be added to the Table as follows: "For low exposure 

uses, a 2-Generation Study is required if there effects observed in a reproductive screening test or 

effects on reproductive organs are observed in acute or subchronic tests." 

e. The EPA should clarify footnote 28. 

Response: see responses 80.36 and 80.38 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27357 

Comment Code: 86000 

Comment: Reproductive and Developmental Toxicity 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 573 

The studies in this section of Tier I testing are designed to ensure adequate coverage of all life 

stages, e.g. preconception, fetal development, and neonatal development (Cooper et al., 2006). Two 

studies are proposed to address these endpoints. They are a developmental toxicity study in the 

rabbit, and an F1- extended one-generation reproduction study in the rat. 

The proposed testing scheme for this section of Tier I testing does not provide for effects on 

prenatal development in the rodent. However, triggers for potential effects on fetal development in 

the rat will be identified by observations of pup death, pup weight, and gross structural anomalies 

(Cooper et al., 2006). An analysis of the sensitivity of the rat and rabbit to developmental toxicity 

demonstrates that no single species was capable of detecting more than 61% of developmental 

toxicants (Hurtt et al., 2003). This observation clearly supports the use of two species to assess 

developmental toxicity. However, this need not require the use of two conventional developmental 

toxicity studies (Cooper et al., 2006). The proposed testing package of a developmental toxicity 

study in the rabbit, and an assessment of developmental toxicity in the rat by examining pups in the 

F1- extended (to post-natal day 70) one-generation reproduction study will suffice to determine the 

potential for effects to reproduction and development. If neither test produces findings of concern 

regarding reproductive potential and fetal development, and if there is no more than a 10-fold 

difference in developmental lowest-observed-adverse-effect levels (LOAELs) between the two 

species using the same route of administration, and if there is a sufficient margin of exposure (> 

1000) for the lowest no-observed-adverse-effect level (NOAEL), then no further testing would be 

required in Tier II for reproduction and developmental toxicity. 

The F1-extended one-generation reproduction study proposed in this testing scheme has been 

evaluated by the ACSA Life Stages Task Force (Cooper et al., 2006) The conclusion of this Task 

Force is that such a study is sufficient to detect abnormalities of reproductive function and sexual 

development. The study design specifies that larger subsets (3/sex/litter) of F1 offspring be 

maintained and dosed postweaning. This allows an assessment of offspring maturation (including 

the timing of sexual development), along with limited evaluations of delayed or latent manifestations 

of some toxicities, and of additive effects may be related to the amount of time over which exposure 

has occurred. 

According to the ACSA Life Stages Task Force, a limitation of this one- generation design is that it 

would not detect transmissible germ-cell effects because it does not include an evaluation of 

reproduction in animals exposed both prenatally and postnatally. The example given at the 1987 

EPA workshop on latent effects was acrylamide (Shelby et al., 1987), a chemical that produced a 

high frequency of translocation carriers in the F1 male population when animals were conceived 7-

10 days after intraperitoneal dosing of parental mice for 5 days. However, in the overall testing 

paradigm, the potential for related effects of acrylamide should be detected, because it elicits 

mutagenicity, clastogenicity, male reproductive toxicity, prenatal lethality, and peripheral 

neurotoxicity (Tyl and Friedman, 2003). 

Although there is a perception that some compounds might exert an adverse effect only in a second 

generation, preliminary results (unpublished data provided by Makris, 2004) of a recent review of the 

EPA Office of Pesticide Programs Health Effects Division (HED) data set of approximately 350 

pesticide chemicals evaluated since 1996 (post-Food Quality Protection Act) indicate that, with two 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 574 

possible exceptions, adverse effects would have been detected from first generation results and 

other available toxicology data. 

Response: see response 80.34 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27364 

Comment Code: 86000 

Comment: Reproductive and Developmental Toxicity 

If either of the two studies proposed in Tier I to assess reproductive and developmental toxicity 

indicate the potential for adverse effects to fetal developmental, a rodent, preferably in the rat, 

developmental toxicity study would be recommended. 

The design of the one- generation reproduction would allow the option of continuing dosing one of 

the three subsets of F1 offspring and allowing them to mate to extend the one- generation study 

into a second generation (Cooper et al., 2006). The triggers for the extension of the study to a 

second generation are 1) an adverse effect on fertility or fecundity of the parental generation, 2) 

indications of abnormal sexual development of the F1 pups, or 3) deaths or evidence of toxicity to 

the F1 pups preweaning (Cooper et al., 2006). 

If any of the neurotoxicity endpoints in the 90-day subchronic rat study from Tier I, or if the results 

(morphological and brain weight changes or functional or behavioral changes in the F1 offspring) 

from Tier I reproduction and developmental studies indicate the potential for neurotoxicity, a 90-

day subchronic developmental neurotoxicity study in the rat would be recommended. 

Response: See response 80.34. 

Comment Code: 87000 Mutagenicity studies 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26173 

Comment Code: 87000 

Comment: For genotoxicity data requirements, the proposal requires a Reverse mutation assay, in 

vitro mammalian gene mutation, and an in vivo cytogenics study for both "high" and "low exposure 

uses. Inclusion of the Ames Assay as a requirement is inconsistent with the Agency’s prior 

conclusions on the relevance of that assay for antimicrobial pesticides. The Agency has long 

recognized that it is inappropriate. In fact, the draft data requirements proposed in 1997 specifically 

state "for chemicals designed to kill bacteria, a reverse mutation assay may be performed in mouse 

lymphoma L5178Y cells in culture." The problems with requiring an Ames assay with antimicrobials 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 575 

is discussed in some detail in the preamble (page 59397). P&G recommends other options including 

the mammalian cell mutation assay in either mouse lymphoma cells (L5178Y TK locus) or Chinese 

hamster ovary cells (CHO HGPRT locus) and in vitro cytogenetic assay. If the results from Tier I 

studies indicate the potential for genotoxicity, a mouse micronucleus assay in vivo would be 

recommended. If the genetic toxicology testing package indicates the compound produces point 

mutations or clastogenicity, a rodent, preferably the rat, carcinogenicity/chronic toxicity study would 

be recommended. 

Response: see response 80.41 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26237 

Comment Code: 87000 

Comment: * The Agency has not clearly articulated the criteria to determine at what level 

Salmonella spp. and E. coli testing are considered "high enough levels," and states that an applicant 

must consult with the Agency to determine other needed mutagenicity testing if the levels are not 

high enough.[FN#9:Id. at [Section] 158.2230(e)(32).] 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26646 

Comment Code: 87000 

Comment: F. Comments on the Mutagenicity Data Requirements 

The proposed toxicology data requirements for antimicrobial pesticides are consistent with those for 

conventional pesticides except for the Ames Assay. 

Inclusion of the Ames Assay as a requirement is inconsistent with the Agency’s prior conclusions on 

the relevance of that assay for antimicrobial pesticides. The Agency has long recognized that it is 

inappropriate. In fact, the draft data requirements proposed in 1997 specifically state "for chemicals 

designed to kill bacteria, a reverse mutation assay may be performed in mouse lymphoma L5178Y 

cells in culture." The problems with requiring an Ames assay with antimicrobials is discussed in 

some detail in the preamble (page 59397). It is unclear from either the preamble or the proposed 

rule why the Agency would still require this study be conducted, then decide whether or not to 

consider it valid and require additional testing. It would be more appropriate to provide other 

options and allow the registrant to conduct the appropriate study for the compound of concern. 

Studies such as a forward mutation assay in mouse lymphoma cells is one possible option. 

1. The table (Antimicrobial Toxicology Data Requirements) found on page 59434 has an incorrect 

guideline number listed under in vivo cytogenetics. The EPA should remove 870.5380 - Mammalian 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 576 

Spermatogonial Chromosome Aberration Test. 2. The guidance is not clear as to what constitutes an 

invalid Ames Assay. EPA mentions that the Ames Assay is sometimes not valid, but the Agency 

does not specifically explain what the cutoffs are for an invalid test. Clear criteria or cutoffs to 

declare a test invalid are needed. 3. If the Ames Assay is not valid, the Agency does not explicitly say 

what would be acceptable. For example, the Agency should address whether a CHO/HGPRT, Rat 

Lymphocyte Chromosomal Aberration Test, Micronucleus Test would be enough if the Ames Assay 

is not valid. Guidance should be added to help determine the next level of testing that would be 

required. 4. The Panel also suggests that the EPA harmonize these guidelines with the Global EU 

guidance which includes doing the Ames and/or the Mouse Lymphoma Assay without doing an in 

vivo test unless there is a positive or equivocal test in the in vitro tests. This would eliminate the use 

of animals unless a positive result was found. 5. On page 59,397, the EPA states that "Most 

antimicrobial pesticides are toxic to bacteria, and, therefore can only be tested at very low doses in 

bacterial systems." "Cytotoxicity and the test levels used in the study are critical factors to consider 

when determining if the results of an Ames test is acceptable or not., that is, whether the test fulfills 

the data requirement." The Agency should clarify why a study conducted at low, non-cytotoxic levels 

would not be acceptable for antimicrobial pesticides. 6. Although footnote 31 states "[a] reference 

list of all studies and papers known to the applicant concerning the mutagenicity of the test chemical 

must be submitted with the required studies," the preamble implies this is optional. 7. In footnote 

32, the Agency needs to define what it considers "high enough levels." 

Response: see responses 80.41, 80.42, 3, and 80.43, and testnotes 80.31 and 80.32 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26668 

Comment Code: 87000 

Other EPA Comment Codes and Descriptions: 85000 Prenatal development studies 

Comment: Genetic Toxicity 

The proposed testing for the evaluation of genetic toxicity in Tier I includes the 3 tests as follows: 

Mammalian cell mutation assay in either mouse lymphoma cells (L5178Y TK locus) or Chinese 

hamster ovary cells (CHO HGPRT locus) In vitro cytogenetic assay 

The Ames/Salmonella bacterial point mutation assay is not recommended because antimicrobial 

chemicals are designed to produce cytotoxicity to the test cells used in this assay. Therefore, the 

validity of the results is questionable, and the high probability of a false positive must be assumed. 

Response: see response 80.41 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26748 

Comment Code: 87000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 577 

Comment: * The Agency has not clearly articulated the criteria used to determine at what level 

Salmonella spp. and E. coli testing are considered "high enough levels," and states that an applicant 

must consult with the Agency to determine other needed mutagenicity testing if the levels are not 

high enough.[FN9: Id. at [section] 158.2230(e)(32).] 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26963 

Comment Code: 87000 

Comment: 16. Proposed Regulation # [Section] 158.2230(e)(32) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "Testing in 

Salmonella and E. coli may be acceptable, if the testing can be conducted at high enough levels, as 

determined by the Agency. If the testing cannot be conducted at high enough levels, then the 

applicant must consult with the Agency to determine other needed mutagenicity testing." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine if Salmonella and E. coli are acceptable. These required private 

negotiations are a procedure for the development of later tests. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27338 

Comment Code: 87000 

Comment: F. Comments on the Mutagenicity Data Requirements 

The proposed toxicology data requirements for antimicrobial pesticides are consistent with those for 

conventional pesticides except for the Ames Assay. 

Inclusion of the Ames Assay as a requirement is inconsistent with the Agency’s prior conclusions on 

the relevance of that assay for antimicrobial pesticides. The Agency has long recognized that it is 

inappropriate. In fact, the draft data requirements proposed in 1997 specifically state "for chemicals 

designed to kill bacteria, a reverse mutation assay may be performed in mouse lymphoma L5178Y 

cells in culture." The problems with requiring an Ames assay with antimicrobials is discussed in 

some detail in the preamble (page 59397). It is unclear from either the preamble or the proposed 

rule why the Agency would still require this study be conducted, then decide whether or not to 

consider it valid and require additional testing. It would be more appropriate to provide other 

options and allow the registrant to conduct the appropriate study for the compound of concern. 

Studies such as a forward mutation assay in mouse lymphoma cells is one possible option. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 578 

1. The table (Antimicrobial Toxicology Data Requirements) found on page 59434 has an incorrect 

guideline number listed under in vivo cytogenetics. The EPA should remove 870.5380 - Mammalian 

Spermatogonial Chromosome Aberration Test. 

2. The guidance is not clear as to what constitutes an invalid Ames Assay. EPA mentions that the 

Ames Assay is sometimes not valid, but the Agency does not specifically explain what the cutoffs are 

for an invalid test. Clear criteria or cutoffs to declare a test invalid are needed. 

3. If the Ames Assay is not valid, the Agency does not explicitly say what would be acceptable. For 

example, the Agency should address whether a CHO/HGPRT, Rat Lymphocyte Chromosomal 

Aberration Test, Micronucleus Test would be enough if the Ames Assay is not valid. Guidance 

should be added to help determine the next level of testing that would be required. 

4. LANXESS also suggests that the EPA harmonize these guidelines with the Global EU guidance 

which includes doing the Ames and/or the Mouse Lymphoma Assay without doing an in vivo test 

unless there is a positive or equivocal test in the in vitro tests. This would eliminate the use of 

animals unless a positive result was found. 

5. On page 59,397, the EPA states that "Most antimicrobial pesticides are toxic to bacteria, and, 

therefore can only be tested at very low doses in bacterial systems." "Cytotoxicity and the test levels 

used in the study are critical factors to consider when determining if the results of an Ames test is 

acceptable or not., that is, whether the test fulfills the data requirement." The Agency should clarify 

why a study conducted at low, non-cytotoxic levels would not be acceptable for antimicrobial 

pesticides. 

6. Although footnote 31 states "[a] reference list of all studies and papers known to the applicant 

concerning the mutagenicity of the test chemical must be submitted with the required studies," the 

preamble implies this is optional. 

7. In footnote 32, the Agency needs to define what it considers "high enough levels." 

Response: see responses 80.41, 80.42, 3, and 80.43, and testnotes 80.31 and 80.32 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27358 

Comment Code: 87000 

Other EPA Comment Codes and Descriptions: 85000 Prenatal development studies 

Comment: Genetic Toxicity 

The proposed testing for the evaluation of genetic toxicity in Tier I includes the 3 tests as follows: 

Mammalian cell mutation assay in either mouse lymphoma cells (L5178Y TK locus) or Chinese 

hamster ovary cells (CHO HGPRT locus) In vitro cytogenetic assay 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 579 

The Ames/Salmonella bacterial point mutation assay is not recommended because antimicrobial 

chemicals are designed to produce cytotoxicity to the test cells used in this assay. Therefore, the 

validity of the results is questionable, and the high probability of a false positive must be assumed. 

Response: see response 80.41 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27365 

Comment Code: 87000 

Other EPA Comment Codes and Descriptions: 85000 Prenatal development studies 

Comment: Genetic Toxicity 

If the results from Tier I studies indicate the potential for genotoxicity, a mouse micronucleus assay 

in vivo would be recommended. 

Response: The mouse lymphoma study is one of the studies that can fulfill the data requirement for 

an in vitro mammalian gene mutation study 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27682 

Comment Code: 87000 

Comment: 16. Proposed Regulation # [Section] 158.2230(e)(32) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "Testing in 

Salmonella and E. coli may be acceptable, if the testing can be conducted at high enough levels, as 

determined by the Agency. If the testing cannot be conducted at high enough levels, then the 

applicant must consult with the Agency to determine other needed mutagenicity testing." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine if Salmonella and E. coli are acceptable. These required private 

negotiations are a procedure for the development of later tests. 

Response: see response 3 

Comment Code: 88000 Neurotoxicity studies (including comments on 90-day studies) 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25582 

Comment Code: 88000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 580 

Comment: Section Number VIII. 

Title Toxicology Data Requirements 

Paragraph H. 90-day Dermal and 90- day Inhalation Testing for HVAC&R Uses Paragraph 2, p. 

59395 

Excerpt from Federal Register HVAC&R is a unique use site which must be specifically identified 

on the label of the antimicrobial product. The application of an antimicrobial product to an 

HVAC&R system represents a use pattern substantially different from other hard surface 

disinfection or sanitizer treatments. Application to HVAC&R systems may require that larger 

volumes of the antimicrobial be applied to both internal and external system components than 

would typically be used as a disinfection/sanitizer application to a hard surface such as a desktop. 

Thus, there is a greater potential for the applicator to be exposed to large amounts of pesticide. In 

addition, many of the components of HVAC&R systems are typically inaccessible and could create 

unique exposure scenarios for applicators. Postapplication exposure to building occupants is also a 

concern. When the treated system resumes operation, the potential exists for the pesticide to be 

readily spread throughout the building. For these reasons, the Agency is proposing to modify the 

requirement for 90-day subchronic studies to address HVAC&R uses. Specifically, the Agency is 

proposing to replace the 90-day oral toxicity test with two 90-day toxicity tests, one by the dermal 

route, and one by the inhalation route. 

HC Comment The PMRA does not currently distinguish HVAC&R uses, but will give further 

consideration to the proposal outlined in this section of CFR 158W. 

 Section Number VIII. 

Title Toxicology Data Requirements 

Paragraph M. Developmental Toxicity (DNT) Paragraph 3, p. 59396 

Excerpt from Federal Register EPA proposes the addition of the developmental neurotoxicity study 

to the toxicology testing requirements as a conditional requirement. The two required developmental 

toxicity studies do not include an in-depth assessment of the development of the nervous system 

and therefore do not provide the same information as the DNT. In implementing this conditional 

requirement, applicants are encouraged to apply what is known about the chemical and its toxicity to 

develop a rational, science-based approach to this testing. 

HC Comment The PMRA suggests amending this paragraph to also include the fact that the design 

of the developmental toxicity studies does not allow for testing of the same parameters as the DNT 

study. 

Response: The Agency acknowledges PMRA's consideration of distinguishing HVAC&R uses. 

Also see response 80.46. 

Commenter Name: Marion Law 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 581 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25593 

Comment Code: 88000 

Comment: Section Number Subpart W 

Title Antimicrobial Pesticide Data Requirements 

Paragraph [Section]158.2230 Toxicology data, (e) Test notes p. 59434 

Excerpt from Federal Register 6. For low exposure uses, data are required if the neurotoxicity screen 

in the 90-day oral rodent study or other data indicate neurotoxicity. 

HC Comment The 90-day oral rodent study does not always necessarily incorporate a neurotoxicity 

screen. The PMRA seeks the EPA’s comment on whether a test note should be added to indicate 

that for low exposure chemicals, a neurotoxicity screen should be included in the 90-day oral rodent 

study? 

 Section Number Subpart W 

Title Antimicrobial Pesticide Data Requirements 

Paragraph [Section]158.2230 Toxicology data, (e) Test notes p. 59434 

Excerpt from Federal Register 9. The 90-day study is required in the rodent for hazard 

characterization (possibly endpoint selection) and dose-setting for the chronic carcinogenicity study. 

It is not required in the mouse... 

HC Comment The PMRA suggests replacing the word ‘rodent’ in the first sentence with ‘rat’. 

 Section Number Subpart W 

Title Antimicrobial Pesticide Data Requirements 

Paragraph [Section]158.2230 Toxicology data, (e) Test notes p. 59434 

Excerpt from Federal Register 15. A 90-day oral toxicity test is not required for heating, ventilation, 

air conditioning, and refrigeration systems (collectively referred to as HVAC), and two 90-day 

toxicity tests, one by the dermal route and one by the inhalation route are required. 

HC Comment The PMRA suggests replacing "HVAC" with "HVAC & R" and adding the word 

"instead" to the end of the sentence for sake of clarity. 

Response: see response 80.6 and testnotes 80.6 and 80.15 

Commenter Name: James A. Westerhaus 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 582 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25758 

Comment Code: 88000 

Comment: Ecolab does agree with the other components of the ACC biocides panel toxicology 

data requirements proposal. We particularly note that the acute neurotoxicity study not be required 

because the neurotoxicity component of the 90-study will address this question; the subchronic 21-

day and 90-day dermal studies should be not be considered for the end-use- product, but only the 

active ingredient; and the mouse-carcinogenicity study should not be included because it does not 

add significant information over and above the 24-month male and female rat study. 

Response: see responses 80.15, 80.24, and 80.47 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26626 

Comment Code: 88000 

Comment: Specific Comments on Test Notes 

Test Footnote 18 

Test Note Number 18 for Chronic oral toxicity (rodent) states "[b]ased on the positive results of the 

acute and/or 90-day neurotoxicity studies, or on other data indicating neurotoxicity, a 

chronic/neurotoxicity study (i.e. a chronic study with additional neurotoxicity evaluations) may be 

required to provide information about potential neurotoxic effects from long-term exposures". 

The use of "and/or" implies that findings in an acute neurotoxicity study alone could trigger a 

chronic neurotoxicity study. Yet chemicals that produce acute neurotoxicity effects alone do not 

produce cumulative type changes that need to be investigated in a chronic toxicity study. This test 

note should read as the same as it does with conventional pesticides: "Based on the results of the 

acute and subchronic neurotoxicity studies, or other available data, a combined chronic toxicity and 

neurotoxicity study may be required". 

In addition, to establish transparency in the test guidelines, the Agency should define or give other 

examples of what type of "other available data" would trigger the requirement for a chronic 

neurotoxicity study. 

Response: The commenter is correct. EPA will replace the "and/or" in proposed testnote 18 with 

"or", so that the testnote reads identical to that in 158.500. Also see testnote 80.18 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26643 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 583 

Comment Code: 88000 

Comment: 3. Developmental Neurotoxicity 

a. The criteria used to "trigger" the DNT study should be more clearly defined. Specifically, if acute 

and subchronic neurotoxicity tests show no effects, then findings as outlined for the decision should 

depend on these studies alone for adults or if effects are observed in offspring from any 

reproductive screening or definitive tests (as currently written, other studies could still "trigger" the 

DNT even if the neurotoxicity studies show no effects and no offspring effects are observed). b. For 

"High" and "Low" exposure, the need for a DNT using observations in other studies should be 

based on dose and the NOAEL used for Risk Assessment. For example, if effects "triggering" the 

DNT occur only at very high doses (such that they do not impact the NOAEL for risk assessment) 

and, it can be determined that there is de minimis exposure to the fetus and the neonates at doses 

below the established NOAEL for risk assessment, then the need for the animal intensive DNT 

study should be eliminated. c. For "Low" exposure, the need for a DNT using observations in other 

studies should also be based on exposure. For example, if effects "triggering" the DNT occur only at 

very high doses that are orders of magnitude greater than the potential exposure, the DNT study 

cannot result in effects that would alter the risk assessments. d. The criteria for "triggering" the 

DNT should be included in a footnote to the Table for clarity.[FN#10: The criteria for triggering a 

DNT study is currently listed in Section M on page 59396 of the Federal Register notice (FR 73, No. 

196. October 8, 2008).] e. A footnote should be added as follows: The DNT may be required if 

potential neurotoxicity is observed in adults in the Acute or 90-Day neurotoxicity assessments or in 

offspring from a reproduction study. f. A footnote should be added as follows: The DNT study is 

not required if the results of other studies indicate that the results of a DNT study will not alter the 

Agency’s risk assessments based on dose and/or exposure. g. The EPA should clarify footnote 28. 

Response: see responses 80.32, 80.38, 80.46 and testnotes 80.28 and 80.30 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26665 

Comment Code: 88000 

Comment: Regimen of Repeated Dosing to Evaluate the Endpoints of Systemic Toxicity 

The assessment of systemic toxicity is a key component in the overall assessment of a chemical’s 

potential to cause adverse effects on health. The objective of this assessment is to develop an 

approach that ensures evaluation of all relevant toxicity parameters, and identify a hierarchy of study 

types, endpoints and triggers that would be used in a tiered approach (Doe et al., 2006). A study that 

serves to predict systemic or target organ toxicity beyond acute exposure is one in which the selected 

animal species is administered the test chemical in a multiple doses regimen. It is important to 

recognize that a key aspect of such a study is to provide data that describe the shape of the doseresponse curve, rather than emphasizing effects that may occur only at high doses that are irrelevant 

to situations encountered by humans and other organisms in the environment from use of products 

that contain antimicrobial pesticides. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 584 

The study of choice to achieve this objective is the 90-day subchronic oral toxicity study in the 

rodent with the rat as the preferred species. This study is designed to assess the toxicity to target 

organs. An evaluation of clinical conditions and observations, clinical chemistry, hematology, and 

histopathological change in the set of organs is conducted to answer this question. However, there 

are endpoints, e.g. neurotoxicity and immunotoxicity, which may not be covered adequately by a 

basic subchronic study. Therefore, we propose to enhance this study by including assessments for 

neurotoxicity and immunotoxicity. 

The 90-day study should include clinical observations (cage-side monitoring of animals, as well as 

during handling at the time of dosing or body weight determination), a functional observational 

battery, and motor activity assessment (Moser and MacPhail, 1990). Endpoints that should be 

evaluated include changes in motor function (e.g. disturbances in gait, abnormal posture, or muscle 

tone), level of arousal (e.g. hyperactivity and lethargy), autonomic functions (e.g. salivation, 

lacrimation, urination, and defecation), psychological status (e.g. stereotypy, aggression, biting, 

licking, and self- mutilation), and pharmacological effects (e.g. sedation). In addition to the extensive 

functional assessment just described, this study should also include a satellite group of animals for 

morphological evaluation of the central and peripheral nervous systems following fixation by 

perfusion. This study as proposed should be sufficient to detect any potential effects on the nervous 

system. 

Assessment of potential adverse effects on the immune system is an important component of the 

overall toxicity evaluation of chemicals. When appropriate endpoints are included in the study 

design, evidence of immunotoxicity can be observed in a subchronic rat study. Evidence of 

immunotoxicity should be evaluated as follows: 

* Full hematology - CBC including leukocyte differential and cell morphology; 

* Assessment of immune system organ weights and histopathological change (e.g. hypocelluarity of 

immune system tissues such as the thymus, spleen, lymph nodes, and bone marrow); and 

* Measurement of serum globulin levels (IgA, IgG, IgM) 

* In addition, the lymphoid tissue that drains or contacts the site of chemical administration should 

be specifically examined (Basketter et al., 1995). The endpoints listed above are considered sufficient 

to detect any potential effects on the immune system. 

The Panel considers the results from the proposed 90-day study in the rat sufficient to detect any 

effects to target organs including the potential to produce specific toxicity to the nervous system and 

the immune system. 

Response: see response 80.19 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26672 

Comment Code: 88000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 585 

Comment: Systemic Toxicity 

If the rodent 90-day subchronic toxicity yields an inadequate margin of exposure (<1000), a 90-day 

non-rodent subchronic toxicity study, preferably in the dog, would be recommended. A margin of 

exposure of 1000 was selected because if the dog is found to be more sensitive than the rat, this 

sensitivity typically does not exceed 10-fold. An analysis of the NOAEL from rat and dog 90-day 

studies of 28 pesticides (Doe et al., 2006) indicated that when the dog was more sensitive than the 

rat, this sensitivity was not more than 10-fold in all cases except one, if cholinesterase inhibitors 

were excluded. The lone example, in the chemical class of phenoxyacids, was 15 times more 

sensitive in the dog. But in this case the effects in the dog were to the liver and kidneys, and not in 

the organ systems involving neural or immune function. 

If any of the neurotoxicity endpoints in the 90-day subchronic rat study from Tier I indicate the 

potential for neurotoxicity, a 90-day subchronic neurotoxicity study in the rat would be 

recommended. 

If any of the immunotoxicity endpoints in the 90-day subchronic rat study from Tier I indicate the 

potential for immunotoxicity, a 90-day subchronic immunotoxicity study in the rat would be 

recommended. 

Reproductive and Developmental Toxicity 

If either of the two studies proposed in Tier I to assess reproductive and developmental toxicity 

indicate the potential for adverse effects to fetal developmental, a rodent, preferably in the rat, 

developmental toxicity study would be recommended. 

The design of the one- generation reproduction would allow the option of continuing dosing one of 

the three subsets of F1 offspring and allowing them to mate to extend the one- generation study 

into a second generation (Cooper et al., 2006). The triggers for the extension of the study to a 

second generation are 1) an adverse effect on fertility or fecundity of the parental generation, 2) 

indications of abnormal sexual development of the F1 pups, or 3) deaths or evidence of toxicity to 

the F1 pups preweaning (Cooper et al., 2006). 

If any of the neurotoxicity endpoints in the 90-day subchronic rat study from Tier I, or if the results 

(morphological and brain weight changes or functional or behavioral changes in the F1 offspring) 

from Tier I reproduction and developmental studies indicate the potential for neurotoxicity, a 90-

day subchronic developmental neurotoxicity study in the rat would be recommended. 

Response: see response 80.19 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26777 

Comment Code: 88000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 586 

Comment: 5. Proposed Regulation # [Section] 158.2230(e)(10) 

Text of the Proposed Regulation (emphasis added) 

Toxicology data: Test notes. "A 1-year non-rodent study (i.e., 1-year dog study) may be required if 

the Agency finds that a pesticide chemical is highly bioaccumulating and is eliminated slowly. Thus it 

does not achieve steady state or sufficient tissue concentrations to elicit an effect during a 90-day 

study." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria to determine if a pesticide chemical is highly bioaccumulating and eliminated 

slowly. Any guidelines published on this matter would effectively surpass the notice and comment 

rulemaking procedures. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27318 

Comment Code: 88000 

Comment: Specific Comments on Test Notes 

Test Footnote 18 

Test Note Number 18 for Chronic oral toxicity (rodent) states "[b]ased on the positive results of the 

acute and/or 90-day neurotoxicity studies, or on other data indicating neurotoxicity, a 

chronic/neurotoxicity study (i.e. a chronic study with additional neurotoxicity evaluations) may be 

required to provide information about potential neurotoxic effects from long-term exposures". 

The use of "and/or" implies that findings in an acute neurotoxicity study alone could trigger a 

chronic neurotoxicity study. Yet chemicals that produce acute neurotoxicity effects alone do not 

produce cumulative type changes that need to be investigated in a chronic toxicity study. This test 

note should read as the same as it does with conventional pesticides: "Based on the results of the 

acute and subchronic neurotoxicity studies, or other available data, a combined chronic toxicity and 

neurotoxicity study may be required". 

In addition, to establish transparency in the test guidelines, the Agency should define or give other 

examples of what type of "other available data" would trigger the requirement for a chronic 

neurotoxicity study. 

Response: The commenter is correct. EPA will replace the "and/or" in proposed testnote 18 with 

"or", so that the testnote reads identical to that in 158.500. Also see testnote 80.18 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 587 

Letter ID: 0064 

Comment ID: 27336 

Comment Code: 88000 

Comment: 3. Developmental Neurotoxicity 

a. The criteria used to "trigger" the DNT study should be more clearly defined. Specifically, if acute 

and subchronic neurotoxicity tests show no effects, then findings as outlined for the decision should 

depend on these studies alone for adults or if effects are observed in offspring from any 

reproductive screening or definitive tests (as currently written, other studies could still "trigger" the 

DNT even if the neurotoxicity studies show no effects and no offspring effects are observed). 

b. For "High" and "Low" exposure, the need for a DNT using observations in other studies should 

be based on dose and the NOAEL used for Risk Assessment. For example, if effects "triggering" 

the DNT occur only at very high doses (such that they do not impact the NOAEL for risk 

assessment) and, it can be determined that there is de minimis exposure to the fetus and the 

neonates at doses below the established NOAEL for risk assessment, then the need for the animal 

intensive DNT study should be eliminated. 

c. For "Low" exposure, the need for a DNT using observations in other studies should also be 

based on exposure. For example, if effects "triggering" the DNT occur only at very high doses that 

are orders of magnitude greater than the potential exposure, the DNT study cannot result in effects 

that would alter the risk assessments. 

d. The criteria for "triggering" the DNT should be included in a footnote to the Table for 

clarity.[FN10: The criteria for triggering a DNT study is currently listed in Section M on page 59396 

of the Federal Register notice (FR 73, No. 196. October 8, 2008).] 

e. A footnote should be added as follows: The DNT may be required if potential neurotoxicity is 

observed in adults in the Acute or 90-Day neurotoxicity assessments or in offspring from a 

reproduction study. 

f. A footnote should be added as follows: The DNT study is not required if the results of other 

studies indicate that the results of a DNT study will not alter the Agency’s risk assessments based on 

dose and/or exposure. 

g. The EPA should clarify footnote 28. 

Response: see responses 80.32, 80.38, 80.46 and testnotes 80.28 and 80.30 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27355 

Comment Code: 88000 

Comment: Regimen of Repeated Dosing to Evaluate the Endpoints of Systemic Toxicity 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 588 

The assessment of systemic toxicity is a key component in the overall assessment of a chemical’s 

potential to cause adverse effects on health. The objective of this assessment is to develop an 

approach that ensures evaluation of all relevant toxicity parameters, and identify a hierarchy of study 

types, endpoints and triggers that would be used in a tiered approach (Doe et al., 2006). A study that 

serves to predict systemic or target organ toxicity beyond acute exposure is one in which the selected 

animal species is administered the test chemical in a multiple doses regimen. It is important to 

recognize that a key aspect of such a study is to provide data that describe the shape of the doseresponse curve, rather than emphasizing effects that may occur only at high doses that are irrelevant 

to situations encountered by humans and other organisms in the environment from use of products 

that contain antimicrobial pesticides. 

The study of choice to achieve this objective is the 90-day subchronic oral toxicity study in the 

rodent with the rat as the preferred species. This study is designed to assess the toxicity to target 

organs. An evaluation of clinical conditions and observations, clinical chemistry, hematology, and 

histopathological change in the set of organs is conducted to answer this question. However, there 

are endpoints, e.g. neurotoxicity and immunotoxicity, which may not be covered adequately by a 

basic subchronic study. Therefore, we propose to enhance this study by including assessments for 

neurotoxicity and immunotoxicity. 

The 90-day study should include clinical observations (cage-side monitoring of animals, as well as 

during handling at the time of dosing or body weight determination), a functional observational 

battery, and motor activity assessment (Moser and MacPhail, 1990). Endpoints that should be 

evaluated include changes in motor function (e.g. disturbances in gait, abnormal posture, or muscle 

tone), level of arousal (e.g. hyperactivity and lethargy), autonomic functions (e.g. salivation, 

lacrimation, urination, and defecation), psychological status (e.g. stereotypy, aggression, biting, 

licking, and self- mutilation), and pharmacological effects (e.g. sedation). In addition to the extensive 

functional assessment just described, this study should also include a satellite group of animals for 

morphological evaluation of the central and peripheral nervous systems following fixation by 

perfusion. This study as proposed should be sufficient to detect any potential effects on the nervous 

system. 

Assessment of potential adverse effects on the immune system is an important component of the 

overall toxicity evaluation of chemicals. When appropriate endpoints are included in the study 

design, evidence of immunotoxicity can be observed in a subchronic rat study. Evidence of 

immunotoxicity should be evaluated as follows: 

* Full hematology - CBC including leukocyte differential and cell morphology; 

* Assessment of immune system organ weights and histopathological change (e.g. hypocelluarity of 

immune system tissues such as the thymus, spleen, lymph nodes, and bone marrow); and 

* Measurement of serum globulin levels (IgA, IgG, IgM) 

* In addition, the lymphoid tissue that drains or contacts the site of chemical administration should 

be specifically examined (Basketter et al., 1995). The endpoints listed above are considered sufficient 

to detect any potential effects on the immune system. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 589 

LANXESS considers the results from the proposed 90-day study in the rat sufficient to detect any 

effects to target organs including the potential to produce specific toxicity to the nervous system and 

the immune system. 

Response: see response 80.19 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27361 

Comment Code: 88000 

Comment: Systemic Toxicity 

If the rodent 90-day subchronic toxicity yields an inadequate margin of exposure (<1000), a 90-day 

non-rodent subchronic toxicity study, preferably in the dog, would be recommended. A margin of 

exposure of 1000 was selected because if the dog is found to be more sensitive than the rat, this 

sensitivity typically does not exceed 10-fold. An analysis of the NOAEL from rat and dog 90-day 

studies of 28 pesticides (Doe et al., 2006) indicated that when the dog was more sensitive than the 

rat, this sensitivity was not more than 10-fold in all cases except one, if cholinesterase inhibitors 

were excluded. The lone example, in the chemical class of phenoxyacids, was 15 times more 

sensitive in the dog. But in this case the effects in the dog were to the liver and kidneys, and not in 

the organ systems involving neural or immune function. 

If any of the neurotoxicity endpoints in the 90-day subchronic rat study from Tier I indicate the 

potential for neurotoxicity, a 90-day subchronic neurotoxicity study in the rat would be 

recommended. 

If any of the immunotoxicity endpoints in the 90-day subchronic rat study from Tier I indicate the 

potential for immunotoxicity, a 90-day subchronic immunotoxicity study in the rat would be 

recommended. 

Response: see response 80.19 

Comment Code: 89000 Immunotoxicity studies 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25583 

Comment Code: 89000 

Comment: Section Number VIII. 

Title Toxicology Data Requirements 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 590 

Paragraph O. Immunotoxicity Paragraph 2, p. 59397 

Excerpt from Federal Register While data from hematology, lymphoid organ weights, and 

histopathology of routine chronic or subchronic toxicity studies may offer useful information on 

potential immunotoxic effects, these endpoints alone are insufficient to predict effects on 

immunotoxic function (Refs. 15 and 16). Therefore, the Agency is proposing to require functional 

immunotoxicity testing along with the data from immunotoxicity endpoints in other studies to 

predict the potential risk of pesticides on the immune system more accurately. 

HC Comment It is unclear whether the EPA is recommending the modification of the 90-day 

studies to include satellite groups to assess immunotoxicity, or whether separate immunotoxicity 

studies are being required. The PMRA suggests including text that outlines the specific 

immunotoxicity data/studies that will be required. 

Response: see response 80.52 and testnote 80.8 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25676 

Comment Code: 89000 

Comment: Immunotoxicity testing 

SFE strongly supports the proposed addition of immunotoxicity testing for all antimicrobial 

pesticides. 

Response: EPA acknowledges SF Environment's support for immunotoxicity testing. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26656 

Comment Code: 89000 

Comment: J. Comments on Immunotoxicity Data Requirements 

If the weight of evidence in mice, e.g. a 90-day subchronic study, suggests no concerns for 

immunotoxicity , the Agency should require the registrant to test only the rat in a 28-day 

immunotoxicity test, and should not require a mouse study if the results in the rat show no effect on 

the immune system. Also, the Agency guidelines indicate that rats and/or mice can be used; 

however, EPA has previously commented that if the rat data shows no effect on the immune 

system, the potential for immunotoxicity would still need to be evaluated in the mouse. The Agency 

needs to provide clarification on this inconsistency. The Agency has indicated previously that the 

female mouse is the animal of choice, yet reference is made to use of the rat and/or mouse in these 

studies. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 591 

The Agency has indicated that a positive control should be included in each immunotoxicity study. 

The Agency should allow a positive control to be evaluated at a specified frequency, for example 

every 6 to 12 months, and not evaluated concurrently with each study. 

The Agency needs to provide guidance as to when degree of exposure via inhalation or the skin is 

sufficient to change its preference from a study via the oral route to another route of exposure. 

Agency guidelines indicate that the T cell dependent antigen and sheep red blood cells should be 

administered at 24 days after the first dosing with the test substance, and that the optimum response 

time is usually 4 days after immunization. Some strains of animals, however, may deviate from this 

time point. The Agency should provide guidance on optimum response time for various species and 

strains that are allowed to be used in immunotoxicity studies. 

The Agency guideline for immunotoxicity studies specifies "enumeration of splenic or peripheral 

blood total B cells, total T cells, and T cell subpopulations from the spleen or peripheral blood by 

flow cytometry should be performed after at least 28 days of dosing. However, it may be performed 

at a later time point if data from ADME studies suggest that a longer exposure is more appropriate. 

If an exposure period longer than 28 days is used, then the test may be performed in conjunction 

with subchronic (90-day oral, dermal, or inhalation) toxicity studies." If the immunotoxicity assay is 

performed in conjunction with a subchronic study, the Agency needs to provide guidance that if the 

rat study shows no immunotoxicity a mouse study will not be required to capture the phenotypic 

analysis of the total T and B cells. 

Also, the Agency needs to provide guidance as to what constitutes a toxicologically relevant 

response in light of the many factors that can influence the immune system, for example, stress or 

seasonal differences. The EPA should also clarify what testing is required for immunotoxicity. 

The Agency should add a footnote to indicate if a combined study, for example, an immunotoxicity 

component added to a 90-day subchronic study, is acceptable. 

A number of antimicrobial pesticides are known to be dermal sensitizers. Sensitization is an 

immunological response. However, the Agency has not addressed whether or how known sensitizers 

should be evaluated for immunotoxicity. The Agency needs to discuss and justify the use of animals 

in those evaluations if there will be no additional regulatory benefit provided beyond what the 

sensitization itself provides 

Response: See responses 80.51, 80.52, and 80.53, and testnote 80.8. EPA also notes that some the 

comments are not directed toward the proposed rule, but to the the guidelines for immunotoxicity 

studies. EPA will consider these guideline comments at another time. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27346 

Comment Code: 89000 

Comment: J. Comments on Immunotoxicity Data Requirements 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 592 

If the weight of evidence in mice, e.g. a 90-day subchronic study, suggests no concerns for 

immunotoxicity , the Agency should require the registrant to test only the rat in a 28-day 

immunotoxicity test, and should not require a mouse study if the results in the rat show no effect on 

the immune system. Also, the Agency guidelines indicate that rats and/or mice can be used; 

however, EPA has previously commented that if the rat data shows no effect on the immune 

system, the potential for immunotoxicity would still need to be evaluated in the mouse. The Agency 

needs to provide clarification on this inconsistency. The Agency has indicated previously that the 

female mouse is the animal of choice, yet reference is made to use of the rat and/or mouse in these 

studies. 

The Agency has indicated that a positive control should be included in each immunotoxicity study. 

The Agency should allow a positive control to be evaluated at a specified frequency, for example 

every 6 to 12 months, and not evaluated concurrently with each study. 

The Agency needs to provide guidance as to when degree of exposure via inhalation or the skin is 

sufficient to change its preference from a study via the oral route to another route of exposure. 

Agency guidelines indicate that the T cell dependent antigen and sheep red blood cells should be 

administered at 24 days after the first dosing with the test substance, and that the optimum response 

time is usually 4 days after immunization. Some strains of animals, however, may deviate from this 

time point. The Agency should provide guidance on optimum response time for various species and 

strains that are allowed to be used in immunotoxicity studies. 

The Agency guideline for immunotoxicity studies specifies "enumeration of splenic or peripheral 

blood total B cells, total T cells, and T cell subpopulations from the spleen or peripheral blood by 

flow cytometry should be performed after at least 28 days of dosing. However, it may be performed 

at a later time point if data from ADME studies suggest that a longer exposure is more appropriate. 

If an exposure period longer than 28 days is used, then the test may be performed in conjunction 

with subchronic (90-day oral, dermal, or inhalation) toxicity studies." If the immunotoxicity assay is 

performed in conjunction with a subchronic study, the Agency needs to provide guidance that if the 

rat study shows no immunotoxicity a mouse study will not be required to capture the phenotypic 

analysis of the total T and B cells. 

Also, the Agency needs to provide guidance as to what constitutes a toxicologically relevant 

response in light of the many factors that can influence the immune system, for example, stress or 

seasonal differences. The EPA should also clarify what testing is required for immunotoxicity. 

The Agency should add a footnote to indicate if a combined study, for example, an immunotoxicity 

component added to a 90-day subchronic study, is acceptable. 

A number of antimicrobial pesticides are known to be dermal sensitizers. Sensitization is an 

immunological response. However, the Agency has not addressed whether or how known sensitizers 

should be evaluated for immunotoxicity. The Agency needs to discuss and justify the use of animals 

in those evaluations if there will be no additional regulatory benefit provided beyond what the 

sensitization itself provides 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 593 

Response: See responses 80.51, 80.52, and 80.53, and testnote 80.8. EPA also notes that some the 

comments are not directed toward the proposed rule, but to the the guidelines for immunotoxicity 

studies. EPA will consider these guideline comments at another time. 

Comment Code: 89100 Dermal Penetration studies 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26183 

Comment Code: 89100 

Comment: The proposed rule does not take into consideration scientific advances in the area of 

dermal penetration. The Agency is requiring animal dermal penetration studies when there are well 

established OECD guidelines for in vitro dermal penetration studies available.[FN#4: OECD 

Guideline 428] This is not consistent with the Agency’s desire to move to alternative toxicology 

testing. P&G urges the Agency to accept in vitro skin penetration data. The in vitro dermal 

penetration method is the preferred and accepted testing method in most other OECD member 

counties and should be the study of choice to fulfill the data requirement. The proposed rule also 

states the Agency is looking to incorporate (Q)SAR approaches to help make regulatory decisions. 

Many predictive computational models (e.g. based on molecular structure; based on molecular 

weight and octanol/water partition coefficient) have been developed to assess dermal 

absorption/penetration that should be considered in fulfilling data requirements. Furthermore, 

dermal penetration can be estimated/predicted using science-based approaches such as comparing 

LOAELs from repeat-dose oral and dermal studies to derive an approximate dermal penetration. 

The Agency should not require the use of animals for dermal absorption, but should incorporate the 

best science in moving toward a strategic change in its approach to addressing how anti-microbial 

actives are evaluated. These data 1) are scientifically adequate, and in many cases, superior to in vivo 

studies; 2) would harmonize EPA requirements with those in the EU and elsewhere; and 3) reduces 

the unnecessary use of live animals. 

Response: see responses 4 and 80.56 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26198 

Comment Code: 89100 

Comment: P&G further recommends in vitro dermal penetration data along with the data from 90-

day oral subchronic study be allowed to address the subchronic dermal toxicity data requirements 

when this study is triggered based on the results from the 90-day subchronic oral toxicity study and 

knowledge of the amount of the chemical that is absorbed dermally, considering the assumption that 

100% of the chemical is absorbed from oral administration. 

Response: see response 80.20 and 80.56 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 594 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26319 

Comment Code: 89100 

Comment: The National Research Council (NRC) 2006 Report regarding EPA testing approaches 

emphasized that required data should be premised on a clear need in the risk assessment process, 

rather than just for the sake of completeness. The NRC concluded that "tiered testing approaches 

should be designed to expedite regulatory decisions and to discourage toxicity testing that is not 

used to address regulatory questions."[FN#36:National Research Council (NRC). 2006. Toxicity 

Testing for Assessment of Environmental Agents. Interim Report. National Academies Press. 

Washington, D.C. Pages 8-13.] EPA currently is developing its strategic vision and an 

implementation plan to address the NRC 2007 vision for the Agency.[FN#37:National Research 

Council (NRC). 2007. Toxicity Testing in the 21st Century. A Vision and a Strategy. National 

Academies Press. Washington, D.C.] The Agency should use this Proposal to take the initial steps to 

incorporate a tiering process that avoids unnecessary testing. The Panel suggests alternative data 

requirements in the section-by- section analyses that better clarify tiering of requirements and 

conditions when requirements are applicable. 

Response: see response 4 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26616 

Comment Code: 89100 

Comment: *Immunotoxicity 

- Full hematology-CBC including leukocyte differential and cell morphology; 

- Assessment of immune system organ weights and histopathological change (e.g. hypocelluarity of 

immune system tissues such as the thymus, spleen, lymph nodes, Peyer’s patches, and bone 

marrow); and 

- Measurement of serum globulin levels (IgA, IgG, IgM) 

- In addition, the lymphoid tissue that drains or contacts the site of chemical administration should 

be specifically examined (Basketter et al., 1995). The endpoints listed above are considered sufficient 

to detect any potential effects on the immune system. 

Support for use of the above program to assess the potential for neurotoxicity and immunotoxicity 

is provided by Doe et al. (2006). 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 595 

* Doe, J. E., A. R. Boobis, A. Blacker, V. Dellarco, N. G. Doerrer, C. Franklin, J. I. Goodman, J. M. 

Kronenberg, R. Lewis, E. E. McConnell, T. Mercier, A. Moretto, C. Nolan, S. Padilla, W. Phang, R. 

Solecki. L. Tilbury, B. van Ravenzwaay, and D. C. Wolf. 2006. A Tiered Approach to Systemic 

Toxicity Testing for Agricultural Chemical Safety Assessment. Crit. Rev. Toxicol. 36: 37-68. 

Response: EPA notes that these comments are not directed toward the proposed rule, but to the 

the guidelines for immunotoxicity studies. EPA will consider these guideline comments at another 

time. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26621 

Comment Code: 89100 

Comment: The Panel urges EPA to consider the following alternative approach to the dermal data 

requirement in assessing the hazard and risk associated with dermal exposure of the antimicrobial 

pesticide products. 

1. The dermal studies (21/28-day or 90-day) should be made as ‘Choice’ studies instead of CR 

(Conditionally Required). 

2. The risk assessment for dermal route of exposure can be assessed by using: a. Oral study with 

TGAI in conjunction with dermal penetration data or b. Using the 21/28-day or 90-day dermal 

studies as such. 

3. The registrant should have a choice of conducting either dermal study and/or dermal penetration 

study. 

4. In general, dermal study on TGAI may only be required under special circumstances and should 

be based on indications from other data (e.g. acute 5 40 CFR 158.500 studies, SAR) that a greater 

degree of toxicity may be expressed via the dermal route of exposure. 

5. From a regulatory perspective, toxicological studies conducted via the dermal route are generally 

less conservative than equivalent oral studies as the systemic dose is difficult to define in the dermal 

studies. 

6. Test note 12(ii) does not define when ‘human exposure is not purposeful’ and the scope of a 

‘limited portion of the human life span’. The Agency should do so. Triggers for the studies should 

be based on scientific information. Since the Agency intends to determine when the magnitude, 

frequency and duration of exposure, the above approach is well suited to define when the study is 

absolutely warranted. The test note should be revised to reflect the practical approach to achieve the 

objectives of the study requirement. 

Additionally, test note 12(iii) implicates a short term dermal toxicological study may be required with 

an EP if a 90-day dermal study is not conducted. Nonetheless, the test note also implies that dermal 

data must be included to adequately characterize or regulate an EP. The EPA should explain which 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 596 

one the proposed rule suggests. With the low concentration of AI, it is difficult to apply sufficient 

amount in order to achieve an MTD and conduct a meaningful and acceptable study. Alternatively, 

hazard can be assessed by using the oral TGAI study in conjunction with dermal absorption data. 

The influence of ingredients in the EP can be assessed by comparing dermal absorption data of the 

AI and EP, obtained from in vitro studies. 

In footnote 13, the Agency states that it will "require subchronic dermal testing of the end-use 

product if the product or any component of the product may increase dermal absorption of the 

active ingredient(s) or could potentiate toxic or pharmacologic effects." EPA needs to provide 

guidance as to how this should be determined for the components. Additionally, the dermal studies 

for the EP should not be required, but should be made as ‘Choice’ studies. Dermal studies on the 

EP are not the best way to assess the hazard of formulating ingredients in end use products because: 

1) The concentration of the AI is generally very low, 2) With the low concentration of AI, it is 

difficult to apply sufficient amount in order to achieve MTD and conduct a meaningful and 

acceptable study. 3) The systemic dose cannot be defined. Thus, a dermal study on EP will not be 

more robust compared to that conducted with the TGAI if and when triggered. Alternatively, 

hazard can be assessed by using the oral study with TGAI in conjunction with dermal absorption 

data. The influence of ingredients in the EP can be assessed by comparative dermal absorption data 

with TGAI and EP, obtained from in vitro studies. 

In footnotes 14 and 16, a 90-Day dermal or inhalation study is required if dermal or inhalation 

exposure is major route, even though footnote 7 indicates the EPA may substitute another route for 

the oral route. The Agency needs to clarify when the requirement exists for other routes compared 

to when a 90-day dermal or inhalation study may be substituted for the 90-day oral study. 

Response: see responses 80.20, 80.54, 80.16, 80.47, 80.69, and 80.55, and testnotes 80.7, 80.14, and 

80.16 Additionally, EPA notes that it is unclear what is meant by a "choice" study, and therefore the 

Agency cannot respond 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26654 

Comment Code: 89100 

Comment: I. Comments on Dermal Penetration Data Requirements 

The Panel urges the Agency to accept in vitro skin penetration data. These data 1) are scientifically 

adequate, and in many cases, superior to in vivo studies; 2) would harmonize EPA requirements 

with those in the EU and elsewhere; and 3) reduces the unnecessary use of live animals. 

The proposed rule does not take into consideration scientific advances in the area of dermal 

penetration. The Agency is requiring animal dermal penetration studies when there are well 

established OECD guidelines for in vitro dermal penetration studies available.12 This is not 

consistent with the Agency’s desire to move to alternative toxicology testing. The in vitro dermal 

penetration method is the preferred and accepted testing method in most other OECD member 

countries and should be the study of choice to fulfill the data requirement. The proposed rule also 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 597 

states the Agency is looking to incorporate (Q)SAR approaches to help make regulatory decisions. 

Many predictive computational models (e.g. based on molecular structure; based on molecular 

weight and octanol/water partition coefficient) have been developed to assess dermal 

absorption/penetration that should be considered in fulfilling data requirements. Furthermore, 

dermal penetration can be estimated/predicted using science-based approaches such as comparing 

LOAELs from repeat-dose oral and dermal studies to derive an approximate dermal penetration. 

The Agency should not require the use of animals for dermal absorption, but should incorporate the 

best science in moving toward a strategic change in its approach to addressing how anti-microbial 

actives are evaluated. 

Specific Comments on the Test Footnotes 

Test note 37 does not apply to corrosive/irritant products which produce corrosivity before any 

systemic toxicity. In this case, such substances are simply destructive to the dermal barrier. The 

Agency should provide guidance specific to corrosive/irritant products since the risk assessment 

assumption that dermal absorption is equal to oral absorption does not apply. 

Response: see responses 80.56, 4, 80.4, and testnote 80.37 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26669 

Comment Code: 89100 

Comment: Dermal Penetration In Vitro 

This study, conducted using in vitro methodology, provides an assessment of the degree of dermal 

absorption, and allows determination of the risk from dermal exposure based on the results from 

the 90-day subchronic toxicity study and knowledge of the amount of the chemical that is absorbed 

dermally, considering the assumption that 100% of the chemical is absorbed from oral 

administration. In vitro methods have been validated, and have been demonstrated to provide an 

accurate prediction of the degree of dermal absorption compared to in vivo methods. 

Response: see response 80.56 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27313 

Comment Code: 89100 

Comment: LANXESS urges EPA to consider the following alternative approach to the dermal data 

requirement in assessing the hazard and risk associated with dermal exposure of the antimicrobial 

pesticide products. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 598 

1. The dermal studies (21/28-day or 90-day) should be made as ‘Choice’ studies instead of CR 

(Conditionally Required). 

2. The risk assessment for dermal route of exposure can be assessed by using: 

a. Oral study with TGAI in conjunction with dermal penetration data or 

b. Using the 21/28-day or 90-day dermal studies as such. 

3. The registrant should have a choice of conducting either dermal study and/or dermal penetration 

study. 

4. In general, dermal study on TGAI may only be required under special circumstances and should 

be based on indications from other data (e.g. acute studies, SAR) that a greater degree of toxicity 

may be expressed via the dermal route of exposure. 

5. From a regulatory perspective, toxicological studies conducted via the dermal route are generally 

less conservative than equivalent oral studies as the systemic dose is difficult to define in the dermal 

studies. 

6. Test note 12(ii) does not define when ‘human exposure is not purposeful’ and the scope of a 

‘limited portion of the human life span’. The Agency should do so. Triggers for the studies should 

be based on scientific information. Since the Agency intends to determine when the magnitude, 

frequency and duration of exposure, the above approach is well suited to define when the study is 

absolutely warranted. The test note should be revised to reflect the practical approach to achieve the 

objectives of the study requirement. 

Additionally, test note 12(iii) implicates a short term dermal toxicological study may be required with 

an EP if a 90-day dermal study is not conducted. Nonetheless, the test note also implies that dermal 

data must be included to adequately characterize or regulate an EP. The EPA should explain which 

one the proposed rule suggests. With the low concentration of AI, it is difficult to apply sufficient 

amount in order to achieve an MTD and conduct a meaningful and acceptable study. Alternatively, 

hazard can be assessed by using the oral TGAI study in conjunction with dermal absorption data. 

The influence of ingredients in the EP can be assessed by comparing dermal absorption data of the 

AI and EP, obtained from in vitro studies. 

In footnote 13, the Agency states that it will "require subchronic dermal testing of the end-use 

product if the product or any component of the product may increase dermal absorption of the 

active ingredient(s) or could potentiate toxic or pharmacologic effects." EPA needs to provide 

guidance as to how this should be determined for the components. Additionally, the dermal studies 

for the EP should not be required, but should be made as ‘Choice’ studies. Dermal studies on the 

EP are not the best way to assess the hazard of formulating ingredients in end use products because: 

1) The concentration of the AI is generally very low, 2) With the low concentration of AI, it is 

difficult to apply sufficient amount in order to achieve MTD and conduct a meaningful and 

acceptable study. 3) The systemic dose cannot be defined. Thus, a dermal study on EP will not be 

more robust compared to that conducted with the TGAI if and when triggered. Alternatively, 

hazard can be assessed by using the oral study with TGAI in conjunction with dermal absorption 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 599 

data. The influence of ingredients in the EP can be assessed by comparative dermal absorption data 

with TGAI and EP, obtained from in vitro studies. 

In footnotes 14 and 16, a 90-Day dermal or inhalation study is required if dermal or inhalation 

exposure is major route, even though footnote 7 indicates the EPA may substitute another route for 

the oral route. The Agency needs to clarify when the requirement exists for other routes compared 

to when a 90-day dermal or inhalation study may be substituted for the 90-day oral study. 

Response: see responses 80.20, 80.54, 80.16, 80.47, 80.69, and 80.55, and testnotes 80.7, 80.14, and 

80.16 

Additionally, EPA notes that it is unclear what is meant by a "choice" study, and therefore the 

Agency cannot respond 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27344 

Comment Code: 89100 

Comment: I. Comments on Dermal Penetration Data Requirements 

LANXESS urges the Agency to accept in vitro skin penetration data. These data 1) are scientifically 

adequate, and in many cases, superior to in vivo studies; 2) would harmonize EPA requirements 

with those in the EU and elsewhere; and 3) reduces the unnecessary use of live animals. 

The proposed rule does not take into consideration scientific advances in the area of dermal 

penetration. The Agency is requiring animal dermal penetration studies when there are well 

established OECD guidelines for in vitro dermal penetration studies available.[FN12: OECD 

Guideline 428.] This is not consistent with the Agency’s desire to move to alternative toxicology 

testing. The in vitro dermal penetration method is the preferred and accepted testing method in 

most other OECD member countries and should be the study of choice to fulfill the data 

requirement. The proposed rule also states the Agency is looking to incorporate (Q)SAR approaches 

to help make regulatory decisions. Many predictive computational models (e.g. based on molecular 

structure; based on molecular weight and octanol/water partition coefficient) have been developed 

to assess dermal absorption/penetration that should be considered in fulfilling data requirements. 

Furthermore, dermal penetration can be estimated/predicted using science-based approaches such 

as comparing LOAELs from repeat-dose oral and dermal studies to derive an approximate dermal 

penetration. The Agency should not require the use of animals for dermal absorption, but should 

incorporate the best science in moving toward a strategic change in its approach to addressing how 

anti-microbial actives are evaluated. 

Specific Comments on the Test Footnotes 

Test note 37 does not apply to corrosive/irritant products which produce corrosivity before any 

systemic toxicity. In this case, such substances are simply destructive to the dermal barrier. The 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 600 

Agency should provide guidance specific to corrosive/irritant products since the risk assessment 

assumption that dermal absorption is equal to oral absorption does not apply. 

Response: see responses 80.56, 4, 80.4, and testnote 80.37 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27359 

Comment Code: 89100 

Other EPA Comment Codes and Descriptions: 85000 Prenatal development studies 

Comment: Dermal Penetration In Vitro 

This study, conducted using in vitro methodology, provides an assessment of the degree of dermal 

absorption, and allows determination of the risk from dermal exposure based on the results from 

the 90-day subchronic toxicity study and knowledge of the amount of the chemical that is absorbed 

dermally, considering the assumption that 100% of the chemical is absorbed from oral 

administration. In vitro methods have been validated, and have been demonstrated to provide an 

accurate prediction of the degree of dermal absorption compared to in vivo methods. 

Response: see responses 80.20 and 80.56 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27360 

Comment Code: 89100 

Other EPA Comment Codes and Descriptions: 89110 Tiered approach to toxicology studies; 

89111 High exposure uses (including: food and drinking water; outdoor aquatic uses; indirect food 

uses with residues equal to or greater than 200 parts per billion (ppb); wood preservatives; 

metalworking fluids; swimming pools) 

Comment: 2. Tier II 

Testing would proceed to Tier II if any of the results from studies in Tier I indicate that the risk 

from exposure to the antimicrobial pesticide cannot be adequately characterized. Thus, evaluation of 

the endpoints of systemic toxicity and the impact on life stages will inform the decision to conduct 

additional tests. 

Response: see response 80.72 

Comment Code: 89101 Metabolism and pharmacokinetics 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25596 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 601 

Comment Code: 89101 

Comment: Section Number Subpart W 

Title Antimicrobial Pesticide Data Requirements 

Paragraph [Section] 158.2230 Toxicology data, (e) Test notes p. 59435 

Excerpt from Federal Register 35. For low exposure, [metabolism and pharmacokinetics] data are 

required when chronic or carcinogenicity studies are also required. These data may be required if 

significant adverse effects are seen in available toxicology studies and these effects can be further 

elucidated by metabolism studies. 

HC Comment The PMRA considers metabolism and pharmacokinetic data to be important in the 

evaluation and interpretation of toxicology data, and notes that they may assist in the extrapolation 

of animal toxicity data to humans. Consequently, the PMRA requires these data for all pesticides, 

regardless of the level of exposure, or use pattern associated with the product. In addition, the 

PMRA notes that these data may provide critical information for use in an integrated testing 

strategy. 

The PMRA seeks the EPA’s opinion on the above points, and suggests listing this data element as 

‘required’ for low exposure antimicrobials, rather than ‘conditionally required.’ 

Response: See response 80.57 and testnote 80.35 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26648 

Comment Code: 89101 

Comment: G. Comments on Metabolism and Pharmacokinetics Data Requirements 

Comparison of requirement for metabolism and pharmacokinetic studies 

For conventional chemicals (CC), metabolism and pharmacokinetic (PK) studies are required (R) for 

food use patterns, and conditionally required (CR) for non-food use patterns using pure active 

ingredient (PAI) or pure active ingredient radiolabeled (PAIRA). For antimicrobials (AM), 

metabolism and pharmacokinetic (PK) studies (870.7485) are required (R) for high human exposure 

uses and conditionally required for low human exposure uses. 

The Agency plans to continue this requirement by requiring a metabolism and PK study for high 

human exposures, and conditionally requiring the study for low human exposures. For the purpose 

of determining toxicology data requirements for AM, high human exposure is defined as that 

resulting in human exposures over a considerable portion of the human life span. By this definition, 

exposure to food and water is therefore a high human exposure. For CC, nonfood use patterns only 

have a conditional requirement for a metabolism and PK study. For AM, the Agency has also 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 602 

categorized certain nonfood uses as high human exposures that require a metabolism and PK study. 

The nonfood uses include, but are not limited to, outdoor aquatic uses in bodies of water that have 

the potential to contaminate potable water and applicator exposure to wood preservatives, 

metalworking fluids, and swimming pools. 

The footnote for the metabolism and pharmacokinetic study requirement for both AM and CC 

indicates that this study is required when chronic or carcinogenicity studies are also required. In both 

AM and CC, the footnote indicates that the metabolism and PK study may be required (CR) if 

significant adverse effects are seen in available toxicology studies, and these effects can be further 

elucidated by metabolism. Table 1 below summarizes R and CR studies. 

For both CC and AM, a 1-year non-rodent study (i.e., 1-year dog study) would be required if the 

Agency finds that a pesticide is highly bioaccumulating and is eliminated so slowly that it does not 

achieve steady state or sufficient tissue concentrations to elicit an effect during a 90-day study. In 

such a case, a tier II metabolism and PK study is needed. 

[See Table 1:Required and Conditionally-required metabolism and pharmacokinetic studies by use 

pattern and exposure level, PDF docket ID EPA-HQ- OPP-2008-0110-0088] 

The rationale for conducting metabolism and PK studies is consistent with the recommendations of 

the ILSI/HESI project, Agricultural Chemical Safety Assessment (ACSA). It is recognized in the 

proposed rule for data requirements for antimicrobial pesticides that ACSA represents toxicity 

testing for agricultural pesticides, but the results would be applicable to antimicrobial pesticides. The 

basis for that decision has not been provided, particularly in relation to the requirements of FIFRA 

3(h). 

Response: see response 1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26650 

Comment Code: 89101 

Comment: Critique of metabolism and PK studies in the proposed rule for antimicrobial pesticides 

data requirements 

a) Similar triggers are found between the CC and AM requirements. For example, for "low human 

exposure non-food use pattern", a metabolism and PK study is required when chronic or 

carcinogenicity studies are also required. However, it is unclear whether high/low exposure is 

another layer of categorization for triggering metabolism and pharmacokinetic studies, as in Table 1, 

or if it replaces the food/non-food use pattern classification. b) In the AM rule the EPA defines low 

human exposure uses as those that are not high human exposure uses. However, the definition of 

high human exposure uses is extremely broad and is described as "not exhaustive." It would be 

useful for the EPA to more clearly define examples of low human exposure uses or to bring the AM 

terminology back into accord with the CC terminology. c) The scientific rationale for conducting 

metabolism and PK studies is from results of the ACSA program, as well as developments from 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 603 

EPA’s NCCT and the NAS’ Toxicity Testing. Though it is appropriate to apply the results of the 

ACSA program for antimicrobials, the approach may need to be modified for non-food use 

patterns, for example, inclusion of dermal route of exposure. d) Metabolism and pharmacokinetic 

studies are helpful for designing acute/chronic health effects studies, for example, establishing the 

top dose based on saturation of ADME processes. The proposed rule for antimicrobials does not 

clearly explain how metabolism and PK studies are integrated into a toxicity testing program, and 

more specifically for making informed decisions when designing health effects studies. e) Overall, 

the EPA fails to clarify triggers for high-tier metabolism and pharmacokinetics studies. These 

triggers should be consistent with the ILSI/HESI recommendations, if the ACSA program is to be 

adopted, and with results from tier I studies, as stated by Barton et al. (2006)[FN#11:Barton, H. A., 

T. P. Pastoor, K. Baetcke, J. E. Chambers, J. Diliberto, N. G. Dorrrer, J. H. Driver, C. E. Hastings, 

S. Iyengar, R. Krieger, B. Stahl, and C. Timchalk. 2006. The Acquisition and Application of 

Absorption, Distribution, Metabolism, and Excretion (ADME) Data in Agricultural Chemical Safety 

Assessments. Crit. Rev. Toxicol. 36: 9-35]. 

Specific Comments on the Test Footnotes 

1. The Panel recommends that test note 35 be modified to read: "For low exposure, these data may 

be required when chronic..." There may be instances where corrosive/irritant effects in chronic or 

carcinogenic studies result in no adverse effect or carcinogenic endpoint. In that case, metabolism 

and pharmacokinetics tests are unnecessary. 

2. The footnotes in the proposed rule for metabolism studies state the following: "For low exposure, 

these data are required when chronic or carcinogenicity studies are also required. These data may be 

required if significant adverse effects are seen in available toxicology studies and these effects can be 

further elucidated by metabolism studies." The Agency should clarify these triggers. 

Response: see responses 80.4 and 80.57, and testnote 80.35 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26662 

Comment Code: 89101 

Comment: Absorption, Distribution, Metabolism, and Excretion Basic kinetic and metabolism data 

are included in Tier I because this information can be used as a key resource to design toxicity 

studies with knowledge of the dose that saturates absorptive, metabolic and excretory processes 

(Barton et al., 2006). ADME data, in conjunction with exposure information, can also allow 

limitation of the top dose in a study so that it does not exceed a dose that is irrelevant to levels to 

which humans would be exposed. If human exposure, under all circumstances in the intended use 

pattern of a chemical, would never reach a dose that saturates metabolism and excretion, it is 

unnecessary to test at a dose above that which produces saturation. 

Information describing the dose of chemical equivalents that reach target tissue can be among the 

most valuable data for interpreting toxicity study results and developing or supporting mode-ofaction hypotheses (Barton et al., 2006). It is customary in the initial stages of toxicological 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 604 

investigation to develop data that describes what a chemical does to the mammalian system. We 

maintain that data describing what the mammalian system does to a chemical should also be 

generated in the initial stages of a toxicological investigation. Both sets of data are highly 

complementary, and are valuable in designing future studies in higher tier testing. 

Response: see response 80.57 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26779 

Comment Code: 89101 

Comment: 6. Proposed Regulation # [Section] 158.2230(e)(10) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "EPA may require 

the appropriate tier II metabolism and pharmacokinetic studies to evaluate more precisely 

bioavailability, half life, and steady state to determine if a longer duration dog toxicity study is 

needed." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria to determine if the Agency will require tier II metabolism and pharmacokinetic 

studies. 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26977 

Comment Code: 89101 

Comment: 17. Proposed Regulation # [Section] 158.2230(e)(35) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "For low exposure, 

these data are required when chronic or carcinogenicity studies are also required. These data may be 

required if significant adverse effects are seen in available toxicology studies and these effects can be 

further elucidated by metabolism studies." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated when the data is required or not. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 605 

Comment ID: 27339 

Comment Code: 89101 

Comment: G. Comments on Metabolism and Pharmacokinetics Data Requirements 

Comparison of requirement for metabolism and pharmacokinetic studies 

For conventional chemicals (CC), metabolism and pharmacokinetic (PK) studies are required (R) for 

food use patterns, and conditionally required (CR) for non-food use patterns using pure active 

ingredient (PAI) or pure active ingredient radiolabeled (PAIRA). For antimicrobials (AM), 

metabolism and pharmacokinetic (PK) studies (870.7485) are required (R) for high human exposure 

uses and conditionally required for low human exposure uses. 

The Agency plans to continue this requirement by requiring a metabolism and PK study for high 

human exposures, and conditionally requiring the study for low human exposures. For the purpose 

of determining toxicology data requirements for AM, high human exposure is defined as that 

resulting in human exposures over a considerable portion of the human life span. By this definition, 

exposure to food and water is therefore a high human exposure. For CC, nonfood use patterns only 

have a conditional requirement for a metabolism and PK study. For AM, the Agency has also 

categorized certain nonfood uses as high human exposures that require a metabolism and PK study. 

The nonfood uses include, but are not limited to, outdoor aquatic uses in bodies of water that have 

the potential to contaminate potable water and applicator exposure to wood preservatives, 

metalworking fluids, and swimming pools. 

The footnote for the metabolism and pharmacokinetic study requirement for both AM and CC 

indicates that this study is required when chronic or carcinogenicity studies are also required. In both 

AM and CC, the footnote indicates that the metabolism and PK study may be required (CR) if 

significant adverse effects are seen in available toxicology studies, and these effects can be further 

elucidated by metabolism. Table 1 below summarizes R and CR studies. 

For both CC and AM, a 1-year non-rodent study (i.e., 1-year dog study) would be required if the 

Agency finds that a pesticide is highly bioaccumulating and is eliminated so slowly that it does not 

achieve steady state or sufficient tissue concentrations to elicit an effect during a 90-day study. In 

such a case, a tier II metabolism and PK study is needed. 

Table 1. Required and Conditionally-required metabolism and pharmacokinetic studies by use 

pattern and exposure level. 

Food use pattern and high human exposure - R Food use pattern and low human exposure - R 

Non-food use pattern and high human exposure - R Non-food use pattern and low human exposure 

- CR 

The rationale for conducting metabolism and PK studies is consistent with the recommendations of 

the ILSI/HESI project, Agricultural Chemical Safety Assessment (ACSA). It is recognized in the 

proposed rule for data requirements for antimicrobial pesticides that ACSA represents toxicity 

testing for agricultural pesticides, but the results would be applicable to antimicrobial pesticides. The 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 606 

basis for that decision has not been provided, particularly in relation to the requirements of FIFRA 

3(h). 

Critique of metabolism and PK studies in the proposed rule for antimicrobial pesticides data 

requirements 

a) Similar triggers are found between the CC and AM requirements. For example, for "low human 

exposure non-food use pattern", a metabolism and PK study is required when chronic or 

carcinogenicity studies are also required. However, it is unclear whether high/low exposure is 

another layer of categorization for triggering metabolism and pharmacokinetic studies, as in Table 1, 

or if it replaces the food/non-food use pattern classification. 

b) In the AM rule the EPA defines low human exposure uses as those that are not high human 

exposure uses. However, the definition of high human exposure uses is extremely broad and is 

described as "not exhaustive." It would be useful for the EPA to more clearly define examples of 

low human exposure uses or to bring the AM terminology back into accord with the CC 

terminology. 

c) The scientific rationale for conducting metabolism and PK studies is from results of the ACSA 

program, as well as developments from EPA’s NCCT and the NAS’ Toxicity Testing. Though it is 

appropriate to apply the results of the ACSA program for antimicrobials, the approach may need to 

be modified for non-food use patterns, for example, inclusion of dermal route of exposure. 

d) Metabolism and pharmacokinetic studies are helpful for designing acute/chronic health effects 

studies, for example, establishing the top dose based on saturation of ADME processes. The 

proposed rule for antimicrobials does not clearly explain how metabolism and PK studies are 

integrated into a toxicity testing program, and more specifically for making informed decisions when 

designing health effects studies. 

e) Overall, the EPA fails to clarify triggers for high-tier metabolism and pharmacokinetics studies. 

These triggers should be consistent with the ILSI/HESI recommendations, if the ACSA program is 

to be adopted, and with results from tier I studies, as stated by Barton et al. (2006).[FN11: Barton, 

H. A., T. P. Pastoor, K. Baetcke, J. E. Chambers, J. Diliberto, N. G. Dorrrer, J. H. Driver, C. E. 

Hastings, S. Iyengar, R. Krieger, B. Stahl, and C. Timchalk. 2006. The Acquisition and Application 

of Absorption, Distribution, Metabolism, and Excretion (ADME) Data in Agricultural Chemical 

Safety Assessments. Crit. Rev. Toxicol. 36: 9-35] 

Specific Comments on the Test Footnotes 

1. LANXESS recommends that test note 35 be modified to read: "For low exposure, these data may 

be required when chronic..." There may be instances where corrosive/irritant effects in chronic or 

carcinogenic studies result in no adverse effect or carcinogenic endpoint. In that case, metabolism 

and pharmacokinetics tests are unnecessary. 

2. The footnotes in the proposed rule for metabolism studies state the following: "For low exposure, 

these data are required when chronic or carcinogenicity studies are also required. These data may be 
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Comments and Response References: 

Toxicology Section (80) Page 607 

required if significant adverse effects are seen in available toxicology studies and these effects can be 

further elucidated by metabolism studies." The Agency should clarify these triggers. 

Response: see responses 1, 80.4, and 80.57, and testnote 80.35 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27352 

Comment Code: 89101 

Comment: Absorption, Distribution, Metabolism, and Excretion 

Basic kinetic and metabolism data are included in Tier I because this information can be used as a 

key resource to design toxicity studies with knowledge of the dose that saturates absorptive, 

metabolic and excretory processes (Barton et al., 2006). ADME data, in conjunction with exposure 

information, can also allow limitation of the top dose in a study so that it does not exceed a dose 

that is irrelevant to levels to which humans would be exposed. If human exposure, under all 

circumstances in the intended use pattern of a chemical, would never reach a dose that saturates 

metabolism and excretion, it is unnecessary to test at a dose above that which produces saturation. 

Information describing the dose of chemical equivalents that reach target tissue can be among the 

most valuable data for interpreting toxicity study results and developing or supporting mode-ofaction hypotheses (Barton et al., 2006). It is customary in the initial stages of toxicological 

investigation to develop data that describes what a chemical does to the mammalian system. We 

maintain that data describing what the mammalian system does to a chemical should also be 

generated in the initial stages of a toxicological investigation. Both sets of data are highly 

complementary, and are valuable in designing future studies in higher tier testing. 

Response: see response 80.57 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27684 

Comment Code: 89101 

Comment: 17. Proposed Regulation # [Section] 158.2230(e)(35) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "For low exposure, 

these data are required when chronic or carcinogenicity studies are also required. These data may be 

required if significant adverse effects are seen in available toxicology studies and these effects can be 

further elucidated by metabolism studies." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated when the data is required or not. 
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Comments and Response References: 

Toxicology Section (80) Page 608 

Response: see response 3 

Comment Code: 89110 Tiered approach to toxicology studies 

Commenter Name: Abigail Trueblood 

Commenter Organization: Dow Chemical Company 

Letter ID: 0082 

Comment ID: 25479 

Comment Code: 89110 

Comment: We point the Agency to Appendix E of the ACC Biocides Panel letter, which contains 

extensive comments on the Mammalian Toxicology data requirements. Dow concurs with the 

Panel's concern that a tiering approach based on "high" and "low" exposure categories is 

inappropriate for antimicrobials. We urge the Agency to incorporate the Panel's suggestions for 

tiering of mammalian toxicology data in a reproposal of this rule. Dow has been actively involved in 

the Panel collaborate project with EPA and ILSI-RF to determine whether a threshold of 

toxicological concern (TTC) approach can be used for regulatory decision-making for 

antimicrobials. We agree with the Panel recommendation that the Agency should include this project 

work in a reproposal of this rule. 

Response: see responses 80.3 and 80.59 

Commenter Name: Patrick H. Quinn 

Commenter Organization: Innovation and Reform Group (IRG) 

Letter ID: 0080 

Comment ID: 25491 

Comment Code: 89110 

Comment: As important, the Proposed Rule insists upon specifically mandating the animal assay 

required for each toxicological endpoint, producing a rigidity that will not permit EPA to 

appropriately change its testing requirements as 21st Century toxicology offers OPP opportunities to 

continuously improve the quality of its science. 

Response: see response 4 

Commenter Name: Rodger Curren 

Commenter Organization: Alternative Testing Working Group (ATWG) 

Letter ID: 0092 

Comment ID: 25511 

Comment Code: 89110 

Comment: Disappointingly, the Proposed Rule insists upon specifically mandating the animal assay 

required for each toxicological endpoint, producing a rigidity that will not permit EPA to 

appropriately change its testing requirements as 21st Century toxicology offers OPP opportunities to 

continuously improve the quality of its science. 
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Comments and Response References: 

Toxicology Section (80) Page 609 

Response: see response 4 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25565 

Comment Code: 89110 

Comment: *There is some uncertainty regarding the tiered data system proposed in the CFR 158W 

document. For example, in the case of human toxicology data requirements, two tiers of data for 

both the low and high exposure scenarios are described (13 required studies for the lower tier of the 

low exposure scenario, and 19 required studies for the lower tier of the high exposure scenario). The 

PMRA requests clarification regarding the following: 

-It is our understanding that the test notes in the data tables in proposed subpart W set out the 

conditions for ‘triggering" the higher tier of studies. Is this correct? -Is the onus on the applicant to 

determine whether the use of the product fits within the high vs. low human exposure scenario? (i.e., 

Is a rationale required to support the submission of the lower ‘core set’ of data?) -Are applicants 

expected to determine when the ‘higher’ tier of data would be triggered and submit these additional 

data with their original submissions, or would this be determined by the Agency following a review 

of the lower tier of data? If it is the latter, how would this impact deadlines under the Pesticide 

Registration Improvement Act (PRIA), as well as joint reviews? 

Response: see responses 3, and 80.59 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25620 

Comment Code: 89110 

Comment: IV. Comments on Toxicology Data Requirements 

This section shares with EPA CSPA's comments on EPA's proposed Antimicrobial Toxicology 

Data Requirements. (40 C.F.R. § 158.2230). The introduction first reviews CSPA's concerns over 

EPA's high/low human exposure use criteria and proposes that EPA differentiate between first and 

second-tier testing of antimicrobial based on their food or nonfood use. CSPA then offers its 

comments and suggestion on particular toxicology requirements and some of the accompanying 37 

test notes. 

EPA's Antimicrobial Toxicology Data Requirements, in the main, adopt the Agency's Toxicology 

Data Requirements for conventional pesticides.[FN#2: EPA published its toxicology data 

requirements for conventional pesticides in the Federal Register on October 26, 2007. (72 Fed. Reg. 

60934). They are codified now at 40 C.F.R. [Section] 158.2230.] The Agency's March 11, 2005 

Notice of Proposed Rulemaking for its toxicology requirements for conventional pesticides 

explained the purpose of toxicology data: "Toxicology studies are required by the Agency to assess 

the hazard of the pesticide to humans and domestic animals. These hazard data, when combined 
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Comments and Response References: 

Toxicology Section (80) Page 610 

with exposure data, form the basis for the human risk assessment...The duration of the toxicity study 

approximates the estimated duration of human exposure...If a pesticide is used on food and requires 

a tolerance, the dietary exposure may be over a lifetime, and thus chronic/cancer and multigeneration reproductive studies would be required." [FN#3: 47 Fed. Reg. at 12292.] 

The Agency's proposed antimicrobial Toxicology Data Requirements raise two principal issues: 1) 

for antimicrobials, what are the scientifically appropriate criteria for differentiating among first, 

second and third tiered testing? 2) Within each tier what studies are reasonable and appropriate in 

light of the toxicity of antimicrobials and likely and realistic human exposure to antimicrobials? 

a. CSPA Urges EPA To Differentiate Between First and Second Tier Testing of Antimicrobials On 

The Basis of Food/Nonfood Uses Rather Than High/Low Human Exposure Uses 

For conventional pesticides EPA determined that the typical nonfood pesticide presents only limited 

opportunities for significant repeat or lifetime human exposure, while residues resulting from the 

agricultural uses of pesticides on food and feed present opportunities for lifetime dietary exposure. 

While the use criteria separating the first and second-tier testing for conventional pesticides -- 

food/nonfood -- makes scientific sense and are susceptible to consistent and systematic application 

by EPA, the Agency's counterpart use criteria for antimicrobials -- high/low -- makes less sense, as 

explained below. 

Response: see response 80.64 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25621 

Comment Code: 89110 

Comment: The Agency's definition of "high" human exposure differs in material ways from its 

counterpart for conventional pesticides: 

b. EPA’s Proposed Definition of "High" Human Exposure Uses for Antimicrobials ([Section] 

158.2230(b)(1)): 

"[H]igh human exposure includes those uses which are likely to result in human exposure over a 

considerable portion of the human lifespan, and which are significant in terms of frequency, 

duration, or magnitude of exposure (i.e., uses for which there is an expectation of high, prolonged, 

or repeated exposure)...." 

EPA derived its definition of high human exposure antimicrobials from criteria it adopted in 2007 

for determining when a registrant or applicant of a conventional nonfood pesticide must submit to 

EPA a chronic rat study (note 17) and/or a mouse oncogenicity study (note 20). The criteria in note 

17 and note 20, however, materially differ from EPA's proposed "high human exposure use" 

definition for antimicrobials. 
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Comments and Response References: 

Toxicology Section (80) Page 611 

c. EPA’s Note 17 accompanying [Section]158.500 (first of two criteria for requiring a chronic rat 

study for nonfood use conventional pesticide): 

"The use of the pesticide is likely to result in repeated human exposure over a considerable portion 

of the human lifespan, as determined by the Agency;..." 

Response: see response 80.59 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25627 

Comment Code: 89110 

Comment: To address the above limitations CSPA proposes that EPA substitute food/nonfood for 

its proposed high/low paradigm for antimicrobials. The CR notes for higher tiered studies for 

nonfood uses of antimicrobials should then reflect scientifically reasonable and appropriate criteria 

for requiring higher tiered testing of nonfood antimicrobials. 

Response: see response 80.64 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25628 

Comment Code: 89110 

Comment: 1. In the preamble to the proposed rule, EPA indicates that it may require the testing of 

the most concentrated use-dilution for biocide concentrates. Testing may be required if the Agency 

believes that the use dilution may result in "significant exposure." [FN#4: Federal Register, 73(196), 

10/8/2008, p. 59394- "EPA proposes to add a test note to clarify that the currently required six 

acute toxicity studies are to be conducted on the product as formulated for sale and distribution. 

The six acute studies may also be needed for the product as diluted for use. Many antimicrobial 

products are diluted at the point of use, but can still lead to significant exposure."] Test note #2, 

however, indicates that use-dilution testing is optional and at the discretion of the registrant. The 

Agency needs to reconcile their guidance on this matter. CSPA recommends that testing of the usedilution of biocide concentrates remain at the discretion of the registrant. Alternatively, the Agency 

needs to clearly define "significant exposure" and rewrite test note #2 in order to provide clear 

guidance to registrants. 

Response: see response 80.11 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25642 

Comment Code: 89110 
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Comments and Response References: 

Toxicology Section (80) Page 612 

Comment: Many biocidal products are corrosive concentrates that are intended to be diluted prior 

to use. Current Agency practice requires inhalation toxicity testing on the concentrate. If classified in 

Toxicity Category I or II for inhalation toxicity, significant precautionary labeling and protective 

equipment (e.g. respiratory protection) is required. 

Once diluted, however, these products typically have a much different toxicity profile. In some 

segments, concentrates are diluted up to 1:1024. The labeling and PPE requirements for the 

concentrate can be inappropriate for the use- dilution. The PPE requirements for many concentrates 

are also inconsistent with common practice. For example, it is not practical to train janitorial staff to 

use respiratory protection when handling diluted sanitizers or disinfectants in schools or healthcare 

facilities. 

In these situations, registrants must be given the discretion to test the inhalation toxicity of the usedilution in order to justify appropriate precautionary labeling and PPE requirements for the usesolution. 

4. Test note #2 specifies that the "six acute toxicity studies conducted with the end-use 

product...must be conducted with the product formulated for sale and distribution." While CSPA 

essentially agrees with the Agency position on this issue, we recommend the following clarifications: 

i. The current wording of test note #2 may be perceived as prohibiting proper conduct of studies 

for dermal sensitization. These protocols require dilution of the test product in order to identify 

doses that distinguish between irritation and allergy. The irritating or corrosive natures of many 

antimicrobial formulations preclude testing the "product as formulated for sale and distribution" in 

these studies. 

ii. Secondly, there are instances where it may not be possible to test the formulated product in a 

humane manner. The wording of test note #2 should provide for some flexibility to allow for 

modification of the test material on a case-by-case basis. 

For example, in the dermal toxicity test, corrosive materials can cause significant skin injury during 

the 24 hours of exposure required by the study. While the study can be waived, in the absence of 

data, the Agency will classify the product in Toxicity Category I, require skull and crossbones and 

mandate the statement "Fatal if absorbed through skin." For corrosive materials, with no significant 

systemic toxicity, this approach can result in inaccurate labeling. 

In these instances it can be desirable to dilute the product to reduce the amount of irritation while 

maintaining the same overall dose of the test material. (e.g. the test product could be diluted by 50% 

and dosed at 10 g/kg vs. 5 g/kg). In some cases, this approach can allow the study to go forward 

while reducing unnecessary stress to the test animals. Of course, such procedural changes must be 

the exception and subject to approval by Agency toxicologists. 

Therefore, CSPA recommends that FN 2 be modified as follows: 
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Comments and Response References: 

Toxicology Section (80) Page 613 

"For the six acute toxicity studies conducted with the end-use product, the test must be conducted 

using the product as formulated for sale and distribution except as required by study protocols or a 

variance is granted after consultation with the Agency". 

5. Registrants and the Agency both have the desire to reduce the need for unnecessary animal 

testing. The increased use of bridging and study waivers can significantly reduce the number of 

toxicity studies that are needed to support antimicrobial registrations. Unnecessary toxicity testing 

imposes a significant financial and resource burden on both the registrants and the Agency. 

Registrants shoulder the direct cost to pay for the studies and the Agency has to dedicate resources 

to review the studies after submission. In addition, these studies also require the use of a significant 

number of experimental animals; one "six-pack" can require 70-75 test animals. 

In 2007, the ACC Biocides Panel proposed to the Agency a framework for capturing the Agency's 

past guidance on these topics and improving their use and acceptance.[FN#5:Framework for Acute 

Toxicity Waiver and for Acute Toxicity Bridging for Antimicrobial Pesticides. AMERICAN 

CHEMISTRY COUNCIL- Biocides Panel. September 17, 2007. Updated October 30, 2007.] CSPA 

requests that EPA complete their review of and implement the recommendations in the ACC 

Biocides Panel Framework Document. We also recommend that the Agency add a new test note 

that accepts waiver and bridging principles as appropriate methods to satisfy all acute toxicity data 

requirements. 

6. There is confusion between the statement that EPA may require the testing of the most 

concentrated use-dilution for biocide concentrates, but in footnote 2 EPA indicates that use-dilution 

is optional. This apparent inconsistency requires clarification. 

7. In both the preamble and in footnote 2, the Agency states that "consultation with the Agency is 

highly suggested to assure that the appropriate product and any appropriate dilutions are tested." 

CSPA believes that consultation should not be needed prior to conducting routine acute studies and 

that the Agency needs to clarify under what circumstances they feel that consultation is needed. 

Response: see responses 80.12, 80.13, 80.11, 80.65, and 3 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25671 

Comment Code: 89110 

Comment: HUMAN HEALTH PROTECTION DATA REQUIREMENTS 

Exposure classifications 

While SFE is generally comfortable with the proposal to distinguish between "high" and "low" 

exposure use patterns, the definition of the "high exposure" category needs to be reworked to 

include additional use patterns that involve repeated exposures, particularly repeated exposures to 

children and to workers like janitorial workers. Unless data requirements are restructured, EPA 

would not routinely receive the data necessary to ensure the safety of children (who often have daily, 
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Comments and Response References: 

Toxicology Section (80) Page 614 

long-term exposures to treated toys, fabrics, or play areas), the safety of workers who use the same 

cleaning products daily (often for years), or even residents who frequently clean their homes. At a 

minimum, EPA should add cleaning products and indoor use impregnated products like toys, 

clothing, and bedding to the list of "high exposure" product categories. 

Response: see response 80.71 

Commenter Name: Jay Feldman 

Commenter Organization: Beyond Pesticides 

Letter ID: 0067 

Comment ID: 25713 

Comment Code: 89110 

Comment: The agency has proposed to delineate between high and low indirect food use 

exposures. Low exposures are to be defined as those which result in residues in or on food of less 

than 200 ppb. It is not apparent whether the agency recognizes that continual exposure to "low 

exposure residues" over the long-term results in high exposure. Continual low dose exposure has 

been shown in the scientific literature to pose significant long term risk, especially for developing 

infants.[FN3: Lassiter et al. 2008. Exposure of Neonatal Rats to Parathion Elicits Sex-Selective 

Reprogramming of Metabolism and Alters the Response to a High-Fat Diet in Adulthood. Environ. 

Health Perspectives. 116(11); Lu et al. 2008. Dietary Intake and Its Contribution to Longitudinal 

Organophosphorus Pesticide Exposure in Urban/Suburban Children. Environ. Health Perspectives. 

116 (4).] According to the Federal Registrar Notice,[FN4: U.S. EPA. 2008. Data Requirements for 

Antimicrobial Pesticides; Proposed Rule. Federal Registrar, Vol. 73, No. 196, October 8,2008.] the 

EPA once considered all food use antimicrobials high exposure. We suggest that all uses, whether 

direct or indirect food uses, be considered high exposure instead of delineating between high and 

low exposures. This should be the case since the agency has defined high exposure as "that resulting 

in human exposures over a considerable portion of the human lifespan," such as (but not limited to) 

food and water exposures. [FN4] 

Response: see response 80.62 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25746 

Comment Code: 89110 

Comment: Draft 158 W Definition of "High" and "Low" Exposure The use of the term "exposure" 

within the proposed rule is unclear, inconsistent, arbitrary, and unrelated to any scientific 

justification for requiring exposure and environmental data. The proposed rule divides antimicrobial 

pesticides into "high exposure" and "low exposure" categories. These terms were used in the 1987 

Antimicrobial Data Call-In which used high, medium, and low exposure categories to indicate the 

general level of concern the Agency had with different uses of antimicrobials, irrespective of the true 

toxicity/exposure of those compounds. However, such a categorization today is indeed archaic and 

irrelevant, especially in light of the exposure data being generated through the CSPA AEJV and the 

ACC Biocides Panel AEATF II. Further, it is highly prejudicial to arbitrarily label an antimicrobial 
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Comments and Response References: 

Toxicology Section (80) Page 615 

use as "high exposure" when there is neither scientific evidence to support exposure to humans or 

the environment, nor are there clear criteria for stating that any exposures are "high" without 

qualification. 

The rule contains a significant increase of data requirements for exposure to humans and the 

environment. Where in some cases such data may be warranted, the rule unfairly and arbitrarily 

places a very costly data generation burden on chemicals without sound scientific basis for data 

requirements for "high exposure" products. The basic scientific principle underlying all data 

requirements and risk assessments addresses both the nature of the hazard and the magnitude of 

exposure. If a compound is very toxic, there may be risks of concern if there are resulting exposures 

of concern. If a compound is not highly toxic or if the exposure is primarily through routes by 

which there is limited potential toxicity, then a high exposure would be of little concern and 

therefore data could well be unnecessary. As currently written the proposed rule requires 19 

different toxicity studies for products categorized as "high" exposure. 

Ecolab proposes a tiered approach for guiding the testing requirements proposed in the rule. In all 

cases, the arbitrary low and high exposure use patterns must be eliminated. However, a clear 

designation of use patterns similar to those defined in the environmental fate section of the rule may 

be a good starting point. Once acceptable use patterns are established, the Agency could then apply 

the risk characterization tools similar to those being applied to determine the environmental fate of 

conventional pesticides. 

Through a risk characterization methodology, the Agency can extrapolate risk by using a either 

deterministic or probabilistic approach based upon predicted environmental concentrations (PEC), 

which would be developed around predicted rates of release into the environment from any use, 

followed by the predicted no effect concentration (PNEC) based upon existing data or preliminary 

data requirements. The resulting risk quotient (RQ) can then be used to identify whether or not 

further testing should be required. This is a simple, screening- level estimate that the Agency can use 

to establish a tiered testing format based upon the outcome of the risk quotient: 

RQ = (Exposure)/(Toxicity) 

The Agency would then be able to establish a threshold value for each use pattern founded upon the 

accepted baseline existing, or initial required toxicity data; the 6-pack for example, divided by data 

which more accurately characterizes exposure; physical/chemical properties, use, environmental fate, 

etc. In cases where the data does not meet the accepted TCCR principle (transparent, clear, 

consistent, and reasonable) standards, a safety factor could be applied to the risk quotient that would 

address uncertainty in the predictions. 

A methodology characterizing risk with existing and preliminary test data is founded in objective 

scientific principles and provides the applicant with more clarity than the proposed arbitrary 

standards. As stated earlier, the exposure scenario as proposed is not well defined and only addresses 

one leg of risk characterization. Including a deterministic or probabilistic analysis of the hazard as 

well as the potential exposure provides a more objective tool for determining data requirements. 

This type of approach could be applied to each of the data requirements outlined in the proposed 

rule. 
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Comments and Response References: 

Toxicology Section (80) Page 616 

Response: see response 80.59 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25756 

Comment Code: 89110 

Comment: Section 158.2230 - Toxicology Data As previously stated, the proposed rule divides 

antimicrobial pesticides into "high exposure" and "low exposure" categories in the absence of sound 

scientific justification. Ecolab proposes a tiered testing approach that is triggered for each use 

pattern through a deterministic or risk quotient methodology as presented previously. 

Response: see response 80.59 

Commenter Name: William C. Balek 

Commenter Organization: ISSA 

Letter ID: 0074 

Comment ID: 25862 

Comment Code: 89110 

Comment: [In particular, ISSA supports the following aspects of the ACC Biocides Panel 

Comments:] * The proposal does not include meaningful tiering; 

Response: see response 80.59 

Commenter Name: William C. Balek 

Commenter Organization: ISSA 

Letter ID: 0074 

Comment ID: 25865 

Comment Code: 89110 

Comment: [In particular, ISSA supports the following aspects of the ACC Biocides Panel 

Comments:] * Potential exposures are different for antimicrobial products and require different 

approaches; 

Response: see response 1 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25909 

Comment Code: 89110 

Comment: [In the Panel's comments, 12 major discussion points are presented as follows:] * The 

proposal does not include meaningful tiering 
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Comments and Response References: 

Toxicology Section (80) Page 617 

Response: see response 80.59 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25912 

Comment Code: 89110 

Comment: [In the Panel's comments, 12 major discussion points are presented as follows:] * 

Potential exposures are different for antimicrobials and demand different approaches 

Response: see response 1 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25923 

Comment Code: 89110 

Comment: Toxicology Data Requirements and Use Patterns 

Clorox is in agreement with the Biocides Panel's comments that the EPA's proposal departs 

dramatically from the Agency's practice and commonly held toxicology concepts. We agree that the 

two-tiered approaches provided by the Panel would better meet the Toxicology data requirements. 

Also, we support the elimination of "low" and -high exposure and the inclusion of the proposed 

alternative Use Pattern categories described by the Panel. The approaches are both scientifically 

valid and provide an integrated approach to testing. 

Response: see response 80.59 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25957 

Comment Code: 89110 

Comment: The use of two different exposure categories, such as "High" and "Low" exposure, also 

does not lend to transparency of the data requirements. Under wood use, for example, the data are 

indicative of high exposure, whereas uses such as joinery and indoor wood stains would not be 

considered high exposure. 

Response: see response 80.22 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26165 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 618 

Comment Code: 89110 

Comment: Tiering of Data Requirements The Agency’s Proposal for antimicrobial data 

requirements has eliminated the potential for effective tiering of data requirements. In both the 

proposed and final rules for conventional chemical pesticides, the Agency identified the importance 

of tiering data requirements based upon both exposure and hazard considerations.[FN#1: Proposed 

Rule, 70 Fed. Reg. 12,276 (March 11, 2005); Final Rule, 72 Fed. Reg. 60,934 (Oct. 26, 2007). For 

toxicology data requirements, EPA provided a specific approach to tiering for conventional 

chemicals at 40 C.F.R. § 158.510 and has incorporated tiered testing into other disciplines. Tiering is 

also part of the data requirement regulation for biochemical pesticides.] This is a basic tenet of the 

risk assessment process. If a compound is very toxic, there may be risks of concern if there are even 

low exposures. On the other hand, if a compound is not highly toxic or if there is limited potential 

for toxicity in the routes of exposure, then less data may be necessary. 

In the Proposal, the Agency claims that it proposes to "tier" the data requirements by assigning 

certain categories of antimicrobial products to "high" or "low" exposure categories. 

The Agency fails to provide any explanation for its decision to include certain uses in one or another 

category, justify the basis for the two broad exposure categories or to explain how the 

characterizations as "high" or "low" justify different data requirements. Exposure levels cannot 

simply be assumed based on product types. 

The requirements should be tiered based on pertinent factors such as the chemical and/or physical 

characteristics of the compound being assessed, routes of exposure, hazard as related to the routes 

of exposure, and the results of initial testing. The proper tiering of data depends upon these 

considerations, not arbitrary assignment of "high" or "low" exposure. Further, the approach to 

satisfying data requirements must incorporate current science and allow for future improvements in 

risk assessment, including use of integrated approaches to determining potential data requirements, 

hazard characterization, and risk assessment. 

Response: see response 80.59 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26172 

Comment Code: 89110 

Comment: As stated earlier, this proposal has eliminated the potential for effective tiering. P&G 

recommends an alternative approach be incorporated that will allow effective tiering providing 

adequate data to come to a regulatory decision. 

Response: see response 80.59 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 619 

Comment ID: 26223 

Comment Code: 89110 

Comment: In addition, the Proposal uses overly broad categorizations of "high" and "low" 

exposures, and even those categories can be interpreted so that all antimicrobial uses can be 

classified as having "high" exposure potential. The Proposal therefore also does not include 

meaningful tiering of data requirements to conform the degree of review to the potential risks 

presented by various antimicrobial uses. 

Response: see response 80.59 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26236 

Comment Code: 89110 

Comment: * The Agency has not explained how it will assess the criteria that would trigger data 

requirements for low exposure, and encourages consultation with the Agency.[FN#8:Id. at [Section] 

158.2230(e)(21).] 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26295 

Comment Code: 89110 

Comment: III. The Proposal Does Not Include Meaningful Tiering 

The Proposal for antimicrobial data requirements has eliminated the potential for effective tiering of 

data requirements. In both the proposed and final rules for conventional chemical pesticides, the 

Agency identified the importance of tiering data requirements based upon both exposure and hazard 

considerations.[FN#31:Proposed Rule, 70 Fed. Reg. 12276 (Mar. 11, 2005); Final Rule, 72 Fed. Reg. 

60,934 (Oct. 26, 2007). For toxicology data requirements, EPA provided a specific approach to 

tiering for conventional chemicals at 40 C.F.R. § 158.510 and has incorporated tiered testing into 

other disciplines. Tiering is also part of the data requirement regulation for biochemical pesticides.] 

This is a basic tenet of the risk assessment process. If a compound is very toxic, there may be risks 

of concern if there are even low exposures. On the other hand, if a compound is not highly toxic or 

if there is limited potential for toxicity in the routes of exposure, then less data may be necessary. 

The conventional pesticide regulation makes clear that the Agency can use tiering to clarify what 

data are needed and why, recognizing that compounds with greater potential hazard or with greater 

potential exposure generally require more information than compounds with lower potential hazard 

or exposure. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 620 

In the Proposal for antimicrobials, however, the Agency has eliminated any potential for effective 

tiering of data requirements by the unsubstantiated assignment of exposure categories and by the 

conditions under which data requirements must be addressed. In the Proposal, the Agency claims 

that it proposes to "tier" the data requirements by assigning certain categories of antimicrobial 

products to "high" or "low" exposure categories. 

Response: see response 80.59 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26315 

Comment Code: 89110 

Comment: The Agency proposes setting a level of 200 ppb as a dividing line between "low" and 

"high" exposures for certain antimicrobial pesticide food uses, but the Proposal is unclear as to what 

that value refers to specifically or how it is calculated. 

The Panel assumes that the 200 ppb value refers to a concentration of a substance in an adult’s daily 

food consumption. 

Response: see response 80.60 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26318 

Comment Code: 89110 

Comment: If that is the case, EPA apparently adopted this value from FDA’s guidance for food 

contact substances.[FN#32:FDA, Guidance for Industry: Preparation of Premarket Notifications 

for Food Contact Substances: Toxicology Recommendations, April 2002; and FDA, Guidance for 

Industry: Preparation of Food Contact Notifications and Food Additive Petitions for Food Contact 

Substances: Chemistry Recommendations - Final Guidance, April 2002. See also FDA, Estimating 

Dietary Intake of Substances in Food, August 2006; and FDA, Guidance for Industry; Preparation 

of Premarket Submissions for Food Contact Substances: Chemistry Recommendations, December 

2007.] In any event, EPA should be clear about the source. The Panel is encouraged by EPA’s 

recognition of "the historic usefulness of the FDA’s tiered approach and [that it] proposes to adopt 

it conceptually." 73 Fed. Reg. at 59394. But if EPA plans to adopt FDA’s tiering approach with 

regard to food contact substances, it is essential that EPA rely on the complete body of knowledge 

that supports the FDA approach. Since it is not apparent from the Proposal what EPA intends, 

some aspects of the FDA approach are summarized below. 

FDA identifies a dietary concentration of 200 ppb as equivalent to an estimated dietary intake (EDI) 

of 10 μg/kg of body weight/day. It is calculated in accordance with FDA’s guidance and 

assumptions. This is only one of several approaches that FDA uses for food additives; different 

exposure levels are used to tier data requirements for other types of food additives (e.g., those added 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 621 

directly to food and other indirect additives) than are used for food contact substances. Further, 

even for biocides as food contact substances, the 200 ppb dietary concentration is not an absolute 

level with absolute data requirements or an absolute decision regarding safety; FDA takes into 

consideration numerous other factors in deciding what mammalian toxicity data may be needed and 

whether the potential exposure is acceptable. FDA’s bases for identifying the various thresholds it 

uses, including as part of its Threshold of Regulation decisions, are based on sound, scientific data 

regarding thresholds of toxicological concern in association with FDA policies and guidance on how 

it makes its safety determination. The Panel believes that the toxicology data requirements it 

suggests in the appended section-by-section analysis are a more appropriate way to incorporate 

tiering into the data requirements than the current Proposal. 

Moreover, the Panel concurs with the opinion and recommendation of the SAP that EPA should 

consider some of FDA’s methods for estimating levels of exposure.[FN#33:Report of the June 1997 

Meeting of the FIFRA Science Advisory Panel, at 

http://www.epa.gov/scipoly/sap/meetings/1997/june/report.pdf.] Unfortunately, the Proposal 

fails to adequately consider such approaches. In fact, despite some acknowledgement of FDA’s 

approaches for exposure estimates, EPA continues to reject the use of FDA methodologies. For 

example, FDA provided comments to EPA in its review of 1,4- Bis(bromomoacetoxy)-2-butene, 

wherein FDA provided information on how it would calculate exposure, if that compound actually 

had an approval for use in food- contact paper production.[FN#34:FDA letter of December 14, 

2000, available at EPA-HQ-OPP-2007-0151.] EPA rejected the FDA methodology and instead used 

an unsubstantiated approach to estimate dietary exposures nearly 100 times higher.{FN#35: March 

19, 2001 memo, available at EPA-HQ-OPP-2007-0151.] 

In other contexts, the Panel previously has provided EPA with a detailed explanation of how FDA 

calculated exposures for different types of indirect food additives and has offered to open a dialogue 

as to how the extensive experience and documentation might be helpful in informing an approach 

relevant to pesticides. The Panel reiterates its willingness to do so and reemphasizes the need for this 

guidance to be developed in a timely manner through a transparent and public process. A copy of 

the documentation concerning the FDA process for estimating exposure of indirect food additives is 

attached as Appendix L. 

Response: see responses 80.60 and 80.3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26453 

Comment Code: 89110 

Comment: EPA has inappropriately relied upon the 1997 SAP review. EPA has now proposed 

more and higher tier toxicology studies for both its designated low and high exposure antimicrobial 

uses than those considered in 1997. The state of the science has changed significantly since 1997, as 

reflected by the many EPA initiatives currently underway to address alternatives to traditional 

reliance on animal testing and risk assessment methods. See Section VII for the Panel’s 

recommendations on alternate risk assessment approaches that should be incorporated into the 

Proposal that would benefit from SAP review. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 622 

Further, the Panel believes that the Proposal does not implement many of the recommendations 

made by the 1997 SAP and fails to provide any rationale for not doing so. For example, the 1997 

SAP stated that 

Use of the "threshold of regulation" concept used by FDA and levels of human exposure to trigger 

Tier I and Tier II is highly encouraged to minimize unnecessary testing in cases of minimal human 

exposure.[FN#83:1997 SAP Report at page 8.] 

As discussed more fully in Section III and Appendix E, the Proposal does not incorporate 

meaningful tiered testing or the threshold of regulation concept. 

Response: see responses 80.59, 80.67, and 1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26573 

Comment Code: 89110 

Comment: The Panel is concerned that the approach taken by EPA based upon "high" and "low" 

exposure categories is not appropriate for antimicrobials, and will prove unworkable if adopted. The 

Panel agrees with EPA that tiering is appropriate. The Panel does not believe exposure is an 

appropriate criterion to use for tiering. Moreover, in the Panel’s view, the conditions applied to 

determining when studies are required (i.e. higher tiered studies triggered by exposure over a "limited 

portion" of a lifespan) neutralize any potential for tiering or otherwise limiting testing (See Panel’s 

General Comments at Section III). The Panel is concerned that EPA is effectively eliminating tiering 

of data requirements for antimicrobials without any rationale. There is clearly identified tiering for 

conventional pesticides,[FN#1:40 CFR 158.510.] and biochemical pesticides.[FN#2:40 CFR 

158.2050.] The Proposal should be revised to incorporate meaningful tiering for antimicrobial 

pesticides. The Panel’s suggested approach for doing so is set forth below. 

Response: see responses 80.59 and 80.16 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26574 

Comment Code: 89110 

Comment: The Panel supports tiering data requirements on the basis of exposure and risk, as it has 

been demonstrated to be scientifically valid and is a critical component of any integrative approach 

to testing. The concept of a threshold for toxicological effects is well established scientifically. This 

is a very different approach than assigning exposures based upon a particular concentration in food. 

Response: see response 80.59 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 623 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26660 

Comment Code: 89110 

Other EPA Comment Codes and Descriptions: 89111 High exposure uses (including: food and 

drinking water; outdoor aquatic uses; indirect food uses with residues equal to or greater than 200 

parts per billion (ppb); wood preservatives; metalworking fluids; swimming pools) 

Comment: A. Alternative Proposal 1 

This Panel’s first proposal is comprised of three tiers and incorporates many of the 

recommendations in the ACSA proposal. The proposal has scientifically appropriate studies without 

redundancy and emphasizes evaluation of toxicological endpoints with greater efficiency, fewer 

animals, and better use of resources. While the ACSA proposal was developed with conventional 

chemicals and broad-scale applications to food crops, and the environment in mind, the same 

principles are applicable to antimicrobial pesticides. 

Under the Panel’s proposed alternative toxicology testing regulation, Tier I is the base set of testing 

that would be conducted for all antimicrobial pesticides. The studies in Tiers II and III would be 

required based on the results from the testing in Tier I and the margin of exposure for a particular 

use. When the margin of exposure is large, e.g. greater than 1000, Tier II and Tier III studies may be 

unnecessary. This tiered approach requires expert scientific judgment. Informed decisions must be 

made regarding the interpretation of the Tier I studies and whether to pursue tests in Tier II and 

Tier III. 

This tiered approach is designed to 1) provide information that can be applied to a range of relevant 

human exposure situations; 2) characterize effects that have the potential to damage human health at 

exposure levels approximating those that might be encountered in the use of antimicrobial 

compounds; 3) avoid high doses that cause unnecessary public concern, for example, safety 

assessments should focus on doses that are relevant to realistic human exposures while maintaining 

adequate power for the experimental studies to detect toxicity; 4) use the minimum number of 

animals necessary to produce a thorough safety assessment for antimicrobial pesticides; 5) minimize 

excessive and unnecessary use of resources by regulatory authorities and industry which could be 

used to address other issues of concern; and 6) increase both the efficiency and relevance of the 

current safety assessment process. 

Response: see response 80.72 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26670 

Comment Code: 89110 

Other EPA Comment Codes and Descriptions: 89111 High exposure uses (including: food and 

drinking water; outdoor aquatic uses; indirect food uses with residues equal to or greater than 200 

parts per billion (ppb); wood preservatives; metalworking fluids; swimming pools) 

Comment: 2. Tier II 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 624 

Testing would proceed to Tier II if any of the results from studies in Tier I indicate that the risk 

from exposure to the antimicrobial pesticide cannot be adequately characterized. Thus, evaluation of 

the endpoints of systemic toxicity and the impact on life stages will inform the decision to conduct 

additional tests. 

Response: see response 80.72 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26727 

Comment Code: 89110 

Comment: In addition, the Proposal uses overly broad categorizations of "high" and "low" 

exposures, and even those categories can be interpreted so that all antimicrobials uses can be 

classified as having "high" exposure potential. The Proposal therefore also does not include the 

establishment of meaningful tiers of data requirements to conform the degree of review to the 

potential risks presented by various antimicrobial uses. 

Response: see response 80.59 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26747 

Comment Code: 89110 

Comment: * The Agency has not explained how it will assess the criteria that would trigger data 

requirements for low exposure, and encourages consultation with the Agency.[FN8: Id. at [section] 

158.2230(e)(21).] 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26755 

Comment Code: 89110 

Comment: 3. Proposed Regulation # [Section] 158.2230(b) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Uses. "The applicant for 

registration must first determine whether the use is a high human exposure use or a low human 

exposure use. If an applicant is not sure if a specific use is a high human exposure or a low human 

exposure use, the applicant should consult the Agency." 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 625 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria to determine whether a specific use is a high human exposure or a low human 

exposure, and requires private consultation with the Agency. 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26781 

Comment Code: 89110 

Comment: 7. Proposed Regulation # [Section] 158.2230(e)(11) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "For low human 

exposure uses, data are required if any of the following criteria are met: (i) the use of the pesticide is 

likely to result in repeated human exposure over a limited portion of the human lifespan, as 

determined by the Agency . . ." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine if the use of the pesticide is likely to result in repeated human 

exposure over a limited portion of the human lifespan. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26817 

Comment Code: 89110 

Comment: III. The Proposal Does Not Include Meaningful Tiering 

The Proposal for antimicrobial data requirements has eliminated the potential for effective tiering of 

data requirements. In both the proposed and final rules for conventional chemical pesticides, the 

Agency identified the importance of tiering data requirements based upon both exposure and hazard 

considerations.[FN31: Proposed Rule,70 Fed.Reg.12276(Mar.11,2005); Final Rule,72 Fed.Reg. 

60,934 (Oct.26,2007). For toxicology data requirements, EPA provided a specific approach to tiering 

for conventional chemicals at 40 C.F.R. [section] 158.510 and has incorporated tiered testing into 

other disciplines. Tiering is also part of the data requirement regulation for biochemical pesticides.] 

This is a basic tenet of the risk assessment process. If a compound is very toxic, there may be risks 

of concern if there are even low exposures. On the other hand, if a compound is not highly toxic or 

if there is limited potential for toxicity in the routes of exposure, then less data may be necessary. 

The conventional pesticide regulation makes clear that the Agency can use tiering to clarify what 

data are needed and why, recognizing that compounds with greater potential hazard or with greater 

potential exposure generally require more information than compounds with lower potential hazard 

or exposure. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 626 

Response: see response 80.59 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26827 

Comment Code: 89110 

Comment: Assumptions that product types and/or uses relate to levels of exposure and should be a 

basis for determining data requirements are insupportable and should be removed from the 

Proposal. Instead, requirements should be tiered based on pertinent factors such as the chemical 

and/or physical characteristics of the compound being assessed, routes of exposure, hazard as 

related to the routes of exposure, and the results of initial testing. The proper tiering of data depends 

upon these considerations, not arbitrary assignment of "high" or "low" exposure. Further, the 

approach to satisfying data requirements must incorporate current science and allow for future 

improvements in risk assessment, including use of integrated approaches to determining potential 

data requirements, hazard characterization, and risk assessment. 

Assuming the Agency continues to be interested in pursuing "high" and "low" exposure categories 

as a vehicle for tiering data requirements, additional issues must be addressed. 

Response: see responses 4, 80.59, and 80.64 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26829 

Comment Code: 89110 

Comment: The Agency proposes setting a level of 200 ppb as a dividing line between "low" and 

"high" exposures for certain antimicrobial pesticide food uses, but the Proposal is unclear as to what 

that value refers to specifically or how it is calculated. 

LANXESS assumes that the 200 ppb value refers to a concentration of a substance in an adult’s 

daily food consumption. 

Response: see response 80.60 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26831 

Comment Code: 89110 

Comment: If that is the case, EPA apparently adopted this value from FDA’s guidance for food 

contact substances.[FN32: FDA, Guidance for Industry: Preparation of Premarket Notifications for 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 627 

Food Contact Substances: Toxicology Recommendations, April 2002; and FDA, Guidance for 

Industry: Preparation of Food Contact Notifications and Food Additive Petitions for Food Contact 

Substances: Chemistry Recommendations - Final Guidance, April 2002. See also FDA, Estimating 

Dietary Intake of Substances in Food, August 2006; and FDA, Guidance for Industry; Preparation 

of Premarket Submissions for Food Contact Substances: Chemistry Recommendations, December 

2007.] In any event, EPA should be clear about the source. LANXESS is encouraged by EPA’s 

recognition of "the historic usefulness of the FDA’s tiered approach and [that it] proposes to adopt 

it conceptually." 73 Fed.Reg. at 59394. But if EPA plans to adopt FDA’s tiering approach with 

regard to food contact substances, it is essential that EPA understand and rely on the complete body 

of knowledge that supports the FDA approach. Since it is not apparent from the Proposal whether 

EPA has done so, some aspects of the FDA approach are summarized below. 

FDA identifies a dietary concentration of 200 ppb as equivalent to an estimated dietary intake (EDI) 

of 10 ug/kg of body weight/day. It is calculated in accordance with FDA’s guidance and 

assumptions. This is only one of several approaches that FDA uses for food additives; different 

exposure levels are used to tier data requirements for other types of food additives (e.g., those added 

directly to food and other indirect additives) than are used for food contact substances. Further, 

even for biocides as food contact substances, the 200 ppb dietary concentration is not an absolute 

level with absolute data requirements or an absolute decision regarding safety; FDA takes into 

consideration numerous other factors in deciding what mammalian toxicity data may be needed and 

whether the potential exposure is acceptable. FDA’s bases for identifying the various thresholds it 

uses, including as part of its Threshold of Regulation decisions, are based on sound, scientific data 

regarding thresholds of toxicological concern in association with FDA policies and guidance on how 

it makes its safety determination. LANXESS believes that the toxicology data requirements it 

suggests in the section-by-section analysis are a more appropriate way to incorporate tiering into the 

data requirements than the current Proposal. 

Moreover, LANXESS concurs with the opinion and recommendation of the SAP that EPA should 

consider some of FDA’s methods for estimating levels of exposure.[FN33: Report of the June 1997 

Meeting of the FIFRA Science Advisory Panel, at 

http://www.epa.gov/scipoly/sap/meetings/1997/june/report.pdf.] Unfortunately, the Proposal 

fails to adequately consider such approaches. In fact, despite some acknowledgement of FDA’s 

approaches for exposure estimates, EPA continues to reject the use of FDA methodologies. For 

example, FDA provided comments to EPA in its review of 1,4-Bis(bromomoacetoxy)-2-butene, 

wherein FDA provided information on how it would calculate exposure, if that compound actually 

had an approval for use in food-contact paper production.[FN34: FDA letter of December 14, 2000, 

available at EPA-HQ-OPP-2007-0151.] EPA rejected the FDA methodology and instead used an 

unsubstantiated approach to estimate dietary exposures nearly 100 times higher.[FN35: March 

19,2001 memo, available at EPA-HQ-OPP-2007-0151.] 

In other contexts, the ACC Biocides Panel previously has provided EPA with a detailed explanation 

of how FDA calculated exposures for different types of indirect food additives and has offered to 

open a dialogue as to how the extensive experience and documentation might be helpful in 

informing an approach relevant to pesticides. LANXESS will participate in this dialog and 

emphasizes the need for this guidance to be developed in a timely manner through a transparent and 

public process. A copy of the documentation concerning the FDA process for estimating exposure 

of indirect food additives has been provided by the Americam Chemical Council’s Biocides Panel. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 628 

Response: see responses 80.60 and 80.3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26838 

Comment Code: 89110 

Comment: The National Research Council (NRC) 2006 Report regarding EPA testing approaches 

emphasized that required data should be premised on a clear need in the risk assessment process, 

rather than just for the sake of completeness. The NRC concluded that "tiered testing approaches 

should be designed to expedite regulatory decisions and to discourage toxicity testing that is not 

used to address regulatory questions."[FN36: National Research Council (NRC). 2006. Toxicity 

Testing for Assessment of Environmental Agents. Interim Report. National Academies Press. 

Washington, D.C. Pages 8-13.] EPA is currently developing its strategic vision and an 

implementation plan to address the NRC 2007 vision for the Agency.[FN37: National Research 

Council (NRC). 2007. Toxicity Testing in the 21st Century. A Vision and a Strategy. National 

Academies Press. Washington, D.C.] The Agency should use this Proposal to take the initial steps to 

incorporate a tiering process that avoids unnecessary testing. LANXESS suggests alternative data 

requirements in the section-by- section analysis that better clarify tiering of requirements and 

conditions when requirements are applicable. 

Response: see response 4 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26879 

Comment Code: 89110 

Comment: 10. Proposed Regulation # [Section] 158.2230(e)(20) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "For low exposure, 

data are required if either of the following criteria are met . . . (i) The use of the pesticide is likely to 

result in repeated human exposure over a limited portion of the human lifespan, as determined by 

the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine if the use of the pesticide is likely to result in repeated human 

exposure over a limited portion of the human lifespan. 

11. Proposed Regulation # [Section] 158.2230(e)(21) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "For low exposure, 

data are required if any of the following criteria, as determined by the Agency are met . . ." 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 629 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated how it will assess the criteria set out in this subsection. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27204 

Comment Code: 89110 

Comment: EPA has inappropriately relied upon the 1997 SAP review. EPA has now proposed 

more and higher tier toxicology studies for both its designated low and high exposure antimicrobial 

uses than those considered in 1997. The state of the science has changed significantly since 1997, as 

reflected by the many EPA initiatives currently underway to address alternatives to traditional 

reliance on animal testing and risk assessment methods. See Section VII for LANXESS’s 

recommendations on alternate risk assessment approaches that should be incorporated into the 

Proposal that would benefit from SAP review. 

Further, LANXESS believes that the Proposal does not implement many of the recommendations 

made by the 1997 SAP and fails to provide any rationale for not doing so. For example, the 1997 

SAP stated that 

"Use of the "threshold of regulation" concept used by FDA and levels of human exposure to trigger 

Tier I and Tier II is highly encouraged to minimize unnecessary testing in cases of minimal human 

exposure."[FN85: 1997 SAP Report at page 8.] 

As discussed more fully in Section III and Appendix E, the Proposal does not incorporate 

meaningful tiered testing or the threshold of regulation concept. 

Response: see responses 80.59, 80.67, and 1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27285 

Comment Code: 89110 

Comment: LANXESS is concerned that the approach taken by EPA based upon "high" and "low" 

exposure categories is not appropriate for antimicrobials, and will prove unworkable if adopted. 

LANXESS agrees with EPA that tiering is appropriate. LANXESS does not believe exposure is an 

appropriate criterion to use for tiering. Moreover, in LANXESS’s view, the conditions applied to 

determining when studies are required (i.e. higher tiered studies triggered by exposure over a "limited 

portion" of a lifespan) neutralize any potential for tiering or otherwise limiting testing (See 

LANXESS’s General Comments at Section III). LANXESS is concerned that EPA is effectively 

eliminating tiering of data requirements for antimicrobials without any rationale. There is clearly 

identified tiering for conventional pesticides,[FN1: 40 CFR 158.510.] and biochemical 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 630 

pesticides.[FN2: 40 CFR 158.2050.] The Proposal should be revised to incorporate meaningful 

tiering for antimicrobial pesticides. LANXESS’s suggested approach for doing so is set forth below. 

Response: see responses 80.16 and 80.59 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27286 

Comment Code: 89110 

Comment: LANXESS supports tiering data requirements on the basis of exposure and risk, as it 

has been demonstrated to be scientifically valid and is a critical component of any integrative 

approach to testing. The concept of a threshold for toxicological effects is well established 

scientifically. This is a very different approach than assigning exposures based upon a particular 

concentration in food. 

Response: see response 80.59 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27350 

Comment Code: 89110 

Other EPA Comment Codes and Descriptions: 89111 High exposure uses (including: food and 

drinking water; outdoor aquatic uses; indirect food uses with residues equal to or greater than 200 

parts per billion (ppb); wood preservatives; metalworking fluids; swimming pools) 

Comment: A. Alternative Proposal 1 

LANXESS’s first proposal is comprised of three tiers and incorporates many of the 

recommendations in the ACSA proposal. The proposal has scientifically appropriate studies without 

redundancy and emphasizes evaluation of toxicological endpoints with greater efficiency, fewer 

animals, and better use of resources. While the ACSA proposal was developed with conventional 

chemicals and broad-scale applications to food crops, and the environment in mind, the same 

principles are applicable to antimicrobial pesticides. 

Under LANXESS’s proposed alternative toxicology testing regulation, Tier I is the base set of 

testing that would be conducted for all antimicrobial pesticides. The studies in Tiers II and III would 

be required based on the results from the testing in Tier I and the margin of exposure for a 

particular use. When the margin of exposure is large, e.g. greater than 1000, Tier II and Tier III 

studies may be unnecessary. This tiered approach requires expert scientific judgment. Informed 

decisions must be made regarding the interpretation of the Tier I studies and whether to pursue tests 

in Tier II and Tier III. 

This tiered approach is designed to 1) provide information that can be applied to a range of relevant 

human exposure situations; 2) characterize effects that have the potential to damage human health at 

exposure levels approximating those that might be encountered in the use of antimicrobial 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 631 

compounds; 3) avoid high doses that cause unnecessary public concern, for example, safety 

assessments should focus on doses that are relevant to realistic human exposures while maintaining 

adequate power for the experimental studies to detect toxicity; 4) use the minimum number of 

animals necessary to produce a thorough safety assessment for antimicrobial pesticides; 5) minimize 

excessive and unnecessary use of resources by regulatory authorities and industry which could be 

used to address other issues of concern; and 6) increase both the efficiency and relevance of the 

current safety assessment process. 

Response: see response 80.72 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27360 

Comment Code: 89110 

Other EPA Comment Codes and Descriptions: 89100 Dermal Penetration studies; 89111 High 

exposure uses (including: food and drinking water; outdoor aquatic uses; indirect food uses with 

residues equal to or greater than 200 parts per billion (ppb); wood preservatives; metalworking 

fluids; swimming pools) 

Comment: 2. Tier II 

Testing would proceed to Tier II if any of the results from studies in Tier I indicate that the risk 

from exposure to the antimicrobial pesticide cannot be adequately characterized. Thus, evaluation of 

the endpoints of systemic toxicity and the impact on life stages will inform the decision to conduct 

additional tests. 

Response: see response 80.72 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27665 

Comment Code: 89110 

Comment: 3. Proposed Regulation # [Section] 158.2230(b) 

Text of the proposed regulation (emphasis added) toxicology data: uses. "The applicant for 

registration must first determine whether the use is a high human exposure use or a low human 

exposure use. If an applicant is not sure if a specific use is a high human exposure or a low human 

exposure use, the applicant should consult the agency." 

The proposed regulations are vague for the following reasons the agency has not adequately stated 

the criteria to determine whether a specific use is a high human exposure or a low human exposure, 

and requires private consultation with the agency. 

Response: see response 3 
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Comments and Response References: 

Toxicology Section (80) Page 632 

Comment Code: 89111 High exposure uses (including: food and drinking water; outdoor aquatic 

uses; indirect food uses with residues equal to or greater than 200 parts per billion (ppb); wood 

preservatives; metalworking fluids; swimming pools) 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26660 

Comment Code: 89111 

Other EPA Comment Codes and Descriptions: 89110 Tiered approach to toxicology studies 

Comment: A. Alternative Proposal 1 

This Panel’s first proposal is comprised of three tiers and incorporates many of the 

recommendations in the ACSA proposal. The proposal has scientifically appropriate studies without 

redundancy and emphasizes evaluation of toxicological endpoints with greater efficiency, fewer 

animals, and better use of resources. While the ACSA proposal was developed with conventional 

chemicals and broad-scale applications to food crops, and the environment in mind, the same 

principles are applicable to antimicrobial pesticides. 

Under the Panel’s proposed alternative toxicology testing regulation, Tier I is the base set of testing 

that would be conducted for all antimicrobial pesticides. The studies in Tiers II and III would be 

required based on the results from the testing in Tier I and the margin of exposure for a particular 

use. When the margin of exposure is large, e.g. greater than 1000, Tier II and Tier III studies may be 

unnecessary. This tiered approach requires expert scientific judgment. Informed decisions must be 

made regarding the interpretation of the Tier I studies and whether to pursue tests in Tier II and 

Tier III. 

This tiered approach is designed to 1) provide information that can be applied to a range of relevant 

human exposure situations; 2) characterize effects that have the potential to damage human health at 

exposure levels approximating those that might be encountered in the use of antimicrobial 

compounds; 3) avoid high doses that cause unnecessary public concern, for example, safety 

assessments should focus on doses that are relevant to realistic human exposures while maintaining 

adequate power for the experimental studies to detect toxicity; 4) use the minimum number of 

animals necessary to produce a thorough safety assessment for antimicrobial pesticides; 5) minimize 

excessive and unnecessary use of resources by regulatory authorities and industry which could be 

used to address other issues of concern; and 6) increase both the efficiency and relevance of the 

current safety assessment process. 

Response: see response 80.72 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26670 

Comment Code: 89111 

Other EPA Comment Codes and Descriptions: 89110 Tiered approach to toxicology studies 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 633 

Comment: 2. Tier II 

Testing would proceed to Tier II if any of the results from studies in Tier I indicate that the risk 

from exposure to the antimicrobial pesticide cannot be adequately characterized. Thus, evaluation of 

the endpoints of systemic toxicity and the impact on life stages will inform the decision to conduct 

additional tests. 

Response: see response 80.72 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27350 

Comment Code: 89111 

Other EPA Comment Codes and Descriptions: 89110 Tiered approach to toxicology studies 

Comment: A. Alternative Proposal 1 

LANXESS’s first proposal is comprised of three tiers and incorporates many of the 

recommendations in the ACSA proposal. The proposal has scientifically appropriate studies without 

redundancy and emphasizes evaluation of toxicological endpoints with greater efficiency, fewer 

animals, and better use of resources. While the ACSA proposal was developed with conventional 

chemicals and broad-scale applications to food crops, and the environment in mind, the same 

principles are applicable to antimicrobial pesticides. 

Under LANXESS’s proposed alternative toxicology testing regulation, Tier I is the base set of 

testing that would be conducted for all antimicrobial pesticides. The studies in Tiers II and III would 

be required based on the results from the testing in Tier I and the margin of exposure for a 

particular use. When the margin of exposure is large, e.g. greater than 1000, Tier II and Tier III 

studies may be unnecessary. This tiered approach requires expert scientific judgment. Informed 

decisions must be made regarding the interpretation of the Tier I studies and whether to pursue tests 

in Tier II and Tier III. 

This tiered approach is designed to 1) provide information that can be applied to a range of relevant 

human exposure situations; 2) characterize effects that have the potential to damage human health at 

exposure levels approximating those that might be encountered in the use of antimicrobial 

compounds; 3) avoid high doses that cause unnecessary public concern, for example, safety 

assessments should focus on doses that are relevant to realistic human exposures while maintaining 

adequate power for the experimental studies to detect toxicity; 4) use the minimum number of 

animals necessary to produce a thorough safety assessment for antimicrobial pesticides; 5) minimize 

excessive and unnecessary use of resources by regulatory authorities and industry which could be 

used to address other issues of concern; and 6) increase both the efficiency and relevance of the 

current safety assessment process. 

Response: see response 80.72 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 634 

Letter ID: 0064 

Comment ID: 27360 

Comment Code: 89111 

Other EPA Comment Codes and Descriptions: 89100 Dermal Penetration studies; 89110 Tiered 

approach to toxicology studies 

Comment: 2. Tier II 

Testing would proceed to Tier II if any of the results from studies in Tier I indicate that the risk 

from exposure to the antimicrobial pesticide cannot be adequately characterized. Thus, evaluation of 

the endpoints of systemic toxicity and the impact on life stages will inform the decision to conduct 

additional tests. 

Response: see response 80.72 

Comment Code: 89120 Toxicology data table (suggested additions, deletions, etc.) 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25592 

Comment Code: 89120 

Comment: Section Number Subpart W 

Title Antimicrobial Pesticide Data Requirements 

Paragraph [Section]158.2230 Toxicology data, (d) Table p. 59433 

Excerpt from Federal Register 870.3250 21/28-Day dermal toxicity CR CR 

870.2500 90-Day dermal toxicity CR CR 

HC Comment The PMRA notes that test notes 12 & 14 stipulate the conditions under which repeatdose dermal studies are required. However, as the studies are listed in the proposed table (i.e. 

conditionally required for both low and high exposure), it gives the appearance that in some cases 

the repeat-dose dermal data element may not need to be addressed. The PMRA seeks the EPA’s 

comment on this, and suggests that the EPA may want to consider listing the 21/28/day study as 

‘required’ to indicate that at a minimum, this data element is required for all uses. 

Response: see response 80.69 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26605 

Comment Code: 89120 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 635 

Comment: In 2007, the Panel proposed to the Agency a framework for capturing the Agency’s past 

guidance on these topics and improving their use and acceptance. The Panel requests that EPA 

complete their review of and implement the recommendations in the Panel’s Framework Document. 

We also recommend that the Agency add a new test note that accepts waiver and bridging principles 

as appropriate methods to satisfy all acute toxicity data requirements. 

Response: see response 80.65 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27305 

Comment Code: 89120 

Comment: In 2007, the ACC Biocide Panel proposed to the Agency a framework for capturing the 

Agency’s past guidance on these topics and improving their use and acceptance. LANXESS requests 

that EPA complete their review of and implement the recommendations in the Panel’s Framework 

Document. We also recommend that the Agency add a new test note that accepts waiver and 

bridging principles as appropriate methods to satisfy all acute toxicity data requirements. 

Response: see response 80.65 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27668 

Comment Code: 89120 

Comment: 5. Proposed Regulation # [Section] 158.2230(e)(10) 

Text of the Proposed Regulation (emphasis added) 

Toxicology data: Test notes. "A 1-year non-rodent study (i.e., 1-year dog study) may be required if 

the Agency finds that a pesticide chemical is highly bioaccumulating and is eliminated slowly. Thus it 

does not achieve steady state or sufficient tissue concentrations to elicit an effect during a 90-day 

study." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria to determine if a pesticide chemical is highly bioaccumulating and eliminated 

slowly. Any guidelines published on this matter would effectively surpass the notice and comment 

rulemaking procedures. 

Response: see response 3 

Comment Code: 89130 Animal safety studies 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 636 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25590 

Comment Code: 89130 

Comment: Section Number VIII. 

Title Toxicology Data Requirements 

Paragraph Q. Companion Animal Safety Paragraph 1, p. 59397 

Excerpt from Federal Register The test note specifies that the study would be triggered if the 

product’s use would result in exposure to domestic animals. 

HC Comment The PMRA seeks clarification regarding whether the term "domestic animals" 

includes livestock, eg. Horses, cattle, etc.? 

Response: see response 80.98 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26651 

Comment Code: 89130 

Comment: H. Comments on Companion Animal Safety Data Requirements 

The proposed toxicology data requirements for antimicrobial pesticides are consistent with those for 

conventional pesticides. However, application of antimicrobials to companion animals likely 

removes those uses from the definition of pesticide, as such uses would be considered as animal 

drugs. The Agency should clarify how this data requirement is relevant to antimicrobials or eliminate 

this requirement. 

Response: see response 80.97 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26980 

Comment Code: 89130 

Comment: 18. Proposed Regulation # [Section] 158.2230(e)(36) 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 637 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "These data may be 

required if the product’s use will result in exposure to domestic animals through, but not limited to, 

direct application." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine when the data is required or not. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27342 

Comment Code: 89130 

Comment: H. Comments on Companion Animal Safety Data Requirements 

The proposed toxicology data requirements for antimicrobial pesticides are consistent with those for 

conventional pesticides. However, application of antimicrobials to companion animals likely 

removes those uses from the definition of pesticide, as such uses would be considered as animal 

drugs. The Agency should clarify how this data requirement is relevant to antimicrobials or eliminate 

this requirement. 

Response: see response 80.97 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27686 

Comment Code: 89130 

Comment: 18. Proposed Regulation # [Section] 158.2230(e)(36) 

Text of the Proposed Regulation (emphasis added) Toxicology data: Test notes. "These data may be 

required if the product’s use will result in exposure to domestic animals through, but not limited to, 

direct application." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine when the data is required or not. 

Response: see response 3 

Comment Code: 89140 Protocols on animal testing and animal testing alternatives 

Commenter Name: Patrick H. Quinn 

Commenter Organization: Innovation and Reform Group (IRG) 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 638 

Letter ID: 0080 

Comment ID: 25494 

Comment Code: 89140 

Comment: The Proposed Rule, itself, does not contain any specific direction or guidance regarding 

EPA’s willingness to consider non-animal alternatives. Instead, the discussion of alternative 

approaches (in vitro, QSAR, SAR) is limited to the "Preamble" to the Proposal and to the EPA 

"White Paper" on QSAR/SAR. 

The Rule, itself, must contain a clear policy statement of EPA’s intent to consider alternative 

approaches. The Rule should also be specific in identifying areas where alternative approaches can 

and should be considered now, and it should clearly identify the OPP internal review process and 

applicability of PRIA review timeframes. 

As presently structured, the Proposed Rule specifically mandates the animal assay(s) required to 

satisfy each toxicological endpoint. IRG strongly encourages OPP to instead describe the endpoint 

in question and the information needed for the EPA’s assessment while not specifying the test 

requirements. Specific testing requirements could then be contained in the Agency’s Test Guidelines, 

which can be changed far more quickly and with fewer process encumberments. 

EPA’s stated goal of encouraging alternative approaches (in vitro methods, computational 

toxicology) will not be realized under the structure of the Proposed Rule. Historical experience 

would indicate that even modest rulemaking changes--which would be required for each test 

modification under the Proposal-- would require 18-24 months and perhaps longer. 

Response: see responses 4, 80.88, 80.83, 80.99, 170.1, and 170.2 

Commenter Name: Rodger Curren 

Commenter Organization: Alternative Testing Working Group (ATWG) 

Letter ID: 0092 

Comment ID: 25509 

Comment Code: 89140 

Comment: Non-Animal Eye Irritation Project 

The ATWG companies, working with the technical assistance of scientists at the Institute for In 

Vitro Sciences (IIVS), have sought to develop a specific non- animal approach that would meet 

OPP’s need to evaluate, categorize and label antimicrobial cleaning products for eye irritation. The 

Group’s goal has been to draw upon a robust set of existing data for these products which include 

both the Draize Rabbit Eye results as well as paired results on products tested with the Bovine 

Corneal Opacity/Permeability (BCOP), EpiOcular(tm), and Cytosensor in vitro assays. 

Recently, OPP senior managers have considered implementing a Pilot Program to gain more 

experience and review more in vitro data from these assays. The Pilot, tentatively scheduled for 

launch in the summer of 2009, will last 18 months and will inform OPP of the readiness of the 

approach using these assays as a full replacement for the Draize Rabbit for these products. 
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Comments and Response References: 

Toxicology Section (80) Page 639 

The ATWG’s experience in undertaking this initiative has been mixed. Despite strong leadership 

support within OPP and the quality of the science underlying the proposal, progress has been slow. 

Our experience leads us to believe that EPA’s final Subpart 158W rule must be structured in a 

manner which anticipates, encourages, and is able to adopt new alternative approaches in toxicology 

envisioned by the NAS Toxicology Testing in the 21st Century: A Vision and Strategy and the 

Agency itself in its own 2009 Strategic Plan for Evaluating the Toxicity of Chemicals. 

Response: see responses 4 and 80.82 

Commenter Name: Rodger Curren 

Commenter Organization: Alternative Testing Working Group (ATWG) 

Letter ID: 0092 

Comment ID: 25512 

Comment Code: 89140 

Comment: The Proposed Rule, itself, does not contain any specific direction or guidance regarding 

EPA’s willingness to consider non-animal alternatives. Instead, the discussion of alternative 

approaches (in vitro, QSAR, SAR) is limited to the "Preamble" to the Proposal and to the EPA 

"White Paper" on QSAR/SAR. 

The Rule, itself, must contain a clear policy statement of EPA’s intent to consider alternative 

approaches. The Rule should also be specific in identifying areas where alternative approaches can 

and should be considered now, and it should clearly identify the OPP internal review process and 

applicability of PRIA review timeframes. 

Since the ATWG’s work has focused on advancing established alternative toxicology methods which 

reduces or eliminates the use of animals, we find it to be critical that OPP design a Subpart 158W 

Rule which properly anticipates and quickly recognizes the toxicological innovations which are 

anticipated over the next 10-20 years. A Final Rule which does not have these characteristics - but 

instead relies on the federal rulemaking process to update each science advancement - will not 

succeed in achieving the NAS/EPA strategic vision for future evaluation of the toxicity of 

chemicals. 

As presently structured, the Proposed Rule specifically mandates the animal assay(s) required to 

satisfy each toxicological endpoint. A preferable approach would be for OPP to describe the 

endpoint in question and the information needed for the EPA assessment while not specifying the 

test requirements. Specific testing requirements could then be contained in the Agency’s Test 

Guidelines, which can be changed far more quickly and with fewer process encumberments. 

EPA’s stated goal of encouraging alternative approaches (in vitro methods, computational 

toxicology) will not be realized under the structure of the Proposed Rule. Historical experience 

would indicate that even modest rulemaking changes - which would be required for each test 

modification under the Proposal - would require 18-24 months and perhaps longer. 

The Final Rule must clearly permit and encourage the incorporation of new approaches without the 

need for rulemaking. Changes in acute toxicology, for example, will come rapidly during the next 5 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 640 

years with OPP needing to update its testing guidelines for eye irritation, skin irritation, and likely 

other endpoints far more quickly than rulemaking would allow. 

Conclusion 

The ATWG looks forward to a successful launch and execution of the Non-Animal Antimicrobial 

Cleaning Product Pilot. The information gained by both OPP and the ATWG will almost certainly 

help inform and accelerate adoption of toxicology alternatives in the years ahead. 

The ATWG’s comments are limited to these recommendations on changes to the Proposal intended 

to integrate alternative and emerging science, and to improve Subpart 158W’s capacity to quickly 

respond to future advances in toxicology. The ATWG salutes the OPP leadership team’s 

commitment to these innovations and to the reduced use of animals, but those goals can only be 

achieved by a substantially altered and more flexible rule. 

Finally, the ATWG fully supports the more comprehensive comments of the ACC Biocides Panel 

on the Proposed Subpart 158W Rule, including the Panel’s suggestion that EPA should re-propose 

the Regulation with the benefit of public comment. This action will avoid hasty adoption of a flawed 

Final Rule while producing a far better antimicrobial data requirements rule consistent with the 

Agency’s 21st Century toxicology strategic plan. 

Response: see responses 2, 4, 80.83, and 80.99 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25661 

Comment Code: 89140 

Comment: Avoiding unnecessary animal testing 

The additional data requirements proposed by EPA-as well as the suggestions of SFE and otherscould result in a considerable increase in the number of animals needed for testing. SFE recognizes 

that animal testing is essential to pesticide registration, but it should not be done when alternative 

methods are available or when adequate data already exist. Therefore, we urge that EPA develop 

procedures to allow it to use high-quality data from other testing of the same chemical when such 

data exist (to avoid redundant testing on the same chemical) and that EPA substitute in vitro or 

non- animal tests to the extent that they are available and validated. We also thank EPA for 

encouraging registrants, whenever possible, to combine tests and assess multiple outcomes in order 

to reduce the number of animals needed. To further the Agency’s ability to avoid redundant testing, 

we suggest that where data in existing studies are comprehensive, registrants be required to submit 

the results of literature searches and provide copies of studies that may fulfill the requirements 

without the need for duplicate testing. 

Response: see responses 4 and 80.82 

Commenter Name: Chris Geiger 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 641 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25673 

Comment Code: 89140 

Comment: To reduce the need for animal testing, we encourage a transition to non-animal or in 

vitro testing as such testing becomes available and validated. 

Response: see responses 4 and 80.82 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25809 

Comment Code: 89140 

Comment: * We appreciate that "OPP recognizes the usefulness of incorporating predictive 

techniques into its hazard and risk assessments, and that for certain chemicals SAR assessments and 

QSAR modeling could potentially form a scientifically-sound basis for hazard and risk assessments 

used for regulatory decisions." 

Response: EPA acknowledges the Humane Society's support for SAR and QSAR approaches for 

assessing hazard and risk. 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25810 

Comment Code: 89140 

Comment: * We welcome OPP’s openness to a streamlined testing paradigm for chemicals of 

potential lower toxicity, i.e., "through use of a screening-level assessment procedure rather than 

multiple tiers of assessments with progressively more data requirements." However, we question 

whether the specifications of the proposed two-exposurecategory approach allow sufficient 

flexibility to achieve the Agency’s stated goal, and therefore favor a return to the three-category 

approach provided for in the 1987 Antimicrobial Toxicology Data Call-In. 

Response: see response 80.68 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25811 

Comment Code: 89140 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 642 

Comment: * We likewise support in principle OPP’s attempt to provide a tiered testing paradigm 

for antimicrobials, but believe that the model outlined in the Proposed Rule could be improved in a 

number of respects. 

Response: no response is needed 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25813 

Comment Code: 89140 

Comment: * We have a number of comments and recommendations germane to the proposed 

toxicological and ecotoxicological data requirements and the testing methods with which they may 

be satisfied. We particularly urge OPP to give careful consideration to alternatives to requiring 

clearly duplicative in vivo testing. More generally, we urge OPP to move away from specifying test 

guidelines and animal species in association with individual data requirements in the interests of 

promoting maximum flexibility and limiting the rate at which provisions within the final rule 

become obsolete. More flexible data requirements may then be supplemented, as appropriate, with 

harmonized Agency guidance on recommended test methods and testing strategies. 

Response: see response 80.83 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25814 

Comment Code: 89140 

Comment: * Test note #3 (i.e., "Not required if test material is corrosive to skin or has pH less 

than 2 or greater than 11.5") should apply without exception to all in vivo data requirements. 

Response: see response 80.76 and testnote 3 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25815 

Comment Code: 89140 

Comment: We have many other comments germane to specific provisions of the Proposed Rule, 

which are provided below in our section-by-section analysis. 

Response: no response is needed 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 643 

Letter ID: 0090 

Comment ID: 25816 

Comment Code: 89140 

Comment: CROSSCUTTING ISSUES 

* Setting data requirements based on realistic estimates of hazard and exposure 

The Proposed Rule states at 59387: "Today’s proposal reflects the Agency’s current needs for risk 

assessment of antimicrobials," and that "subpart W does not differ greatly from the data 

requirements for conventional pesticides promulgated in October 2007." While there is no question 

as to the veracity of the second statement, whether an antimicrobial risk assessment truly requires 

the extensive quantities of data prescribed in this Proposed Rule is questionable. As previously 

noted, a number of the 250+ of the substances subject to this rulemaking on the basis of an 

antimicrobial label claim are also lawfully marketed in the U.S. under different regulatory schemes, 

which bear little resemblance to the data-intense pesticide sector. If, from a scientific and public 

health perspective, the safety of a chemical can be assured according to one regulatory framework 

with a fraction of the data prescribed under the Proposed Rule, how does OPP rationalize this 

significant disparity, and the seemingly excessive nature of its current proposals? We understand that 

a new initiative aimed at developing a threshold of toxicological concern-based approach for the 

evaluation of antimicrobial pesticides is soon to begin under the auspices of the ILSI Research 

Foundation, and trust that OPP will use the findings of this activity to develop and implement more 

appropriate data requirements for antimicrobials. 

Response: see responses 30.3 and 80.3 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25817 

Comment Code: 89140 

Comment: * Codifying endpoint requirements without specifying test methods; development of 

guidance on testing strategies 

Evolution in the field of toxicology is occurring at an unprecedented pace. In the past three years 

alone, leading scientific bodies have issued independent calls for a break from conventional "tickbox" testing in favor of more thoughtful approaches ranging from streamlined, "hypothesis-driven" 

testing strategies (Carmichael et al., 2006) to a fundamental paradigm shift away from the evaluation 

of high-dose, apical effects in whole animals, toward a mechanistic understanding of the source-tooutcome continuum between xenobiotic exposure and adverse health effects in humans (NRC, 

2007). In light of these emerging opportunities, and the ever-increasing number of validated nonanimal testing methods, we urge OPP to grant registrants the maximum degree of flexibility in 

determining how best to fulfill a data requirement by listing endpoint requirements without 

reference to specific test methods, guidelines, or animal species. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 644 

For instance, the data requirement for Primary eye irritation specifies the use of rabbits, despite the 

availability of validated in vitro methods that have been endorsed by ICCVAM as suitable 

replacements to the Draize rabbit test for the classification of ocular corrosives and severe irritants 

(ICCVAM, 2008; see discussion below). Similar specifications are made for the endpoints of acute 

oral and inhalation toxicity, 90-day oral and inhalation toxicity, acute and 90- day neurotoxicity, 

chronic oral toxicity, carcinogenicity, and prenatal developmental toxicity. Proposed Rule at 59433. 

While we acknowledge the clarifying remark at 59387 that OPPTS Test Guidelines "are guidance 

documents, which the applicant is not required to use... but may instead seek to fulfill the data 

requirement by other appropriate means such as alternative test methods, submission of an article 

from open literature, or use of modeling," we are nonetheless concerned that the specification of (in 

most cases) conventional, animal-based test guidelines could be interpreted as a preference on 

OPP’s part for data from such studies at the expense of other approaches, and therefore urge OPP 

to revise the tables of data requirements in the final rule to delete references both to animal species 

as well as test guidelines. 

Response: see response 80.83 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25818 

Comment Code: 89140 

Comment: In lieu of highly prescriptive data tables, we recommend that OPP develop a series of 

non-binding guidance or science-policy documents, as needed, to provide registrants with up-todate information concerning Agency-accepted alternative methods, testing strategies, and best 

practices in general for satisfying data requirements. Recent examples include interpretive guidance 

developed for use in relation to the European Union’s REACH chemicals legislation (ECHA, 2008). 

Response: see response 80.83 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25819 

Comment Code: 89140 

Comment: * Tiered testing strategies & streamlined approach for lower-toxicity substances 

We welcome OPP’s efforts to provide a tiered testing paradigm for antimicrobials, including a 

streamlined approach for chemicals of potential lower toxicity, for which Agency guidance has been 

available for a number of years (OPP, 2002). However, we question whether the specifications of 

the proposed two-category (low/high) exposure paradigm will permit the flexibility necessary to 

achieve the Agency’s stated goal of utilizing "a screening-level assessment procedure rather than 

multiple tiers of assessments with progressively more data requirements." Proposed Rule at 59422. 

Response: see response 80.68 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 645 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25821 

Comment Code: 89140 

Comment: Firstly, relative to the three-exposure-category (low/medium/high) approach provided 

for in the 1987 DCI, the proposed new approach collapses the previous medium/low categories into 

a single, much more animal test-heavy, low-exposure category. Thus, for example, while the former 

approach provided for a stepwise strategy for the assessment of prenatal developmental toxicity, 

with testing in a second species contingent upon the results of tier 1 studies, the Proposed Rule at 

59392 envisions two-species developmental studies as an unconditional requirement for all 

antimicrobials, irrespective of both hazard and exposure considerations. The same can be said of 

proposed ecotoxicity data requirements, for which "the Agency requires a first tier of required data 

for all antimicrobials regardless of the use pattern" (emphasis supplied). Proposed Rule at 59388. 

Response: see response 80.59 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25823 

Comment Code: 89140 

Comment: For these reasons, we strongly favor a return to a three-category exposure model, under 

which empirical exposure data -rather than default assumptions- are used to assign a chemical to its 

relevant exposure band. 

Response: see response 80.68 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25824 

Comment Code: 89140 

Comment: * Moving away from multi-route and multi-species studies 

There are a number of instances in which the Proposed Rule prescribes in vivo testing that is clearly 

duplicative. Examples (without restating the full contents of the test notes) include the following: 

o Acute systemic toxicity testing by three different exposure routes (oral, dermal and inhalation). 

Proposed Rule at 59393, 59433 and 59434. 

o A full acute toxicity "six-pack" for both active ingredients and end-use products. Proposed Rule at 

59433. In addition, "if the end-use product is labeled that the product is to be diluted for use, the 
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Comments and Response References: 

Toxicology Section (80) Page 646 

applicant may also conduct certain studies using the highest diluted concentration (i.e. the lowest 

diluted product) permitted by the labeling. The end-use dilution testing is in addition to the asformulated-for-sale testing and used only for labeling purposes." Proposed Rule at 59434. 

o For wood preservatives, testing of both the active ingredient which is incorporated into the wood 

but also on transformation/degradation products which occur in wood post-treatment. Proposed 

Rule at 59393. 

o 90-day oral toxicity studies in both rodents and non-rodents. Proposed Rule at 59433. 

o 21/28-day dermal and 90-day dermal testing of end-use products. Proposed Rule at 59395. 

o 90-day dermal and 90-day inhalation testing for HVAC&R uses. Proposed Rule at 59395. 

o Prenatal developmental toxicity studies in both rodents and rabbits. Proposed Rule at 59433. 

o Carcinogenicity studies in both rats and mice. Proposed Rule at 59433. 

o Acute avian oral toxicity in both waterfowl and upland game bird species. Proposed Rule at 59437. 

o Avian dietary toxicity in both waterfowl and upland game bird species. Proposed Rule at 59437. 

o Avian reproduction in both waterfowl and upland game bird species. Proposed Rule at 59437. 

o Acute freshwater fish toxicity in both cold and warm water species, possibly for both active 

ingredients and end-use products. Proposed Rule at 59437. 

Such obvious redundancies are not consistent with the Agency’s assurance that it is "committed to 

moving towards a more efficient and refined testing/risk assessment paradigm for antimicrobial 

pesticide chemicals." Proposed Rule at 59421. Moreover, the animal welfare costs associated with 

many of these in vivo studies are very high. 

Response: see responses 80.89, 80.11, 80.73, 80.49, 80.69, 80.75, 80.33, and 80.24 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25825 

Comment Code: 89140 

Comment: Tests for acute systemic toxicity, for example, typically involve dosing animals to the 

point of lethality, while providing only limited data whose main use is to inform classification, 

labeling, and the need for child-resistant packaging (although we question whether this applies 

equally to pesticidal active ingredients, which are not normally available to the general public). 

Proposed Rule at 59392. Consequently, LD/LC50 and related methodologies have been among the 

most widely condemned regulatory tests on ethical grounds (Balls, 2004). It has likewise been 

pointed out that "[t]he test has never been formally validated. The widespread use of the test has 
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Comments and Response References: 

Toxicology Section (80) Page 647 

therefore not been based on a documented good performance, but on the lack of better tests" 

(Ekwall et al., 1998). 

Response: see response 80.89 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25827 

Comment Code: 89140 

Comment: On the specific point of redundancy, we are aware of at least two retrospective analyses 

that have examined the concordance among oral, dermal and inhalation LD/LC50 values and 

associated regulatory classifications for both pesticide active ingredients and industrial chemicals. 

Although scientific manuscripts for these analyses are still in preparation, both have illustrated 

unequivocally that in more than 99 percent of cases, classifications based on oral LD50 data are 

concordant with, or more severe than, dermal classifications (Seidle et al., in preparation; NC3Rs, in 

preparation). This finding suggests that, at least for pure substances, dermal acute systemic data do 

not represent "value added" from a public health perspective, and that this data requirement can 

reasonably be deleted in favor of simple read-across from oral data. Analyses are also under way to 

examine (i) the applicability of these findings to formulated pesticide products, and (ii) the scope for 

increased use of read-across between pesticidal actives and formulation data in lieu of current 

requirements to conduct duplicative six-pack testing of both. 

Response: These analyses were received as references to a letter, dated September 1, 2010. See 

responses 80.91, 80.87, 80.93, 80.101, and 80.102. 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25829 

Comment Code: 89140 

Comment: We specifically question the value of requiring six-pack testing of one or more dilutions 

of an end-use product above and beyond the requisite testing of the product as formulated for sale 

and distribution. Proposed Rule at 59434. Can it ot simply be assumed that the latter represent the 

worst-case scenario, which in any case is normally the basis upon which a labeling decision is made? 

Response: see response 80.11 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25831 

Comment Code: 89140 
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Comments and Response References: 

Toxicology Section (80) Page 648 

Comment: With respect to the proposed requirement of a 90-day oral toxicity study in both rodent 

and non-rodent species for "high exposure" use patterns, we note that the final report of the HESIACSA systemic toxicity technical panel listed only one of these studies as recommended (Doe et al., 

2006). What is OPP’s rationale for failing to take up this specific recommendation by HESI-ACSA? 

We find this clear redundancy to be especially questionable in the case of recognized low-humanexposure use patterns. Proposed Rule at 59395. 

Response: see response 80.49 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25833 

Comment Code: 89140 

Comment: We likewise question the default two-species paradigm proposed for carcinogenicity and 

prenatal developmental toxicity. With respect to the former, EU pesticide regulators and industry 

have reported initial findings of a retrospective analysis of rat and mouse carcinogenicity data for 

195 pesticide actives, which "concluded that in no instance...was the mouse carcinogenicity study 

critical to determining whether the pesticide was safe for authorisation" (Dewhurst et al., 2007). This 

finding is consistent with that of an earlier and smaller analysis reported by Doe et al. (2006), which 

specifically called for elimination of the mouse carcinogenicity study from pesticide data 

requirements, given that "additional information provided by [this] study is of limited value in risk 

assessment." 

Response: see response 80.24 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25834 

Comment Code: 89140 

Comment: With respect to prenatal developmental toxicity, we appreciate OPP’s attention to its 

requirements under FFDCA to consider the special susceptibility/sensitivity of infants and children 

to pesticide chemical residues. Proposed Rule at 59396. Nonetheless, we question the scientific 

necessity and public health value of unconditionally requiring prenatal developmental toxicity data in 

two species for all antimicrobial chemicals, irrespective of actual or anticipated human exposure 

levels and/or relevant toxicological information. On the one hand, it is true that no animal species 

has been shown to be consistently "most sensitive" to developmental insult (Hurtt et al., 2003), and 

therefore negative findings in one species could indeed be "false negative" when applied to humans. 

However, when considered in the context of the wider chemical universe, in which developmental 

toxicity is a relatively low-prevalence effect (Bremer et al., 2007), it follows that the likelihood of 

obtaining a false negative result is equally low. On the other hand, routine testing in a second species 

can inflate the rate of false positive findings as high as 40 percent, which severely detracts from the 

specificity of a testing strategy (Bremer et al., 2007). With this in mind, we remind OPP of HESIACSA’s conclusion that a stand-alone rat developmental toxicity study could generally be waived if 
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Comments and Response References: 

Toxicology Section (80) Page 649 

the results of a rat reproduction study and rabbit developmental toxicity study were both negative 

(Cooper et al., 2006). At the very least, testing in a second species should be contemplated only 

when results from the first species are negative, and even then, in full consideration of the weightof-evidence among all relevant toxicological data, including read-across from related substances. 

Response: see response 80.33 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25836 

Comment Code: 89140 

Comment: * Use of (Q)SAR 

We appreciate that "OPP recognizes the usefulness of incorporating predictive techniques into its 

hazard and risk assessments, and that for certain chemicals SAR assessments and QSAR modeling 

could potentially form a scientifically-sound basis for hazard and risk assessments used for 

regulatory decisions." Proposed Rule at 59422. However, we are also mindful that OPP currently 

does not accept certain validated and internationally recognized alternative approaches as standalone alternatives for regulatory hazard and risk assessment (e.g., OECD TG 428 for dermal 

penetration), even though these methods have achieved a level of scientific and international 

regulatory acceptance well beyond that of most (Q)SAR models - and in the case of OECD Test 

Guidelines, in spite of U.S. obligations in relation to the OECD Council Decision regarding the 

Mutual Acceptance of Data (OECD, 1981). Thus, we will look to OPP’s actions in the coming years 

for proof of its commitment to transitioning to 21st century technologies in its regulatory programs. 

Response: see response 4 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25837 

Comment Code: 89140 

Comment: * Process for updating data requirements 

We strongly support OPP’s stated intention to undertake "mini rulemakings" approximately every 5 

years to ensure that §158 requirements remain up-to-date with the ever-evolving science-policy 

landscape in toxicology. 

Response: EPA acknowledges the Humane Society's support for routine updating of the data 

requirements. 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 
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Comments and Response References: 

Toxicology Section (80) Page 650 

Comment ID: 25838 

Comment Code: 89140 

Comment: ENDPOINT-SPECIFIC ISSUE 

* Acute systemic toxicity 

As previously noted, two retrospective data analyses -comprising nearly 1,900 substances, including 

227 pesticides, tested for acute systemic toxicity via both oral and dermal routes- have found dermal 

classifications to be concordant with or less severe than oral classifications in over 99% of cases. On 

the basis of these findings, which will be provided to OPP as soon as they are published, we 

recommend that the requirement for dermal acute systemic data be deleted in favor of simple readacross from oral data. This approach is considered to be applicable at least to active ingredients, and 

most likely to formulations as well, being that antimicrobial products do not normally contain 

penetration enhancers or other ingredients that would be expected to alter the findings of these 

analyses. 

We further recommend that OPP eliminate any reference to the testing of one or more dilutions of 

an end-use product, and indeed, actively discourage this practice. Being that labeling decisions are 

normally made on the basis of a worst-case-scenario, we see no public health value in the conduct of 

duplicative testing of an end-use product beyond the requisite testing of the product as formulated 

for sale and distribution. 

Response: These analyses were received as references to a letter, dated September 1, 2010. See 

responses 80.91, 80.87, 80.93, 80.101, and 80.102. 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25839 

Comment Code: 89140 

Comment: * Acute dermal irritation 

In 2007/8, European validation authorities endorsed the EpiDerm, EpiSkin and SkinEthic 

reconstructed human epidermal models as being "reliable and relevant stand-alone tests for 

predicting rabbit skin irritation" according to the EU’s classification system.[FN1: Dangerous 

Substances Directive 67/548, whose cut-off criteria for a skin "irritant" cover the whole of GHS 

Category 2 and a portion of Category 3. The DSD scheme will be replaced in 2015 by the new 

Regulation (EC) No 1272/2008 on classification, labeling and packaging (CLP), which is illustrated 

above for comparison.] In February 2009, these tests achieved regulatory acceptance as an official 

European Union test guideline; an OECD Test Guideline has been prepared and is pending 

adoption. 

Because these methods were validated according to the EU’s two-category (irritant/nolabel) 

classification system, these in vitro methods are not entirely compatible with the UN Globally 

Harmonized System and its three- category (irritant/mild irritant/no-label) approach 
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Comments and Response References: 

Toxicology Section (80) Page 651 

[Figure 1: Comparison of EU's two-category classification system with the UN Globally 

Harmonized System - see p. 10 of PDF docket ID EPA-HQ-EPA-2008-0110-0090] 

(see figure above). That is, while the in vitro methods have been shown to reliably identify 

substances falling into GHS Category 2 (irritant), the 2007/8 validation studies did not examine their 

ability to classify substances in the optional GHS Category 3 (mild irritants). Thus, depending on 

country or regional regulatory requirements, as well as registrants’ willingness to accept a certain 

amount of over-labeling, substances or formulations with a Draize irritancy score of <2.3 may be 

classified either as Category 3 (mild irritants) or no- label. For instance, the new EU CLP regulation 

recognizes the oversensitivity and high false positive rate associated with the Draize rabbit test 

(Basketter et al., 2004), and therefore regards a Draize score of 2.3 as being the lower boundary of 

biological relevance for skin irritancy in humans. In an effort to promote broad international 

acceptance of human skin models as full replacements, the creators of EpiDerm have undertaken 

additional studies to evaluate the test’s ability to discriminate between GHS sub-categories - with 

promising results (Hayden et al., 2009). 

* Acute ocular irritation 

As previously discussed, ICCVAM (2007) has endorsed the validity and regulatory applicability of 

two in vitro methods -the Bovine Corneal Opacity and Permeability (BCOP) and Isolated Chicken 

Eye (ICE) tests- for the classification of ocular corrosives and severe eye irritants. More recently, 

internationally harmonized test guidelines for these two methods have been provisionally adopted by 

the OECD, and should be published before the end of 2009. Accordingly, the specification in 

[section]158W data tables that rabbits be used to evaluate eye irritation should be deleted, and a test 

note added to prescribe the use of a tiered testing strategy for eye irritation beginning with available 

in vitro methods. Additionally, we urge OPP to move expeditiously forward with a pilot labeling 

program for antimicrobial cleaning products that has been under development for many years now 

(Curren, 2008). 

* Dermal sensitization 

Classical tests for skin sensitization (i.e., the Guinea Pig Maximization and Buehler tests) consume at 

least 30 guinea pigs and involve multiple, stressful injections. In contrast, the mouse Local Lymph 

Node Assay (LLNA) reduces animal use to 16 per test, and is significantly less invasive. The 

developers of the LLNA have undertaken a retrospective analysis of published data and concluded 

that within the context of a tiered testing strategy, a limit dose version of the LLNA -using only a 

negative control group and the equivalent of the high- dose group from the conventional LLNA- is 

sufficient to distinguish between sensitizers and non-sensitizers. These data and conclusions were 

independently peer reviewed and endorsed by validation authorities in Europe and the US. 

According to ICCVAM (2008): "Based on this analysis, the LLNA limit dose procedure correctly 

identified all 153 non- sensitizers (specificity of 100%) and correctly identified 308 of 313 sensitizers 

(sensitivity of 98.4%)." On the basis of these findings, we urge OPP to add a test note to the 

[section]158W data tables recommending the use of a limit dose LLNA in cases where a full risk 

assessment is deemed not to be necessary. 

* Dermal penetration 
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Comments and Response References: 

Toxicology Section (80) Page 652 

We have been advised by OPP that, despite the availability of a valid and internationally accepted 

non-animal method for the evaluation of dermal penetration is currently available (i.e., OECD TG 

428) and the requirements of OECD Mutual Acceptance of Data (OECD, 1981), the Agency does 

not currently accept this study as a stand-alone -instead requiring the conduct of several duplicative 

studies (i.e. rodent in vivo, rodent in vitro, and human in vitro) to arrive at a more refined estimate 

of in vivo dermal penetration in humans. We question the appropriateness (and legality, vis-à-vis 

OECD MAD) of this position, and strongly urge OPP to join other OECD countries in accepting 

data from this test as stand-alone for the evaluation of dermal absorption, and to make this position 

clear to registrants in the final [section]158W Rule. 

Additionally, given OPP’s stated concerns regarding the potential for dermal exposure in relation to 

antimicrobial use patterns (Proposed Rule at 59395), we recommend making in vitro dermal 

absorption a Tier 1 data requirement, as alluded to by HESI-ACSA (Barton et al., 2006). Such an 

approach would not only ensure appropriate use of an available animal replacement method, but 

evidence of marginal penetration in vitro could provide a scientific basis for waiving in vivo 21-, 28- 

and/or 90-day systemic studies via the dermal route (Stoick et al., 2006). 

Response: see responses 80.56, 80.91, 80.88, 80.93, and 80.95 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25841 

Comment Code: 89140 

Comment: * 90-day Toxicity 

For the reasons previously discussed, we urge OPP to discontinue requiring routine testing in both 

rodent and non-rodent species and, ideally, to settle on one or the other for subchronic testing. 

Additionally, provided the Agency accepts our preceding recommendations concerning in vitro 

dermal penetration, we recommend adding a test note specifying that the results of an in vitro 

dermal penetration study may assist in determining the necessity of subacute and/or subchronic 

dermal studies. 

While recognizing the value of a subchronic range-finding study in advance of a chronic test, we 

question the need for such a study in mice (Proposed Rule at 59395) in light of the highly dubious 

value of the mouse carcinogenicity bioassay, and therefore recommend that the Final Rule not 

recommend or encourage the conduct of such a study in mice. 

Response: see responses 80.49, 80.20, and 80.24 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25843 

Comment Code: 89140 
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Comments and Response References: 

Toxicology Section (80) Page 653 

Comment: * Reproductive toxicity 

In the past several years, a number of publications have called into question the value of routine 

production of a second generation for the evaluation of reproductive toxicity (Janer et al., 2007; 

Reaves et al., 2008; PMRA, in preparation). These analyses were driven by a proposal by HESIACSA for the replacement of the conventional two-generation study with an "extended onegeneration" study (Cooper et al., 2006). The ACSA design provides for the subdivision of F1 

offspring into up to three "cohorts" for the evaluation of (i) reproduction and fertility, (ii) 

developmental neurotoxicity, and/or (iii) developmental immunotoxicity. Evaluation of these 

endpoints in a single study could reduce animal use by up to 70% relative to the conduct of three 

stand- alone studies. Given that this methodology has been subject to extensive scientific discussion 

and peer review, and an OECD Test Guideline is currently in preparation, we urge OPP to revise 

[section]158W data tables, as well as test notes 26-29, to reflect the preferential use of a flexible, 

extended one- generation model in lieu of the two-generation study. 

Additionally, for low-exposure substances, it may be appropriate to waive a generational study if 

positive effects in male animals (i.e., testes histopathology and/or sperm parameters) are noted in a 

90-day study, given that these are often more sensitive than parameters in generational studies 

(Mangelsdorf et al., 2003). 

Response: see response 80.34 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25845 

Comment Code: 89140 

Comment: * Prenatal developmental toxicity 

For the reasons previously discussed, we urge OPP to move away from requiring routine testing in 

both rodent and non-rodent species as an unconditional requirement for developmental toxicity. 

While we appreciate the Agency’s efforts to "encourage applicants for registration to consider the 

use of combined study protocols" whereby "a prenatal developmental toxicity study segment could 

be added to a two-generation reproduction study in rodents" (Proposed Rule at 59396), we also 

recognize the many logistical barriers that are likely to limit such an approach in practice (e.g., feed 

vs. oral gavage exposure routes in the different guidelines, the impact of exposure methods on 

Cmax, whether the high dose needed for the prenatal development module would be appropriate for 

other modules, the feasibility of a staggered start in a multi-module design in order to handle 1,200 

caesarean sections, etc.; ECETOC-ECVAM, 2008). We also remind the Agency of HESI-ACSA’s 

conclusion that a stand-alone rat developmental toxicity study could generally be waived if the 

results of a rat reproduction study and rabbit developmental toxicity study were both negative 

(Cooper et al., 2006). Furthermore, routine testing in a second species can inflate the rate of false 

positive findings as high as 40 percent, which severely detracts from the specificity of a testing 

strategy (Bremer et al., 2007). At the very least, testing in a second species should be contemplated 

only when results from the first species are negative, and even then, in full consideration of the 
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Comments and Response References: 

Toxicology Section (80) Page 654 

weight- of-evidence among all relevant toxicological data, including read-across from related 

substances. 

Response: see response 80.33 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25848 

Comment Code: 89140 

Comment: * Developmental neurotoxicity 

We appreciate OPP’s efforts to make developmental neurotoxicity testing a higher-tier data 

requirement, but note that to do so would almost invariably lead to the conduct of a standalone 

study, whereas evaluation of neurodevelopmental endpoints in the context of an extended onegeneration reproduction study would allow for a reduction of both costs and animal use. Although 

we still question the public health value of routine DNT testing, we believe it would be preferable 

for registrants to examine DNT parameters earlier -as part of a combination study- rather than later. 

We also recommend revising test note 29 to refer to an extended one- generation vs. two-generation 

reproduction study. 

Response: see responses 80.34 and 80.50, and testnote 80.29 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25849 

Comment Code: 89140 

Comment: * Immunotoxicity 

Would it be feasible to add a test note specifying that the required parameters for an adult 

immunotoxicity study may (or ideally should) also be incorporated into a 90-day feeding study in lieu 

of conducting a stand-alone immunotoxicity study? Alternatively, if an extended one-generation 

design -including an immunotoxicity Cohort 3- is used to evaluate reproductive toxicity, the 

requirement for an adult immunotoxicity study should be waived on the basis of comparable data 

from an arguably more sensitive exposure scenario? 

Response: see response 80.52 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25851 

Comment Code: 89140 
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Comments and Response References: 

Toxicology Section (80) Page 655 

Comment: * Genotoxicity 

In the pharmaceutical sector, it is becoming increasingly common to incorporate micronucleus 

assays into subacute or subchronic general toxicity studies in rats as a means of efficiently gathering 

mutagenicity data without a stand-alone in vivo study in mice. According to this approach, 

micronucleus induction is determined through collection of peripheral blood at several time- points 

throughout a study, as well as from bone marrow collection at termination (Hamada et al., 2001; 

2003). We invite OPP to explore the feasibility of this approach for pesticide hazard assessment, and 

if appropriate, add a test note encouraging registrants to avail themselves of this option for satisfying 

the in vivo cytogenetics data requirement. 

Response: see response 80.44 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25852 

Comment Code: 89140 

Comment: * Chronic toxicity & carcinogenicity 

We appreciate that OPP has removed the 1-year dog study from its testing requirements for chronic 

toxicity and strongly urge the Agency to take similar action in relation to the mouse carcinogenicity 

study. We further recommend test note #19 be amended to more strongly encourage the use of a 

combined chronic toxicity/carcinogenicity study design, and that test notes #20 and 21 be revised 

by deleting sub-point (i) in both. 

Response: see response 80.24, and testnotes 80.19, 80.20, and 80.21 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25854 

Comment Code: 89140 

Comment: * Avian and fish studies 

As previously noted, we urge OPP to discontinue requiring routine testing in more than one avian 

and fish species. Additionally, we strongly challenge the proposed requirement of lethality studies in 

birds and fish to support indoor uses of antimicrobials. 

Response: see response 80.96 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25856 
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Comments and Response References: 

Toxicology Section (80) Page 656 

Comment Code: 89140 

Comment: CONCLUSIONS 

We appreciate the opportunity to provide comments on the Proposed Rule. As stated above, we feel 

there are significant issues that must be fully addressed before the Proposed Rule can be finalized. 

Response: no response is needed 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25925 

Comment Code: 89140 

Comment: * We would like for the Agency to incorporate and provide guidance on how to apply 

ongoing efforts involving the use of Thresholds of Toxicological Concern (TIC), (Q)SAR, and other 

validated in vitro alternatives to animal testing. 

Response: see responses 80.3, 80.88, 170.1, and 170.2 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25965 

Comment Code: 89140 

Comment: Registrants should be encouraged to use non-animal or in-silico means of testing to 

meet the data requirements. This would allow the use of models or other computational approaches 

such as that contemplated by the Agency's ToxCast program as a means to support regulatory 

requirements. Not only does this provide a relatively inexpensive way to provide data but it also 

avoids the unnecessary use of test animals which is a sensitive topic for many Non- Government 

Organizations (NGO 's). Clearly, Agency programs such as EPIWeb 4.0 or ECOSAR should be 

acceptable as a means to address preliminary environmental concerns. These programs are utilized 

by the Office of Pesticide Programs and Toxic Substances; therefore, why can't they be used here? 

Finally, the use of alternative means to address the data requirements are elaborated within the 

Agency's own document, entitled, 'The U. S. Environmental Protection Agency's Strategic Plan for 

Evaluating the Toxicity of Chemicals" EPA 100/K-09/001. From this document it is clear that the 

Agency is moving towards the goal of utilizing toxicity pathways and other alternative means to 

assess chemical toxicity with the only drawback being a level of confidence in the current state of 

science for use in regulatory decision making. Until such time as current research programs such as 

ToxCast have been finalized, we would hope the Agency will utilize an interim approach in 

regulatory data development. That is, there must be a medium between straight forward animal 

testing and the use of alternative methods such as models to satisfy regulatory concerns. We hope 

the Agency will use elements of its "Strategic Plan" as they review and implement the revised Part 

158 for antimicrobials. 
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Comments and Response References: 

Toxicology Section (80) Page 657 

Response: see response 4 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26163 

Comment Code: 89140 

Comment: Human Safety: 

P&G’s Policy on Animal Research and Testing Research involving animals is a last resort at P&G. It 

is only considered once every other reasonable alternative has been explored. The vast majority of 

P&G tests do not use animals. Whenever possible, P&G uses in vitro and ex vivo alternatives, 

computer models, weight of evidence analysis and published scientific literature in product safety 

evaluations. P&G tests its products on animals only when required to do so by Federal law or 

regulation such as FIFRA. Even under those constraints, P&G has offered non-animal options to 

regulators for consideration when Federal or State laws indicate an animal model. 

P&G has invested over $200M in the development and validation of alternative methods. P&G 

actively collaborates with government institutions, academia, and animal welfare organizations to 

advance the development of alternative methods based upon the refinement, reduction, and 

replacement of animal testing. The Non-Animal Approach to Eye Irritation Testing for 

Antimicrobial Cleaning Products developed with our industry colleagues in the Alternative Testing 

Working Group (ATWG) is one example of these efforts. 

P&G applauds the decision by the OPP leadership team to move forward with launching a Pilot 

Program based upon the ATWG approach in the near future. Fully 95% of P&G’s cleaning 

products sold in the U.S. are non-FIFRA, and eye safety for all of these products is effectively 

determined by in vitro and ex vivo methods. We look forward to continuing our work with OPP on 

the Non- Animal Eye Irritation Pilot and similar replacement opportunities in the future. 

Response: see response 80.82 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26167 

Comment Code: 89140 

Comment: Recommendations for Alternative Methods These alternatives may include the use of 

OECD in bridging, waivers, and in vitro assays. The use of SAR (QSAR) methods is recommended 

to allow bridging in the absence of the data and there is precedence of the use of this approach 

within the Agency (e.g. the use of a single compound in ADBAC and DDAC clusters of quaternary 

ammonium compounds to represent the entire clusters). For end- product formulations, P&G 

recommends that formulations similar in composition be allowed to bridge to existing registered 

formulations where data exist. The use of waivers is recommended for studies that would not be 

necessary based on physical characteristics (e.g. an oral or dermal penetration study not being 
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Comments and Response References: 

Toxicology Section (80) Page 658 

required for a gas or a volatile liquid, an inhalation study for a nonvolatile chemical, or a corrosive 

material in a dermal sensitization study). P&G urges the Agency to incorporate the in vitro eye 

irritation battery, which industry has worked closely with the OPP Non- Animal Eye Irritation Pilot 

planning team, and begin accepting these non- animal submissions immediately. The increased use 

of bridging, study waivers, and in vitro alternatives can significantly reduce the number of toxicity 

studies that are needed to support antimicrobial registrations. Unnecessary toxicity testing negatively 

impacts animal welfare and imposes additional resource burdens on both the registrants and the 

Agency. 

Response: see responses 80.65, 80.82, 170.1 and 170.2 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26171 

Comment Code: 89140 

Comment: There may also be instances where it may not be possible to test the formulated product 

in a humane manner. For example, in the dermal toxicity test, corrosive materials can cause 

significant skin injury during the 24 hours of exposure required by the study. While the study can be 

waived, in the absence of data, the Agency will classify the product in Toxicity Category I, require 

skull and crossbones and mandate the statement "Fatal if absorbed through skin." For corrosive 

materials, with no significant systemic toxicity, this approach can result in inaccurate labeling. In 

these instances it can be desirable to dilute the product to reduce the amount of irritation while 

maintaining the same overall dose of the test material. For example, the test product could be 

diluted by 50% and dosed at 10 g/kg vs. 5 g/kg. In some cases, this approach can allow the study to 

go forward while reducing unnecessary stress to the test animals. P&G recommends that the 

proposal be revised to give this flexibility for use-dilution testing. 

Response: see response 80.4 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26184 

Comment Code: 89140 

Comment: The proposed rule does not take into consideration scientific advances in the area of 

dermal penetration. The Agency is requiring animal dermal penetration studies when there are well 

established OECD guidelines for in vitro dermal penetration studies available.[FN#4: OECD 

Guideline 428] This is not consistent with the Agency’s desire to move to alternative toxicology 

testing. P&G urges the Agency to accept in vitro skin penetration data. The in vitro dermal 

penetration method is the preferred and accepted testing method in most other OECD member 

counties and should be the study of choice to fulfill the data requirement. The proposed rule also 

states the Agency is looking to incorporate (Q)SAR approaches to help make regulatory decisions. 

Many predictive computational models (e.g. based on molecular structure; based on molecular 

weight and octanol/water partition coefficient) have been developed to assess dermal 
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Comments and Response References: 

Toxicology Section (80) Page 659 

absorption/penetration that should be considered in fulfilling data requirements. Furthermore, 

dermal penetration can be estimated/predicted using science-based approaches such as comparing 

LOAELs from repeat-dose oral and dermal studies to derive an approximate dermal penetration. 

The Agency should not require the use of animals for dermal absorption, but should incorporate the 

best science in moving toward a strategic change in its approach to addressing how anti-microbial 

actives are evaluated. These data 1) are scientifically adequate, and in many cases, superior to in vivo 

studies; 2) would harmonize EPA requirements with those in the EU and elsewhere; and 3) reduces 

the unnecessary use of live animals. 

Response: see responses 4, 80.86, and 80.56 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26199 

Comment Code: 89140 

Comment: Incorporation of the Use of Animal Alternatives to Address Data Requirements: The 

Agency has identified its commitment to moving towards a more efficient and refined approach to 

risk assessment and risk management which is to include the use of animal alternatives. In the 

preamble to the Proposal for antimicrobials, the following language is found: "EPA is committed to 

moving towards alternative testing paradigms that are more efficient, reduce the use of animal 

testing, take full advantage of advances in science, and provide a sufficient credible amount of data 

for use in a risk assessment that will support a risk management decision." However, the proposal 

fails to incorporate the use of animal alternatives. P&G strongly recommends that the proposal be 

rewritten and guidelines be developed to encourage new science and approaches in meeting the data 

requirements for antimicrobial pesticides, such as structure activity relationship analyses, in vitro 

approaches, or computational toxicology. The regulations should explicitly allow the use of these 

and other new methods and approaches. 

As highlighted earlier, P&G further recommends that the Agency expand its efforts to adopt 

alternative approaches to addressing data requirements such as a threshold-type of approach (e.g. 

TTC). The ACC Biocides Panel has initiated a cooperative project through ILSI-Research 

Foundation to consider whether alternative approaches to risk assessment using a threshold- type 

approach may be appropriate for assessment of some antimicrobials. This type of approach is used 

within other regulatory bodies, e.g. FDA’s Threshold of Regulation. This approach would lead to a 

significant reduction in animal usage, reduce the financial burden of the registrants, and free up 

resources for both the registrants and the Agency. 

Response: see responses 4, 80.3, 170.1 and 170.2 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26231 

Comment Code: 89140 
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Comments and Response References: 

Toxicology Section (80) Page 660 

Comment: 10) The use of validated alternative testing methods, SAR/QSAR, open literature 

citations, and other means to satisfy data requirements should be embraced by the Agency. Likewise, 

the term "weight-of-evidence" as used in the EPA proposal is conceptually good, but lacks 

specificity. P&G supports the use of such non- animal methodologies when possible. Data should 

not be required unless their use to assess the substance tested is clear and scientifically justified. 

Response: see responses 4, 80.3, 80.81, 170.1, and 170.2 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26610 

Comment Code: 89140 

Comment: While the data requirements in the Proposal should not specifically identify study 

protocols or methodology, P&G would recommend citing the Agency’s recommendation to 

consider alternate non- animal methods in the regulations, not just the preamble of the Proposal. 

This is consistent with the approach recommended by National Research Council (2006) Toxicity 

Testing for Assessment of Environmental Agents. (national Academies Press, Washington D.C.) 

"The committee cautions against adding testing requirements only for the sake of theoretical 

thoroughness, because such an approach could result in substantial waste of animals and resources" 

(p. 8) 

"That it is important to recognize that ‘toxicity testing for regulatory purposes should be conducted 

primarily to serve the needs of risk management." (p. 12) 

"[T]iered testing approaches should be designed to expedite regulatory decisions and to discourage 

toxicity testing that is not used to address regulatory questions." (p. 13) 

Response: see responses 4, 80.88, and 80.83 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26658 

Comment Code: 89140 

Other EPA Comment Codes and Descriptions: 80000 Toxicology 

Comment: K. Overall Comments 

As proposed, the toxicology data requirements for antimicrobial pesticides raise many issues and are 

too vague to permit a registrant to determine the kinds of data and information necessary. (See 

Panel’s General Comments at Section I.) The Panel urges EPA to repropose these requirements 

based upon these comments and other input received during the process. 

Response: see responses 2 and 3 
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Comments and Response References: 

Toxicology Section (80) Page 661 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27027 

Comment Code: 89140 

Comment: [The following are some of the problems identified in the proposed rule:] 

10) The use of validated alternative testing methods, SAR/QSAR, open literature citations, and 

other means to satisfy data requirements should be embraced by the Agency. Likewise, the term 

"weight-of-evidence" as used in the EPA proposal is conceptually good, but lacks clarity and 

specificity. Data should not be required unless their use to assess the substance tested is clear and 

scientifically justified. 

Response: see responses 4, 80.3, 80.81, 170.1, and 170.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27537 

Comment Code: 89140 

Comment: 10) The use of validated alternative testing methods, SAR/QSAR, open literature 

citations, and other means to satisfy data requirements should be embraced by the Agency. Likewise, 

the term "weight-of-evidence" as used in the EPA proposal is conceptually good, but lacks clarity 

and specificity. Data should not be required unless their use to assess the substance tested is clear 

and scientifically justified. 

Response: see responses 4 and 80.81 

Commenter Name: Kristie Sullivan 

Commenter Organization: PCRM; HSA; and PETA 

Letter ID: 0104 

Comment ID: 31556 

Comment Code: 89140 

Comment: September 1, 2010 Regulatory Public Docket (7502P) Office of Pesticide Programs 

Environmental Protection Agency 1200 Pennsylvania Ave. N.W. Washington, DC 20460-0001 

RE: Proposed revisions to U.S. pesticide data requirements for antimicrobial chemicals, 73 Fed. Reg. 

59382 (October 8, 2008), Docket ID # EPA-HQ- OPP-2008-0110 

To Whom it May Concern: 

This letter is submitted on behalf of the Physicians Committee for Responsible Medicine, Humane 

Society International, and the People for the Ethical Treatment of Animals. The intent of this letter 

is to call the Agency’s attention to developments in toxicological testing methods that have occurred 
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Comments and Response References: 

Toxicology Section (80) Page 662 

since our original comments on this proposed rule, submitted April 6, 2009. While we understand 

the Agency is not required to consider late comments, we hope that they are received in the spirit in 

which they are intended: ensuring that the Agency publishes a final rule that is as up-to-date as 

possible and that every opportunity is taken to reduce the use of animals in product registration. 

Skin Irritation 

As the Agency is aware, the OECD has adopted a test guideline for in vitro skin irritation testing, 

TG 439: In Vitro Skin Irritation: Reconstructed Human Epidermis (RhE) Test Method, which 

allows the use of three validated methods (SkinEthic RHE, Episkin, and EpiDerm), or other 

methods that can meet the stated performance standards, to assess skin irritation potential.[FN1: 

OECD Test Guideline 439: In Vitro Skin Irritation: Reconstructed Human Epidermis (RhE) Test 

Method. Available at http://puck.sourceoecd.org/vl=3875911/cl=41/nw=1/rpsv/cgibin/ 

fulltextew.pl?prpsv=/ij/oecdjournals/1607310x/v1n4/s59/p1.idx. Accessed 27 August 2010.] 

These methods can be combined with a number of protocols for measuring skin corrosion in vitro 

to completely replace the rabbit Draize skin irritation test in most circumstances, and their approval 

is truly a breakthrough moment for the international regulatory community. 

These methods have been validated to comply with the Globally Harmonized System (GHS) of 

labeling, which is accepted internationally. We are aware that the Office of Pesticide Programs 

(OPP) is currently exploring the adoption of GHS labeling, and encourage the Agency to reach a 

solution that would accommodate the use of in vitro skin corrosion and irritation test methods as 

full replacements for new antimicrobial registrations. 

Eye Irritation 

The Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) 

recommended two ex vivo methods, the Bovine Corneal Opacity and Permeability (BCOP) and the 

Isolated Chicken Eye (ICE) test methods, to classify substances for severe eye irritation, in 2008. 

These methods were also recommended for use by the European Committee for the Validation of 

Alternative Methods (ECVAM) Science Advisory Council (ESAC), in 2007, and an OECD test 

guideline was published in 2009. 

Furthermore, in July 2009 the ESAC endorsed the use of a combined "bottom up" and "top down" 

approach to classify, by process of elimination, substances into a threetiered classification system [i.e. 

not irritating (EPA Category IV), irritating, or severely irritating (EPA Category IV)], using the the 

BCOP, the ICE, the Cytosensor Microphysiometer, or the Fluorescein Leakage tests.[FN2: ESAC. 

Statement on the Scientific Validity of Cytotoxicity/Cell-function Based In vitro Assays for Eye 

Irritation Testing. 10 July 2009. Available at http://ecvam.jrc.ec.europa.eu. Accessed 2 July 2010. ] 

Though this strategy is not recommended for all substances it should be considered before 

commencing the rabbit test. 

In fact these methods (BCOP, ICE, and CM) are utilized in a pilot labeling program for 

antimicrobial cleaning products announced by the EPA in June of 2009.[FN3: 

http://www.epa.gov/oppfead1/cb/csb_page/updates/2009/eye-study.html] We encourage the 

Agency to take steps to expand this program to other antimicrobial product classes in an expeditious 

manner. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 663 

We again ask the Agency to remove recommendations to conduct the Draize eye test from the Part 

158W data tables and communicate instead the potential for registrants to test for eye irritation using 

new validated methods, as full replacements or screens as appropriate. 

Dermal Sensitization 

In our previous comments, we requested that the Agency consider the LLNA and "limit" LLNA 

protocols for skin sensitization testing of Active Ingredients and End Use 

Products.[FN4:Comments submitted 6 April 2009 by the Humane Society of the United States and 

Humane Society Legislative Fund, and co-signed by PCRM and PETA. Available in Federal Docket 

ID EPA-HQ-OPP- 2008-0110.] Since that time the OECD has accepted this approach in a 

modified protocol, termed "reduced LLNA" (rLLNA). The new approach can be found in revised 

OECD test guideline 429, published earlier this summer.[FN5: OECD No. 429: Skin Sensitisation: 

Local Lymph Node Assay. Available at 

http://puck.sourceoecd.org/vl=3875911/cl=41/nw=1/rpsv/cgibin/ 

fulltextew.pl?prpsv=/ij/oecdjournals/1607310x/v1n4/s29/p1.idx. Accessed 27 August 2010.] We 

urge the Agency to codify these reduction and refinement measures into the new Part 158W 

regulations. 

Dermal Systemic Toxicity 

There are a number of potential ways in which the Agency could modify its across-theboard 

requirement to conduct this test. In follow-up meetings and exchanges with OPP, we provided a 

2007 publication by the UK Pesticide Safety Directorate [FN6: Thomas and Dewhurst 2007. What 

does a dermal acute toxicity study add to the information on a plant protection pesticide? 

Toxicology 231:114-115.] which examined unpublished acute oral and dermal toxicity data for 195 

pesticide active ingredients and 3,111 formulated products, concluding that "the dermal acute 

toxicity study adds little if anything to the database on pesticide active substances" and that a 

"similar result was indicated for formulated products." A 2010 update to this analysis, using a slightly 

expanded data set of 240 pesticide active ingredients tested subject to acute toxicity testing by both 

oral and dermal routes found that in only two cases (0.8%) did substances receive a more severe 

classification via the dermal route than the oral route.[FN7: Creton et al. 2010. Acute toxicity testing 

of chemicals-- Opportunities to avoid redundant testing and use alternative approaches. Crit Rev in 

Toxicol 40(1):50-83.] These findings are further reinforced by an analysis by Seidle and colleagues 

[FN8: Seidle et al. 2010. Examining the regulatory value of multi-route mammalian acute systemic 

toxicity studies. Regulat Toxicol Pharmacol (submitted for publication).], which examined an 

additional 337 pesticide active ingredients - largely obtained from the US EPA REDs and other 

public data sources that were not considered in the aforementioned analyses - and found the dermal 

test to be more sensitive in only six cases (1.78%), several of which were borderline. Similar, and 

even more compelling, results have been obtained in independent reviews of industrial 

chemicals.[FN8: Seidle et al. 2010. Examining the regulatory value of multi- route mammalian acute 

systemic toxicity studies. Regulat Toxicol Pharmacol (submitted for publication).] [FN9: Indans et al 

1998. Classification and labelling of new industrial chemicals for acute toxicity, skin and eye 

irritation. Hum Exp Toxicol. 17:529.] Taken together, these analyses clearly illustrate the limited 

value of acute systemic toxicity testing via the dermal route for the purpose of classification and 

labeling, which is the primary driver for such studies [FN10: Seidle et al. 2010. Cross- Sector Review 
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Comments and Response References: 

Toxicology Section (80) Page 664 

of Drivers and Available 3Rs Approaches for Acute Systemic Toxicity Testing. Tox Sci; doi: 

10.1093/toxsci/kfq143.], and call into question the appropriateness of regulations that continue to 

require redundant dermal route testing when oral data are already available. The extent to which 

dermal acute data provide added value for the regulation of formulated products/articles is also 

questionable [FN6: Thomas and Dewhurst 2007. What does a dermal acute toxicity study add to the 

information on a plant protection pesticide? Toxicology 231:114-115.], and warrants further 

investigation. Finally, we reiterate our suggestion to make in vitro dermal penetration assessment a 

Tier I information requirement, as such information can be used in a weight-of-evidence approach 

to avoid acute or even repeated-dose dermal toxicity studies. 

Step-wise Approaches for Acute Toxicity 

In the past 18 months progress has been made to reduce the numbers of animals used in acute 

toxicity tests in three area: mammalian acute inhalation toxicity, acute fish toxicity, and acute avian 

toxicity. This progress has come in the form of internationally accepted OECD test guidelines [Test 

No. 436: Acute Inhalation Toxicity - Acute Toxic Class Method [FN11: 

http://lysander.sourceoecd.org/vl=1969840/cl=12/nw= 

1/rpsv/ij/oecdjournals/1607310x/v1n4/s53/p1] and revised Test No. 223: Avian Acute Oral 

Toxicity Test [FN12: http://www.oecd.org/dataoecd/2/6/44074180.pdf ]] and a guidance 

document [No 126: Short Guidance on the Threshold approach for Acute Fish Toxicity [FN13: 

http://www.oecd.org/document/30/0,3343,en_2649_34377_1916638_1_1_1_1,00.html]]. 

Each of these procedures has the potential to reduce the number of animals killed in LD50-type 

poisoning tests significantly, and we urge the Agency to consider incorporating them into the new 

Part 158W information requirements. 

Sincerely, 

Kristie Sullivan, MPH Science Policy Advisor Physicians Committee for Responsible Medicine 

Troy Seidle Director, Research & Toxicology Department Humane Society International 

Catherine Willett, PhD Science Policy Advisor People for the Ethical Treatment of Animals 

Response: see responses 80.91, 80.87, 80.93, 80.101, and 80.102 

Comment Code: 89200 Commenter's Concept of Toxicology Data Requirements Table Revisions 

Comment Summary: As part of their comments, the commenter provided an alternate 

Antimicrobial Toxicology Data Requirements Table with testnotes. EPA’s response is for the entire 

alternate testing scheme and not the individual parts. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 28956 
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Comments and Response References: 

Toxicology Section (80) Page 665 

Comment Code: 89200 

Comment: B. Alternative Proposal 2 

The Panel believes its Alternative 1, above, is the best approach to promulgating new toxicology 

data requirements. However, the Panel also recognizes that this proposal is a dramatic change from 

EPA’s Proposal. In the event the Agency is unwilling to adopt the full Alternative 1, the Panel urges 

it to consider the following Alternative 2. This approach provides a bridge between the past and the 

future, as well as addressing the FIFRA 3(h) mandated special considerations for antimicrobial 

pesticides. However, even for this proposal to be consistent with the Agency’s strategic direction, 

the Agency must develop appropriate guidance for when information actually is needed, based on 

estimated exposures and incorporating integrated approaches to minimize unnecessary animal 

testing. The Agency, in fact, has many initiatives currently underway in this area and this regulation 

needs to be crafted in a manner that permits these activities to be integrated as soon as possible. 

Section 158.2230(c) and (e) should be replaced by the following: 

Data Requirements Use Pattern Test Note No. 

Food Nonfood 

Acute Testing 

Acute oral toxicity R R 1, 2 

Acute dermal toxicity R R 1, 2, 3 

Acute inhalation toxicity R R 4 

Primary eye irritation R R 1, 2, 3 

Primary dermal 

irritation 

R R 1, 2, 3 

Dermal sensitization R R 1, 2, 3, 5 

Acute neurotoxicity NR NR 6 

Subchronic Testing 

90-day Oral toxicity -

rodent 

R R 7, 8 

90-day Oral toxicity – 

nonrodent 

CR NR 9 

21-Day Repeat Dose 

Dermal Irritation Study 

CR CR 10 

90-day Dermal toxicity CR CR 8, 11, 12 

90-day Inhalation – rat CR CR 8, 13, 14 

90-day Neurotoxicity – 

rat 

CR CR 15 

Chronic Testing 

Chronic oral – rodent R CR 16, 17, 18 

Carcinogenicity – rat R CR 17, 19, 20 

Carcinogenicity -mouse NR NR 21 

Developmental Toxicity and Reproduction 

Prenatal developmental 

toxicity – rabbit 

R R 22, 23, 24 

Prenatal developmental 

-rat 

R CR 22, 23, 24, 25 
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Comments and Response References: 

Toxicology Section (80) Page 666 

Data Requirements Use Pattern Test Note No. 

Food Nonfood 

Reproduction and 

fertility effects 

CR CR 26, 27, 28 

Developmental 

neurotoxicity 

CR CR 27, 28, 29 

Mutagenicity 

Bacterial reverse 

mutation assay 

NR NR 30 

In vitro mammalian cell 

assay 

R R 31 

In vivo cytogenetics R CR 32 

Special Testing 

Metabolism and 

pharmacokinetics 

R CR 33 

Dermal penetration NR CR 34 

Immunotoxicity CR CR 35 

 (e) Test Notes 

1. Data are not required if test material is a gas or highly volatile liquid. 

2. For the six acute toxicity studies conducted with the end-use product, the test must be conducted 

using the product as formulated for sale and distribution except as required by study protocols or 

unless a variance is granted after consultation with the Agency. . 

3. Data are not required if test material is corrosive to skin or has pH less than 2 or greater than 

11.5. 

4. Data are required when the end-use product consists of, or under conditions of use will result in, 

a respirable material, e.g. gas, vapor, aerosol or particulate. 

5. Data are required if repeated dermal exposure is likely to occur under conditions of use. 

6. The acute neurotoxicity study should not be required because the neurotoxicity component of the 

oral 90-day study will address the potential for neurotoxic effects more effectively than a single 

exposure acute study. 

7. The 90-day oral toxicity study should include evaluation of enhanced endpoints for neurotoxicity 

and immunotoxicity. 

8. The 90-day dermal toxicity study or 90-day inhalation toxicity study may be substituted for the 90-

day oral toxicity study if dermal or inhalation exposure is a major route of exposure and/or the 

physical/chemical properties of the active ingredient prohibit testing via the oral route. 

9. The 90-day oral non- rodent study is conditionally required for the active ingredient (TGAI) for 

which food uses occur. The 90-day non-rodent study is not required for food use chemicals if the 

results for the oral 90-day rodent study indicate no organ- specific toxicity or when the physical 
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Comments and Response References: 

Toxicology Section (80) Page 667 

properties (e.g. corrosion) preclude administration of a dose that is consistent with Guideline 

requirements of causing systemic toxicity. 

10. A repeat dose dermal irritation study is required for antimicrobial pesticides with irritant 

properties, based on the primary skin irritation study and with intentional human skin exposure 

when the 90-day oral, dermal or inhalation study indicates that there is no organ-specific systemic 

toxicity (toxicity is restricted to non-specific effects such as reduced body weight) and/or skin 

penetration is less than 10% of the applied dose from in vitro or in vivo studies. The study should 

evaluate the TGAI at or above use concentrations applying the test substance on the basis of a 

[u]g/cm2 of skin with non-occluded exposure for 5 days/week for 3 weeks. 

11. Data are required if the subchronic oral study indicates organ-specific toxicity, the use pattern is 

such that the dermal route will be the major route of exposure, and the physical/chemical properties 

allow for doses consistent with guideline requirements, i.e. at least one dose causing systemic 

toxicity. Data may also be required if the active ingredient has >10% dermal absorption based on in 

vitro or in vivo testing, is known or expected to be metabolized differently by the dermal route of 

exposure than by the oral route, and a metabolite of the active ingredient is the toxic moiety. 

12. The 90-day dermal study is not required if the active ingredient is corrosive at point of entry, or 

the no- observed-adverse-effect level from the 90-day oral study is higher than the dose which 

would be received dermally based on the results from the dermal penetration study. 

13. Data are required if there is the likelihood of repeated inhalation exposure to the active 

ingredient as a gas, vapor, or aerosol and the physical/chemical properties of the active ingredient 

are consistent with potential exposure and allow for inhalation of doses consistent with Guideline 

requirements, i.e. at least one dose causing systemic toxicity. 

14. Based on the estimates of the magnitude of human exposure, studies of shorter duration, e.g. 21 

or 28 days, may be sufficient to satisfy this requirement. Registrants may consult the Agency to 

determine if studies of shorter duration would meet a requirement for data from a study of longer 

duration. 

15. The subchronic neurotoxicity study is required only if the evaluation of neurotoxicological 

endpoints in the 90-day oral, dermal, or inhalation toxicity study indicate a positive response for 

neurotoxicity and occur at doses that could result in changes to a risk assessment. 

16. Based on the results of the acute and subchronic studies, or other available data indicating 

evidence of neurotoxicity following multiple exposures, a subchronic neurotoxicity component of a 

chronic study may be required. 

17. Studies which are designed to simultaneously fulfill the requirements of both the chronic oral 

and carcinogenicity studies (i.e., a combined study) may be conducted. 

18. Required if any of the following are met: (i) The use requires a tolerance or an exemption from 

the requirement of a tolerance or, (ii) The use of the antimicrobial pesticide is likely to result in 

significant human exposure over a considerable portion of the human life span , as reflected by an 

estimated margin of exposure. 
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Comments and Response References: 

Toxicology Section (80) Page 668 

19. Required if any of the following are met: (i) The use requires a tolerance or an exemption from 

the requirement of a tolerance or, (ii) The use of the antimicrobial pesticide is likely to result in 

significant human exposure over a considerable portion of the human life span as reflected by the 

margin of exposure or, (iii) The active ingredient, metabolite, degradate, or impurity (a) is structurally 

related to a recognized carcinogen, (b) causes mutagenic effects based on the weight of evidence in a 

battery of in vitro and in vivo assays, or (c) produces a morphologic effect in any organ (e.g., 

hyperplasia, metaplasia) in subchronic studies that has consistently been shown to lead to a 

neoplastic change. 

20. If this study is modified or waived, a subchronic 90-day oral study conducted in the rat is 

required. 

21. A study in the mouse is not recommended. 

22. Testing in two species is required for food use active ingredients. For non- food active 

ingredients, the study in rabbits is preferred. The second species using the rat may be necessary if 

developmental toxicity is observed in the rabbit. For active ingredients for which dosing in rabbits 

may be complicated by physical/chemical properties, e.g. corrosive substances, the study in rats may 

be conducted first. If neither test produces findings of concern regarding embryonic and fetal 

development, and if there is no more than a 10-fold difference in developmental lowest-observedadverse-effect levels between the two species using the same route of administration, and if there is a 

sufficient margin of exposure for the lowest no-observed-adverse-effect level, then the 

developmental toxicity would not be required in the rat. 

23. The oral route, by intubation, is preferred unless the chemical or physical properties of the test 

substance, or the pattern of exposure suggest a more appropriate route of exposure. 

24. Additional testing by other routes of exposure may be required if the active ingredient is 

determined to be a prenatal developmental toxicant after oral exposure. 

25. The developmental toxicity study in rodents may be combined with the two- generation 

reproduction study in rodents by using a second mating of the parental animals in either generation. 

Protocols must be approved by the Agency prior to the initiation of the study. Details for 

developing protocols are available from the Agency. 

26. A two-generation reproduction study is required for food use active ingredients and for nonfood active ingredients for which repeated exposure is anticipated and toxicity to reproductive 

organs is observed in the subchronic study. For food use and non-food use active ingredients not 

meeting these criteria, a reproductive screening study is considered adequate if no effects are 

observed to reproduction in this screening study. 

27. An information-based approach to testing is preferred, which utilizes the best available 

knowledge for the chemical (hazard, pharmacokinetic, or mechanistic data) to determine whether a 

standard guideline study, an enhanced guideline study, or an alternative study should be conducted 

to assess potential hazard to the developing animal, or in some cases to support a waiver for such 

testing. Applicants must submit any alternative proposed testing protocols and supporting scientific 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 669 

rationale to the Agency. Protocols must be approved by the Agency prior to the initiation of the 

study. Details for developing protocols are available from the Agency. 

28. If required, the use of a combined two-generation reproduction/developmental neurotoxicity 

(DNT) study that utilizes the two- generation reproduction study in rodents as a basic protocol for 

the addition of other endpoints or functional assessments in the immature animal is encouraged. 

29. A DNT study is required using a weight-of-evidence approach when one or more of the 

following effects is observed at doses for which further evaluation in developing offspring can 

impact the NOAEL for risk assessments (including evidence that there is sufficient exposure to the 

neonate to warrant such further testing: 

i. The active ingredient causes treatment-related neurological effects in the 90-day subchronic study 

in the adult animal. ii. The active ingredient causes treatment-related neurological effects or 

neuropathy in developing animals, brain weight changes in offspring, or functional or behavioral 

changes in the offspring. iii. The active ingredient elicits a causative association between exposure 

and adverse neurological effects in human epidemiological studies. iv. The active ingredient evokes a 

mechanism that is associated with adverse effects on the development of the nervous system, e.g. 

structure-activity relationship to known neurotoxicants, altered neuroreceptor or neurotransmitter 

responses. 

30. The bacterial reverse mutation assay conducted with Salmonella typhimurium and Escherichia 

coli is not recommended because antimicrobial pesticides are, by definition, toxic and biocidal to 

these organisms. Thus, it must be assumed that the biochemistry and physiology of these two 

bacteria used in the test system have been compromised, and can lead to false positive results even 

when no apparent toxicity has been demonstrated. Thus, the utility of this assay as a mutagenic 

screen for antimicrobial pesticides is highly limited. 

31. The mammalian cell culture assays will detect a wider spectrum of possible genetic endpoints 

and should include an in vitro gene mutation assay accompanied by an appropriate in vitro test for 

clastogenicity. For the in vitro gene mutation assay the mouse lymphoma (MLA) L5178Y cell 

thymidine kinase (tk), Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast, 

hypoxanthine- guanine phosphoribosyl transferase (hgprt) gene locus are acceptable options when 

accompanied by an appropriate in vitro clastogenicity assay. 

32. The in vivo cytogenetics assay is required for food contact use active ingredients to enhance the 

overall weight-of-evidence determination for the mutagenicity. For non-food use active ingredients, 

data are required if the in vitro mammalian cell assay is positive or equivocal. The micronucleus 

rodent bone marrow assay is preferred; however, rodent bone marrow assays using metaphase 

analysis (aberrations) are acceptable. 

33. Data are required if a chronic or carcinogenicity study is required. 

34. Data are required for active ingredients if there is the potential for dermal absorption during 

product use. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 670 

35. The subchronic immunotoxicity study is required only if the evaluation of immunotoxicological 

endpoints in the 90-day oral, dermal, or inhalation toxicity study indicate a positive response for 

immunotoxicity. 

1. Tiered Testing Options for Antimicrobial Pesticides 

The data requirement regulation for conventional chemicals contains specific provision for tiering of 

toxicology data requirements for nonfood use products.[FN#14:40 CFR [Section] 158.510.] The 

regulation for biochemical pesticides specifically incorporates tiered testing in the toxicology data 

requirements.[FN#15:40 CFR [Section] 158.2050.] Because the uses of antimicrobial pesticides 

addressed by Subpart W result largely in low level and indirect contact with food, rather than 

deliberate addition, given the SAP 1997 recommendation to incorporate similar approaches for 

antimicrobial food uses as those used by FDA, and considering the requirements of FIFRA 3(h), a 

proposal for tiering of toxicology data requirements appears both reasonable and necessary. Such a 

tiered approach does not exist in the proposed rule, and the use of footnotes to the table is 

insufficient to provide adequate direction to applicants. 

The Panel’s Alternative Proposal 1, as described above, already incorporates specific tiering. 

However, similar explicit tiering has not been incorporated in the Panel’s Alternative Proposal 2. 

The Panel, therefore, proposes that a new section be added to immediately follow the toxicology 

data requirement section that would provide the following tiered approach for antimicrobial 

pesticides, to be used in association with the Panel’s Alternative Proposal 2. This proposal is similar 

to the regulation established for conventional pesticides but takes into account the special 

considerations for antimicrobial pesticides and the Panel’s recommendations made elsewhere. The 

below reference to 40 CFR [Section] 158.70 presumes that the Panel’s recommended revision to that 

section has been incorporated to explicitly direct applicants to consider alternative approaches. 

Section 158.2235. Tiered Testing Options for Antimicrobial Pesticides 

Applicants have two options for addressing the required toxicology ([Section] 158.2230) and human 

exposure (158.2260, 158.2270 and 158.2290) data requirements. In all cases, applicants should take 

into account the provisions of [Section]158.70. Applicants are to select one of the following: 

(a) Acute, subchronic, chronic, and other toxicological studies on the active ingredient must be 

submitted together. The specific makeup of the set of toxicology study requirements is based on the 

anticipated exposure to the pesticide. If hazards are identified based upon review of these studies, 

specific exposure data will be required to evaluate risk. 

(b) Certain toxicological and exposure studies must be submitted simultaneously with the toxicology 

data submitted in a tiered system. Exposure data must be submitted along with first tier toxicology 

data. The requirement for additional second and third level toxicology testing will be determined by 

the Agency based on the results of the first tiered studies. 

(1) The required first-tier toxicology studies consist of: 

(i) Battery of acute studies. (ii) A subchronic 90-day oral study must be submitted for food uses and 

may be submitted for nonfood uses. A subchronic 90-day dermal study or a subchronic 90-day 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 671 

inhalation study may be submitted in lieu of the oral study for nonfood uses only. (iii) An acute and 

subchronic neurotoxicity screening battery in the rat. (iv) Prenatal developmental toxicity studies in 

both the rat and rabbit. For nonfood uses, a single species study may be submitted (rabbit preferred 

except in the case of corrosive materials). (v) Reproduction and fertility studies in rats. (vi) Battery of 

mutagenicity studies. (vii) Immunotoxicity study. 

(2) The conditionally required second-tier studies include: 

(i) Subchronic 90-day feeding studies in both the rodent and nonrodent. (ii) Dermal penetration 

study. 

(3) The conditionally required third-tier studies include: 

(i) Chronic feeding studies in the rodent. (ii) Carcinogenicity. (iii) Metabolism study. (iv) Additional 

mutagenicity testing. 

Response: see response 80.72 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 28957 

Comment Code: 89200 

Comment: B. Alternative Proposal 2 

LANXESS believes its Alternative 1, above, is the best approach to promulgating new toxicology 

data requirements. However, LANXESS also recognizes that this proposal is a dramatic change 

from EPA’s Proposal. In the event the Agency is unwilling to adopt the full Alternative 1, 

LANXESS urges it to consider the following Alternative 2. This approach provides a bridge 

between the past and the future, as well as addressing the FIFRA 3(h) mandated special 

considerations for antimicrobial pesticides. However, even for this proposal to be consistent with 

the Agency’s strategic direction, the Agency must develop appropriate guidance for when 

information actually is needed, based on estimated exposures and incorporating integrated 

approaches to minimize unnecessary animal testing. The Agency, in fact, has many initiatives 

currently underway in this area and this regulation needs to be crafted in a manner that permits these 

activities to be integrated as soon as possible. 

Section 158.2230(c) and (e) should be replaced by the following: 

[See table on page 34 of appendix E of PDF docket ID EPA-HQ-OPP-2008-0110-0064] 

(e) Test Notes 

1. Data are not required if test material is a gas or highly volatile liquid. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 672 

2. For the six acute toxicity studies conducted with the end-use product, the test must be conducted 

using the product as formulated for sale and distribution except as required by study protocols or 

unless a variance is granted after consultation with the Agency. 

3. Data are not required if test material is corrosive to skin or has pH less than 2 or greater than 

11.5. 

4. Data are required when the end-use product consists of, or under conditions of use will result in, 

a respirable material, e.g. gas, vapor, aerosol or particulate. 

5. Data are required if repeated dermal exposure is likely to occur under conditions of use. 

6. The acute neurotoxicity study should not be required because the neurotoxicity component of the 

oral 90-day study will address the potential for neurotoxic effects more effectively than a single 

exposure acute study. 

[Section 158.2230(c) and (e) should be replaced by the following: 

[See table on page 34 of appendix E of PDF docket ID EPA-HQ-OPP-2008-0110-0064] 

(e) Test Notes] 7. The 90-day oral toxicity study should include evaluation of enhanced endpoints 

for neurotoxicity and immunotoxicity. 

8. The 90-day dermal toxicity study or 90-day inhalation toxicity study may be substituted for the 90-

day oral toxicity study if dermal or inhalation exposure is a major route of exposure and/or the 

physical/chemical properties of the active ingredient prohibit testing via the oral route. 

9. The 90-day oral non- rodent study is conditionally required for the active ingredient (TGAI) for 

which food uses occur. The 90-day non-rodent study is not required for food use chemicals if the 

results for the oral 90-day rodent study indicate no organ- specific toxicity or when the physical 

properties (e.g. corrosion) preclude administration of a dose that is consistent with Guideline 

requirements of causing systemic toxicity. 

10. A repeat dose dermal irritation study is required for antimicrobial pesticides with irritant 

properties, based on the primary skin irritation study and with intentional human skin exposure 

when the 90-day oral, dermal or inhalation study indicates that there is no organ-specific systemic 

toxicity (toxicity is restricted to non-specific effects such as reduced body weight) and/or skin 

penetration is less than 10% of the applied dose from in vitro or in vivo studies. The study should 

evaluate the TGAI at or above use concentrations applying the test substance on the basis of a 

μg/cm2 of skin with non-occluded exposure for 5 days/week for 3 weeks. 

11. Data are required if the subchronic oral study indicates organ-specific toxicity, the use pattern is 

such that the dermal route will be the major route of exposure, and the physical/chemical properties 

allow for doses consistent with guideline requirements, i.e. at least one dose causing systemic 

toxicity. Data may also be required if the active ingredient has >10% dermal absorption based on in 

vitro or in vivo testing, is known or expected to be metabolized differently by the dermal route of 

exposure than by the oral route, and a metabolite of the active ingredient is the toxic moiety. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 673 

12. The 90-day dermal study is not required if the active ingredient is corrosive at point of entry, or 

the no- observed-adverse-effect level from the 90-day oral study is higher than the dose which 

would be received dermally based on the results from the dermal penetration study. 

13. Data are required if there is the likelihood of repeated inhalation exposure to the active 

ingredient as a gas, vapor, or aerosol and the physical/chemical properties of the active ingredient 

are consistent with potential exposure and allow for inhalation of doses consistent with Guideline 

requirements, i.e. at least one dose causing systemic toxicity. 

14. Based on the estimates of the magnitude of human exposure, studies of shorter duration, e.g. 21 

or 28 days, may be sufficient to satisfy this requirement. Registrants may consult the Agency to 

determine if studies of shorter duration would meet a requirement for data from a study of longer 

duration. 

15. The subchronic neurotoxicity study is required only if the evaluation of neurotoxicological 

endpoints in the 90-day oral, dermal, or inhalation toxicity study indicate a positive response for 

neurotoxicity and occur at doses that could result in changes to a risk assessment. 

16. Based on the results of the acute and subchronic studies, or other available data indicating 

evidence of neurotoxicity following multiple exposures, a subchronic neurotoxicity component of a 

chronic study may be required. 

17. Studies which are designed to simultaneously fulfill the requirements of both the chronic oral 

and carcinogenicity studies (i.e., a combined study) may be conducted. 

[Section 158.2230(c) and (e) should be replaced by the following: 

[See table on page 34 of appendix E of PDF docket ID EPA-HQ-OPP-2008-0110-0064] 

(e) Test Notes] 18. Required if any of the following are met: (i) The use requires a tolerance or an 

exemption from the requirement of a tolerance or, (ii) The use of the antimicrobial pesticide is likely 

to result in significant human exposure over a considerable portion of the human life span , as 

reflected by an estimated margin of exposure. 

19. Required if any of the following are met: (i) The use requires a tolerance or an exemption from 

the requirement of a tolerance or, (ii) The use of the antimicrobial pesticide is likely to result in 

significant human exposure over a considerable portion of the human life span as reflected by the 

margin of exposure or, (iii) The active ingredient, metabolite, degradate, or impurity (a) is structurally 

related to a recognized carcinogen, (b) causes mutagenic effects based on the weight of evidence in a 

battery of in vitro and in vivo assays, or (c) produces a morphologic effect in any organ (e.g., 

hyperplasia, metaplasia) in subchronic studies that has consistently been shown to lead to a 

neoplastic change. 

20. If this study is modified or waived, a subchronic 90-day oral study conducted in the rat is 

required. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 674 

21. A study in the mouse is not recommended. 

22. Testing in two species is required for food use active ingredients. For non- food active 

ingredients, the study in rabbits is preferred. The second species using the rat may be necessary if 

developmental toxicity is observed in the rabbit. For active ingredients for which dosing in rabbits 

may be complicated by physical/chemical properties, e.g. corrosive substances, the study in rats may 

be conducted first. If neither test produces findings of concern regarding embryonic and fetal 

development, and if there is no more than a 10-fold difference in developmental lowest-observedadverse-effect levels between the two species using the same route of administration, and if there is a 

sufficient margin of exposure for the lowest no-observed-adverse-effect level, then the 

developmental toxicity would not be required in the rat. 

[Section 158.2230(c) and (e) should be replaced by the following: 

[See table on page 34 of appendix E of PDF docket ID EPA-HQ-OPP-2008-0110-0064] 

(e) Test Notes] 23. The oral route, by intubation, is preferred unless the chemical or physical 

properties of the test substance, or the pattern of exposure suggest a more appropriate route of 

exposure. 

24. Additional testing by other routes of exposure may be required if the active ingredient is 

determined to be a prenatal developmental toxicant after oral exposure. 

25. The developmental toxicity study in rodents may be combined with the two- generation 

reproduction study in rodents by using a second mating of the parental animals in either generation. 

Protocols must be approved by the Agency prior to the initiation of the study. Details for 

developing protocols are available from the Agency. 

26. A two-generation reproduction study is required for food use active ingredients and for nonfood active ingredients for which repeated exposure is anticipated and toxicity to reproductive 

organs is observed in the subchronic study. For food use and non-food use active ingredients not 

meeting these criteria, a reproductive screening study is considered adequate if no effects are 

observed to reproduction in this screening study. 

27. An information-based approach to testing is preferred, which utilizes the best available 

knowledge for the chemical (hazard, pharmacokinetic, or mechanistic data) to determine whether a 

standard guideline study, an enhanced guideline study, or an alternative study should be conducted 

to assess potential hazard to the developing animal, or in some cases to support a waiver for such 

testing. Applicants must submit any alternative proposed testing protocols and supporting scientific 

rationale to the Agency. Protocols must be approved by the Agency prior to the initiation of the 

study. Details for developing protocols are available from the Agency. 

28. If required, the use of a combined two-generation reproduction/developmental neurotoxicity 

(DNT) study that utilizes the two- generation reproduction study in rodents as a basic protocol for 

the addition of other endpoints or functional assessments in the immature animal is encouraged. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 675 

29. A DNT study is required using a weight-of-evidence approach when one or more of the 

following effects is observed at doses for which further evaluation in developing offspring can 

impact the NOAEL for risk assessments (including evidence that there is sufficient exposure to the 

neonate to warrant such further testing: i. The active ingredient causes treatment-related neurological 

effects in the 90-day subchronic study in the adult animal. ii. The active ingredient causes treatmentrelated neurological effects or neuropathy in developing animals, brain weight changes in offspring, 

or functional or behavioral changes in the offspring. iii. The active ingredient elicits a causative 

association between exposure and adverse neurological effects in human epidemiological studies. iv. 

The active ingredient evokes a mechanism that is associated with adverse effects on the 

development of the nervous system, e.g. structure-activity relationship to known neurotoxicants, 

altered neuroreceptor or neurotransmitter responses. 

30. The bacterial reverse mutation assay conducted with Salmonella typhimurium and Escherichia 

coli is not recommended because antimicrobial pesticides are, by definition, toxic and biocidal to 

these organisms. Thus, it must be assumed that the biochemistry and physiology of these two 

bacteria used in the test system have been compromised, and can lead to false positive results even 

when no apparent toxicity has been demonstrated. Thus, the utility of this assay as a mutagenic 

screen for antimicrobial pesticides is highly limited. 

[Section 158.2230(c) and (e) should be replaced by the following: 

[See table on page 34 of appendix E of PDF docket ID EPA-HQ-OPP-2008-0110-0064] 

(e) Test Notes] 31. The mammalian cell culture assays will detect a wider spectrum of possible 

genetic endpoints and should include an in vitro gene mutation assay accompanied by an 

appropriate in vitro test for clastogenicity. For the in vitro gene mutation assay the mouse 

lymphoma (MLA) L5178Y cell thymidine kinase (tk), Chinese hamster ovary (CHO) or Chinese 

hamster lung fibroblast, hypoxanthine- guanine phosphoribosyl transferase (hgprt) gene locus are 

acceptable options when accompanied by an appropriate in vitro clastogenicity assay. 

32. The in vivo cytogenetics assay is required for food contact use active ingredients to enhance the 

overall weight-of-evidence determination for the mutagenicity. For non-food use active ingredients, 

data are required if the in vitro mammalian cell assay is positive or equivocal. The micronucleus 

rodent bone marrow assay is preferred; however, rodent bone marrow assays using metaphase 

analysis (aberrations) are acceptable. 

33. Data are required if a chronic or carcinogenicity study is required. 

34. Data are required for active ingredients if there is the potential for dermal absorption during 

product use. 

[Section 158.2230(c) and (e) should be replaced by the following: 

[See table on page 34 of appendix E of PDF docket ID EPA-HQ-OPP-2008-0110-0064] 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 676 

(e) Test Notes] 35. The subchronic immunotoxicity study is required only if the evaluation of 

immunotoxicological endpoints in the 90-day oral, dermal, or inhalation toxicity study indicate a 

positive response for immunotoxicity. 

1. Tiered Testing Options for Antimicrobial Pesticides 

The data requirement regulation for conventional chemicals contains specific provision for tiering of 

toxicology data requirements for nonfood use products.[FN#14:40 CFR [Section] 158.510.] The 

regulation for biochemical pesticides specifically incorporates tiered testing in the toxicology data 

requirements.[FN#15:40 CFR [Section] 158.2050.] Because the uses of antimicrobial pesticides 

addressed by Subpart W result largely in low level and indirect contact with food, rather than 

deliberate addition, given the SAP 1997 recommendation to incorporate similar approaches for 

antimicrobial food uses as those used by FDA, and considering the requirements of FIFRA 3(h), a 

proposal for tiering of toxicology data requirements appears both reasonable and necessary. Such a 

tiered approach does not exist in the proposed rule, and the use of footnotes to the table is 

insufficient to provide adequate direction to applicants. 

LANXESS’s Alternative Proposal 1, as described above, already incorporates specific tiering. 

However, similar explicit tiering has not been incorporated in LANXESS’s Alternative Proposal 2. 

LANXESS, therefore, proposes that a new section be added to immediately follow the toxicology 

data requirement section that would provide the following tiered approach for antimicrobial 

pesticides, to be used in association with LANXESS’s Alternative Proposal 2. This proposal is 

similar to the regulation established for conventional pesticides but takes into account the special 

considerations for antimicrobial pesticides and LANXESS’s recommendations made elsewhere. The 

below reference to 40 CFR [Section] 158.70 presumes that LANXESS’s recommended revision to 

that section has been incorporated to explicitly direct applicants to consider alternative approaches. 

Section 158.2235. Tiered Testing Options for Antimicrobial Pesticides 

Applicants have two options for addressing the required toxicology ([Section] 158.2230) and human 

exposure (158.2260, 158.2270 and 158.2290) data requirements. In all cases, applicants should take 

into account the provisions of [Section]158.70. Applicants are to select one of the following: 

(a) Acute, subchronic, chronic, and other toxicological studies on the active ingredient must be 

submitted together. The specific makeup of the set of toxicology study requirements is based on the 

anticipated exposure to the pesticide. If hazards are identified based upon review of these studies, 

specific exposure data will be required to evaluate risk. 

(b) Certain toxicological and exposure studies must be submitted simultaneously with the toxicology 

data submitted in a tiered system. Exposure data must be submitted along with first tier toxicology 

data. The requirement for additional second and third level toxicology testing will be determined by 

the Agency based on the results of the first tiered studies. 

(1) The required first-tier toxicology studies consist of: (i) Battery of acute studies. (ii) A subchronic 

90-day oral study must be submitted for food uses and may be submitted for nonfood uses. A 

subchronic 90-day dermal study or a subchronic 90- day inhalation study may be submitted in lieu of 

the oral study for nonfood uses only. (iii) An acute and subchronic neurotoxicity screening battery in 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Toxicology Section (80) Page 677 

the rat. (iv) Prenatal developmental toxicity studies in both the rat and rabbit. For nonfood uses, a 

single species study may be submitted (rabbit preferred except in the case of corrosive materials). (v) 

Reproduction and fertility studies in rats. (vi) Battery of mutagenicity studies. (vii) Immunotoxicity 

study. 

(2) The conditionally required second-tier studies include: (i) Subchronic 90-day feeding studies in 

both the rodent and nonrodent. (ii) Dermal penetration study. 

(3) The conditionally required third-tier studies include: (i) Chronic feeding studies in the rodent. (ii) 

Carcinogenicity. (iii) Metabolism study. (iv) Additional mutagenicity testing. 

Response: see response 80.72 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 678 

Applicator/Handler (Human Exposure) (90)

Verbatim Comments and Response References for the Applicator/Handler 

(Human Exposure) Section 

Comment Code: 90000 Applicator/Handler (human exposure) 

Commenter Name: Susan E. Little 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0068 

Comment ID: 25514 

Comment Code: 90000 

Comment: To that end, the AEJV has generated a set of survey and product usage data, submitted 

to the Agency as outlined below: 

"Antimicrobial Exposure Joint Venture National Antimicrobial Use Survey: Pilot Study (Phase I) 

Screener Report," MRID #46624201; 

"Antimicrobial Exposure Joint Venture National Antimicrobial Use Survey: Diary Pilot Study (Phase 

II)," MRID #46730501; 

"Antimicrobial Exposure Joint Venture National Antimicrobial Use Survey: Swimming Pool/Spa 

Satellite Study," MRID #46822101; 

"Antimicrobial Exposure Joint Venture National Antimicrobial Use Survey: Diary Study (Phase II), 

MRID #46799301; and 

"AEJV 'Amount Used' Study," MRID #46799302. 

Response: no response is needed 

Commenter Name: Susan E. Little 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0068 

Comment ID: 25517 

Comment Code: 90000 

Comment: The submitted data address the proposed Guideline Requirements 875.1700 (Product 

Use Information for Applicator Exposure § 158.2260), 875.2700(Product Use Information) and 

875.2800 (Description of Human Activity) for Post Application Exposure § 158.2270. 

We concur with the Agency that such data should be required for antimicrobial actives that are used 

in residential settings. Such data are essential to the EPA and the registrants when determining the 

use of and exposure to antimicrobial pesticides. In addition, these data provide a more accurate 

estimate of exposure which is also used in determining the safety of these products. We feel these 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 679 

data are relevant to all active ingredients being formulated into consumer residential and institutional 

antimicrobial pesticide products with indoor and outdoor uses. 

Response: EPA acknowledges CSPA's support for requiring Product Use Information for both 

applicator and post-application exposures, and Description of Human Activity for post-application 

exposures. 

Commenter Name: Susan E. Little 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0068 

Comment ID: 25520 

Comment Code: 90000 

Comment: Because the AEJV data have already been submitted and used by the Agency, we believe 

it is appropriate that the Agency highlight the acceptability of these data by specifically adding the 

Antimicrobial Exposure Joint Venture to the preamble discussion of the use of surrogate data in 

section IX - Handler and Post- Application Exposure Data Requirements, section B. 

Response: see response 90.7 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25649 

Comment Code: 90000 

Comment: V. Human Exposure 

CSPA applauds the Agency's consideration of surrogate data where appropriate. This not only 

conserves resources but provides consistency in assumptions and estimates when conducting risk 

assessments. 

Response: EPA acknowledges CSPA's support for use of surrogate data. 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25650 

Comment Code: 90000 

Comment: We are concerned that the guidance provided in the draft about toxicity and exposure 

triggers are so vague that the registrant would be at a loss in determining if additional data would be 

required or not. It is suggested that the Agency provide greater clarity on the toxicity triggers in 

particular in this section (158.2260 (3) (b)). The manner in which poisoning incident data are used as 

a trigger should be carefully considered. Often these data can be misinterpreted because they lack 

critical information regarding the products and the exposures thus leading to erroneous conclusions 

regarding the toxicity and hazards associated with a particular active ingredient. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 680 

It is important the Agency clarify the difference between applicator-, bystander- and postapplication exposures as the risks associated with each of these situations can be very different. In 

particular, bystander and post- application exposures must be clearly delineated. 

Response: see responses 90.5, and 90.6 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25653 

Comment Code: 90000 

Comment: In spite of the lack of direct guidance in the antimicrobial arena, the Antimicrobial 

Division of OPP has worked successfully with the Antimicrobial Exposure Joint Venture (AEJV) to 

develop product use and usage data collected in an observational manner. These studies consisted of 

in-home observations of informed/consented consumers with respect to their use of products 

present in their household inventory and prospective diary survey instruments provided by 

informed/consented consumer participants. Additionally, some surveys were recall studies which 

did not involve product usage. Since these data have been generated by AEJV and submitted and 

used by the Agency, we encourage the Agency to incorporate similar survey tool recommendations 

in their product use guidelines, particularly in those areas where AEJV data would not suffice. 

The AEJV has worked with the Antimicrobial Division to maximize the value and utility of product 

use/usage data through the use of personal computer- or web- based, front-end data mining 

software tools (e.g., notitia(TM) - see www.infoscientific.com). These software tools offer powerful 

and user-friendly data and model management capabilities. Product use/usage data and associated 

"meta" information can be stored and effectively accessed and analyzed in numerous ways. Product 

use/usage data can also be readily applied in modeling algorithms, e.g., exposure assessment 

equations which include product use parameters. Desirable software features for utilizing product 

use/usage include viewing data in a grid format, decoding coded fields with either text descriptions 

or graphical representations, determining unique values in each field, querying based on structured 

queries, or simple text and phonetic searches, generating simple summary statistics, generating 

simple graphs, exporting data to familiar formats, printing data tables, using customized analytical 

tools (e.g., to determine the co-occurrence of multiple product use events containing an active 

ingredient of interest during a specified time frame that is of toxicological relevance), accessing files 

in local area networks and via the Internet. Desirable features of model- related functions include 

using a standardized approach to running models (e.g., exposure assessment standard operating 

procedures), constructing intuitive, icon-based collection of modules in which product use/usage 

data can be linked and applied, viewing model inputs through tables and customized pick lists, and 

viewing modeling outputs through tables, graphs, and reports. 

Response: see response 90.7 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 681 

Comment ID: 25935 

Comment Code: 90000 

Comment: The AEJV has worked with the Antimicrobial Division to maximize the value and utility 

of product use/usage data through the use of personal computer- or web- based, front-end data 

mining software tools (e.g., notitia(TM) - see www.infoscientific.com). These software tools offer 

powerful and user-friendly data and model management capabilities. Product use/usage data and 

associated "meta" information can be stored and effectively accessed and analyzed in numerous 

ways. Product use/usage data can also be readily applied in modeling algorithms, e.g., exposure 

assessment equations which include product use parameters. Desirable software features for utilizing 

product use/usage include viewing data in a grid format, decoding coded fields with either text 

descriptions or graphical representations, determining unique values in each field, querying based on 

structured queries, or simple text and phonetic searches, generating simple summary statistics, 

generating simple graphs, exporting data to familiar formats, printing data tables, using customized 

analytical tools (e.g., to determine the co-occurrence of multiple product use events containing an 

active ingredient of interest during a specified time frame that is of toxicological relevance), 

accessing files in local area networks and via the Internet. Desirable features of model related 

functions include using a standardized approach to running models (e.g., exposure assessment 

standard operating procedures), constructing intuitive, icon-based collection of modules in which 

product use/usage data can be linked and applied, viewing model inputs through tables and 

customized pick lists, and viewing modeling outputs through tables, graphs, and reports. 

Response: no response is needed 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26280 

Comment Code: 90000 

Comment: * The RED for 3-tri(methoxysily)quat, EPA applied an additional safety factor of three 

(for a MOE of 300), based on the "potential for residential exposure." (Note: The RED, scheduled 

for September 2008, currently is not available on the EPA REDs webpage.) Such an application of 

an additional safety factor is not consistent with FQPA or with any OPP guidance known to the 

Panel. In the Panel’s view, this is an ad hoc decision with regard to uncertainty factors used in risk 

assessment. 

Response: see response 90.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26391 

Comment Code: 90000 

Comment: VI. Potential Exposures to Antimicrobials Differ from Other Pesticides and Require 

Different Approaches Instead of conforming the regulation to the degree of risk posed by various 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 682 

antimicrobial uses as required by FIFRA [Section] 3(h), the Proposal’s data requirements are based 

upon unsubstantiated and often overstated assumptions about exposure. See the discussions in 

Appendices G and H for greater detail on the types of review that must be incorporated into the 

data requirements to conform the review to reasonable worst case assumptions regarding human 

and environmental risk. 

Response: see response 1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26413 

Comment Code: 90000 

Comment: The Panel fully supports the generation of applicator exposure monitoring data. 

Through the Antimicrobial Exposure Assessment Task Force II (AEATF II), many antimicrobial 

registrants have committed to generating extensive applicator exposure data. These data will be 

invaluable to EPA, registrants and users. They will replace previous overestimations of exposure, 

and provide scientifically sound estimates of exposures that are essential to refine and improve the 

quality of antimicrobial risk assessments. 

Response: EPA acknowledges Lanxess' support for the generation of applicator exposure 

monitoring data such as that of the Antimicrobial Exposure Assessment Task Force II. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26515 

Comment Code: 90000 

Comment: When the registered pesticide is applied, the Agency needs to consider potential 

applicator and post application exposures, as well as potential for environmental exposures that are 

significantly different from those associated with the use of material preservative. 

Response: see response 90.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26796 

Comment Code: 90000 

Comment: * The RED for 3-tri(methoxysily)quat, EPA applied an additional safety factor of three 

(for a MOE of 300), based on the "potential for residential exposure." (Note: The RED, scheduled 

for September 2008, currently is not available on the EPA REDs webpage.) Such an application of 

an additional safety factor is not consistent FQPA or with any OPP guidance known to the Panel. In 

the Panel’s view, this is an ad hoc decision with regard to uncertainty factors used in risk assessment. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 683 

Response: see response 90.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26909 

Comment Code: 90000 

Comment: APPENDIX G 

COMMENTS ON PROPOSED DATA REQUIREMENTS FOR PESTICIDE APPLICATOR 

AND POST APPLICATION HUMAN EXPOSURE 

I. Introduction The Panel supports the conduct of exposure monitoring studies for antimicrobial 

applications. But the Panel also encourages EPA to avail itself of other sources of data that would be 

useful in enhancing the Agency’s understanding of expally, including antimicrobials, are extensively 

regulated by the Occupational Safety and Health Administration (OSHA), as well as other state and 

federal programs. These regulatory programs have well developed bodies of information on 

occupational exposures, that the Agency should consider in particular cases before seeking 

additional data. Sections 158.2260 (a)(1) and 158.7720(a)(2) acknowledge the existence of industrial 

worker health and safety standards. These standards apply to institutional and commercial 

enterprises as well. 

Occupational conditions for antimicrobial applicators are very different than those for most 

agricultural workers and EPA should not apply the same assumptions and approaches to both. Most 

workplaces in which antimicrobials are applied present the potential for exposures to multiple 

chemical products. The Panel believes that most employers and employees look to OSHA 

requirements to ensure that those exposures are properly regulated. EPA jurisdiction over 

antimicrobials is in addition to these more comprehensive programs. In developing data 

requirements applicable to occupational antimicrobial applications, the Panel believes it is important 

for EPA to consider OSHA regulation. 

Insofar as practical, the Panel urges EPA to rely upon data developed for OSHA, whether by 

companies, researchers or the National Institute of Occupational Safety and Health. When these 

data exist, EPA should evaluate them. If EPA concludes additional data are necessary, it should 

explain why. Similarly, EPA should establish a process for explaining regulatory conclusions that are 

more stringent or otherwise differ from those of other regulatory agencies or standard setting 

organizations in ways that limit or eliminate selected uses. For example, if EPA determines use of an 

antimicrobial pesticide consistent with standards established by OSHA or ACGIH are not 

adequately protective, that finding should be explained. The Agency should be particularly cautious 

in making such determinations in cases where its assumptions, rather than data, result in a risk 

assessment finding that requires exposure below detectable ambient level deemed safe by other 

regulatory bodies. 

Response: see response 90.4 
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Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 684 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26910 

Comment Code: 90000 

Comment: The Panel fully supports the need for the creation of a generic database on unit 

exposures to antimicrobials with different application methods and for multiple use scenarios. These 

data are essential to moving beyond the assumptions on exposure that so far has dominated 

antimicrobial human health risk assessments. However, the Panel does not believe it is appropriate 

to require an exposure/risk assessment for each of these routes of exposure for every compound or 

use. 

Response: see response 90.10 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26913 

Comment Code: 90000 

Comment: II. Comments on Proposed Rule (pages 59439-40, section 158.2260). Applicator 

Exposure Data Requirements 

The "toxicity criteria" for applicator exposure data that trigger the requirements raise several 

questions. First, Section 158.2260(b)(1)(i) proposes as a criterion "evidence of potentially significant 

adverse effects...observed in any applicable toxicity studies." This is an ambiguous standard and is 

disconnected from the test notes in the proposal that contain statements such as "if human activity 

data indicate the potential for exposure." A toxicity study alone should not be used to determine 

when a risk assessment is needed. It must be teamed with information on exposure to make a 

decision on the need for a risk assessment. Therefore, the regulation should be revised to state that 

that the triggering mechanism for determining when a quantitative risk assessment by a particular 

route of exposure is necessary is based on a finding of "significant adverse effects" and sufficient 

data on exposure to determine that exposure by the relevant route leads to a concern. 

The second criterion also raises questions. There is a large body of knowledge around evaluating 

whether epidemiological data are scientifically sound and of sufficient power to raise concerns and 

initiate further investigation. However, there is no similar understanding of the process or criteria 

EPA would use to evaluate "poisoning incident data" to trigger exposure data requirements needs. 

Before "poisoning incident data" are incorporated into this regulation as a trigger, the Agency needs 

to provide the criteria it believes would have to be met to provide evidence of the need. The Panel 

notes that, due to the breadth of EPA’s adverse effect reporting regulation and the absence of any 

information on the quality of information in reports, regulating based upon anecdotal reports of 

"poisoning" in most cases does not appear appropriate. 

Response: See responses 90.5 and 90.6. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 685 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26915 

Comment Code: 90000 

Comment: The applicator data requirements table requires indoor and outdoor exposure data for all 

product types. This designation of indoor or outdoor is not explained and, the Panel believes, is 

probably an artifact of the conventional pesticide data requirements. The Panel believes this 

distinction should not be included in a final regulation. Section 158.2260(e) test note 3 is sufficient 

to explain how one determines the venue for testing. This was the approach used during the 

presentation made by EPA at its public meeting on the Proposal on November 6, 2008.[FN#2:EPA 

hosted a public meeting on the proposed antimicrobial data requirement regulation at its offices in 

Arlington, VA on November 6. 2008. See 73 Fed. Reg. 63112 *October 23, 2008).] In that 

presentation, the EPA representative stressed that either indoor or outdoor data would be required, 

but not both, with rare exceptions. The table should be revised to be appropriate for antimicrobials. 

Test note 4 (applied to both dermal and inhalation) refers to "written guidance concerning exposure, 

toxicity and other data requirements for open and closed MWF (metalworking fluid) systems." This 

information should be included in the test notes as it would appear it bears materially on when data 

will be required. The Panel cannot comment on the reasonableness of this distinction or the manner 

in which EPA plans to draw it until this guidance is available for public comment. 

Response: see response 90.3 and testnotes 90.3 and 90.4 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26973 

Comment Code: 90000 

Comment: VI. Potential Exposures are Different for Antimicrobials and Require Different 

Approaches 

Instead of conforming the regulation to the degree of risk posed by various antimicrobial uses as 

required by FIFRA §3(h), the Proposal’s data requirements are based upon unsubstantiated and 

often overstated assumptions about exposure. See the discussions in Appendices G and H for 

greater detail on the types of review that must be incorporated into the data requirements to 

conform the review to reasonable worst case assumptions regarding human and environmental risk. 

Response: See Response 1. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27018 

Comment Code: 90000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 686 

Comment: 24. Proposed Regulation # [Section] 158.2260(a)(1) 

Text of the Proposed Regulation (emphasis added) Applicator exposure: General. "If EPA 

determines that industrial standards, such as the workplace standards set by the Occupational safety 

and Health Administration, provide adequate protection for a particular pesticide or a particular use 

pattern, applicator exposure data may not be required for that pesticide or the use pattern. 

Applicants should consult with the Agency on appropriate testing before the initiation of the 

studies." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated what the "appropriate testing" entails, and instead advises the applicant to consult with the 

Agency. These required private negotiations are a procedure for the development of later tests. 

Response: See responses 3 and 30.1. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27022 

Comment Code: 90000 

Comment: 26. Proposed Regulation # [Section] 158.2260(e)(4) 

Text of the Proposed Regulation (emphasis added) Applicator exposure: Test notes. "The following 

test notes apply to the data requirements [for applicator exposure] . . . For metal working fluids 

(MWFs), the Agency can provide written guidance concerning exposure, toxicity, and other data 

requirements for "open" and "closed" MWF systems." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the data requirements for metal working fluids, and instead says that it will publish guidelines 

outside of the notice and comment rulemaking procedures. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27048 

Comment Code: 90000 

Comment: LANXESS fully supports the generation of applicator exposure monitoring data. 

Through the Antimicrobial Exposure Assessment Task Force II (AEATF II), many antimicrobial 

registrants have committed to generating extensive applicator exposure data. These data will be 

invaluable to EPA, registrants and users. They will replace previous overestimations of exposure, 

instead providing scientifically sound estimates of exposures that are essential to refine and improve 

the quality of antimicrobial risk assessments. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 687 

Response: EPA acknowledges Lanxess' support for the generation of applicator exposure 

monitoring data such as that of the Antimicrobial Exposure Assessment Task Force II. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27261 

Comment Code: 90000 

Comment: When the registered pesticide is applied, the Agency needs to consider potential 

applicator and post application exposures, as well as potential for environmental exposures that are 

significantly different from those associated with the use of material preservative. 

Response: see response 90.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27409 

Comment Code: 90000 

Comment: LANXESS in general supports the proposed requirements for applicator exposure at 

proposed 158.2260, but believes that refinements are necessary to tailor them more appropriately to 

antimicrobials product types and use patterns. Further, LANXESS commends EPA for its position 

on the use of surrogate data, particularly for unit exposure monitoring of individual work tasks, such 

as pouring, mopping, etc. The resources required on the part of both the Agency and registrants 

would not be sufficient to generate unit exposure data on hundreds of individual chemicals in the 

numerous work task scenarios. Fortunately, there is no scientific need for unit exposure data for 

each and every individual active ingredient, especially in light of the rigorous research methodology 

that generates exceedingly high quality data for use in estimating unit exposures. 

The applicator data requirements table requires indoor and outdoor exposure data for all product 

types. This designation of indoor or outdoor is an artifact of the conventional pesticide data 

requirements and is not applicable to antimicrobials. 158.2260(e) test note 3 is sufficient to explain 

how one determines the venue for testing. This was the approach used during the presentation made 

by EPA on December 5, 2008,[FN#1:EPA hosted a public meeting on the proposed antimicrobial 

data requirement regulation at its offices in Arlington, VA on December 5. 2008. See 73 Fed. Reg. 

63112 *October 23, 2008).] when it was stressed that either indoor or outdoor data would be 

required, but not both, with rare exceptions. Eliminating the reference to indoor and outdoor and 

using test note 3 is a much more reasonable structure for the table and provides much better 

guidance than listing separate data requirements, merely because they mimic the conventional 

pesticides applicator exposure data table. 

Test note 4 (applied to both dermal and inhalation) refers to "written guidance concerning exposure, 

toxicity and other data requirements for open and closed MWF (metalworking fluid) systems." This 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 688 

information should be included in the test notes as it would appear it bears materially on when data 

will be required 

Response: EPA notes that the public meeting was held on November 6th. See also response 90.3, 

and testnotes 90.3 and 90.4 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27411 

Comment Code: 90000 

Comment: For both dermal and inhalation exposure, it is important to understand that the 

applicability of these data requirements is essential to developing a data base for the human health 

risk assessments of antimicrobials. However, as discussed above, it also is important the Agency 

acknowledge that just because these data are required, both risk assessments are not needed for all 

antimicrobials. The triggering event for conducting a risk assessment is whether the available toxicity 

and exposure data indicate a risk of potential concern. If no concern exists, then no quantitative risk 

assessment is necessary. 

Response: see response 90.10 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27565 

Comment Code: 90000 

Comment: APPENDIX G 

COMMENTS ON PROPOSED DATA REQUIREMENTS FOR PESTICIDE APPLICATOR 

AND POST APPLICATION HUMAN EXPOSURE 

I. Introduction 

LANXESS supports the conduct of exposure monitoring studies for antimicrobial applications. But 

LANXESS also encourages EPA to avail itself of other sources of data that would be useful to the 

Agency’s understanding of workplace exposures and the regulations that are in place for most 

workplaces where antimicrobials are used. EPA is encouraged to recognize the mature regulatory 

programs administered by the Occupational Safety and Health Administration (OSHA), as well as 

other state and federal programs that regulate industrial, institutional and commercial facilities. 

Sections 158.2260 (a)(1) and 158.7720(a)(2) acknowledge the existence of industrial worker health 

and safety standards. But it should be noted that these standards have broader applicability to 

institutional and commercial enterprises as well. 

Moreover, it is essential that EPA understand that occupational conditions for antimicrobial 

applicators are dramatically different than those for most agricultural workers and the same 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 689 

assumptions and approaches cannot be applied to both. EPA regulations are not the first or major 

line of protection of individuals occupationally exposed to chemicals. EPA- registered antimicrobial 

pesticides are the exception to the regulatory scheme for individuals occupationally exposed. In 

almost all occupational settings, the number of non- pesticidal chemicals and articles far exceed 

antimicrobial pesticides. These workplaces must be and are regulated in a comprehensive manner to 

assure safety across the broad range of activities and exposures that may occur. 

LANXESS urges EPA to be consistent with OSHA and other standards with regard to exposure 

limits and handling practices and incorporate the OSHA standards into risk assessment evaluations. 

In particular, EPA should establish a process for explaining regulatory conclusions that are more 

stringent or otherwise differ from those of other regulatory agencies or standard setting 

organizations in ways that limit or eliminate selected uses. For example, if EPA determines use of an 

antimicrobial pesticide consistent with standards established by OSHA or ACGIH are not 

adequately protective, that finding should be substantiated. LANXESS believes that the regulatory 

process for antimicrobial pesticides must be sufficiently transparent to allow a clear understanding 

why EPA finds unacceptable a particular level of exposure acceptable to other regulators. In 

addition, EPA should take into account the costs to antimicrobial users when it determines that 

more stringent standards of exposure are necessary than those established by OSHA or other 

regulatory or standard setting bodies. This is particularly true if Agency assumptions result in a risk 

assessment finding that requires exposure below detectable ambient levels deemed safe by other 

regulatory bodies. 

Response: see response 90.4 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27572 

Comment Code: 90000 

Comment: LANXESS fully supports the need for the creation of a generic data base on unit 

exposures to antimicrobials with different application methods and for multiple use scenarios. These 

data are essential to moving beyond the assumptions on exposure that so far have dominated 

antimicrobial human health risk assessments. However, it is essential for EPA to recognize that 

while LANXESS believes it is appropriate to require both inhalation and dermal applicator exposure 

studies, such requirements do not necessitate a requirement to perform an exposure/ risk 

assessment for each of these routes of exposure for every compound or use. 

Response: see response 90.10 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27575 

Comment Code: 90000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 690 

Comment: II. Comments on Proposed Rule (pages 56439-40, section 158.2260). Applicator 

Exposure Data Requirements 

The "toxicity criteria" for applicator exposure data that trigger the requirements raise several 

questions. First, Section 158.2260(b)(1)(i) proposed as a criterion "evidence of potentially significant 

adverse effects...observed in any applicable toxicity studies." This is an ambiguous standard and is 

disconnected from the test notes in the proposal that contain statements such as "if human activity 

data indicate the potential for exposure." LANXESS believes the appropriate criterion is that 

contained in the test notes. A toxicity study alone cannot be used to determine when a risk 

assessment is needed. It must be teamed with information on exposure to make a decision on the 

need for a risk assessment. Therefore, the regulation should be revised to state that that the 

triggering mechanism for determining when a quantitative risk assessment by a particular route of 

exposure is necessary is based on a finding of "significant adverse effects" and sufficient data on 

exposure to determine that exposure by the relevant route leads to a concern. 

The second criterion also raises questions. There is a large body of knowledge around evaluating 

whether epidemiological data are scientifically sound and of sufficient power to raise concerns and 

pursue further investigation. However, there is no similar understanding of the process or criteria 

EPA would use to evaluate "poisoning incident data" to trigger exposure data requirements needs. 

Before "poisoning incident data" are incorporated into this regulation as a trigger, the Agency needs 

to provide the criteria it believes would have to be met to provide evidence of the need. 

Response: see responses 90.5 and 90.6 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27698 

Comment Code: 90000 

Comment: 24. Proposed Regulation # [Section] 158.2260(a)(1) 

Text of the Proposed Regulation (emphasis added) Applicator exposure: General. "If EPA 

determines that industrial standards, such as the workplace standards set by the Occupational safety 

and Health Administration, provide adequate protection for a particular pesticide or a particular use 

pattern, applicator exposure data may not be required for that pesticide or the use pattern. 

Applicants should consult with the Agency on appropriate testing before the initiation of the 

studies." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated what the "appropriate testing" entails, and instead advises the applicant to consult with the 

Agency. These required private negotiations are a procedure for the development of later tests. 

Response: See responses 3 and 30.1. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 691 

Letter ID: 0064 

Comment ID: 27703 

Comment Code: 90000 

Comment: 26. Proposed Regulation # [Section] 158.2260(e)(4) 

Text of the Proposed Regulation (emphasis added) Applicator exposure: Test notes. "The following 

test notes apply to the data requirements [for applicator exposure] . . . For metal working fluids 

(MWFs), the Agency can provide written guidance concerning exposure, toxicity, and other data 

requirements for "open" and "closed" MWF systems." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the data requirements for metal working fluids, and instead says that it will publish guidelines 

outside of the notice and comment rulemaking procedures. 

Response: See responses 3 and 30.1 

Comment Code: 91000 Biological monitoring 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25598 

Comment Code: 91000 

Comment: Section Number IX. 

Title Handler and postapplication exposure data requirements 

Paragraph C. Handler exposure p. 59398 

Excerpt from Federal Register Biological monitoring: conditionally required applicator exposure 

study. In addition or in lieu of the dermal or inhalation exposure data. It cannot be done using 

surrogate material 

HC Comment Only one of these are required by the PMRA: Passive dosimetry, Biological 

monitoring data, or acceptable scientific rationale. 

Response: see response 90.9 

Comment Code: 92000 Dermal exposure 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 692 

Comment ID: 25597 

Comment Code: 92000 

Comment: b. Occupational Exposure 

Detailed Considerations: 

Section Number IX. 

Title Handler and postapplication exposure data requirements 

Paragraph C. Handler exposure p.59398 

Excerpt from Federal Register Dermal exposure studies. EPA proposes to require data for both 

outdoor and indoor dermal exposures to estimate the dermal exposure to persons directly handling 

pesticides. The number of exposure studies that may be required depends on the variety of use sites, 

their similarities, and whether the uses are indoor or outdoor. 

HC Comment Both Dermal and inhalation exposure studies are always required by the PMRA. 

Response: see response 90.10 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27412 

Comment Code: 92000 

Comment: Reg. at 59441. However, no criteria are provided in the proposal. 

Similarly, in the introductory section to the post-application data table, EPA proposes the following 

text: 

(b) Criteria for Testing. 

(2) Exposure Criteria. (i) Outdoor uses. 

Response: no response is needed 

Comment Code: 94000 Surrogate studies 

Commenter Name: Abigail Trueblood 

Commenter Organization: Dow Chemical Company 

Letter ID: 0082 

Comment ID: 25484 

Comment Code: 94000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 693 

Comment: We are very supportive of the use of surrogate data such as that developed by the 

AEATF II, but EPA must recognize that other regulations make the collection of some data, such 

as that related to children's exposure or biomonitoring, virtually impossible collect in this day and 

age. The exposure guidance needs to be specified within a context that complies with other existing 

regulations. 

Response: see response 90.11 

Commenter Name: Susan E. Little 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0068 

Comment ID: 25518 

Comment Code: 94000 

Comment: The AEJV worked closely and successfully with the Antimicrobial Division of OPP to 

ensure the highest quality data would be developed for Risk Assessment purposes. The advantage of 

cooperative joint venture data generation is that it provides much richer information on a wide 

variety of active ingredients rather than focusing on individual actives. 

Response: see response 90.7 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27020 

Comment Code: 94000 

Comment: 25. Proposed Regulation # [Section] 158.2260(a)(2) 

Text of the Proposed Regulation (emphasis added) Applicator exposure: General. "The Agency may 

accept surrogate exposure data estimations from other sources to satisfy applicator exposure data 

requirements . . . The Agency will consider using such surrogate data for evaluating human exposure 

on a case-by-case basis." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

explained the criteria used to determine if such surrogate data will be used or not. These required 

private negotiations are a procedure for the development of later tests. 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27038 

Comment Code: 94000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 694 

Comment: 28. Proposed Regulation # [Section] 158.2270(a)(3) 

Text of the Proposed Regulation (emphasis added) Post-application exposure: General. "The 

Agency may accept surrogate exposure data estimations from other sources to satisfy applicator 

exposure data requirements if the data meet the basic quality assurance, quality control, and other 

scientific requirements set by EPA . . . The Agency will consider using such surrogate data for 

evaluating human exposure on a case-by-case basis." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether it will accept surrogate exposure data. These required 

private negotiations are a procedure for the development of later tests. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27701 

Comment Code: 94000 

Comment: 25. Proposed Regulation # [Section] 158.2260(a)(2) 

Text of the Proposed Regulation (emphasis added) Applicator exposure: General. "The Agency may 

accept surrogate exposure data estimations from other sources to satisfy applicator exposure data 

requirements . . . The Agency will consider using such surrogate data for evaluating human exposure 

on a case-by-case basis." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

explained the criteria used to determine if such surrogate data will be used or not. These required 

private negotiations are a procedure for the development of later tests. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27706 

Comment Code: 94000 

Comment: 28. Proposed Regulation # [Section] 158.2270(a)(3) 

Text of the Proposed Regulation (emphasis added) Post-application exposure: General. "The 

Agency may accept surrogate exposure data estimations from other sources to satisfy applicator 

exposure data requirements if the data meet the basic quality assurance, quality control, and other 

scientific requirements set by EPA . . . The Agency will consider using such surrogate data for 

evaluating human exposure on a case-by-case basis." 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 695 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether it will accept surrogate exposure data. These required 

private negotiations are a procedure for the development of later tests. 

Response: see response 3 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 29016 

Comment Code: 94000 

Comment: Antimicrobial Exposure Joint Venture Comments 

Comments submitted by AEJV centered on Human Exposure Data Requirements. We agree with 

AEJV that cooperative joint venture data generation provides richer information than individual 

companies can generate and that such data can be utilized for many active ingredients. 

Response: see response 90.7 

Comment Code: 96000 Data and reporting requirements table for applicator/handler (suggested 

additions, deletions, etc.) 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25599 

Comment Code: 96000 

Comment: Section Number IX. 

Title Handler and postapplication exposure data requirements 

Paragraph C. Handler exposure p. 59399 

Excerpt from Federal Register Data reporting and calculations is required with each exposure study. 

HC Comment These data are only required by the PMRA for Use Site Categories where postapplication data are required. 

 Section Number IX. 

Title Handler and postapplication exposure data requirements 

Paragraph D. Postapplication Exposure p. 59399 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 696 

Excerpt from Federal Register Product use information and description of human activity for 

postapplication 

HC Comment Use description of human activities for applicators, workers, post-applications, and 

consumers are always required by the PMRA. 

Response: See response 90.14. Also, EPA acknowledges PMRA's support for requiring Product 

Use Information. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26941 

Comment Code: 96000 

Comment: E. Comments on Biological Monitoring Data Requirement 

Test note 10 states biological monitoring data are required for uses such as swimming pools where 

passive dosimetry is not an option and "exposure estimates from modeling techniques used in 

conjunction with the toxicity data indicate a risk of concern." The Panel is concerned that this data 

requirement raises serious issues under EPA’s Protection of Human Subjects Regulation that the 

Proposal does not appear to consider. Due to the restrictions EPA has imposed on research 

involving human subjects, and the absence of current guidelines, the Panel questions the manner in 

which EPA believes this study can be conducted. EPA has provided no guidance on how to 

perform such a study consistent with 40 CFR Part 26, nor has it included the burden of such studies 

in its economic analysis. This requirement, in the Panel’s view, is inappropriate. The Panel strongly 

urges EPA to reconsider this requirement in light of feasibility issues with human subjects research. 

Response: see response 90.12 and testnote 100.10 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27463 

Comment Code: 96000 

Comment: E. Comments on Biological Monitoring Data Requirement 

Test note 10 states biological monitoring data are required for uses such as swimming pools where 

passive dosimetry is not an option and "exposure estimates from modeling techniques used in 

conjunction with the toxicity data indicate a risk of concern.' It would seem that any such study 

would raise significant ethical questions. LANXESS strongly recommends that EPA reevaluate this 

test note. On the other hand, there is no information in the proposed regulation that otherwise 

would assist a registrant in determining what, if any, data are required when passive dosimetry is not 

an option. 

Response: see response 90.12 and testnote 90.10 
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Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 697 

Comment Code: 97000 Ethical conduct of the research (Human Studies Review Board) 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25681 

Comment Code: 97000 

Comment: Post-application exposure data 

We applaud EPA’s proposal to expand criteria that would flag potentially significant postapplication exposures, especially in residential environments. There are, however, potentially serious 

ethical issues that arise in biological monitoring and exposure studies. We caution EPA to be vigilant 

and firm in rejecting studies that violate ethical standards, including but not limited to deliberate 

dosing of humans with pesticides, supplying test subjects with pesticides, or requiring pesticide use 

by subjects that would not have otherwise occurred. 

Response: EPA acknowledges SF Environment's support for expanding the criteria for augmenting 

post-application studies. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26912 

Comment Code: 97000 

Comment: Further, the Panel believes EPA should make certain that its exposure data requirements 

are consistent with the regulations governing human subject studies used for pesticide regulation. 

EPA has issued extensive regulations at 20 CFR Part 26, addressing research using human subjects. 

These regulations have dramatically increased the complexity of designing and conducting these 

studies. The time and expense involved in performing any particular monitoring study have more 

than doubled, as explained in section IX of the Panel’s General Comments.[FN#1:While the Agency 

has mentioned the role of the HSRB in the Preamble (73 Red. Reg. at 59398.), the Agency’s 

economic analysis does not even acknowledge the increased costs associated with its work. The 

Agency must estimate these costs and consider them in its analysis of the burdens of the Proposal.] 

Equally important, the Panel questions whether EPA can impose data requirements that its own 

HSRB may disapprove. This effectively would make it impossible for an applicant or registrant to 

proceed. The Agency should fully explain the manner in which it expects registrants to comply with 

both its data requirements and its Protection of Human Subjects Regulation. Those situations in 

which data requirements will trigger HSRB review should be identified and the process envisioned 

by EPA explained. 

Response: see responses 90.11 and 90.13, and testnotes 90.1 and 100.1 

Commenter Name: Hasmukh C. Shah 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 698 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26914 

Comment Code: 97000 

Comment: Finally, the issue of the guidelines referenced in the table needs to be addressed. 

Guidelines 875.1100 through 875.1700 do not conform to typical antimicrobial use patterns and are 

outdated in any event. These guidelines must be revised to apply to antimicrobial use sites and also 

to accommodate the requirements of EPA’s Protection of Human Subjects Regulation. In the 

absence of these revisions, the guidelines do not provide meaningful information on which 

registrants and applicants can rely. In addition, the absence of these guidelines has impaired the 

Panel’s ability to comment on and assess the impact of the Proposal. 

Response: see responses 191.1 and 90.13 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27574 

Comment Code: 97000 

Comment: Further, it is critical for EPA to make sure that it is not requiring testing that is 

impractical or could not meet the review requirements mandated by EPA’s regulation on the 

protection of human subjects. EPA’s expansion of its regulation on the protection of human 

subjects at 20 CFR Part 26 to pesticide exposure monitoring studies has vastly increased the 

complexity of designing and conducting these studies. The time and expense involved have more 

than doubled. While the Agency has mentioned the role of the HSRB in the Preamble, it has 

underestimated greatly the increased burdens HSRB review has placed on both the Agency and 

entities conducting these studies (73 Red. Reg. at 59398.) It is of the utmost importance that both 

this regulation and its implementation not force registrants into a Catch-22 situation where 

conducting a study to comply with a data requirement will not be consistent with other Agency 

regulations. 

Response: see responses 90.11 and 90.13, and testnotes 90.1 and 100.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27576 

Comment Code: 97000 

Comment: Finally, the issue of the guidelines referenced in the table needs to be addressed. 

Guidelines 875.1100 through 875.1700 do not conform to typical antimicrobial use patterns. The 

guidelines needs to be revisited in the context of the manner in which AEATF has been required to 

meet the requirements of EPA and the Human Subject Review Board with the implementation of 

EPA’s regulation on the protection of human subjects at 40 CFR Part 26. One of the most critical 

needs is clear guidance on the characteristics and procedures that distinguish observational studies as 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 699 

opposed to investigational or intentional exposure studies. With the revision of EPA’s regulation on 

human subject protection, this issue has become central to the manner in which exposure 

monitoring studies are conducted. 

Response: see responses 191.1 and 90.13 

Comment Code: 98000 Commenter's Concept of Human Exposure Data Requirements Table 

Revisions 

Comment Summary: As part of their comments, the commenter provided an alternate 

Antimicrobial Applicator Data Requirements Table with testnotes. EPA’s response is for the entire 

alternate testing scheme and not the individual parts. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26920 

Comment Code: 98000 

Comment: III. Alternate Proposal for Applicator Data Requirements 

Following is the Panel’s recommendations on revisions to the applicator exposure data requirement 

regulation. 

158.2260 Applicator exposure 

(b) Delete and revise as discussed above. 

Replace table and test notes with the following: 

Table – Antimicrobial Applicator Exposure Data Requirements 

Guideline Number Data Requirements Occupational Residential Test 

Substance 

Test 

Note 

No. 

875.1100 and/or 

875.1200 Dermal Exposure CR CR TEP 1, 2, 3, 4, 5 

875.1300 and/or 

875.1400 Inhalation Exposure CR CR TEP 1, 2, 3, 4, 6 

875.1500 Biological Monitoring NR NR TEP 1, 2, 3 

875.1600 Data Reporting and 

Calculations CR CR TEP 4 

875.1700 Product Usage 

Information R R TEP 

Test notes: 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 700 

1. Consultation with the Agency is encouraged in the event the test guideline does not provide 

adequate information on all important aspects of the study. If the study will involve human subjects, 

the applicant should meet with EPA regarding the compliance with 40 CFR Part 26. 

2. Biological monitoring data acceptable under EPA’s Protection of Human Subjects Regulation may 

be submitted in addition to, or in lieu of, dermal and inhalation passive dosimetry exposure data, 

provided the human pharmacokinetics of the pesticide or metabolite/analog compounds (i.e., 

whichever method is selected as an indicator of body burden or internal dose) allow for the back 

calculation to the total internal dose. 

3. For products with both indoor and outdoor uses, and similar conditions of use, data are generally 

required for the indoor applications only. However, data for outdoor uses are required if the Agency 

expects outdoor uses to result in greater exposure than indoor uses (e.g., higher use rates and/or 

application frequency, or longer exposure duration, or application methods/equipment create 

potential for increased dermal or inhalation exposure in outdoor versus indoor use sites). In certain 

cases, when a pesticide is used both indoors and outdoors under dissimilar conditions of use, the 

Agency may require submission of applicator exposure data for both use patterns. 

4. Data reporting and calculations are required when applicator exposure data are required. 

 5. The dermal information would be required only when the application is likely to result in 

measurable dermal dosage under normal usage conditions. For example, applications which are via 

closed systems do not require data collection. Mandatory mitigation (i.e. label instructions) with PPE 

that would prevent dermal exposure can be the basis for a waiver. The dermal exposure requirement 

also may be met by reliance on surrogate data. 

 6. Inhalation information would be required when the application is likely to result in measurable 

inhalation exposure to respirable material under normal usage conditions. Mandatory mitigation with 

PPE that would prevent potential inhalation exposure can be the basis for a waiver. The inhalation 

exposure requirement also may be met by reliance on surrogate data. 

Response: See response 90.15.

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27427 

Comment Code: 98000 

Comment: III. Alternate Proposal for Applicator Data Requirements 

Following is LANXESS’s recommendations on revisions to the applicator exposure data 

requirement regulation. 

158.2260 Applicator exposure 

(b) Delete and revise as discussed above. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Applicator/Handler (Human Exposure) Section (90) Page 701 

Replace table and test notes with the following: 

[See table "Antimicrobial Applicator Exposure Data Requirements" in appendix F of PDF docket 

ID EPA-HQ-OPP-2008-0110-0064] 

Test notes: 

1. Protocols must be approved by the Agency prior to the initiation of the study. Details for 

developing protocols are available from the Agency. 

2. Biological monitoring data may be submitted in addition to, or in lieu of, dermal and inhalation 

passive dosimetry exposure data, provided the human pharmacokinetics of the pesticide or 

metabolite/analog compounds (i.e., whichever method is selected as an indicator of body burden or 

internal dose) allow for the back calculation to the total internal dose. 

3. For products with both indoor and outdoor uses, and similar conditions of use, data are generally 

required for the indoor applications only. However, data for outdoor uses are required if the Agency 

expects outdoor uses to result in greater exposure than indoor uses (e.g., higher use rates and/or 

application frequency, or longer exposure duration, or application methods/equipment create 

potential for increased dermal or inhalation exposure in outdoor versus indoor use sites). In certain 

cases, when a pesticide is used both indoors and outdoors under dissimilar conditions of use, the 

Agency may require submission of applicator exposure data for both use patterns. 

4. Data reporting and calculations are required when applicator exposure data are required. 

5. The dermal information would be required when the application is likely to result in measurable 

dermal contact under normal usage conditions. Applications which are via closed systems would not 

require data collection. In addition, mandatory mitigation with PPE that would prevent dermal 

exposure can be the basis for a waiver. The dermal exposure requirement also may be met by 

reliance on surrogate data. 

6. Inhalation information would be required when the application is likely to result in measurable 

inhalation exposure under normal usage conditions. In addition, planned mitigation with PPE that 

would prevent potential inhalation exposure can be the basis for a waiver. The inhalation exposure 

requirement also may be met by reliance on surrogate data. 

Response: See response 90.15. 

 
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Comments and Response References: 

Post-application (Human Exposure) (100) Page 702 

Post-application (Human Exposure) (100) 

Verbatim Comments and Response References for the Post-application 

(Human Exposure) Section 

Comment Code: 100000 Post-application (human exposure) 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25728 

Comment Code: 100000 

Comment: In general, Ecolab supports the comments provided by the Consumer Specialty 

Products Association (CSPA) and the American Chemistry Council (ACC) Biocides Panel. This 

document provides Ecolab's specific comments which, in some instances, may differ from or 

expand on the comments provided by ACC and CSPA. 

Response: no response is needed 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25945 

Comment Code: 100000 

Comment: Our comments on the current proposal are generic and more specific comments are 

provided by the ACC Biocides Panel. Comments are provided which address the unique nature of 

antimicrobials, transparency, tiering of data and use of alternative means to address regulatory 

concerns. 

Response: no response is needed 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26240 

Comment Code: 100000 

Comment: * The Agency has not clearly articulated the criteria to determine whether the toxicity 

criteria and exposure criteria are met to trigger post- application human exposure monitoring data. 

Without consultation, an applicant cannot determine whether EPA requires post-application 

exposure data.[FN#11:Id. at [Section] 158.2270(b).] 

Response: see response 3 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Post-application (Human Exposure) (100) Page 703 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26412 

Comment Code: 100000 

Comment: Another area of concern to the Panel is occupational exposure. EPA is proposing to 

require post-application exposure data for occupational settings in which it apparently believes 

people may be exposed (beyond conventional food, feed and fiber crop agriculture), regardless of 

whether they are on-the-job or bystanders. 73 Fed. Reg. at 59399. However, there is nothing in the 

administrative record to show EPA reviewed the extensive data available through OSHA, private 

standard setting organizations, industry groups, and other federal and state agencies to determine 

whether it still needs additional information. In the Panel’s view, it is important for the Agency to 

review and consider existing industrial monitoring data before determining whether additional data 

are needed. 

Response: See responses 90.4 and 100.3. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26751 

Comment Code: 100000 

Comment: * The Agency has not clearly articulated the criteria it will use to determine whether the 

toxicity criteria and exposure criteria are met to trigger post- application human exposure 

monitoring data. Without consultation, an applicant cannot determine whether post-application 

exposure data are needed.[FN11: Id. at [section] 158.2270(b).] 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26925 

Comment Code: 100000 

Comment: IV. Comments on Proposed Rule (pages 59440-41, section 158.2260). Post- Application 

Exposure Data Requirements 

The Panel’s comments related to "toxicity criteria" and "poisoning incident data" in section II above 

are equally applicable to the post- application exposure provision at 158.2270 (b)(1)(i) and are 

incorporated here by reference. In addition, the Panel has many concerns about the purpose of 

EPA’s post-application data requirements, the feasibility of several, and the fact that they are 

required as opposed to conditionally required. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Post-application (Human Exposure) (100) Page 704 

The data table for the most part lists all post application studies as "required." However, the Panel 

submits that post-application data requirements should be conditionally required, based on factors 

that would create the opportunity for such exposures. The Panel urges EPA to provide more clarity 

with regard to the triggers that would create a need for post-application exposure data. There are 

various statements about the triggers to testing, but none is sufficient to enable an applicant or 

registrant to determine when post- application data must be provided or otherwise addressed. 

For example, EPA states that it will require post- application exposure data for antimicrobials "when 

the toxicity and exposure criteria are triggered." 73 Fed. Reg. at 59441. However, no criteria are 

provided in the proposal. 

Similarly, in the introductory section to the post- application data table, EPA proposes the following 

text: 

(b) Criteria for Testing. (2) Exposure Criteria. (i) Outdoor uses. (B) Residential human postapplication exposure to residues of antimicrobial pesticides could occur following the application of 

antimicrobial pesticides to indoor spaces or surfaces at residential sites, such as, but not limited to 

homes, daycare centers, hospitals, schools, and other public buildings 

Proposed 158.2270(b)(2) (i)(B). This description is too vague and the standard too subjective to be 

useful to those outside the Agency in understanding when post-application data are required. 

Among the conditions that the Panel believes might be useful in making such determinations are: 

whether any particular human activity would lead to the likelihood of measurable exposure; the 

results of applicator exposure testing and whether those results support the expectation of 

measurable post- application exposure; and chemical or physical characteristics of the antimicrobial 

that make measurable exposure possible. These are examples of the types of considerations that 

should be considered by EPA, not an exhaustive list. 

The Preamble also states that 

[t]he Agency has become increasingly concerned about post-applications risks to person in 

occupational settings other than conventional food, feed, and fiber crop agriculture. The Agency is 

now proposing to require post-application exposure data for other settings where people may be 

exposed, regardless of whether they are on-the-job or bystanders. 73 Fed. Reg. at 59399. This is a 

vague statement given the huge variety of occupational settings in which antimicrobials are used. As 

also discussed in the Panel’s General Comments at section VI, a post-application requirement 

should not even be considered in occupational settings without solid evidence of exposure at levels 

of potential concern from standard industrial hygiene data. This condition should be reflected in the 

test notes as a condition for requiring post-application occupational data. 

Response: See responses 90.5, 90.6, 100.4, 100.5, and 100.6 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26926 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Post-application (Human Exposure) (100) Page 705 

Comment Code: 100000 

Comment: The Proposal would require two new studies, soil residue dissipation and indoor surface 

residue dissipation. The Panel believes these are not appropriate for antimicrobials, as proposed. 

One of the reasons given for these requirements is harmonization with conventional pesticides. 

However, the uses of antimicrobial products have little in common with the uses of conventional 

pesticides, and, therefore, there would appear to be little justification for the harmonization of postapplication exposure requirements for these pesticide classes. 

Response: see responses 1 and 100.7 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26942 

Comment Code: 100000 

Comment: F. Comments on product use information and description of human activity data 

requirements 

It is essential that guidelines be proposed and finalized for these requirements and that the 

regulation be reproposed for comment once that is completed. Without guidance, it will be 

impossible for registrants and applicants to anticipate the manner in which EPA will interpret these 

requirements and the consequent burden they will impose. 

Response: see response 191.3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27035 

Comment Code: 100000 

Comment: Another area of concern to LANXESS is occupational exposure. EPA is proposing to 

require post-application exposure data for occupational settings in which it apparently believes 

people may be exposed (beyond conventional food, feed and fiber crop agriculture), regardless of 

whether they are on-the-job or bystanders. 73 Fed. Reg. at 59399. This proposal is without any 

documentation or scientific rationale. There is nothing in the administrative record to show EPA 

reviewed the extensive data available through Occupational Safety and Health Administration 

(OSHA), private standard setting organizations, industry groups, nd other federal and state agencies 

to determine whether it still needs additional information. In LANXESS’s view, it is important for 

the Agency to review and consider existing industrial monitoring data before determining whether 

additional data are needed. 

Response: see response 100.3 

Commenter Name: Hasmukh C. Shah 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Post-application (Human Exposure) (100) Page 706 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27036 

Comment Code: 100000 

Comment: 27. Proposed Regulation # [Section] 158.2270(a)(2) 

Text of the Proposed Regulation (emphasis added) Post-application exposure: General. "If EPA 

determines that industrial standards, such as the workplace standards set by the Occupational Safety 

and Health Administration, provide adequate protection for a particular pesticide or a particular use 

pattern, post-application exposure data may not be required for that pesticide or the use pattern. 

Applicants should consult with the Agency on appropriate testing before the initiation of the 

studies." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether post-application exposure data is required or not. 

These required private negotiations are a procedure for the development of later tests. 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27040 

Comment Code: 100000 

Comment: 29. Proposed Regulation # [Section] 158.2270(b) 

Text of the Proposed Regulation (emphasis added) Post-application exposure: Criteria for testing. 

"Post-application exposure data . . . are required based on toxicity and exposure criteria. Data are 

required if a product meets, as determined by the Agency, at least one of the toxicity criteria in 

paragraph (b)(1) of this section, and at least one of the exposure criteria in paragraph (b)(2) of this 

section." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether the data meets one of the toxicity criteria and one of 

the exposure criteria. 

30. Proposed Regulation # [Section] 158.2270(e)(1) 

Text of the Proposed Regulation (emphasis added) Post-application exposure: Test notes. 

"Protocols must be approved by the Agency prior to the initiation of the study. Details for 

developing protocols are available from the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether the protocol will be approved. These required private 

negotiations are a procedure for the development of later tests. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Post-application (Human Exposure) (100) Page 707 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27050 

Comment Code: 100000 

Comment: It is essential that EPA recognize that there are enormous data resources available that 

can be used as the first tier in any appropriately structured data requirement proposal for postapplication exposures. EPA should obtain and analyze these data and only then make decisions as to 

how much additional regulation may be necessary and appropriate under FIFRA. 

Response: see response 100.3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27437 

Comment Code: 100000 

Comment: IV. Comments on Proposed Rule (pages 56440-41, section 158.2260). Post- Application 

Exposure Data Requirements 

LANXESS’s comments related to "toxicity criteria" and "poisoning incident data" in section II. 

above are equally applicable to the post-application exposure provision at 158.2270 (b)(1)(i) and are 

incorporated here by reference. In addition, LANXESS has numerous concerns about the purpose 

of EPA’s post- application data requirements, the feasibility of several, and the fact that they are 

required as opposed to conditionally required. The data table for the most part lists all the studies as 

"required." However, it should be obvious that post-application requirements are not required (R), 

but instead are conditioned on factors that would create the opportunity for such exposures. There 

has to be far more clarity with regard to the triggers that would create a need for post-application 

exposure data. There are various statements about the triggers to testing, but none is sufficient to 

explain how to determine when post-application data must be addressed. 

For example, EPA states that it will require post-application exposure data for antimicrobials "when 

the toxicity and exposure criteria are triggered." 73 Fed. Reg. at 59441. However, no criteria are 

provided in the proposal. 

Similarly, in the introductory section to the post-application data table, EPA proposes the following 

text: 

(b) Criteria for Testing. 

(2) Exposure Criteria. (i) Outdoor uses. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Post-application (Human Exposure) (100) Page 708 

(B) Residential human post- application exposure to residues of antimicrobial pesticides could occur 

following the application of antimicrobial pesticides to indoor spaces or surfaces at residential sites, 

such as, but not limited to homes, daycare centers, hospitals, schools, and other public buildings 

Proposed 158.2270(b)(2) (i)(B). This is a far too subjective statement to be useful in the context of 

understanding when post-application data are required. 

There have to be conditions useful to determining whether exposures could be of a magnitude that 

could be of potential toxicological significance. Among the conditions that should be considered are 

the particular use patterns, whether any particular human activity would lead to the likelihood of 

measurable exposure, the results of applicator exposure testing and whether those results support 

the expectation of measurable post-application exposure, and chemical or physical characteristics of 

the antimicrobial that make measurable exposure possible. There are likely additional conditions as 

well that would be useful in making a determination on whether there was a need for postapplication exposure data in order to protect human health. 

The Preamble also states that 

[t]he Agency has become increasingly concerned about post-applications risks to person in 

occupational settings other than conventional food, feed, and fiber crop agriculture. The Agency is 

now proposing to require post-application exposure data for other settings where people may be 

exposed, regardless of whether they are on-the-job or bystanders. 

73 Red. Reg. at 59399. This is an exceedingly vague statement given the huge variety of occupational 

settings where antimicrobials are used. As also discussed in LANXESS’s General Comments at 

section VI, a post-application requirement should not even be considered in occupational settings 

without solid evidence of exposure at levels of potential concern from standard industrial hygiene 

data. This condition should be reflected in the test notes as a condition for requiring postapplication occupational data. It is also essential that any requirement for such data be required only 

after taking into consideration the engineering controls, process restrictions, and personal protective 

equipment that are required under OSHA or other applicable health and safety standards. 

Response: see responses 90.5, 90.6, 100.4, 100.5, and 100.6 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27439 

Comment Code: 100000 

Comment: The proposed requirement for two new studies, soil residue dissipation and indoor 

surface residue dissipation appear to be misplaced as required (R) for antimicrobials. One of the 

reasons given for these requirements is harmonization with conventional pesticides. However, the 

uses of antimicrobial products have little in common with the uses of conventional pesticides, and, 

therefore, there would appear to be little justification for the harmonization of post- application 

exposure requirements for these pesticide classes. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Post-application (Human Exposure) (100) Page 709 

Response: See responses 1 and 100.7. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27464 

Comment Code: 100000 

Comment: F. Comments on product use information and description of human activity data 

requirements 

It is essential that guidelines be proposed and finalized for these requirements. Without guidance, 

these requirements will be highly subjective. Guidance that establishes the scope of these 

requirements is critical to assuring that there is consistent and reasonable implementation of these 

requirements. 

Response: see response 191.3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27705 

Comment Code: 100000 

Comment: 27. Proposed Regulation # [Section] 158.2270(a)(2) 

Text of the Proposed Regulation (emphasis added) Post-application exposure: General. "If EPA 

determines that industrial standards, such as the workplace standards set by the Occupational Safety 

and Health Administration, provide adequate protection for a particular pesticide or a particular use 

pattern, post-application exposure data may not be required for that pesticide or the use pattern. 

Applicants should consult with the Agency on appropriate testing before the initiation of the 

studies." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether post-application exposure data is required or not. 

These required private negotiations are a procedure for the development of later tests. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27707 

Comment Code: 100000 

Comment: 28. Proposed Regulation # [Section] 158.2270(a)(3) 
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Comments and Response References: 

Post-application (Human Exposure) (100) Page 710 

Text of the Proposed Regulation (emphasis added) Post-application exposure: General. "The 

Agency may accept surrogate exposure data estimations from other sources to satisfy applicator 

exposure data requirements if the data meet the basic quality assurance, quality control, and other 

scientific requirements set by EPA . . . The Agency will consider using such surrogate data for 

evaluating human exposure on a case-by-case basis." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether it will accept surrogate exposure data. These required 

private negotiations are a procedure for the development of later tests. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27709 

Comment Code: 100000 

Comment: 29. Proposed Regulation # [Section] 158.2270(b) 

Text of the Proposed Regulation (emphasis added) Post-application exposure: Criteria for testing. 

"Post-application exposure data . . . are required based on toxicity and exposure criteria. Data are 

required if a product meets, as determined by the Agency, at least one of the toxicity criteria in 

paragraph (b) (1) of this section, and at least one of the exposure criteria in paragraph (b) (2) of this 

section." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether the data meets one of the toxicity criteria and one of 

the exposure criteria. 

30. Proposed Regulation # [Section] 158.2270(e)(1) 

Text of the Proposed Regulation (emphasis added) Post-application exposure: Test notes. 

"Protocols must be approved by the Agency prior to the initiation of the study. Details for 

developing protocols are available from the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether the protocol will be approved. These required private 

negotiations are a procedure for the development of later tests. 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27738 

Comment Code: 100000 
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Comments and Response References: 

Post-application (Human Exposure) (100) Page 711 

Comment: Nonetheless, it is essential that EPA recognize that there are enormous data resources 

available that can be used as the first tier in any appropriately structured data requirement proposal 

for post-application exposures. EPA should obtain and analyze these data and only then make 

decisions as to how much additional regulation may be necessary and appropriate under FIFRA. 

Response: see response 100.3 

Comment Code: 101000 Soil residue dissipation studies 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26928 

Comment Code: 101000 

Comment: A. Comments on Soil Residue Dissipation Data Requirement 

The need for a soil residue dissipation study should be very limited. At a minimum, this study should 

be conditioned upon selected chemical characteristics and environmental fate data, as well as 

product use information, leaching characteristics and relevant environmental fate data. Chemical 

characteristics are essential to determine whether there is a reasonable expectation of persistence in 

the soil over a reasonable time period. Also, as a first tier, a leach profile should be determined, 

relying on a methodology for determining a reasonable worst case leach profile, not data generated 

by the AWPA E-20 method, which dramatically overstate environmental leach rates and would lead 

to inaccurate conclusions. See also the comments in Appendix H. 

Response: See response 100.1. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26929 

Comment Code: 101000 

Comment: Test note 2 leaves open the scope of uses of preserved wood that would be subject to 

this requirement. Moreover, the guideline referenced for this data requirement (875.2200) is 

inappropriate for this requirement. It is for a conventional soil application; NOT for any known 

antimicrobial application. It is specific to pesticides applied to soil and is intended to address the 

reduction in soil levels following such application. Moreover, it is difficult to understand how this 

measurement would relate to potential human exposure scenarios. Unless the study also measured 

translocation of leachate, exposure would be limited to soil immediately adjacent to a wood 

structure; however, such exposure is not likely or definable. Before this requirement can be adopted, 

applicable guidance on the goal of this testing, its scope, methodology, etc, must be available. In the 

process of developing this guidance, it is likely to become clear that the desired information can be 

derived without requiring this additional study. 
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Comments and Response References: 

Post-application (Human Exposure) (100) Page 712 

Response: See response 100.1 and testnote 100.2. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27440 

Comment Code: 101000 

Comment: A. Comments on Soil Residue Dissipation Data Requirement 

The need for a soil residue dissipation study would be very limited. At a minimum, this study should 

be conditioned upon selected chemical characteristics and environmental fate data, as well as 

product use information, leaching characteristics and relevant environmental fate data. Chemical 

characteristics are essential to determine whether there is a reasonable expectation of persistence in 

the soil over a reasonable time period. Also, as a first tier, a leach profile should be determined, 

relying on a methodology for determining a reasonable worst case leach profile, not data generated 

by the AWPA E-11method, which dramatically overstate environmental leach rates and would lead 

to inaccurate conclusions. See also the comments in Appendix H. 

Response: See response 100.1. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27441 

Comment Code: 101000 

Comment: Test note 2 leaves open the scope of uses of preserved wood that would be subject to 

this requirement. Moreover, the guideline referenced for this data requirement (875.2200) is 

inappropriate for this requirement. It is for a conventional soil application; NOT for any known 

antimicrobial application. It is specific to pesticides applied to soil and is intended to address the 

reduction in soil levels following such application. Moreover, it is difficult to understand how this 

measurement would relate to potential human exposure scenarios. Unless the study also measured 

translocation of leachate, exposure would be limited to soil immediately adjacent to a wood 

structure; however, such exposure is not likely or definable. Therefore, there are real questions about 

how one could adequately characterize potential residues in an area where exposure could be 

reasonably expected to occur. Clearly, this is an area of inquiry that raises more questions than there 

are answers. Before this requirement can be adopted, applicable guidance on the goal of this testing, 

its scope, methodology, etc, must be available. In the process of developing this guidance, it is likely 

to become clear that the desired information can be derived without requiring this additional study. 

Response: See response 100.1 and testnote 100.2. 

Comment Code: 102000 Indoor surface residue dissipation studies 
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Comments and Response References: 

Post-application (Human Exposure) (100) Page 713 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25652 

Comment Code: 102000 

Comment: Regarding post-application data requirements, the Agency should review its guidelines in 

light of antimicrobial product uses. The use of the Indoor surface residue dissipation data (guideline 

number 875.2300) could provide critical lead information obviating the need for additional 

dermal/inhalation exposure. Such information would be particularly useful in the consideration of 

HVAC&R uses. 

It is essential that all of the applicator and post application guidelines be proposed and finalized for 

these requirements. Without guidance, these requirements could be highly subjective. Guidance that 

establishes the scope of these requirements is critical to assuring that there is consistent and 

reasonable implementation of these requirements. 

Response: see responses 100.10 and 191.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26932 

Comment Code: 102000 

Comment: B. Comments on Indoor Surface Residue Dissipation Data Requirement 

There is a fundamental question about the study being required under the name "indoor surface 

residue dissipation." Despite the use of Guideline number 875.2300, it appears that EPA intends to 

require surface residue data, which would not necessarily be indoor or track dissipation. The data 

actually being sought here need to be clarified. Further, the test notes for this requirement are overly 

broad, including with regard to product type, sites of use and human activities. Further, the proposal 

is internally inconsistent with regard to when this study would be required. 

Response: see response 100.9 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26934 

Comment Code: 102000 

Comment: In the Panel’s view, this study is not appropriate to require (R), and at most would be a 

Conditional Requirement (CR). The test notes should provide criteria that would limit testing to 

those situations in which residue would be available to leach in measurable amounts and the 

anticipated human activities that would be sufficient to result in toxicologically significant exposure. 

Moreover, EPA’s proposal is confusing to the Panel with regard to when a study would be required. 
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Comments and Response References: 

Post-application (Human Exposure) (100) Page 714 

For example, the Agency states that it is "primarily concerned with non-dietary exposures 

immediately following application of the antimicrobial pesticide," and that it "would not apply to 

uses that are not surface treatments, e.g., aquatic areas, swimming pools, antifoulant coatings, and 

paints." 73 Fed. Reg. at 59400. Nonetheless, test note 6 provides that 

Data are required for residential sites. This includes but is not limited to the following use patterns: 

commercial, institutional, and industrial premises and equipment (including residential school and 

daycare institutions); residential and public access premises; material preservatives (including but not 

limited to paints and plastic toys) and wood preservatives (when contact with treated wood is likely 

to occur). 

The Panel believes that EPA should resolve the differences between these two notes. The second 

test note is overly broad, requiring testing regardless of whether there is any reasonable expectation 

for exposure. If the Agency retains this note as a basis for testing, the note should be revised to 

accurately reflect when such data would be required. Clearly, there has to be consideration of the 

chemical characteristics that would lead to the availability of residue and clarity with regard to 

whether it is applicable only to direct applications and products for "surface treatment." 

Response: see response 100.9 and testnote 100.6 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26936 

Comment Code: 102000 

Comment: Similarly, test note 5 is overly broad. There are many surfaces on which antimicrobial 

residues could be deposited. However, there needs to be a relationship between the surfaces and the 

human activities occurring around them that would lead to an expectation of significant dermal 

exposure. There is simply no relationship with the types of post-application dermal exposures that 

could occur to agricultural workers entering a treated field and the types of dermal exposures that 

occur in the non-agricultural workplace. This test note is too broadly written and needs to contain 

an objective standard for determining when there is the potential for significant dermal exposure. If 

the surfaces and human activities expected to occur around those surfaces do not create a reasonable 

expectation of measurable exposure, then this study should not be required. 

Response: see response 100.9 and testnote 100.5 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27449 

Comment Code: 102000 

Comment: B. Comments on Indoor Surface Residue Dissipation Data Requirement 
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Comments and Response References: 

Post-application (Human Exposure) (100) Page 715 

There is a fundamental question about the study being required under the name "indoor surface 

residue dissipation." Despite the use of Guideline number 875.2300, it appears that EPA intends to 

require surface residue data, which would not necessarily be indoor or track dissipation. The data 

actually being sought here need to be clarified. Further, the test notes for this requirement are overly 

broad, including with regard to product type, sites of use and human activities. Further, the proposal 

is internally inconsistent with regard to when this study would be required. 

Response: see response 100.9 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27452 

Comment Code: 102000 

Comment: This study clearly is not appropriate to require (R), and at most would be a conditional 

Requirement (CR). The test notes need to provide criteria for testing to determine when residue 

would be available to leach in measurable amounts and the anticipated human activities that would 

be sufficient to result in appreciable exposure. Moreover, EPA’s proposal is contradictory with 

regard to when a study would be required. For example, the Agency states that it is "primarily 

concerned with non-dietary exposures immediately following application of the antimicrobial 

pesticide," and that it "would not apply to uses that are not surface treatments, e.g., aquatic areas, 

swimming pools, antifoulant coatings, and paints." 73 Fed. Reg. at 59400. Nonetheless, test note 6 

provides that 

Data are required for residential sites. This includes but is not limited to the following use patterns: 

commercial, institutional, and industrial premises and equipment (including residential school and 

daycare institutions); residential and public access premises; material preservatives (including but not 

limited to paints and plastic toys) and wood preservatives (when contact with treated wood is likely 

to occur). 

The test note is overly broad, includes every conceivable use regardless of whether there is any 

reasonable expectation for exposure and is inconsistent with EPA’s statements in the Preamble. It 

needs to be revised to accurately reflect when such data would be required. Clearly, there has to be 

consideration of the chemical characteristics that would lead to the availability of residue and clarity 

with regard to whether it is applicable only to direct applications and products for "surface 

treatment." Moreover, if this requirement is applied to wood, it is not an indoor surface test. Wood 

treated with antimicrobials used indoors is totally encased [stud wall] within a structure or overlaid. 

Joinery, the most commonly used indoor wood, has a protective stain or coating applied to it. 

Moreover, uses of joinery do not lend themselves to occasions where dermal exposure would be 

anticipated. Other wood preservative use sites are outdoors. 

Response: see response 100.9 and testnote 100.6 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 
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Comments and Response References: 

Post-application (Human Exposure) (100) Page 716 

Comment ID: 27453 

Comment Code: 102000 

Comment: Similarly, test note 5 is overly broad. There are many surfaces where antimicrobial 

residues could be deposited. However, there needs to be a relationship between the surfaces and the 

human activities occurring around them that would lead to an expectation of significant dermal 

exposure. There is simply no relationship with the types of post-application dermal exposures that 

could occur to agricultural workers entering a treated field and the types of dermal exposures that 

occur in the non-agricultural workplace. This test note is too broadly written and needs to contain 

an objective standard for determining when there is the potential for significant dermal exposure. If 

the surfaces and human activities expected to occur around those surfaces do not create a reasonable 

expectation of measurable exposure, then this study should not be required. 

Response: see response 100.9 and testnote 100.5 

Comment Code: 103000 Dermal exposure studies 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26937 

Comment Code: 103000 

Comment: C. Comments on Dermal Exposure Data Requirement 

The Panel believes it is not appropriate to require post- application dermal exposure. This should be 

a conditional requirement, based on the same types of considerations discussed in the preceding 

section. EPA already seems to recognize this to an extent. For example, test note 7 sets out the 

conditions about when the data would be required, albeit vaguely stated. There should be criteria 

consistent with the discussion in the Preamble on conditions for reasonably anticipating when 

dislogeable residues would be available. 

Response: see response 100.4 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27454 

Comment Code: 103000 

Comment: C. Comments on Dermal Exposure Data Requirement 

It is not appropriate to "require" post-application dermal exposure. This should be a conditional 

requirement, based on the same types of considerations discussed in the preceding section. That this 

is a conditional requirement is clear. For example, test note 7 sets out the conditions about when the 

data would be required, albeit vaguely stated. There should be criteria consistent with the discussion 
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Comments and Response References: 

Post-application (Human Exposure) (100) Page 717 

in the Preamble on conditions for reasonably anticipating when dislogeable residues would be 

available. 

Response: see response 100.4 

Comment Code: 104000 Inhalation studies 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26939 

Comment Code: 104000 

Comment: D. Comments on Inhalation Exposure Data Requirement The test notes for both 

dermal and inhalation post-application exposure are the same as those for applicator exposure. 

However, the test notes for post-application must be more specific to post-application. Clearly, any 

post-application inhalation data need should be premised on the findings from applicator exposure 

testing and applicable ambient measurements. The need for this requirement is quite limited, and 

would not be applicable if the active is not volatile, no aerosol is generated, or if there is no 

expectation of volatility post-application. Moreover, as discussed in the Panel’s General Comments 

at section VI, there is a large body of industrial hygiene data that are useful for determining whether 

post-application inhalation is an issue of concern. The potential to use such alternative data sources 

to meet requirements of the Proposal should be acknowledged in the EPA regulation. In most 

instances, it is possible to use modeling as a first step to determine whether a post-application 

inhalation risk assessment would be needed and therefore post-application inhalation data would be 

necessary. 

Further, the Panel believes test note 9 should be clarified.As currently proposed, the language that 

these data are "required if aerosols are generated where bystanders may be exposed," is too broadly 

worded to be meaningfully applied. The Panel believes that, to provide adequate guidance, this note 

should specify a range of defined conditions, such as chemical characteristics, ambient monitoring, 

human activities and other relevant factors to determine when these data would be needed. 

Response: see response 100.12 and testnote 100.9 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27462 

Comment Code: 104000 

Comment: D. Comments on Inhalation Exposure Data Requirement 

The test notes for both dermal and inhalation post-application exposure are the same as those for 

applicator exposure. However, the test notes for post- application must be more specific to postapplication. Clearly, any post- application inhalation data need should be premised on the findings 
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Comments and Response References: 

Post-application (Human Exposure) (100) Page 718 

from applicator exposure testing and applicable ambient measurements. The need for this 

requirement is quite limited, and would not be applicable if the active is not volatile, no aerosol is 

generated, or if there is no expectation of volatility post-application or post-drying. Moreover, as 

discussed in LANXESS’s General Comments at section VI, there is a plethora of industrial hygiene 

data that are useful for determining whether post-application inhalation is an issue of concern and 

should be acknowledged in the EPA regulation. In most instances, it is possible to use modeling as a 

first step to determine whether a post- application inhalation risk assessment would be needed and 

therefore post- application inhalation data would be necessary. Further, test note 9 is not helpful 

with regard to its condition that data are "required if aerosols are generated where bystanders may be 

exposed." This too is a far too broadly drafted condition. Again, there needs to be reliance on 

conditions such as chemical characteristics, ambient monitoring, human activities and other relevant 

factors to determine when these data would be needed. 

Response: see response 100.12 and testnote 100.9 

Comment Code: 105000 Non-dietary exposure for residential uses 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25679 

Comment Code: 105000 

Comment: Non-dietary ingestion exposure study 

SFE supports the requirement for a non-dietary ingestion exposure study to evaluate potential oral 

exposures to humans-particularly children-from antimicrobial pesticides in homes and other 

locations like schools, parks, and daycare centers where children may be present. We agree that 

incidental oral exposures via hand-to-mouth, object-to- mouth, and direct mouthing/ingestion are 

important exposure pathways and that exposure data are needed as input values for EPA’s 

antimicrobial pesticide evaluations. This requirement is particularly important in light of the growing 

number of antimicrobial-impregnated products that are being marketed for residential use, many of 

which are targeted toward infants and children. 

Response: EPA acknowledges SF Environment's support for requiring a non-dietary ingestion 

exposure study. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26944 

Comment Code: 105000 

Comment: G. Non-dietary Ingestion Exposure 
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Comments and Response References: 

Post-application (Human Exposure) (100) Page 719 

It is not clear from the test notes whether EPA anticipates human subject monitoring data to be 

used to fulfill this requirement. As with the swimming pool biomonitoring requirement, the Panel is 

concerned that non- dietary exposure testing is inappropriate to the extent human subject research is 

contemplated. The Panel submits that there is no need to conduct a study involving human subjects 

to obtain reliable data on non-dietary exposure. Exposure information can and is routinely derived 

from modeling based on chemical-specific surface wipe (referred to herein as indoor surface 

dissipation) test data and information from EPA’s Exposure Factors Handbooks, with regard to 

observed hand-to-mouth activity The data requirement should make clear that these approaches, not 

human testing, are contemplated by the Agency. 

The issue of non-dietary exposure is, linked to the requirement for an indoor surface 

dissipation/surface wipe test. As with the indoor surface dissipation requirement, in the Preamble, 

EPA states that it is "primarily concerned with non-dietary exposures immediately following 

application of the antimicrobial pesticide." 73 Fed. Reg. at 59400. However, this statement appears 

inconsistent with the examples provided in the Preamble. The Panel submits that non-dietary oral 

data should be required only where there is a likelihood of such exposures directly following 

application of the antimicrobial. Although the preamble refers to the possibility of a child eating 

antimicrobial containing paint chips or soil into which some antimicrobial has leached, these are 

remote possibilities and not typical sources of non-dietary exposure. 

Response: see response 100.13 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27466 

Comment Code: 105000 

Comment: G. Non-dietary Ingestion Exposure 

EPA should delete this study requirement from its proposal. It is both impractical and unnecessary. 

Such a study could be conducted only as an "observational" study, not as an "investigational" study 

requiring scientific and ethical review pursuant to EPA’s regulations on the protection of human 

subjects at 40 CFR Part 26. The complexities of conducting an observational study with toddlers or 

children would make it completely impractical. It also is doubtful that such a study could ever be 

conducted, even as observational, without creating controversy about whether it is ethical. 

Fortunately, there is no need to conduct a study to obtain reliable data on non- dietary exposure. 

Exposure information can and is routinely derived from modeling based on chemical-specific 

surface wipe (referred to herein as indoor surface dissipation) test data and information from EPA’s 

Exposure Factors Handbooks, with regard to observed hand-to-mouth activity. This approach is 

clearly preferable to the technical and ethical morass that would arise from trying to conduct an 

observational study to satisfy this requirement. 

The entire issue of non-dietary exposure relates directly to the requirement for an indoor surface 

dissipation/surface wipe test. As with the indoor surface dissipation requirement, in the Preamble, 

EPA states that it is "primarily concerned with non-dietary exposures immediately following 
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Comments and Response References: 

Post-application (Human Exposure) (100) Page 720 

application of the antimicrobial pesticide." 73 Red. Reg. at 59400. However, this statement is entirely 

inconsistent with the examples provided in the Preamble. These examples do not represent 

reasonable criteria for when non- dietary oral ingestion exposure is necessary for risk assessment 

purposes. As with the indoor surface dissipation requirement, there needs to be clarity on whether 

this requirement is limited to exposures immediately following application of the antimicrobial. 

Clearly, this is the most likely scenario under which such exposure would occur. Moreover, the 

canard of the "antimicrobial pesticide-treated paint chip" finally must be laid to rest. No EPA 

registration requirement should be conditioned on incidental, episodic events such as eating a paint 

chip, which is in fact, part of poisoning event, not a routine exposure. It is simply inappropriate to 

consider products such as paint that is applied to walls as part of a routine non-dietary exposure 

scenario. Again, the prospect of exposure to soils is invoked. This begs the question of how this 

requirement is related to the soil dissipation requirement. As discussed above, estimates of exposure 

from soil is a function of modeling existing EPA exposure assumptions and applicable 

environmental fate data. 

Response: see response 100.13 

Comment Code: 107000 Commenter's Concept of Post-Application Exposure Data Requirements 

Table Revisions 

Comment Summary: As part of their comments, the commenter provided an alternate 

Antimicrobial Post-Application Data Requirements Table with testnotes. EPA’s response is for the 

entire alternate testing scheme and not the individual parts. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26945 

Comment Code: 107000 

Comment: V. Alternative Proposal for Post-Application Exposure Data Requirements 

Following is the Panel’s recommendations on revisions to the applicator exposure data requirement 

regulation. 

158.2270 Post-applicator exposure 

(b) Delete and revise as discussed above. 

Replace table and test notes with the following: 

Table – Antimicrobial Post-Application Exposure Data Requirements 

 Use Sites 

Guideline 

Number Data Requirements Occupational Residential Test 

Substance 

Test Note 

No. 

???? Indoor Surface Residue CR CR TEP 1, 2, 4 
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Post-application (Human Exposure) (100) Page 721 

 Use Sites 

Guideline 

Number Data Requirements Occupational Residential Test 

Substance 

Test Note 

No. 

875.2400 Dermal Exposure CR CR TEP 1, 3, 4, 

875.2500 Inhalation Exposure CR CR TEP 1, 6, 8 

875.2600 Biological Monitoring NR NR TEP 1, 5, 7 

875.2700 Product Use Information R R TEP 8 

875.2800 Description of Human 

Activity R R TEP 

875.2900 Data Reporting and 

Calculations CR CR TEP 8 

Test Notes: 

1. Consultation with the Agency is encouraged in the event the test guideline does not provide 

adequate information on all important aspects of the study. If the study will involve human subjects, 

the applicant should meet with EPA regarding the compliance with 40 CFR Part 26. 

 2. The applicant must submit residue dissipation data if dermal exposure data are required. The 

dissipation data will be used to establish chemical transfer coefficients used to estimate transfer of 

residues to human skin. 

 3. For occupational uses, data are required if there is direct application of the antimicrobial pesticide 

to surfaces and the typical human activity data indicate that workers are likely to have toxicologically 

significant measurable post application dermal exposures to recently treated indoor surfaces. 

Physical and chemical characteristics data should be considered in determining the likelihood of 

exposure. Modeling potential exposures may be considered to satisfy this requirement. The 

modeling should incorporate generic transfer coefficients and chemical-specific transfer data. 

 4. Data are required for residential, institutional and public access sites if there is direct application 

of the antimicrobial pesticide to surfaces contacted by humans and the typical human activity data 

indicate that there is a reasonable expectation that toxicologically significant measurable post 

application dermal exposures will occur. Data are required for occupational and residential use sites 

if the human activity data indicate that there is a reasonable expectation that toxicologically 

significant post application dermal exposures are likely to occur. Modeling potential exposures may 

be considered to satisfy this requirement. The modeling should incorporate generic transfer 

coefficients and chemical-specific transfer data. 

 5. Biological monitoring data acceptable under EPA’s Protection of Human Subjects Regulation 

may be submitted in addition to, or in lieu of, dermal and inhalation passive dosimetry exposure data 

provided the human pharmacokinetics of the pesticide or metabolite/analog compounds (i.e., 

whichever method is selected as an indicator of body burden or internal dose) allow for a backcalculation to the total internal dose. 

 6. Data are required for occupational sites (i) if the vapor pressure is greater than 1E-3 mmHg at 25 

[deg] C; (ii)) applicable applicator exposure data demonstrate high inhalation exposure levels; (iii) 
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Post-application (Human Exposure) (100) Page 722 

ambient exposure data confirm potential for high levels of inhalation exposure or OSHA, ACGIH 

or other standards are exceeded; and (iv) bystander exposure is regular, that is, greater than episodic. 

Data also are required if aerosols are continuously generated where bystanders are typically or 

regularly exposed. EPA will consider data generated for other purposes to fill this requirement, 

including occupational monitoring data. 

 7. Biological monitoring data may be required when acceptable under EPA’s Protection of Human 

Subjects Regulation and passive dosimetry techniques are not applicable for a particular exposure 

scenario (such as a swimmer/spa exposure). Other sources of data are to be preferred. 

 8. Data reporting and calculations are required when any post-application exposure monitoring data 

are required. 

Response: see response 90.15 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27472 

Comment Code: 107000 

Comment: V. Alternative Proposal for Post-Application Exposure Data Requirements Following is 

LANXESS’s recommendations on revisions to the applicator exposure data requirement regulation. 

158.2270 Post-applicator exposure 

(b) Delete and revise as discussed above. 

Replace table and test notes with the following: 

[See Table "Antimicrobial Post-Application Exposure Data Requirements" on page 9 of appendix 

G, PDF docket ID EPA-HQ-OPP-2008-0110-0064] 

Test Notes: 

1. Protocols must be approved by the Agency prior to the initiation of the study. Details for 

developing protocols are available from the Agency. 

2. The applicant must submit residue dissipation data in conjunction with dermal exposure data, to 

establish chemical transfer coefficients used to estimate transfer of residues to human skin. 

3. For occupational uses, data are required if there is direct application of the antimicrobial pesticide 

to surfaces and the typical human activity data indicate that workers are likely to have measurable 

post application dermal exposures to recently treated indoor surfaces. Physical and chemical 

characteristics data should be considered in determining the likelihood of exposure. Modeling 

potential exposures may be considered to satisfy this requirement. The modeling should incorporate 

generic transfer coefficients and chemical-specific transfer data. 
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Comments and Response References: 

Post-application (Human Exposure) (100) Page 723 

4. Data are required for residential, institutional and public access sites if there is direct application 

of the antimicrobial pesticide to surfaces and the typical human activity data indicate that there is a 

reasonable expectation that measurable post application dermal exposures will occur. Data are 

required for occupational and residential use sites if the human activity data indicate the potential for 

post application dermal exposures while participating in typical activities. Modeling potential 

exposures may be considered to satisfy this requirement. The modeling should incorporate generic 

transfer coefficients and chemical-specific transfer data. 

5. Biological monitoring data may be submitted in addition to, or in lieu of, dermal and inhalation 

passive dosimetry exposure data provided the human pharmacokinetics of the pesticide or 

metabolite/analog compounds (i.e., whichever method is selected as an indicator of body burden or 

internal dose) allow for a back- calculation to the total internal dose. 

6. Data are required for occupational sites (i) if the vapor pressure is greater than 1E-3 mmHg at 25° 

C; (ii)) applicable applicator exposure data demonstrate high inhalation exposure levels; (iii) ambient 

exposure data confirm potential for high levels of inhalation exposure or OSHA, ACGIH or other 

standards are exceeded; and (iv) bystander exposure is regular, that is, greater than episodic. Data 

also are required if aerosols are continuously generated where bystanders are typically or regularly 

exposed. 

7. Biological monitoring data may be required when passive dosimetry techniques are not applicable 

for a particular exposure scenario (such as a swimmer/spa exposure). 

8. Data reporting and calculations are required when any post-application exposure monitoring data 

are required. 

Response: see response 90.15 
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Comments and Response References: 

Residue Chemistry Section (110) Page 724 

Residue Chemistry (110) 

Verbatim Comments and Response References for the Residue Chemistry 

Section 

Comment Code: 110000 Residue chemistry 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25584 

Comment Code: 110000 

Comment: While EPA has stated that these proposed changes will allow EPA to better estimate 

human dietary exposure to ensure that food entering the commercial market meets the "reasonable 

certainty of no harm" standard under FFDCA, CSPA members challenge that some of these 

changes will allow for a "better" estimate of human dietary exposure and that the Agency has 

extended their authority beyond their jurisdiction.. 

There remains a great deal of confusion regarding areas of responsibility between EPA and FDA 

regarding antimicrobial substances with direct and indirect food contact uses. This requires Page 12 

careful attention to EPA's statutory authority to require the setting of tolerances or exemptions from 

food tolerance under section 408 of FFDCA. There need to be very explicit definitions and 

guidance regarding antimicrobials under the jurisdiction of EPA. In the wake of FQPA, ARTCA 

was enacted to return jurisdiction over certain residues on processed Raw Agricultural Commodities 

(RAC) to FDA. However there remains ongoing confusion about antimicrobials applied to process 

water and RAC's. Subsequent to ARTCA, The Antimicrobial Food Additives Guidance (July 1999) 

was developed and published to provide additional clarity to many of the confusing issues such as 

what constitutes food processing and how a food processing facility is defined. The Guidance 

document provides additional explanation of the jurisdictional agreement between EPA and FDA. 

In addition, several of the past Antimicrobial Workshops provided extensive presentations based on 

the clarity provided thru the FDA Antimicrobial Food Additives Guidance Document. 

In addition, the draft Rule for Registration Requirements for Antimicrobial Pesticide Products 

proposing changes to 40 CFR Part 152 and 158 and published in 1999, provided a chart which was 

consistent with the agreements reached through the Antimicrobial Food Additive Guidance 

document. In recent years, Industry has met with EPA management to discuss ways to further 

streamline the approval of food use antimicrobials under EPA and FDA jurisdiction. It is critical 

that the Agency look to the statute to ensure that any proposal to require a 408 clearance is clearly 

within the Agency's statutory authority to require a tolerance or exemption from food tolerance. 

Now is the time to provide clarity through a more detailed description as to the Residue chemistry 

data requirements by providing specific examples which would help to alleviate the continued 

confusion to EPA, industry and local and state Health Department Inspectors. 

Response: see responses 30.26 and 110.1 
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Comments and Response References: 

Residue Chemistry Section (110) Page 725 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25600 

Comment Code: 110000 

Comment: c. Dietary Exposure 

General Considerations: 

*In the Residue Chemistry Data Requirements and in section 158.2290 titled Residue chemistry, the 

expression "residue of concern" should be replaced with "residue definition" to reflect the NAFTA 

and OECD approved terminology. 

Detailed Considerations: 

 Section Number Subpart W 

Title Antimicrobial Pesticide Data Requirements 

Paragraph [Section]158.2290 Residue chemistry, (a) General, p. 59444 

 Excerpt from Federal Register (i) Direct food uses such as antimicrobial products used to treat 

animal or poultry drinking water... (iii) Aquatic uses that have the potential to result in residues in 

potable water, or in water used for livestock and poultry drinking water... 

HC Comment There seems to be an overlap in the uses identified under each of these categories. 

The PMRA suggests limiting potable water and livestock/poultry drinking water to one category 

only. 

Response: see responses 110.6 and 110.7 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25615 

Comment Code: 110000 

Comment: (b)(1)(ii) - Non Exempt Treated articles should be removed from this section for 

clarification purposes. An additional section is recommended to be added to (b) (1) and to the 

section (f) table to provide a clear way to determine criteria for articles. This section should be 

strictly devoted to indoor commercial and institutional uses on hard surfaces. 

Response: see response 110.38 

Commenter Name: Brigid D. Klein 
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Comments and Response References: 

Residue Chemistry Section (110) Page 726 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25617 

Comment Code: 110000 

Comment: Section 408 of FFDCA requires the establishment of a tolerance or exemption from 

food tolerance for pesticide chemical residues when pesticides are applied to foods and which will 

be in "interstate commerce". EPA stated at the 8th Annual Antimicrobial Workshop, that the 

requirements for a tolerance or exemption from food tolerance for antimicrobials applied in the 

home were not applicable. EPA based this statement on that food in household setting is not in 

interstate commerce and therefore does not require the establishment of a tolerance or exemption 

from food tolerance for formulation components comprising a hard surface disinfectant or sanitizer. 

EPA went on to state that although tolerance or tolerance exemption setting is not required due to 

the interstate commerce issue, that the Agency would require a dietary assessment to ensure any 

remaining residues are addressed from a dietary/safety standpoint. CSPA agrees with this approach 

and concurs that tolerance or exemption from tolerance setting is not required for hard surface 

antimicrobials used in residential settings. 

Response: EPA acknowledges CSPA's support for requiring a dietary risk assessment for 

antimicrobials applied in the home setting. 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25618 

Comment Code: 110000 

Comment: (c) Definitions of low toxicity of the active ingredient or theoretical estimates of dietary 

exposure need to be clarified. 

Response: see response 110.37 

Commenter Name: Jay Feldman 

Commenter Organization: Beyond Pesticides 

Letter ID: 0067 

Comment ID: 25707 

Comment Code: 110000 

Comment: The nation’s surface waters are also contaminated with high concentrations of 

antimicrobial compounds.[FN1: Halden, R.U., and Paull, D.H. 2005. Co-occurrence of triclocarban 

and triclosan in US water resources. Environmental Science & Technology 39, 1420-1426. FN2: 

Kolpin, D.W., E.T. Furlong, M.T. Meyer, E.M. Thurman, et al. 2002. Pharmaceuticals, Hormones, 

and other organic wastewater contaminants in U. S. streams, 1999-2000: A national reconnaissance. 

Environ. Sci. Technol. 36, 1202-1211.] This means that not only is drinking water contaminated, but 

fish and other aquatic organisms that are ingested by humans. Under the Federal Food, Drug and 

Cosmetic Act (FFDCA), the EPA is mandated to determine that there is a reasonable certainty that 

no harm will result from aggregate exposure to the pesticide chemical residue, including all 
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Comments and Response References: 

Residue Chemistry Section (110) Page 727 

anticipated dietary exposures and all other exposures for which there is reliable information. 

FFDCA, Sec. 408(b)(2)(A)(ii). 

Response: see response 110.26 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25710 

Comment Code: 110000 

Comment: Potable water residues 

The presence of antimicrobials like triclosan in the nation’s potable water supplies has raised 

concern and controversy across the nation. EPA needs to ensure that it requires the data necessary 

to protect water supplies. The use pattern assignments and test notes associated with the potable 

water residue requirement do not reflect all use patterns that entail the release of antimicrobials into 

potable water supplies. Many drinking water supply intakes are on rivers, downstream of discharges 

from municipal wastewater treatment plants, cooling water systems, and discharge points for urban 

stormwater runoff. To ensure public safety, EPA should clarify its description of "aquatic uses" in 

the residue chemistry requirements (at pp. 59444-59445) to include all antimicrobial pesticides that 

may be present in discharges from municipal wastewater treatment plants, industrial facilities, or 

urban stormwater runoff. 

Response: see response 110.4 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25742 

Comment Code: 110000 

Comment: The Draft 158W Rule Lacks Clarity as Data Requirement for Food Use Antimicrobials 

The regulatory jurisdiction for food use antimicrobials is very complex due to unintended 

consequences of the Food Quality Protection Act (FQPA), the Antimicrobial Regulation Technical 

Corrections Act (ARTCA) and FDA's July 1999 "Antimicrobial Food Additive Guidance 

Document", and a regulatory policy interpretation (Legal Policy Interpretation of the Jurisdiction 

Under the FFDCA and EPA Over the Use of Certain Antimicrobial Substances - October 9, 1998)) 

between EPA and FDA which was rescinded due to the passage of ARTCA. While the 

Congressional intent of ARTCA was to correct the unintended consequences of FQPA, ARTCA 

failed to revert many instances of residue jurisdiction back to FDA as the EPA definition of pest 

remained unchanged to allow certain exemptions from that definition. This jurisdiction quagmire 

has a profound bearing on FIFRA 2 (bb), which in turn drives the FFDCA section 408 data 

requirements for a food use antimicrobial pesticide registration. Some 10 years after the publication 

of FDA's Antimicrobial Food Additive Guidance document, significant confusion remains as to 

where EPA has regulatory jurisdiction over food use antimicrobials, when the jurisdiction is shared 
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Comments and Response References: 

Residue Chemistry Section (110) Page 728 

with FDA, and EPA's statutory authority to require tolerances or exemptions from food tolerance 

for food use antimicrobials. 

In 1999, EPA attempted to provide a scantly written table outlining the jurisdiction between EPA 

and FDA and when residue clearances were required under Sections 408 and 409 of FFDCA. The 

current preamble and §158.2290 Residue Chemistry section of the proposed 158W rule falls 

disappointingly short of providing clarity as to when EPA requires the setting of a tolerance or 

tolerance exemption under section 408 of FFDCA. This section needs significant improvement in 

order for prospective registrants to clearly understand chemistry residue requirements for food use 

antimicrobials subject to EPA's jurisdiction under FIFRA and Section 408 of FFDCA. In addition, 

this section should delineate what constitutes a processed food and a food processing facility as 

defined in the FDA Antimicrobial Food Additive Guidance document. 

Response: see responses 30.26 and 110.1 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25743 

Comment Code: 110000 

Comment: Without a detailed and in depth discussion of these critical points, the 158W food use 

data requirements are meaningless and will only continue to result in confusion to the regulated 

community and the Agency. Ecolab supports the recommendation provided by CSPA to further 

improve the data requirements to align with today's understanding of when a Section 408 

requirement must be met. (See the proposed table in this letter as it relates to Chemistry Residue.) 

Response: EPA acknowledges Ecolab's support for CSPA's concept table for residue chemistry 

data requirements. 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25744 

Comment Code: 110000 

Comment: Ecolab recommends the Agency consider the following example to indicate where EPA 

does and does not have statutory authority to require an FFDCA 408 clearance with respect to 

Residue Chemistry: 

1. Antimicrobial with food contact uses regulated as pesticide chemicals (subject to EPA jurisdiction 

under FFDCA section 408) include the following: 

* Antimicrobials applied to raw agricultural commodities (RACs) or to process water applied to 

RACs in the field, during transportation, or in facilities where no other processing of RACs occurs 

(typically washing/packing houses only where de-stemming, drying, shelling and husking may occur) 
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Comments and Response References: 

Residue Chemistry Section (110) Page 729 

* Antimicrobials applied to surfaces other than food packaging e.g. hard surface food contact 

sanitizer or disinfectant. 

* Antimicrobials included in objects or articles and intended to have an ongoing effect on the food 

contact surface. 

* Antimicrobial applied to food process water to reduce the count in the process water or applied to 

process water to reduce microbial count on the surface of fruits and vegetables. 

2. Antimicrobial with food contact uses regulated as food additives (subject to FFDCA section 409, 

administered by FDA and registered by EPA as a pesticide) include the following: 

* Antimicrobials applied to RACs food in a food processing facility (as defined in FDA's 1999 

Antimicrobial Food Additive Guidance document). 

* Antimicrobials applied as commercial sterilants for aseptic food packaging. 

Response: see responses 30.26 and 110.1 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25763 

Comment Code: 110000 

Comment: Section 158.2290 - Residue Chemistry 

Ecolab concurs with the ACC Biocides Panel and CSPA that the Agency's description of residue 

chemistry requirements in the proposed 158W raise many questions that must be considered before 

this proposal can be finalized. 

Response: no response is needed 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25765 

Comment Code: 110000 

Comment: The table in the proposed 158W is confusing and unclear as to when residue chemistry 

data is required. In order for these data requirements to be meaningful, they Agency needs to clearly 

identify what antimicrobial pesticide uses are subject to FFDCA 408 regulation. It is only those uses 

that EPA has the statutory authority to regulate under Section 408 of FFDCA. 

Response: see responses 30.26 and 110.1 

Commenter Name: James A. Westerhaus 
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Comments and Response References: 

Residue Chemistry Section (110) Page 730 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25766 

Comment Code: 110000 

Comment: In the preamble to Section 158.2290, the Agency needs to include specific examples of 

where it has statutory authority to regulate antimicrobial pesticides under FFDCA Section 408. 

Response: See responses 30.26 and 110.1 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25768 

Comment Code: 110000 

Comment: Also, there needs to be clarification that drying, shelling and husking of RACs does not 

constitute processing as explained in the 1999 Antimicrobial Food Additive Guidance Document 

issued by FDA. The Guidance document is clear that these activities do not constitute processing 

and antimicrobials applied to RAC's in the field, in a washing facility where no further processing 

occurs, or in transportation, or applied to process water is under EPA jurisdiction and requires a 

FFDCA 408 clearance. Conversely, antimicrobials applied to RAC's in a food processing facility 

prior to packing or further processing (cutting, peeling, cooking, slicing) may require a FIFRA 

registration as a pesticide and a FDA 409 FFDCA clearance. 

Response: See responses 30.26, 110.1, and 110.19. 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25769 

Comment Code: 110000 

Comment: Ecolab proposes the following to illustrate when the Agency has statutory authority 

under FFDCA 408 with respect to antimicrobial produce washes and antimicrobials applied to 

process water which contact fruits and vegetables. 

1. Antimicrobial with food contact uses regulated as pesticide chemicals (subject to EPA jurisdiction 

under FFDCA section 408) include the following: 

* Antimicrobials applied to raw agricultural commodities (RACs) or to process water applied to 

RACs in the field, during transportation, or in facilities where no other processing of RACs occurs 

(typically washing/packing houses only where de-stemming, drying, shelling and husking may occur) 

* Antimicrobials applied to surfaces other than food packaging e.g. hard surface food contact 

sanitizer or disinfectant. 
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Comments and Response References: 

Residue Chemistry Section (110) Page 731 

* Antimicrobials included in objects or articles and intended to have an ongoing effect on the food 

contact surface. 

* Antimicrobial applied to food process water to reduce the count in the process water or applied to 

process water to reduce microbial count on the surface of fruits and vegetables. 

Response: See responses 30.26 and 110.1 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25770 

Comment Code: 110000 

Comment: In addition, Ecolab supports the ACC and CSPA proposed data requirement tables 

submitted as comment to this proposed rule. 

Response: EPA acknowledges Ecolab's support for the ACC- and CSPA-generated data 

requirement tables that were submitted as part of their comments on this rule. 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25771 

Comment Code: 110000 

Comment: Section 408 of FFDCA requires the establishment of a tolerance or exemption from 

food tolerance when pesticides are applied to foods and which will be in "interstate commerce". 

EPA stated at the 8th Annual Antimicrobial Workshop, that the requirements for a tolerance or 

exemption from food tolerance for food use antimicrobials applied in the home were not applicable. 

EPA based this statement on the premise that food in household setting is no longer in interstate 

commerce and therefore does not require the establishment of a tolerance or exemption from food 

tolerance for formulation components comprising a hard surface disinfectant or sanitizer. EPA went 

on to state that although tolerance or tolerance exemption setting is not required due to the 

interstate commerce issue, that the Agency would require a dietary assessment to ensure any 

remaining residues are addressed from a dietary/safety standpoint. Ecolab agrees with this approach 

and concurs that tolerance or exemption from tolerance setting is not required for hard surface 

antimicrobials which may have indirect contact with food in the home setting, but an extensive 

dietary risk assessment should be required. 

Response: EPA acknowledges Ecolab's support for requiring a dietary risk assessment for 

antimicrobials applied in the home setting. 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25928 
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Comments and Response References: 

Residue Chemistry Section (110) Page 732 

Comment Code: 110000 

Comment: Use of IDREAM to Estimate Potential Dietary Exposure in Residential Settings 

During the past several years, the Agency has been considering various residential kitchen surfaces 

to be food contact surfaces and that the use of disinfectants on such surfaces may introduce residues 

into food. While such interpretations and implications have been debated, it is clear from a 

regUlatory perspective that these are not uses subject to regulation under FFDCA 408. Thus such 

uses will not trigger the requirement of a tolerance or exemption from tolerance for each chemical 

used in residential kitchen disinfecting products. However, there is general agreement that there 

exists a potential dietary exposure from such uses. In recognition of this, the Panel has developed 

and provided the Agency a tiered exposure assessment model for determining indirect ingestion of 

hard surface disinfectants and cleaning products used on residential kitchen surfaces (Incidental 

Dietary Residential Exposure Assessment Model, IDREAM). We believe this model is an excellent 

tool for estimating dietary exposure and has been used by the Agency and registrants in support of 

registration actions. We believe the Agency should formally recognize this model and refer to it in 

Part 158W. 

Response: see response 110.5 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26269 

Comment Code: 110000 

Comment: For example, a review of recent decisions reveals that, in some cases EPA has 

determined that it will conduct a dietary risk assessment even though the active ingredient has no 

uses that require a tolerance or tolerance exemption, or an indirect food additive approval from 

FDA under FFDCA section 409. This occurred in EPA Case No. 3070, where both the Human 

Health Effects Scoping Document and Registration Review Summary [FN#19:See Docket No. 

EPA-HQ-OPP-2008-0879 at http://www.regulations.gov for the Registration Review case file.] 

state that: 

Dietary (food) exposure could potentially occur because HHT/HMAE is used as a process 

preservative and an in- can preservative for materials containing water as a major ingredient such as 

caulks, adhesives, sealants that may be used in food contact situations such as food preparation, 

food processing, and food serving areas. A dietary exposure and risk assessment has not been 

conducted in the past. However, migration of HHT/HMAE from these preserved materials to food 

may occur to some extent. Therefore, a dietary (food source) risk assessment is recommended 

during the risk assessment stage of Registration Review. However, certain chemistry, use pattern, 

and chronic/cancer studies are being recommended to permit more appropriate exposure estimates 

and the selection of an endpoint for use in a chronic dietary risk assessment. Note that FDA does 

not currently regulate HHT/HMAE as a direct or indirect food additive. 

Human Health Effects Scoping Document at 8 (emphasis added). 
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Comments and Response References: 

Residue Chemistry Section (110) Page 733 

This situation raises two critical issues. First, EPA previously has not required a dietary risk 

assessment; this "recommendation" thus represents a significant change in policy. [FN#20:The 

Panel submits that EPA is incorrect in recommending a dietary risk assessment under these 

circumstances. The products at issue are not registered for uses that reasonably might result in 

residues on food. If indeed sealants, caulks, and adhesives were intended to be used in food- contact 

applications, each and every component of such products, not just the antimicrobial, would have to 

be approved by FDA as an indirect food additive pursuant to FFDCA section 409. If any product 

used in food preparation, processing, or service did not have the requisite FDA approval for each 

component, such product could be considered adulterated pursuant to FFDCA. The Panel believes 

EPA is acting arbitrarily and capriciously in seeking to assess dietary risks and make regulatory 

decisions based on an assumption of misuse under FIFRA and violations of FFDCA.] No such 

change has been publicly vetted or even acknowledged. Second, the same requirement for a dietary 

risk assessment for non-food uses has been advanced in several other Registration Review 

cases.[FN#21:See Case 5026, Busan 1024 Registration Review Final Work Plan, December 14, 2007; 

and Case 5027, Oxazolidine-E Registration Review Final Work Plan, September 17, 2008.] However, 

the requirement has not been applied in other Registration Review cases, even though chemistries 

are similar and use patterns are the same.[FN#22:See Case 3053, Nuosept 145 Registration Review 

Final Work Plan, September 10, 2008.] 

The foregoing example is not an isolated case. Other situations involving ad hoc risk assessment 

processes include: 

* In particular cases, EPA has sought to perform dietary risk assessments and require extensive data 

on antimicrobials used to preserve detergents for washing countertops or cutting boards.23 There is 

no guidance on this and it has not been applied to all such potential preservatives for such products. 

* EPA has asserted that a dietary risk assessment is required in the Registration Review of 

Oxazolidine-E based on the use of the preservative in surfactants that may become components of 

dishwashing liquids and surface cleaners. The Agency acknowledges that these are not "direct or 

indirect food uses," (no approval under FFDCA section 408 or 409 is needed) but nonetheless EPA 

asserts that a "Tier 1 dietary screening level assessment" is triggered [FN#24:The Panel has sought 

but not found any information on what constitutes a "Tier 1 dietary screening level assessment" for 

an active ingredient without food uses. Also, EPA has offered no explanation of its authority to 

require an FQPA risk assessment in this situation.] and that EPA "must conduct risk assessments to 

ensure that Oxazolidine-E meets the safety standards established by FFDCA, as amended by 

FQPA."[FN#25:Oxazolidine-E Registration Review Final Work Plan, December 17, 2008, Docket 

No. EPA-HQ-OPP-2008-0404, http://www.regulations.gov] 

Response: see responses 30.26 and 110.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26278 

Comment Code: 110000 
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Comments and Response References: 

Residue Chemistry Section (110) Page 734 

Comment: * The recent HHT RED provides another example of EPA’s case-by-case approach to 

risk assessment. There, although HHT has no uses requiring clearance under section 408 or 409 of 

FFDCA, EPA conducted "an indirect food use assessment."[FN#26:Grotan RED at 19.] It appears 

there is a policy without publicly available documentation to allow reviewers on a case-by- by case 

basis to decide to perform some type of dietary risk assessments on some unspecified categories of 

uses. [FN#27:In this RED, EPA concluded that that both the aPAD and cPAD "are well below 

100%, dietary exposure does not exceed the Agency’s level of concern." This finding is perplexing, 

as the Panel is unaware of any methodology for determining dietary exposures from the uses 

registered for HHT.] 

Response: see responses 30.26 and 110.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26386 

Comment Code: 110000 

Comment: The Agency should revise the preamble to the Proposal to provide clarification on the 

regulation of food- contact antimicrobials, and revise the use patterns, data tables and test notes to 

ensure conformance to this statutory division of authority. 

Response: see responses 30.26 and 110.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26388 

Comment Code: 110000 

Comment: C. The Proposal Should Clarify that Not All Food Uses Are Subject to Tolerance 

Requirements 

The 158W reproposal should clarify that not all antimicrobial food uses are subject to tolerance 

requirements.[FN#53:See for example at page 59432, proposed 158.2230(b)(1)(ii) through (v) 

compared to (i), which appears to suggest a difference in which food uses require regulation under 

section 408.] This is essential in order to correct certain errors in the Proposal. For example, the 

preamble includes the following assertion of authority: 

Currently in part 161, a proposed tolerance is required for all food-use patterns. Today, the Agency 

is proposing to continue this existing requirement by requiring a proposed tolerance for all 

antimicrobial food-use patterns. 

73 Fed. Reg. at 59402. 

Response: see responses 30.26 and 110.1 
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Comments and Response References: 

Residue Chemistry Section (110) Page 735 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26389 

Comment Code: 110000 

Comment: While the meaning of the term "proposed tolerance" is unclear, it appears EPA intends 

to require tolerances for food uses of antimicrobials, despite the fact that EPA has only limited 

jurisdiction under FFDCA 408 for antimicrobial food uses. Such a move would usurp FDA’s 

statutory grant of jurisdiction under FFDCA 409 and is inconsistent with EPA policy, practice, and 

regulations. EPA should withdraw this subsection from the preamble or provide a better 

explanation for what it is intending and the authority under which it is proposing to act. 

D. EPA Has Not Identified a Clear Basis for Distinguishing Food Uses of Pesticides as Direct or 

Indirect 

In the preamble, EPA mentions both indirect and direct food uses of pesticides and reflects this 

distinction further in the data tables.[FN#54:For example, at pages 59389, 59393, 59394, and 

59401.] However, there is no basis in FFDCA for such a distinction. 

FFDCA Section 201(s) defines "food additives" as follows: 

The term "food additive" means any substance the intended use of which results or may reasonably 

be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the 

characteristics of any food (including any substance intended for use in producing, manufacturing, 

packing, processing, preparing, treating, packaging, transporting, or holding food; and including any 

source of radiation intended for any such use). 

FDA’s regulations implementing this provision distinguish between direct and indirect food 

additives. A direct food additive, as defined by FDA in guidance, is one that is intentionally added to 

food. An indirect food additive is one that may inadvertently become a part of food. This distinction 

does not carry over to the antimicrobials regulated as pesticides, because antimicrobial direct food 

additives are excluded from the definition of a pesticide and therefore are not subject to EPA 

jurisdiction at all. Instead they are solely within FDA’s jurisdiction. FDA regulates both direct and 

indirect food additives based on the potential level of exposure, applying a single safety standard to 

both. [FN#55:FDA regulates as third category as "secondary direct food additives," defined as an 

additive that "has a technical effect in food during processing but not in the finished food (e.g., 

processing aid." See www.cfsan.fda.gov/~dms/opa-def.html. They are also regulated under the 

same safety standards as direct and indirect food additives. An example of an antimicrobial regulated 

as a secondary direct food additive is a chemical to control microorganisms in cane sugar and beet 

sugar mills during processing. 21 CFR 173.320.] 

EPA has not identified a clear basis for distinguishing food uses of pesticides as direct or indirect, 

nor has it elucidated any basis for distinguishing applicable data requirements. The distinction in this 

Proposal between direct and indirect food uses therefore should be eliminated. It serves no purpose, 

and further confuses the issues surrounding the regulation of antimicrobials. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 736 

Response: see responses 30.26, 110.1, and 110.36 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26493 

Comment Code: 110000 

Comment: III. Various Preamble Statements Require Clarification with Regard to Scope of the 

Regulation 

Given the statutory and regulatory definitions of uses that are or are not included in the definition of 

a pesticide, generally, or an antimicrobial pesticide, specifically, questions remain about whether 

some of the uses described in this Proposal, in fact, are uses of antimicrobial pesticides subject to 

this regulation. For example, EPA states that it considers uses that "could result in pesticide residues 

occurring in food or feed" to be high human exposure uses. 73 Fed. Reg. 59391. Similarly, EPA has 

described antimicrobial "direct food uses" to include "livestock" and "livestock feed," with "direct 

food use" defined as a use where "the antimicrobial is applied directly to food or water." 73 Fed. 

Reg. at 59401. However, these statements lead to a number of issues that must be resolved. To the 

Panel’s knowledge, there is no antimicrobial pesticide registered for use on livestock or in animal 

feed. To the extent that an antimicrobial is applied directly to livestock, it is an animal drug. If it is 

added to feed, it is either there as an animal drug or as a preservative in a processed feed. In either 

case, these uses are not antimicrobial pesticide uses and are outside the scope of the Proposal. The 

Panel believes it is essential that the regulation is clear on these points. However, if there is any 

portion of this analysis with which EPA disagrees, it should be addressed in a transparent manner 

before reproposal or promulgation. 

Further, the definition of antimicrobial pesticide specifically excludes agricultural fungicides. In the 

preamble at 59401, EPA notes that there are no currently registered antimicrobials for use on food 

or feed crops, but states that should such a use arise, it would be likely subject to the same 

requirements as those at 158 Subpart O. This statement needs further clarification. To the extent 

that it is an agricultural fungicide, the Panel assumes EPA intends it to be handled as a conventional 

pesticide in the Registration Division or as a biopesticide in the Biopesticides and Pollution 

Prevention Division of OPP.[FN#1:For example, there are antimicrobial active ingredients currently 

registered for application to field crops, e.g., hydrogen peroxide, but such uses are not regulated as 

antimicrobial pesticides. In the case of hydrogen peroxide, it is regulated as a biopesticide when 

registered for application to field crops.] If this assumption is incorrect, the exact meaning of EPA’s 

statement should be provided. 

Response: see responses 30.26 and 110.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26542 

Comment Code: 110000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 737 

Comment: 3. Need for a Tolerance or Exemption from Tolerance under FFDCA Section 408 

A final consideration is whether a product is intended to be used in areas where the potential 

residues are subject to regulation under FFDCA 408, that is, a food use subject to regulation by 

EPA. Uses subject to regulation under FFDCA 408 are considered to be food use, while all others 

are nonfood uses. 

Food uses for antimicrobials are largely indoor, although food use also includes the use of 

antifoulants for nets and pens where plants or animals are deliberately produced in an aquatic 

(marine or fresh water) environment for human consumption. Indoor food uses include use of 

food-contact sanitizing solutions in food processing and handling and storage premises and on 

equipment (generally includes use on inanimate surfaces as part of good housekeeping, good 

manufacturing practice and mandatory microorgansim control programs in food/feed processing 

plants, meat/poultry/seafood processing establishments, dairies, eating establishments, food storage 

and transportation facilities, and food retailers), disinfection/sanitization of empty commercial 

premises where food is to be stored or grown (such as empty greenhouses or mushroom houses), 

application of antimicrobial pesticides to animal drinking water where animals are used for human 

consumption, rinses occurring in the field, during transportation, or in facilities where no further 

processing occurs (i.e., packing houses), and antimicrobial-containing surfaces or articles contacting 

food in the same locations as previously identified and that make claims of surface antimicrobial 

activity (i.e., articles that must be registered as pesticides). 

Response: see responses 30.26 and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26786 

Comment Code: 110000 

Comment: For example, a review of recent decisions reveals that, in some cases EPA has 

determined that it will conduct a dietary risk assessment even though the active ingredient has no 

uses that require a tolerance or tolerance exemption, or an indirect food additive approval from 

FDA under FFDCA section 409. This occurred in EPA Case No. 3070, where both the Human 

Health Effects Scoping Document and Registration Review Summary [FN19: See Docket No. EPAHQ-OPP-2008-0879 at http://www.regulations.gov for the Registration Review case file.] state that: 

"Dietary (food) exposure could potentially occur because HHT/HMAE is used as a process 

preservative and an in-can preservative for materials containing water as a major ingredient such as 

caulks, adhesives, sealants that may be used in food contact situations such as food preparation, 

food processing, and food serving areas. A dietary exposure and risk assessment has not been 

conducted in the past. However, migration of HHT/HMAE from these preserved materials to food 

may occur to some extent. Therefore, a dietary (food source) risk assessment is recommended 

during the risk assessment stage of Registration Review. However, certain chemistry, use pattern, 

and chronic/cancer studies are being recommended to permit more appropriate exposure estimates 

and the selection of an endpoint for use in a chronic dietary risk assessment." 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 738 

Note that FDA does not currently regulate HHT/HMAE as a direct or indirect food additive. 

Human Health Effects Scoping Document at 8 (emphasis added). 

This situation raises two critical issues. First, EPA previously has not required a dietary risk 

assessment; this "recommendation" thus represents a significant change in policy.[FN20: LANXESS 

submits that EPA is incorrect in recommending a dietary risk assessment under these circumstances. 

The products at issue are not registered for uses that reasonably might result in residues on food. If 

indeed sealants, caulks, and adhesives were intended to be used in food-contact applications, each 

and every component of such products, not just the antimicrobial, would have to be approved by 

FDA as an indirect food additive pursuant to FFDCA section 409. If any product used in food 

preparation, processing, or service did not have the requisite FDA approval for each component, 

such product could be considered adulterated pursuant to FFDCA. LANXESS believes EPA is 

acting arbitrarily and capriciously in seeking to assess dietary risks and make regulatory decisions 

based on an assumption of misuse under FIFRA and violations of FFDCA.] No such change has 

been publicly vetted or even acknowledged. Second, the same requirement for a dietary risk 

assessment for non-food uses has been advanced in several other Registration Review cases.[FN21: 

See Case 5026, Busan 1024 Registration Review Final Work Plan, December 14, 2007; and Case 

5027, Oxazolidine-E Registration Review Final Work Plan, September 17, 2008.] However, the 

requirement has not been applied in other Registration Review cases, even though chemistries are 

similar and use patterns are the same.[FN22: See Case 3053, Nuosept 145 Registration Review Final 

Work Plan, September 10, 2008.] 

The foregoing example is not an isolated case. Other situations involving ad hoc risk assessment 

processes include: 

* In particular cases, EPA has sought to perform dietary risk assessments and require extensive data 

on antimicrobials used to preserve detergents for washing countertops or cutting boards.[FN23: See 

Grotan RED, June 2008.] There is no guidance on this and it has not been applied to all such 

potential preservatives for such products. 

* EPA has asserted that a dietary risk assessment is required in the Registration Review of 

Oxazolidine-E based on the use of the preservative in surfactants that may become components of 

dishwashing liquids and surface cleaners. The Agency acknowledges that these are not 'direct or 

indirect food uses," (no approval under FFDCA section 408 or 409 is needed) but nonetheless EPA 

asserts that a "Tier 1 dietary screening level assessment" is triggered [FN24: LANXESS has sought 

but not found any information on what constitutes a "Tier 1 dietary screening level assessment" for 

an active ingredient without food uses. Also, EPA has offered no explanation of its authority to 

require an FQPA risk assessment in this situation.] and that EPA "must conduct risk assessments to 

ensure that Oxazolidine-E meets the safety standards established by FFDCA, as amended by 

FQPA."[FN25: Oxazolidine-E Registration Review Final Work Plan, December 17, 2008, Docket 

No. EPA-HQ-OPP-2008-0404, http://www.regulations.gov] 

Response: see responses 30.26 and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 739 

Letter ID: 0064 

Comment ID: 26794 

Comment Code: 110000 

Comment: * The recent HHT RED provides another example of EPA’s case-by-case approach to 

risk assessment. There, although HHT has no uses requiring clearance under section 408 or 409 of 

FFDCA, EPA conducted "an indirect food use assessment."[FN26: Grotan RED at 19.] It appears 

there is a policy without publicly available documentation to allow reviewers on a case-by-by case 

basis to decide to perform some type of dietary risk assessments on some unspecified categories of 

uses.[FN27: In this RED, EPA concluded that that both the aPAD and cPAD "are well below 

100%, dietary exposure does not exceed the Agency’s level of concern." This finding is perplexing, 

as LANXESS is unaware of any methodology for determining dietary exposures from the uses 

registered for HHT.] 

Response: see responses 30.26 and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26957 

Comment Code: 110000 

Comment: The Agency should revise the preamble to the Proposal to provide clarification on the 

regulation of food- contact antimicrobials, and revise the use patterns, data tables and test notes to 

ensure conformance to this statutory division of authority. 

Response: see responses 30.26 and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26958 

Comment Code: 110000 

Comment: C. The Proposal Should Clarify that Not All Food Uses Are Subject to Tolerance 

Requirements 

The 158W Proposal should clarify that not all antimicrobial food uses are subject to tolerance 

requirements.[FN53: See for example at page 59432, proposed 158.2230(b)(1)(ii) through (v) 

compared to (i), which appears to suggest a difference in which food uses require regulation under 

section 408.] For example, the preamble includes the following assertion of authority: 

"Currently in part 161, a proposed tolerance is required for all food-use patterns. Today, the Agency 

is proposing to continue this existing requirement by requiring a proposed tolerance for all 

antimicrobial food-use patterns." 

73 Fed. Reg. at 59402. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 740 

Response: see responses 30.26 and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26972 

Comment Code: 110000 

Comment: While the meaning of the use term "proposed tolerance" is unclear, it appears EPA 

intends to require tolerances for food uses of antimicrobials, despite the fact that EPA has only 

limited jurisdiction under FFDCA 408 for antimicrobial food uses. Such a move would usurp FDA’s 

statutory grant of jurisdiction under FFDCA 409 and is inconsistent with EPA policy, practice, and 

regulations. EPA should withdraw this subsection from the preamble or provide a better 

explanation for what it is intending and the authority under which it is proposing to act. 

D. EPA Has Not Identified a Clear Basis for Distinguishing Food Uses of Pesticides as Direct or 

Indirect 

In the preamble, EPA mentions both indirect and direct food uses of pesticides and reflects this 

distinction further in the data tables.[FN54: For example, at pages 59389, 59393, 59394, and 59401.] 

However, there is no basis in FFDCA for such a distinction. 

FFDCA Section 201(s) defines "food additives" as follows: 

The term "food additive" means any substance the intended use of which results or may reasonably 

be expected to result, directly or indirectly, in its becoming a component or otherwise affecting the 

characteristics of any food (including any substance intended for use in producing, manufacturing, 

packing, processing, preparing, treating, packaging, transporting, or holding food; and including any 

source of radiation intended for any such use). 

FDA’s regulations implementing this provision distinguish between direct and indirect food 

additives. A direct food additive, as defined by FDA in guidance, is one that is intentionally added to 

food. An indirect food additive is one that may inadvertently become a part of food. This distinction 

does not carry over to the antimicrobials regulated as pesticides, because antimicrobial direct food 

additives are excluded from the definition of a pesticide and therefore are not subject to EPA 

jurisdiction at all. Instead they are solely within FDA’s jurisdiction. FDA regulates both direct and 

indirect food additives based on the potential level of exposure, applying a single safety standard to 

both.[FN55: FDA regulates as third category as "secondary direct food additives," defined as an 

additive that "has a technical effect in food during processing but not in the finished food (e.g., 

processing aid." See www.cfsan.fda.gov/~dms/opa-def.html. They are also regulated under the 

same safety standards as direct and indirect food additives. An example of an antimicrobial regulated 

as a secondary direct food additive is a chemical to control microorganisms in cane sugar and beet 

sugar mills during processing. 21 CFR 173.320.] 

EPA has not identified a clear basis for distinguishing food uses of pesticides as direct or indirect, 

nor has it elucidated any basis for distinguishing applicable data requirements. The distinction in this 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 741 

Proposal between direct and indirect food uses therefore should be eliminated. It serves no purpose, 

and further confuses the issues surrounding the regulation of antimicrobials. EPA should also 

develop its Proposal to the limits of its jurisdiction under FIFRA. 

Response: see responses 30.26, 110.1 and 110.36 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26983 

Comment Code: 110000 

Comment: The definition of antimicrobial pesticide specifically excludes agricultural fungicides 

(where the term fungus is defined at FIFRA Section 2(k) as including "mildew, mold, yeast, and 

bacteria except those on or in living man or other animals and those on or in processed food, 

beverages, or pharmaceuticals") and aquatic herbicides.[FN#1:FIFRA [Section] 2(mm).] Yet the 

proposed rule erroneously includes these within the data requirements for antimicrobial pesticides 

uses. They should be excluded. Wood preservatives with claims for control of organisms other than 

microorganisms also are excluded from the definition of antimicrobial pesticide, and should be 

excluded from the proposed rule.[FN#2:See id.] 

Response: see responses 30.26 and 110.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27175 

Comment Code: 110000 

Comment: I. Introduction 

The Agency’s description of the residue chemistry data requirements and of the background there to 

raise a number of questions that must be considered before this proposal can be finalized. In 

addition, as discussed elsewhere within these comments (See Panel’s General Comments at Section 

III and IV), the proposed regulation does not distinguish between food uses of antimicrobial 

pesticides and those uses regulated by FDA as indirect food additives. As a result, the treatment of 

residue data requirements is confusing and often times inaccurate in its application to antimicrobials. 

With respect to data requirements for residue chemistry, any proposed requirement must first clearly 

identify what antimicrobial pesticides are, and what uses of those pesticides are subject to regulation 

under FFDCA 408. EPA has authority to establish residue requirements only for these uses. Uses of 

antimicrobials that fall under FFDCA 409 or other statutes are not subject to these residue 

regulations. In sum, the proposed rule is confusing and does not provide clarity on the scope of the 

residue data requirements. 

Response: see responses 30.26 and 110.1 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 742 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27177 

Comment Code: 110000 

Comment: Food uses of antimicrobials include certain applications under the aquatic food and 

commercial/institutional indoor food general use patterns (reference Appendix B): 

* Aquatic food use pattern: 

*antifoulants for nets and pens where plants or animals are deliberately produced in an aquatic 

(marine or fresh water) environment for human consumption. 

* Commercial/institutional indoor food use pattern: 

* food-contact sanitizing solutions in food processing and handling and storage premises and on 

equipment (generally includes use on inanimate surfaces as part of good housekeeping, good 

manufacturing practice and mandatory microorganism control programs in food/feed processing 

plants, meat/poultry/seafood processing establishments, dairies, eating establishments, food storage 

and transportation facilities, and food retailers), 

* disinfection/sanitization of empty commercial premises where food is to be stored or grown (such 

as empty greenhouses or mushroom houses), 

* application of antimicrobial pesticides to animal drinking water where animals are used for human 

consumption, 

* application to potable water other than municipally-treated drinking water; 

* rinses occurring in the field, during transportation, or in facilities where no further processing 

occurs (i.e., packing houses), and 

* antimicrobial-containing surfaces or articles contacting food in the same locations as previously 

identified and that make claims of surface antimicrobial activity (i.e., articles that must be registered 

as pesticides) (other than food packaging). 

Response: See responses 30.26 and 110.1. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27179 

Comment Code: 110000 

Comment: II. Comments on the Proposed Rule 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 743 

In this section, the Panel provides the following comments on the proposed rule for residue 

chemistry data requirements. In general, the Panel encourages EPA to explain when residue 

chemistry data are required,[FN#1:Section 158.2290(b)(1).] refrain from regulating uses for which 

EPA does not have jurisdiction under FFDCA 408, and clarify the vague regulations. Because the 

proposed rule appears to be largely a reiteration of existing data requirements at 40 CFR Part 161 or 

those for conventional pesticides at 40 CFR 158.1410, the proposed rule contains numerous 

inapplicable requirements and inappropriate test notes for some antimicrobial applications. In a 

following section, the Panel offers an alternative proposal that is consistent with the statutory 

requirements and the intent for identification of potential residue chemistry data requirements for 

antimicrobial pesticides. 

Response: see responses 3, 30.26 and 110.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27181 

Comment Code: 110000 

Comment: First, contrary to assertions in the preamble and Section 158.2290(b), EPA’s residue 

chemistry data requirements can only legally apply when a tolerance or tolerance exemption under 

FFDCA 408 is required. The statement at proposed 158.2290(b)(1) is confusing as there is no 

established guidance or methodology upon which registrants could rely to make such a 

determination, nor has the Agency provided any justification as to how such a determination is 

consistent with its statutory mandate. 

Response: see responses 30.26 and 110.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27197 

Comment Code: 110000 

Comment: The proposed rule is inconsistent with long-standing EPA policy without explanation 

(e.g., see DIS/TSS 18 and 19). The proposed rule should be consistent with the Agency’s existing 

policy. 

Response: see response 110.23 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27209 

Comment Code: 110000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 744 

Comment: In sum, the proposed rule contains residue chemistry data requirements that are vague 

or appear to be inconsistent with registered antimicrobial pesticide uses. In addition, the regulations 

appear to be inconsistent with EPA’s statutory authority under FFDCA 408. The Panel urges EPA 

to revise the Proposal in accordance with its suggestions below and other input obtained during this 

process, and then repropose it before issuing a final regulation. 

Response: see responses 2, 3, 30.26, and 110.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27223 

Comment Code: 110000 

Comment: The EPA should not specify in this rulemaking how exposure assessments should be 

conducted or what procedures to follow in conducting any necessary studies.[FN#6:40 CFR 

158.1(b)(c): '"This part does not include study protocols, methodology, or standards for conducting 

or reporting test results; nor does this part describe how the Agency uses or evaluates the data and 

information in its risk assessment and risk management decisions, or the regulatory determinations 

that may be based upon the data."] However, the Agency should develop such guidance in a 

transparent and public process and must be open to alternative approaches for addressing any 

relevant data requirements. Similarly, the Panel also believes that existing guidance, such as DIS/TSS 

18 and 19, must be reconfirmed as current. The Agency has not announced that changes to longstanding and well understood policies are intended. However, this regulation as proposed appears to 

be inconsistent with current Agency practices and policies. Therefore, to the extent that EPA 

intends to make changes to its long-standing policies, those changes must be open for peer review 

and public comment prior to implementation 

Response: see response 110.25 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27226 

Comment Code: 110000 

Comment: The Panel believes the Agency should begin by rewriting section 158.2290(a) in order to 

incorporate references to the identification and description of antimicrobial use pattern categories 

described: 

(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the 

residue chemistry data requirements for a particular pesticide product. Notes that apply to an 

individual test and include specific conditions, qualifications, or exceptions to the designated test are 

listed in paragraph (e) of this section 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 745 

If antimicrobial use pattern categories are described elsewhere than in Section 158.100, specific 

reference to the correct identification and description must be incorporated into the above 

paragraph. 

In addition, section 158.2290(b) should be rewritten clearly to identify the conditions under which 

residue chemistry data requirements are applicable. The Panel suggests consideration be given to the 

following wording, referencing its prior proposal on Use Patterns and identification of what falls 

within the scope of each. If antimicrobial use pattern categories are described elsewhere than in 

Section 158.100, then specific reference to the identification and description must be incorporated 

into the following paragraph. 

Response: See responses 2, 50.16, and 110.27. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27228 

Comment Code: 110000 

Comment: (b) Use Patterns 

(1) Data are required or conditionally required for all antimicrobial pesticides used in or on food 

where the use is regulated under FFDCA Sec. 408. Antimicrobial food use patterns include 

(i) products classified under the general antimicrobial use patterns of ‘aquatic food use’ 

(ii) ‘commercial and institutional indoor food use.’ 

(2) Application of products to growing crops, use as aquatic herbicides, or use as agricultural 

fungicides are outside of the scope of these data requirements. Registrants should refer to Subpart O 

or to Sec. 158.2040 of this Part. 

(3) Data may be required for nonfood uses if pesticide residues may occur in food or feed as a result 

of the use. Data requirements for these nonfood uses will be determined on a case-by-case basis. 

For example, most products used in or near residential kitchens require residue data for risk 

assessment purposes even though tolerances may not be necessary in all cases. 

Response: see response 110.27 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27244 

Comment Code: 110000 

Comment: III. Various Preamble Statements Require Clarification with Regard to Scope of the 

Regulation 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 746 

Given the statutory and regulatory definitions of uses that are or are not included in the definition of 

a pesticide, generally, or an antimicrobial pesticide, specifically, questions remain about whether 

some of the uses described in this Proposal, in fact, are uses of antimicrobial pesticides subject to 

this regulation. For example, EPA states that it considers uses that "could result in pesticide residues 

occurring in food or feed" to be high human exposure uses. 73 Fed. Reg. 59391. Similarly, EPA has 

described antimicrobial "direct food uses" to include "livestock" and "livestock feed," with "direct 

food use" defined as a use where "the antimicrobial is applied directly to food or water." 73 Fed. 

Reg. at 59401. However, these statements lead to a number of issues that must be resolved. To 

LANXESS’s knowledge, there is no antimicrobial pesticide registered for use on livestock or in 

animal feed. To the extent that an antimicrobial is applied directly to livestock, it is an animal drug. 

If it is added to feed, it is either there as an animal drug or as a preservative in a processed feed. In 

either case, these uses are not antimicrobial pesticide uses and are outside the scope of the Proposal. 

LANXESS believes it is essential that the regulation is clear on these points. However, if there is any 

portion of this analysis with which EPA disagrees, it should be addressed in a transparent manner 

before reproposal or promulgation. 

Further, the definition of antimicrobial pesticide specifically excludes agricultural fungicides. In the 

preamble at 59401, EPA notes that there are no currently registered antimicrobials for use on food 

or feed crops, but states that should such a use arise, it would be likely subject to the same 

requirements as those at 158 Subpart O. This statement needs further clarification. To the extent 

that it is an agricultural fungicide, LANXESS assumes EPA intends it to be handled as a 

conventional pesticide in the Registration Division or as a biopesticide in the Biopesticides and 

Pollution Prevention Division of OPP.[FN1: For example, there are antimicrobial active ingredients 

currently registered for application to field crops, e.g., hydrogen peroxide, but such uses are not 

regulated as antimicrobial pesticides. In the case of hydrogen peroxide, it is regulated as a 

biopesticide when registered for application to field crops.] If this assumption is incorrect, the exact 

meaning of EPA’s statement should be provided. 

Response: see responses 30.26 and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27266 

Comment Code: 110000 

Comment: 3. Need for a Tolerance or Exemption from Tolerance under FFDCA Section 408 

A final consideration is whether a product is intended to be used in areas where the potential 

residues are subject to regulation under FFDCA 408, that is, a food use subject to regulation by 

EPA. Uses subject to regulation under FFDCA 408 are considered to be food use, while all others 

are nonfood uses. 

Food uses for antimicrobials are largely indoor, although food use also includes the use of 

antifoulants for nets and pens where plants or animals are deliberately produced in an aquatic 

(marine or fresh water) environment for human consumption. Indoor food uses include use of 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 747 

food-contact sanitizing solutions in food processing and handling and storage premises and on 

equipment (generally includes use on inanimate surfaces as part of good housekeeping, good 

manufacturing practice and mandatory microorgansim control programs in food/feed processing 

plants, meat/poultry/seafood processing establishments, dairies, eating establishments, food storage 

and transportation facilities, and food retailers), disinfection/sanitization of empty commercial 

premises where food is to be stored or grown (such as empty greenhouses or mushroom houses), 

application of antimicrobial pesticides to animal drinking water where animals are used for human 

consumption, rinses occurring in the field, during transportation, or in facilities where no further 

processing occurs (i.e., packing houses), and antimicrobial-containing surfaces or articles contacting 

food in the same locations as previously identified and that make claims of surface antimicrobial 

activity (i.e., articles that must be registered as pesticides). 

Response: see responses 30.26 and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27499 

Comment Code: 110000 

Comment: The definition of antimicrobial pesticide specifically excludes agricultural fungicides 

(where the term fungus is defined at FIFRA Section 2(k) as including "mildew, mold, yeast, and 

bacteria except those on or in living man or other animals and those on or in processed food, 

beverages, or pharmaceuticals") and aquatic herbicides.[FN#1:FIFRA [Section] 2(mm).] Yet the 

proposed rule erroneously includes these within the data requirements for antimicrobial pesticides 

uses. They should be excluded. Wood preservatives with claims for control of organisms other than 

microorganisms also are excluded from the definition of antimicrobial pesticide, and should be 

excluded from the proposed rule.[FN#2:See id.] 

Response: see responses 30.26 and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27612 

Comment Code: 110000 

Comment: APPENDIX I 

COMMENTS ON THE PROPOSED DATA REQUIREMENTS FOR RESIDUE CHEMISTRY 

I. Introduction............................................................1 

II. Comments on the Proposed Rule..........................................2 

III. Alternative Proposal for Residue Chemistry Data Requirements..........5 
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Comments and Response References: 

Residue Chemistry Section (110) Page 748 

 I. Introduction The Agency’s description of the residue chemistry data requirements and of the 

background thereto raise a number of questions that must be considered before this proposal can be 

finalized. In addition, as discussed elsewhere within these comments (See LANXESS’s General 

Comments at Section III and IV), the proposed regulation does not distinguish between food uses 

of antimicrobial pesticides and those uses regulated by FDA as indirect food additives. As a result, 

the treatment of residue data requirements is confusing and often times inaccurate in its application 

to antimicrobials. 

With respect to data requirements for residue chemistry, any proposed requirement must first clearly 

identify what antimicrobial pesticides are, and what uses of those pesticides are subject to regulation 

under FFDCA 408. EPA has authority to establish residue requirements only for these uses. Uses of 

antimicrobials that fall under FFDCA 409 or other statutes are not subject to these residue 

regulations. In sum, the proposed rule is confusing and does not provide clarity on the scope of the 

residue data requirements. 

Response: see responses 30.26 and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27614 

Comment Code: 110000 

Comment: Food uses of antimicrobials include certain applications under the aquatic food and 

commercial/institutional indoor food general use patterns (reference Appendix B): 

* Aquatic food use pattern: 

* antifoulants for nets and pens where plants or animals are deliberately produced in an aquatic 

(marine or fresh water) environment for human consumption. 

* Commercial/institutional indoor food use pattern: 

* food-contact sanitizing solutions in food processing and handling and storage premises and on 

equipment (generally includes use on inanimate surfaces as part of good housekeeping, good 

manufacturing practice and mandatory microorganism control programs in food/feed processing 

plants, meat/poultry/seafood processing establishments, dairies, eating establishments, food storage 

and transportation facilities, and food retailers), 

*disinfection/sanitization of empty commercial premises where food is to be stored or grown (such 

as empty greenhouses or mushroom houses), 

* application of antimicrobial pesticides to animal drinking water where animals are used for human 

consumption, 

* application to potable water other than municipally-treated drinking water; 
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Comments and Response References: 

Residue Chemistry Section (110) Page 749 

* rinses occurring in the field, during transportation, or in facilities where no further processing 

occurs (i.e., packing houses), and 

*antimicrobial-containing surfaces or articles contacting food in the same locations as previously 

identified and that make claims of surface antimicrobial activity (i.e., articles that must be registered 

as pesticides) (other than food packaging). 

Response: see responses 30.26 and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27615 

Comment Code: 110000 

Comment: II. Comments on the Proposed Rule 

In this section, LANXESS provides the following comments on the proposed rule for residue 

chemistry data requirements. In general, LANXESS encourages EPA to explain when residue 

chemistry data are required,[FN#1:Section 158.2290(b)(1).] refrain from regulating uses for which 

EPA does not have jurisdiction under FFDCA 408, and clarify the vague regulations. Because the 

proposed rule appears to be largely a reiteration of existing data requirements at 40 CFR Part 161 or 

those for conventional pesticides at 40 CFR 158.1410, the proposed rule contains numerous 

inapplicable requirements and inappropriate test notes for some antimicrobial applications. In a 

following section, LANXESS offers an alternative proposal that is consistent with the statutory 

requirements and the intent for identification of potential residue chemistry data requirements for 

antimicrobial pesticides. 

Response: see responses 3, 30.26, and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27618 

Comment Code: 110000 

Comment: First, contrary to assertions in the preamble and Section 158.2290(b), EPA’s residue 

chemistry data requirements can only legally apply when a tolerance or tolerance exemption under 

FFDCA 408 is required. The statement at proposed 158.2290(b)(1) is confusing as there is no 

established guidance or methodology upon which registrants could rely to make such a 

determination, nor has the Agency provided any justification as to how such a determination is 

consistent with its statutory mandate. 

Response: see responses 30.26 and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
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Comments and Response References: 

Residue Chemistry Section (110) Page 750 

Letter ID: 0064 

Comment ID: 27632 

Comment Code: 110000 

Comment: The proposed rule is inconsistent with long-standing EPA policy without explanation 

(e.g., see DIS/TSS 18 and 19). The proposed rule should be consistent with the Agency’s existing 

policy. 

Response: see response 110.23 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27638 

Comment Code: 110000 

Comment: In sum, the proposed rule contains residue chemistry data requirements that are vague 

or appear to be inconsistent with registered antimicrobial pesticide uses. In addition, the regulations 

appear to be inconsistent with EPA’s statutory authority under FFDCA 408. LANXESS urges EPA 

to revise the Proposal in accordance with its suggestions below and other input obtained during this 

process, and then repropose it before issuing a final regulation." 

Response: see responses 2, 3, 30.26, and 110.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27646 

Comment Code: 110000 

Comment: The EPA should not specify in this rulemaking how exposure assessments should be 

conducted or what procedures to follow in conducting any necessary studies.[FN#6:40 CFR 

158.1(b)(c): "This part does not include study protocols, methodology, or standards for conducting 

or reporting test results; nor does this part describe how the Agency uses or evaluates the data and 

information in its risk assessment and risk management decisions, or the regulatory determinations 

that may be based upon the data."] However, the Agency should develop such guidance in a 

transparent and public process and must be open to alternative approaches for addressing any 

relevant data requirements. Similarly, 

Response: see response 110.25 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27648 

Comment Code: 110000 
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Comments and Response References: 

Residue Chemistry Section (110) Page 751 

Comment: LANXESS also believes that existing guidance, such as DIS/TSS 18 and 19, must be 

reconfirmed as current. The Agency has not announced that changes to long- standing and well 

understood policies are intended. However, this regulation as proposed appears to be inconsistent 

with current Agency practices and policies. Therefore, to the extent that EPA intends to make 

changes to its long-standing policies, those changes must be open for peer review and public 

comment prior to implementation LANXESS believes the Agency should begin by rewriting section 

158.2290 (a) in order to incorporate references to the identification and description of antimicrobial 

use pattern categories described: 

(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the 

residue chemistry data requirements for a particular pesticide product. Notes that apply to an 

individual test and include specific conditions, qualifications, or exceptions to the designated test are 

listed in paragraph (e) of this section 

If antimicrobial use pattern categories are described elsewhere than in Section 158.100, specific 

reference to the correct identification and description must be incorporated into the above 

paragraph. 

In addition, section 158.2290(b) should be rewritten clearly to identify the conditions under which 

residue chemistry data requirements are applicable. LANXESS suggests consideration be given to 

the following wording, referencing its prior proposal on Use Patterns and identification of what falls 

within the scope of each. If antimicrobial use pattern categories are described elsewhere than in 

Section 158.100, then specific reference to the identification and description must be incorporated 

into the following paragraph. 

Response: See responses 2, 50.16, 110.23, and 110.27. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27651 

Comment Code: 110000 

Comment: (b) Use Patterns 

(1) Data are required or conditionally required for all antimicrobial pesticides used in or on food 

where the use is regulated under FFDCA Sec. 408. Antimicrobial food use patterns include 

(i) products classified under the general antimicrobial use patterns of ‘aquatic food use’ 

(ii) ‘commercial and institutional indoor food use.’ 

(2) Application of products to growing crops, use as aquatic herbicides, or use as agricultural 

fungicides are outside of the scope of these data requirements. Registrants should refer to Subpart O 

or to Sec. 158.2040 of this Part. 
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Comments and Response References: 

Residue Chemistry Section (110) Page 752 

(3) Data may be required for nonfood uses if pesticide residues may occur in food or feed as a result 

of the use. Data requirements for these nonfood uses will be determined on a case-by-case basis. 

For example, most products used in or near residential kitchens require residue data for risk 

assessment purposes even though tolerances may not be necessary in all cases. 

Response: see response 110.27 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 28996 

Comment Code: 110000 

Comment: The definition of antimicrobial pesticides [FN#1:FIFRA [Section] 2(mm).] specifically 

excludes agricultural fungicides,[FN#2:Fungus is defined at FIFRA Section 2(k) as including 

"mildew, mold, yeast, and bacteria except those on or in living man or other animals and those on or 

in processed food, beverages, or pharmaceuticals."] and aquatic herbicides, but the proposed rule 

erroneously includes those within the data requirements for antimicrobial pesticides uses. The 

proposed rule arbitrarily assigns product types to ‘high’ or ‘low’ exposure groups. However, the 

Agency has not provided any justification for these assignments. The Agency has not defined these 

terms or how they relate to risk assessments for antimicrobial pesticides. As discussed elsewhere in 

these comments, the Agency should eliminate the use of these categorizations. (See LANXESS’s 

General Comments at section III and IV). 

Response: see responses 30.26 and 110.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 28998 

Comment Code: 110000 

Comment: The definition of antimicrobial pesticides [FN#1:FIFRA [Section] 2(mm).] specifically 

excludes agricultural fungicides,[FN#2:Fungus is defined at FIFRA Section 2(k) as including 

"mildew, mold, yeast, and bacteria except those on or in living man or other animals and those on or 

in processed food, beverages, or pharmaceuticals."] and aquatic herbicides, but the proposed rule 

erroneously includes those within the data requirements for antimicrobial pesticides uses. The 

proposed rule arbitrarily assigns product types to ‘high’ or ‘low’ exposure groups. However, the 

Agency has not provided any justification for these assignments. The Agency has not defined these 

terms or how they relate to risk assessments for antimicrobial pesticides. As discussed elsewhere in 

these comments, the Agency should eliminate the use of these categorizations. (See Panel’s General 

Comments at section III and IV). 

Response: see responses 30.26 and 110.1 

Comment Code: 111000 Direct food use 
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Comments and Response References: 

Residue Chemistry Section (110) Page 753 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25571 

Comment Code: 111000 

Comment: III. Residue Chemistry Data Requirements 

EPA has proposed to adopt the basic residue chemistry data requirements as listed in Subpart O of 

current part 158 to support applications for antimicrobial products. However, EPA also has 

proposed to modify the applicability of those requirements to reflect differing risks and levels of 

exposure of antimicrobials. EPA uses residue data to determine the dietary risk exposure to pesticide 

residues from food. If there are no food uses for the antimicrobial, then no residue chemistry is 

required. 

Response: no response is needed 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25586 

Comment Code: 111000 

Comment: Another clarifying issue that needs to be addressed in this section is a reference to the 

pre-FQPA policy that a 409 clearance is sufficient for a 408 clearance for direct and indirect food 

additives. The clarification of this policy in the data requirements will assist in streamlining the 

approval of products. This should be in the preamble of the section instead of being footnoted. 

Response: see response 110.28 

Comment Code: 112000 Indirect food use 

Commenter Name: Jay Feldman 

Commenter Organization: Beyond Pesticides 

Letter ID: 0067 

Comment ID: 25706 

Comment Code: 112000 

Comment: Indirect Food Use of Antimicrobials 

More attention is needed for the indirect contamination of food by antimicrobial substances. Many 

surfaces and packaging materials have been impregnated with antimicrobial agents, such as silver 

nanoparticles and triclosan. These substances, and/or their degradates, have the ability to migrate 

from these surfaces and unto food, resulting in indirect dietary exposures. 
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Comments and Response References: 

Residue Chemistry Section (110) Page 754 

Response: see response 110.9 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27201 

Comment Code: 112000 

Comment: In addition, EPA should further clarify its statement in the preamble that "in the 

absence of data [the Agency will] evaluate the need for a tolerance or tolerance exemption by 

assuming complete transference of the chemical into food over the lifetime of the treated product." 

[FN#4:Page 59402.] The Panel notes that any claim for surface-sanitizing activity or surface activity 

of any kind requires that the article itself be registered as a pesticide, as the article would not meet 

the exclusion criteria of 40 CFR 152.25(a), and that such surface activity, pursuant to FFDCA 201(q) 

would make that use subject to the tolerance/tolerance exemption requirements of FFDCA 408. On 

the other hand, EPA’s statement is not accurate with regard to material preservative antimicrobial 

uses in exempt treated articles.To the extent that these articles are subject to regulation under 

FFDCA, it is limited to FFDCA 409, under the exclusive purview of FDA. Further, the term 

"complete transference of the chemical into food over the lifetime of the treated product must be 

explained. The Panel is not aware of any guidance on this issue and believes that it is inconsistent 

with the approach EPA has used historically to estimate migration from treated articles. 

Response: see response 110.8 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27636 

Comment Code: 112000 

Comment: In addition, EPA should further clarify its statement in the preamble that "in the 

absence of data [the Agency will] evaluate the need for a tolerance or tolerance exemption by 

assuming complete transference of the chemical into food over the lifetime of the treated product." 

[FN#4:Page 59402.] LANXESS notes that any claim for surface-sanitizing activity or surface activity 

of any kind requires that the article itself be registered as a pesticide, as the article would not meet 

the exclusion criteria of 40 CFR 152.25(a), and that such surface activity, pursuant to FFDCA 201(q) 

would make that use subject to the tolerance/tolerance exemption requirements of FFDCA 408. On 

the other hand, EPA’s statement is not accurate with regard to material preservative antimicrobial 

uses in exempt treated articles. To the extent that these articles are subject to regulation under 

FFDCA, it is limited to FFDCA 409, under the exclusive purview of FDA. Further, the term 

"complete transference of the chemical into food over the lifetime of the treated product must be 

explained. LANXESS is not aware of any guidance on this issue and believes that it is inconsistent 

with the approach EPA has used historically to estimate migration from treated articles. 

Response: see response 110.8 
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Comments and Response References: 

Residue Chemistry Section (110) Page 755 

Comment Code: 113000 Nature of the Residue in Plants 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27183 

Comment Code: 113000 

Comment: Test note 3 suffers from several fundamental flaws that render it of no value in 

providing guidance to regulated parties. It is unclear what EPA means by "postharvest storage of 

commodities" and whether such storage differs from food handling and storage facilities. The Panel 

recommends that the EPA clarify the meaning of test note 4. The proposed rule states there are no 

antimicrobials applied to growing crops (even though there seem to be exemptions listed). If so, 

then there is no reason for guideline requirement 860.1300 ("Nature of residue in plants"). Footnote 

5 provides no guidance to regulated parties as to which crops should be tested for the "nature of 

residue", given that irrigated water could be applied to all crops. As discussed in Appendix A, it is 

the Panel’s understanding that applications to "[c]rops treated directly in the field"’ is excluded from 

the definition of antimicrobial pesticide. This issue needs to be clarified. To the extent the 

requirements are applicable to antimicrobial pesticides and are "conditionally required" (CR) for 

conventional pesticides, they should also be CR for antimicrobial instead of required (R), unless the 

Agency can present reasonable justifications for the more stringent requirements for 

antimicrobials.[FN#2:See, e.g., test notes 5, 6, 9, 10, 11 and their corresponding data requirements.] 

Response: see responses 110.10, 110.11, 110.12, 110.13, and 110.14, and testnotes 110.3, 110.4, 

110.5, 110.6, 110.9, 110.10, and 110.11. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27619 

Comment Code: 113000 

Comment: Test note 3 suffers from several fundamental flaws that render it of no value in 

providing guidance to regulated parties. It is unclear what EPA means by "postharvest storage of 

commodities" and whether such storage differs from food handling and storage facilities. 

LANXESS recommends that the EPA clarify the meaning of test note 4. The proposed rule states 

there are no antimicrobials applied to growing crops (even though there seem to be exemptions 

listed). If so, then there is no reason for guideline requirement 860.1300 ("Nature of residue in 

plants"). Footnote 5 provides no guidance to regulated parties as to which crops should be tested for 

the "nature of residue", given that irrigated water could be applied to all crops. As discussed in 

Appendix A, it is LANXESS’s understanding that applications to "[c]rops treated directly in the 

field"’ is excluded from the definition of antimicrobial pesticide. This issue needs to be clarified. To 

the extent the requirements are applicable to antimicrobial pesticides and are "conditionally 

required" (CR) for conventional pesticides, they should also be CR for antimicrobial instead of 

required (R), unless the Agency can present reasonable justifications for the more stringent 

requirements for antimicrobials.[FN#2:See, e.g., test notes 5, 6, 9, 10, 11 and their corresponding 

data requirements.] 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 756 

Response: see responses 110.10, 110.11, 110.12, 110.13, and 110.14, and testnotes 110.3, 110.4, 

110.5, 110.6, 110.9, 110.10, and 110.11. 

Comment Code: 115000 Residue Analytical Methods 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26145 

Comment Code: 115000 

Comment: Chemical Analysis Methods-Residue methods are insufficient. The lack of aquatic 

toxicity data for antimicrobials has been a barrier to the identification and management of aquatic 

hazards associated with their use. Similarly, the lack of chemical analysis methods to measure 

environmentally relevant concentrations of many pesticides-particularly antimicrobials-effectively 

precludes surface water monitoring. Practical chemical analysis methods suitable for measurement of 

all antimicrobials that could occur at environmentally meaningful concentrations in surface waters 

should be required. Residue method requirements do not fill this need: 

* Residue methods are not required for all pesticides that may be present in surface waters. 

* Residue methods are often not appropriate for environmental monitoring, which generally requires 

lower detection limits (often parts per billion), practical sample handling procedures, and chemical 

measurement methods that are capable of measuring the pesticide in the presence of other natural 

substances and pollutants (which are common in surface water samples). 

Response: see response 110.15 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27066 

Comment Code: 115000 

Comment: 36. Proposed Regulation # [Section] 158.2290(f)(10) 

Text of the Proposed Regulation (emphasis added) Residue chemistry: Test notes. "A residue 

analytical method suitable for collecting data to establish tolerances must quantitate all residues of 

concern, as determined by the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether or how a method should quantitate residues of 

concern. 

Response: see response 3 
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Comments and Response References: 

Residue Chemistry Section (110) Page 757 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27715 

Comment Code: 115000 

Comment: 36. Proposed Regulation # [Section] 158.2290(f)(10) 

Text of the Proposed Regulation (emphasis added) Residue chemistry: Test notes. "A residue 

analytical method suitable for collecting data to establish tolerances must quantitate all residues of 

concern, as determined by the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether or how a method should quantitate residues of 

concern. 

Response: see response 3 

Comment Code: 117000 Magnitude of Residue (MOR) Studies 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27185 

Comment Code: 117000 

Comment: Clarification is needed on why processed food and feed requirements in test note 15 are 

applicable to antimicrobials, especially given that many antimicrobials will have an FFDCA 408 

tolerance exemption for use on RACs in the field, during transportation, and in packing houses and 

also have an FFDCA 409 approval for use in food processing facilities. 

Response: see response 110.16 and testnote 110.15 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27192 

Comment Code: 117000 

Comment: EPA needs to explain what is meant with regard to regulating antimicrobials in human 

drinking water pursuant to FFDCA section 408 residue requirements in test note 18. Use of 

antimicrobials in municipally treated and supplied drinking water is regulated under the Safe 

Drinking Water Act (SDWA), so clarification is needed on "direct application to water" where there 

is "potential" that the use could be in human drinking water. 
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Comments and Response References: 

Residue Chemistry Section (110) Page 758 

Response: see response 110.17 and testnote 110.18 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27194 

Comment Code: 117000 

Comment: Explanation is needed to clarify when an antimicrobial applied to irrigation water for use 

on crops would be an antimicrobial pesticide in test note 20. If the irrigation water containing the 

antimicrobial is applied directly to growing crops, is this use regulated as a conventional or 

biochemical pesticide use? The division of uses among conventional, biochemical and antimicrobial 

regulatory schemes needs to be explained. 

Response: see responses 10.1 and 110.18 and testnote 110.20 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27195 

Comment Code: 117000 

Comment: Test note 21 must be clarified and revised to accurately reflect the statutory division of 

jurisdiction with regard to use of antimicrobials in food handling establishments, as mandated by 

FFDCA 201(q). Residue data requirements would be applicable only to post harvest "fresh fruit and 

vegetables (RACs) that undergo a rinse, if the activity occurs in the field, during transport or in a 

facility where no further processing occurs," e.g., a packing house. Otherwise, the antimicrobial 

application is regulated by FDA as a secondary indirect food additive. EPA must conform this 

regulation to its statutory mandate pursuant to FFDCA 408. 

Response: see response 110.19 and testnote 110.21 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27621 

Comment Code: 117000 

Comment: Clarification is needed on why processed food and feed requirements in test note 15 are 

applicable to antimicrobials, especially given that many antimicrobials will have an FFDCA 408 

tolerance exemption for use on RACs in the field, during transportation, and in packing houses and 

also have an FFDCA 409 approval for use in food processing facilities. 

Response: see response 110.16 and testnote 110.15 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
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Comments and Response References: 

Residue Chemistry Section (110) Page 759 

Letter ID: 0064 

Comment ID: 27627 

Comment Code: 117000 

Comment: EPA needs to explain what is meant with regard to regulating antimicrobials in human 

drinking water pursuant to FFDCA section 408 residue requirements in test note 18. Use of 

antimicrobials in municipally treated and supplied drinking water is regulated under the Safe 

Drinking Water Act (SDWA), so clarification is needed on "direct application to water" where there 

is "potential" that the use could be in human drinking water. 

Response: see response 110.17 and testnote 110.18 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27629 

Comment Code: 117000 

Comment: Explanation is needed to clarify when an antimicrobial applied to irrigation water for use 

on crops would be an antimicrobial pesticide in test note 20. If the irrigation water containing the 

antimicrobial is applied directly to growing crops, is this use regulated as a conventional or 

biochemical pesticide use? The division of uses among conventional, biochemical and antimicrobial 

regulatory schemes needs to be explained. 

Response: see responses 10.1 and 110.18 and testnote 110.20 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27630 

Comment Code: 117000 

Comment: Test note 21 must be clarified and revised to accurately reflect the statutory division of 

jurisdiction with regard to use of antimicrobials in food handling establishments, as mandated by 

FFDCA 201(q). Residue data requirements would be applicable only to post harvest "fresh fruit and 

vegetables (RACs) that undergo a rinse, if the activity occurs in the field, during transport or in a 

facility where no further processing occurs," e.g., a packing house. Otherwise, the antimicrobial 

application is regulated by FDA as a secondary indirect food additive. EPA must conform this 

regulation to its statutory mandate pursuant to FFDCA 408. 

Response: see response 110.19 and testnote 110.21 

Comment Code: 118000 Magnitude of Residue in Meat, Milk, Poultry, and Eggs 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 
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Comments and Response References: 

Residue Chemistry Section (110) Page 760 

Letter ID: 0086 

Comment ID: 25589 

Comment Code: 118000 

Comment: (b)(1)(i) - The statutory authority to regulate products used to clean and/or sanitize eggs 

is unclear. To the extent that eggs are intended for processing, any product used to sanitize the shells 

is outside the scope of FIFRA. Until such time that EPA can clarify its statutory authority under 

FIFRA and/or under FFDCA Sec 408, the CSPA believes that all such uses are outside of both and 

should be excluded from any consideration under this proposed regulation. Also, there needs to be 

clarification that these direct uses are for fruit and vegetable washing for RACs and that drying, 

shelling and husking of RACs does not constitute processing as explain in the 1999 Antimicrobial 

Food Additive Guidance Document issued by FDA. The Guidance document is clear that these 

activities do not constitute processing and antimicrobials applied to RACs in the field, in a washing 

facility where no further processing occurs, or in transportation is under EPA jurisdiction and 

requires a FFDCA 408 clearance for clarification purposes. Conversely, antimicrobials applied to 

RACs in a food processing facility may require a FIFRA registration as a pesticide and an FDA 409 

FFDCA clearance. 

Response: See responses 30.26, 30.1, 110.19, and 110.22. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27187 

Comment Code: 118000 

Comment: Test note 16 and parts of footnote 17 appear to be irrelevant to antimicrobials. 

Furthermore, EPA should clarify what constitutes direct application to livestock or addition to 

livestock feed. If there is such direct application, it would be exempt from FIFRA because it would 

control a pest "on or in living man or other living animals," [FN#3:Section 3(t).] and would be an 

animal drug not subject to FIFRA. Similarly, direct application to livestock feed is not subject to 

FIFRA. 

Response: see response 110.20 and testnotes 110.16 and 110.17 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27189 

Comment Code: 118000 

Comment: EPA must explain why the requirement for meat, milk, poultry, and eggs is more 

stringent for antimicrobials than for conventional pesticides. Conventional pesticides are used in 

livestock premises, but such use does not mandate this requirement. 

Response: See responses 1 and 110.21. 
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Comments and Response References: 

Residue Chemistry Section (110) Page 761 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27199 

Comment Code: 118000 

Comment: The statutory authority to regulate products used to clean and/or sanitize eggs is 

unclear. To the extent that eggs are intended for processing, any product used to sanitize the shells is 

outside the scope of FIFRA. Until such time that EPA can clarify its statutory authority under 

FIFRA and/or under FFDCA Sec 408, the Panel believes that all such uses are outside of both and 

should be excluded from any consideration under this proposed regulation. 

Response: see response 110.22 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27624 

Comment Code: 118000 

Comment: Test note 16 and parts of footnote 17 appear to be irrelevant to antimicrobials. 

Furthermore, EPA should clarify what constitutes direct application to livestock or addition to 

livestock feed. If there is such direct application, it would be exempt from FIFRA because it would 

control a pest "on or in living man or other living animals,"[FN#3:Section 3(t).] and would be an 

animal drug not subject to FIFRA. Similarly, direct application to livestock feed is not subject to 

FIFRA. 

Response: see response 110.20 and testnotes 110.16 and 110.17 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27625 

Comment Code: 118000 

Comment: EPA must explain why the requirement for meat, milk, poultry, and eggs is more 

stringent for antimicrobials than for conventional pesticides. Conventional pesticides are used in 

livestock premises, but such use does not mandate this requirement. 

Response: see response 110.21 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27634 

Comment Code: 118000 
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Comments and Response References: 

Residue Chemistry Section (110) Page 762 

Comment: The statutory authority to regulate products used to clean and/or sanitize eggs is 

unclear. To the extent that eggs are intended for processing, any product used to sanitize the shells is 

outside the scope of FIFRA. Until such time that EPA can clarify its statutory authority under 

FIFRA and/or under FFDCA Sec 408, LANXESS believes that all such uses are outside of both 

and should be excluded from any consideration under this proposed regulation. 

Response: see response 110.22 

Comment Code: 119111 Food migration studies 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26247 

Comment Code: 119111 

Comment: * The Agency has not set forth the criteria to determine whether the protocol for data 

on the migration of residue will be approved. Without consultation, an applicant cannot develop the 

necessary protocol.[FN#12:Id. at [Section] 158.2290(f)(23).] 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26764 

Comment Code: 119111 

Comment: * The Agency has not set forth the criteria it will use to determine whether the protocol 

for data on the migration of residue will be approved. Without consultation, an applicant cannot 

develop the necessary protocol.[FN12: Id. at [section] 158.2290(f)(23).] 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27070 

Comment Code: 119111 

Comment: 37. Proposed Regulation # [Section] 158.2290(f)(23) 

Text of the Proposed Regulation (emphasis added) Residue chemistry: Test notes. "Migration of 

residue data are required for antimicrobial pesticides applied to hard food surfaces or incorporated 

into substrates (wood, plastic, paper, cloth, rubber or similar products) intended for contact with 

food or feed when theoretical (modeled) estimates of the amount of antimicrobial residue 
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Comments and Response References: 

Residue Chemistry Section (110) Page 763 

transferred to the food or feed may result in a risk of concern. Protocols must be approved by the 

Agency prior to the initiation of the study. Details for developing protocols are available from the 

Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether the protocol will be approved. These required private 

negotiations are a procedure for the development of later tests. 

Response: See responses 3 and 30.1. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27211 

Comment Code: 119111 

Comment: III. Alternative Proposal for Residue Chemistry Data Requirements 

The Panel agrees with the Agency’s basic objective to craft a rule that provides it with data necessary 

to make a regulatory judgment on proposed uses of antimicrobial pesticides based upon its duty to 

determine the safety of the pesticide chemical residues under FFDCA Sec. 408. The Panel’s 

alternative proposal is intended to provide clear instructions to registrants, taking into account the 

specific considerations related to requirements for antimicrobial pesticides and the need to design 

appropriate tiering in order to avoid unnecessary testing. 

Response: See response 110.36. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27222 

Comment Code: 119111 

Comment: The Panel agrees that the Agency can evaluate the potential dietary exposure from 

products used indoors in residential settings under FIFRA. Such uses are not subject to regulation 

under FFDCA 408 (See Panel’s General Comments at Section V). The Panel has developed and 

provided to the Agency a tiered exposure assessment model for determining indirect ingestion of 

hard surface disinfectants and cleaning products used on kitchen surfaces in residences (Incidental 

Dietary Residential Exposure Assessment, or IDREAM). These uses are not subject to regulation 

under FFDCA 408. Exposures to such pesticides are at most subject to regulation under 

FIFRA.[FN#5:72 FR 60934, October 26, 2007, at page 60950: "EPA agrees that FFDCA does not 

apply to commodities that are not introduced into interstate commerce and tolerances are not 

established for residues on home garden crops. EPA does assess under FIFRA whether any adverse 

effects (e.g. dietary risks) could occur;" 72 FR 60394, October 26, 2007, at page 60590: "EPA 

considers indoor food uses to be primarily pesticide treatment in food areas of food handling 

establishments (FHEs). FHEs include food servicing, food manufacturing, and food processing. 

Crack, crevice and space treatments are examples of application areas where pests hide or through 
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Comments and Response References: 

Residue Chemistry Section (110) Page 764 

which they enter a building. The FHE uses described above fall under the auspices of FFDCA and 

generally require residue data and tolerances (or exemptions from tolerances) for residues of 

conventional pesticides in food;" EPA. 2007. Response to Comments, EPA-HQ-OPP-2004-0387-

0178, at page 93: "On the other hand, indoor residential uses are nonfood uses that are not subject 

to FFDCA and the requirement for tolerances;" EPA believes that FIFRA section 2(bb)(2) does not 

apply to a registration decision when a tolerance is not required because use of the pesticide does 

not result in residues in or on the food." (EPA Threshold of Regulation Policy, page 12. 

http://www.epa.gov/fedrgstr/EPA-PEST/1999/October/Day-27/6042.pdf )] IDREAM was 

developed specifically to address potential acute and chronic indirect ingestion exposure estimates 

resulting from the use of disinfectants on kitchen surfaces in the home. All underlying assumptions 

in IDREAM are based on behavior of consumers in the home using hard-surface disinfectants, 

including how such products are used and how consumers prepare food in the home. To provide 

transparency, the EPA should provide guidance on relevant potential data requirements to 

registrants of such nonfood use products. 

Response: see response 110.29 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27640 

Comment Code: 119111 

Comment: III. Alternative Proposal for Residue Chemistry Data Requirements 

LANXESS agrees with the Agency’s basic objective to craft a rule that provides it with data 

necessary to make a regulatory judgment on proposed uses of antimicrobial pesticides based upon 

its duty to determine the safety of the pesticide chemical residues under FFDCA Sec. 408. 

LANXESS’s alternative proposal is intended to provide clear instructions to registrants, taking into 

account the specific considerations related to requirements for antimicrobial pesticides and the need 

to design appropriate tiering in order to avoid unnecessary testing. 

Response: See response 110.36. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27644 

Comment Code: 119111 

Comment: LANXESS agrees that the Agency can evaluate the potential dietary exposure from 

products used indoors in residential settings under FIFRA. Such uses are not subject to regulation 

under FFDCA 408 (See Panel’s General Comments at Section V). LANXESS has developed and 

provided to the Agency a tiered exposure assessment model for determining indirect ingestion of 

hard surface disinfectants and cleaning products used on kitchen surfaces in residences (Incidental 

Dietary Residential Exposure Assessment, or IDREAM). These uses are not subject to regulation 

under FFDCA 408. Exposures to such pesticides are at most subject to regulation under 
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Comments and Response References: 

Residue Chemistry Section (110) Page 765 

FIFRA.[FN#5:72 FR 60934, October 26, 2007, at page 60950: "EPA agrees that FFDCA does not 

apply to commodities that are not introduced into interstate commerce and tolerances are not 

established for residues on home garden crops. EPA does assess under FIFRA whether any adverse 

effects (e.g. dietary risks) could occur;" 72 FR 60394, October 26, 2007, at page 60590: "EPA 

considers indoor food uses to be primarily pesticide treatment in food areas of food handling 

establishments (FHEs). FHEs include food servicing, food manufacturing, and food processing. 

Crack, crevice and space treatments are examples of application areas where pests hide or through 

which they enter a building. The FHE uses described above fall under the auspices of FFDCA and 

generally require residue data and tolerances (or exemptions from tolerances) for residues of 

conventional pesticides in food;" EPA. 2007. Response to Comments, EPA-HQ-OPP-2004-0387-

0178, at page 93: "On the other hand, indoor residential uses are nonfood uses that are not subject 

to FFDCA and the requirement for tolerances;" EPA believes that FIFRA section 2(bb)(2) does not 

apply to a registration decision when a tolerance is not required because use of the pesticide does 

not result in residues in or on the food." (EPA Threshold of Regulation Policy, page 12. 

http://www.epa.gov/fedrgstr/EPA-PEST/1999/October/Day-27/6042.pdf )] IDREAM was 

developed specifically to address potential acute and chronic indirect ingestion exposure estimates 

resulting from the use of disinfectants on kitchen surfaces in the home. All underlying assumptions 

in IDREAM are based on behavior of consumers in the home using hard-surface disinfectants, 

including how such products are used and how consumers prepare food in the home. To provide 

transparency, the EPA should provide guidance on relevant potential data requirements to 

registrants of such nonfood use products. 

Response: see response 110.29 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27718 

Comment Code: 119111 

Comment: 37. Proposed Regulation # [Section] 158.2290(f)(23) 

Text of the Proposed Regulation (emphasis added) Residue chemistry: Test notes. "Migration of 

residue data are required for antimicrobial pesticides applied to hard food surfaces or incorporated 

into substrates (wood, plastic, paper, cloth, rubber or similar products) intended for contact with 

food or feed when theoretical (modeled) estimates of the amount of antimicrobial residue 

transferred to the food or feed may result in a risk of concern. Protocols must be approved by the 

Agency prior to the initiation of the study. Details for developing protocols are available from the 

Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether the protocol will be approved. These required private 

negotiations are a procedure for the development of later tests. 

Response: See responses 3 and 30.1. 
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Comments and Response References: 

Residue Chemistry Section (110) Page 766 

Comment Code: 119115 Data and reporting requirements table for residue chemistry (suggested 

additions, deletions, etc.) 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25601 

Comment Code: 119115 

Comment: Section Number Subpart W 

Title Antimicrobial Pesticide Data Requirements 

Paragraph §158.2290 Residue chemistry, Table - Antimicrobial Residue Chemistry Data 

Requirements p. 59444 

Excerpt from Federal Register Direct food contact uses 

HC Comment The preamble (item (i)) to the table describes "direct food uses", yet the heading in 

the table identifies "Direct food contact uses". If there is a difference between these use patterns, the 

PMRA suggests providing an explanation of the difference in the preamble. If there is no difference 

in use patterns, suggest removing 'contact" from the heading in the table to avoid confusion. 

 Section Number Subpart W 

Title Antimicrobial Pesticide Data Requirements 

Paragraph §158.2290 Residue chemistry, Table - Antimicrobial Residue Chemistry Data 

Requirements p. 59444 

Excerpt from Federal Register Nature of the Residue (in Plants/Livestock/Fish- Shellfish) 

(Guidelines 860.1300) 

HC Comment 1- Under aquatic use, the PMRA requirement is conditional upon the aquatic system 

involved and if water/irrigated crops are fed to livestock; and if fish may be exposed to the pesticide 

and its degradation products. The PMRA notes that under EPA Test Note 6, data are required when 

an antimicrobial pesticide is applied directly to livestock, to livestock premises, to livestock drinking 

water, to livestock feed, or to crops used for livestock feed (all of which are direct food contact 

uses). However, this is not consistent with Section X.J (p. 59402) and the CR for direct food contact 

uses and aquatic uses in the Table. 2- Under indirect food uses, an antimicrobial pesticide may be 

used for a feeding station (indirect food use). Therefore, PMRA is seeking clarification as to why the 

requirement is NR. 

 Section Number Subpart W 

Title Antimicrobial Pesticide Data Requirements 
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Comments and Response References: 

Residue Chemistry Section (110) Page 767 

Paragraph §158.2290 Residue chemistry, Table - Antimicrobial Residue Chemistry Data 

Requirements p. 59444 

Excerpt from Federal Register Analytical Methods (Guidelines 860.1340 and 860.1360) 

HC Comment PMRA notes that the requirement for analytical methods is required for direct food 

contact uses and conditionally required for all other use patterns. However, this is inconsistent with 

the requirement for a proposed tolerance (Guideline 860.1550) which is required for all use patterns 

and test notes 9-11, which state that all analytical methods (enforcement, data gathering and 

multiresidue) are required. PMRA is seeking clarification as to the discrepancy, since analytical 

methods should only be required if a tolerance is proposed. 

 Section Number Subpart W 

Title Antimicrobial Pesticide Data Requirements 

Paragraph §158.2290 Residue chemistry, Table - Antimicrobial Residue Chemistry Data 

Requirements p. 59444 

Excerpt from Federal Register Storage Stability (Guideline 860.1380) 

HC Comment PMRA notes that the R requirement for storage stability is inconsistent with the 

requirements for nature of the residues and magnitude of the residue studies. For example, the 

nature of the residue in plants and crop field trials is CR yet the storage stability data is R. 

Clarification is being sought for the discrepancy otherwise suggest revising the data requirement to 

CR. 

 Section Number Subpart W 

Title Antimicrobial Pesticide Data Requirements 

Paragraph §158.2290 Residue chemistry, Table - Antimicrobial Residue Chemistry Data 

Requirements p. 59444 

Excerpt from Federal Register Processed food or feed (Guideline 860.1520) 

HC Comment PMRA notes that under Agricultural Premises and as per test note 3, the data are 

required for nature of the residue studies (for postharvest storage of plant commodities) and CR for 

crop field trials. However, the requirement for processed food/ feed is NR. Clarification is being 

sought for the discrepancy, otherwise suggest revising the data requirement to CR. 

 Section Number Subpart W 

Title Antimicrobial Pesticide Data Requirements 

Paragraph §158.2290 Residue chemistry, Table - Antimicrobial Residue Chemistry Data 

Requirements p. 59444 
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Comments and Response References: 

Residue Chemistry Section (110) Page 768 

Excerpt from Federal Register Potable Water (Guideline 860.1400) 

HC Comment PMRA is seeking clarification as to why, under agricultural premises, the requirement 

is R when the test note 18 indicates that data are required if applied directly to water, if there is the 

potential that the treated water could be used for drinking purposes. 

Response: See responses 110.30, 110.31, 110.32, 110.33, 110.34, and 110.35, and testnotes 110.3, 

110.6, 110.9, 110.10, 110.11, 110.12, and 110.18. 

Comment Code: 119200 FDA regulation of FCSSS 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27836 

Comment Code: 119200 

Comment: AMERICAN CHEMISTRY COUNCIL 

Biocides Panel 

Background on the FDA Regulation of Food-Contact Sanitizing Solutions Under FFDCA And 

Estimation of Dietary Exposure 

November 25, 2008 

Statement of the Issue 

EPA/OPP has altered a method for assessing dietary exposures resulting from the use of hard 

surface disinfectants and cleaners in residential settings developed by the ACC Biocides Panel in 

order to apply it to the use of food contact sanitizing solutions in commercial and institutional 

settings. 

However, as discussed in a separate document, the application to such settings is an inappropriate 

use of the assumptions in the underlying Panel model, herein referred to as IDREAM. 

The Panel believes that an understanding of the FDA models for estimating commercial and 

institutional exposures to sanitizing solutions would be helpful to EPA/OPP. FDA regulated the 

food-contact uses of sanitizing solutions in non- residential settings for almost four decades. Its 

methods were derived from knowledge gained through years of data submissions. The Panel is 

providing this description of the FDA methods to provide EPA/OPP with information that is 

useful for developing a relevant method for estimating non-residential exposures of sanitizing 

solutions. 
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Comments and Response References: 

Residue Chemistry Section (110) Page 769 

The Panel believes that it is essential and in the public interest for EPA/OPP to revisit its approach 

to estimating these exposures. Sanitization of surfaces and equipment in nonresidential settings is 

critical to the prevention of the spread food-borne pathogens, as required for these types of facilities 

(such as by the Food Code, USDA and FDA regulations, and under other federal and state food 

safety programs and regulations). The approach EPA is curently using significantly overestimates 

reasonable worst case or even upper bound exposures. As a direct result, EPA/OPP in its risk 

assessments may require reductions in application rates that reduce the efficacy of such solutions to 

less than acceptable levels or may prevent the registration and use of effective products. Given the 

critical importance of sanitization in nonresidential food handling and production settings, product 

availability should not be compromised by the use of unrealistic overestimtes of exposure. 

Introduction 

With the 1996 FQPA amendments to FFDCA, authority for establishing tolerances for components 

of food contact sanitizing solutions transferred from FDA to EPA/OPP. Since then, EPA/OPP has 

relied, to a degree, on the FDA-developed guidance for determining potential dietary exposures to 

the components of such solutions but also has made modifications. The basis for the FDA guidance 

and its intended use have remained unclear to EPA risk assessors. The current readily available FDA 

guidance itself does not provide sufficient written background on its methodology. Therefore, the 

purpose of this document is to provide improved clarity to the basis for and intended use of the 

FDA guidance. 

The discussions herein are based entirely on FDA memoranda and background materials. It 

asssembles, in a single document, the historical basis and underlying assumptions for the FDA 

methods for estimating exposures from food- contact sanitizing solutions and the regulation of 

those solutions. FDA source materials are referenced in the text and are attached as appendices. 

These referenced source materials should be consulted for additional information or clarification. 

Regulatory Background 

As early as 1962, FDA regulated food contact sanitizing solutions as food additives under Section 

409 of FFDCA (27 FR 8759, September 1, 1962, which codified these food additives at 21 CFR 

121.2547). FDA maintained the authority to regulate these solutions under FFDCA through the 

1977 reorganization and republication, resulting in recodification of the food additive tolerances for 

sanitizing solutions at 21 CFR 178.1010 (42 FR 14609, March 15, 1977). In August 1996, with the 

passage of the FQPA amendments to FFDCA, authority for regulating sanitizing solutions under 

FFDCA was transferred from FDA under Section 409 to EPA under Section 408. 

FDA regulated sanitizing solutions as complete solutions, where the exact composition of a 

particular solution was identified and codified and a minimum at-use concentration identified as part 

of the regulation approving its use in contact with food. That minimum at-use concentration was 

based on the evaluation of efficacy data that petitioners were required to develop and submit to 

FDA as part of the request for establishment of the food additive regulation. Depending upon the 

petitioned uses, the FDA regulations also identified where the solutions could be used and any 

limitations of use. 
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Comments and Response References: 

Residue Chemistry Section (110) Page 770 

Following the transfer of authority for regulation of sanitizing solutions under FFDCA from FDA 

to EPA, EPA eventually recodified the regulations at 21 CFR 178.1010 to 40 CFR 180.940 (69 FR 

23136, April 28, 2004). However, EPA’s recodification separated the solutions into component parts 

and regulates only the chemical components themselves and not sanitizing solutions per se, in 

accordance with EPA’s approach to regulation of pesticide chemicals in food generally. In its 

recodification, EPA generally followed the FDA groupings of where products could be used, 

although the groupings are not exactly the same as the FDA regulations. Further, the concentrations 

identified in 40 CFR 180.940 are maximum allowable levels, which is the manner in which pesticide 

chemical tolerances under FFDCA 408 are regulated. 

FDA Estimates of Dietary Exposure 

The understanding of how to determine whether a particular residue level of the sanitizing solution 

components in food was acceptable under FFDCA 409 changed over the 34 years that FDA 

regulated these food additives, as its knowledge and experience grew. For many years, FDA required 

petitioners to submit actual residue determinations for evaluation of dietary exposure to components 

of sanitizing solutions. However, after reviewing extensive amounts of data, FDA developed models 

for estimating dietary exposure that were highly conservative but based on the extensive actual data 

collected and reviewed over time. 

The actual model used by FDA depended on where a petitioner wanted to use the product but 

generally fell into one of three use scenarios, which are in decreasing order of potential dietary 

exposure (Attachment 1) [see attachment one, page 12 of American Chemistry Council, Biocides 

Panel comment, PDF docket ID EPA-HQ-OPP-2008-0110-0088] : 

1. To include use on china, glassware and silverware in public or institutional eating places 

2. To include uses on all fOod processing equipment and utensils (which included dairy equipment) 

3. To include food processing equipment and utensils, excluding dairy equipment 

The model developed for uses in public eating places resulted in exposures typically 100 times 

greater than the next lower model (all food processing equipment) (Attachment 1). Similarly, the 

model for "all food processing equipment" resulted in much higher exposure when dairy equipment 

was included. While exposures from models 1 and 3 or from 1 and 2 were additive, FDA found that 

including the exposures from 2 or 3 to that from 1 made no meaningful difference for risk 

assessment purposes. Exposures from 2 and 3 are not additive. 

FDA never developed a comprehensive background document that systematically laid out the 

reasoning behind its approach or how the approach was used in establishing regulations. As was 

typical at that time, those involved in the development and the use of the estimates understood the 

background and intent. In fact, the models and their use in establishing regulations were standard 

long before FDA issued its guidance in 1986 and as reissued in 1993 (FDA 1993). Further, members 

of the regulated community who routinely worked with FDA understood the background and intent 

without the need for written documentation. With the passage of time and with the transfer of 

responsibility for these food additive regulations, the background and intent have become 

increasingly misunderstood. However, there is adequate information within FDA memoranda and 
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Comments and Response References: 

Residue Chemistry Section (110) Page 771 

regulations to provide reasonable clarity on the scientific basis for and the scope and intent intent of 

FDA’s methods for assessing risks associated with food-contact sanitizing solutions. 

Beginning in the early 1980’s for certain sanitizing solutions, the FDA regulations established a 

minimum at-use concentration and a maximum concentration. The minimum concentration was 

identified as the minimum necessary to obtain efficacy as identified in the petition as supported by 

data included in the underlying petition (Attachment 5A). At that time, FDA adopted the general 

practice of regulating a maximum concentration that was twice the minimum (Attachment 5A), 

although it sometimes could exceed that level. The basis for the maximum associated with the model 

used for "public eating facilities" was to address the possible need for higher than minimum 

concentrations for efficacy purposes. The different basis for a 2X maximum when models 2 and 3 

were used is clearly defined and is described further below under discussion of those models. The 

changes to include a minimum and a maximum concentration of components are first found in 21 

CFR 178.1010(c)(19). 

Review of FDA memoranda associated with specific petitions provides a basis for understanding the 

background and intent of the dietary exposure models used by FDA to establish regulations for 

food contact sanitizing solutions. It is essential to keep in mind that the models were intended not to 

estimate exposure to specific limited scenarios but to provide the basis for the regulation of the 

sanitizing solutions in one of three general use scenarios. The codified regulations identify what uses 

FDA intended the models to represent. 

FDA’s approach to modeling exposures from the use of sanitizing solutions can be found in several 

petitions for food additive regulations and FDA memoranda on petitions referenced within those 

petitions. These are the seminal documents that represent the positions FDA developed as the basis 

for its modeling and the intent of the models in regulation of the solutions. 

Model 1: Use in public eating facilities The model used to estimate exposure in public eating 

facilities is considered to be the broadest and highest exposure use of a sanitizing solution. This is 

described in the FDA Chemistry Guidance (FDA 1993) as: 

"The broadest coverage includes use of the sanitizer in institutional or public eating facilities." 

"Generally, the estimated consumer exposure for a given "at- use" concentration of a sanitizer 

intended for use in public eating establishments far exceeds the estimated exposure when application 

is restricted to "food processing equipment and utensils."" 

FDA developed a model to estimate exposure in public eating facilities, as a "worst case" While the 

basis of that model was the surface area of silverware, chinaware, and glassware used by a person 

eating three meals per day in a public facility and that 100% of the sanitizing solution following 

drainage is consumed along with the food, it is important to understand why this scenario was 

considered a very conservative "worst case." Sanitizing soulutions are required to be used in 

commercial and institutional settings after washing and rinsing; the sanitizing solution is in essence a 

final rinse. These solutions are not otherwise rinsed or wiped. Instead they are required to either 

drain and/or air dry. Such exposures for all food ingestion clearly represent the most extreme 

example of potential exposure to sanitizing solutions. 
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Comments and Response References: 

Residue Chemistry Section (110) Page 772 

It is equally important to recognize that characterization of use of the sanitizing use on utensils, 

chinaware and glassware was not a limitation to use. When sanitizing solutions were assessed using 

this "worst case" model for dietary exposure, FDA established regulations permitting general use in 

public eating facilities and not just on silverware, china and glassware. 

In its review of FAP 9B4159, FDA modeled exposure using its "worst case" for use in public eating 

facilities. No other exposure estimates were conducted (Attachment 6). In establishing the regulation 

for the use of the food contact sanitizing solution, FDA codified the permitted uses as: 

"In addition to use on food-processing equipment and utensils, this solution may be used on foodcontact surfaces in public eating places." 

See at 21 CFR 178.1010 (b)(41) and 51 FR 43613 (September 22, 1992). 

Further, in its review of FAP 3B4371, FDA states "we will not discuss [petitioner’s] exposure 

estimate using the dairy application model in detail, since this model is not appropriate to support 

the broadest coverage sought by the petitioner (i.e., inclusion of use in public eating facilities). Since 

[petitioner] seeks the broadest possible coverage for their sanitizer, it is appropriate to model 

consumer exposure based on the use of the sanitizer in public eating facilities." (Attachment 7A) 

[See attachment 7A on page 59 of American Chemistry Council, Biocides Panel comments, PDF 

docket ID EPA-HQ- OPP-2008-0110-0088]. 

The petitioned formulation included a range of concentrations of components in the formulation 

and use concentrations for the solution itself, and FDA in this memorandum calculated a minimum 

exposure for each component based on the minimum component level and minimum solution use 

level as well as a maximum exposure based on the maximum component level and maximum 

solution use level.[FN#1:In this particular memorandum, FDA identified that it doubled the highest 

estimated dietary intake to account for misuse, that interpretation is, in fact, inconsistent with the 

clearly stated basis in (Attachment 5A)[See attachment 5A on page 36 of American Chemistry 

Council, Biocides Panel comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088]., which was 

to account for use levels at more than the minimum efficacious concentration. The stated basis in 

(Attachment 7A [See attachment 7A on page 59 of American Chemistry Council, Biocides Panel 

comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088]. for the doubling is, in fact, incorrect 

and should be ignored.] 

In fact, FDA finally used more than one model to estimate exposures for the solution in FAP 

3B4371 when it was identified that there were different at-use concentrations being proposed for 

different use scenarios (Attachment 7B)[See attachment 7B on page 71 of American Chemistry 

Council, Biocides Panel comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088]. The use of 

only model 1 for all use scenarios was inappropriate and overestimated potential dietary exposure 

for some of the petitioned use concentrations. A concentration less than the maximum was 

petitioned for general use in public eating facilities. In this reconsideration, FDA identified that it 

would not specifically assess certain components as those components had been determined to be 

safe for other reasons (including that exposure was expected to be "essentially nil" for components 

such as hydrogen peroxide because of rapid breakdown to oxygen and water). However, one of the 

components required further consideration. For that component, FDA recalculated the potential 

dietary exposure at the appropriate, lower use concentration for the worst case use in public eating 
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Comments and Response References: 

Residue Chemistry Section (110) Page 773 

facilities, using the standard model for that purpose. The reported EDI results from the use of the 

worst-case model, although the specific calculation is not identified in the available memorandum. 

The final regulations (21 CFR 1010(b)(45) and (c)(39), 21 FR 28051, June 4, 1996) established for 

this solution conform to the revised assessments, identifying that one concentration is for use "on 

food processing equipment and utensils, including dairy and beverage processing equipment but 

excluding food contact suraces in public eating places and dairy and beverage containers." A 

different concentration is for use "on food-contact equipment and utensils in warewashing 

machines, including warewashing machines in public eating places." A third concentration is for use 

"on dairy and beverage containers." Clearly FDA did not specifically model each individual pattern 

but used its general models. The final regulation is consistent with the proposed use levels identified 

for the different use scenarios. 

Model 2: "All food processing equipment and utensils, including dairy" 

This model does not include use in public eating establishments. FDA memoranda associated with 

FAP 2B4301 (Attachments 5A-5D)[See attachments 5A-5D on pages 36-54 of American Chemistry 

Council, Biocides Panel comments, PDF docket ID EPA- HQ- OPP-2008-0110-0088], along with 

other memoranda referenced therein provide an explanation of how FDA modeled the exposure for 

this use scenario, which is significantly different than for the broadest use (public eating 

establishments). 

There are 4 FDA memoranda associated with review of FAP 2B4301. This petition originally 

proposed use of the sanitizer in all uses but was amended to limit use to all food processing 

equipment and utensils, including dairy. The first review memorandum (Attachment 5A[See 

attachment 5A on page 36 of American Chemistry Council, Biocides Panel comments, PDF docket 

ID EPA-HQ- OPP-2008-0110-0088]) identifies that EDI’s were calculated using the "worst case" 

model for use in public eating facilities, including a doubling of the estimated exposure to account 

for a minimum and maximum use level. The second memorandum (Attachment 5B [See attachment 

7A on page 43 of American Chemistry Council, Biocides Panel comments, PDF docket ID EPAHQ- OPP-2008-0110-0088]) simply discusses the at use concentrations and the important 

relationship to efficacy. The third memorandum (Attachment 5C [See attachment 5C on page 46 of 

American Chemistry Council, Biocides Panel comments, PDF docket ID EPA-HQ- OPP-2008-

0110-0088]) discusses the different approaches to estimating exposure for direct and indirect uses of 

food additives, particularly in relation to estimating cumulative exposure. FDA concludes that the 

primary source of exposure to the component of concern is from use of sanitizing solutions. FDA’s 

assessment in this memorandum identifies a dietary exposure assuming the "worst case" for public 

eating facilities. Finally, the fourth memorandum (Attachment 5D [See attachment 5D on page 49 of 

American Chemistry Council, Biocides Panel comments, PDF docket ID EPA-HQ- OPP-2008-

0110-0088]) reassesses potential exposure when the proposed use is limited to food processing 

equipment and utensils, including dairy, thereby excluding use in public eating facilities, and 

discusses the basis for the models used to estimate exposure for the revised uses. FDA in this fourth 

memorandum references several earlier memoranda that provide additional explanation for the 

models. 

FDA (Attachment 4D) identifies a review performed elsewhere (Attachment 4 [See Attachements 

4A and 4B on page 23 of American Chemistry Council, Biocides Panel comments, PDF docket ID 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 774 

EPA-HQ- OPP-2008-0110-0088] ); this model covers all types of potential surfaces, with the 

exception of china, dishes and silverware in commercial eating facilities. FDA (Attachment 3 [See 

attachment 3 on page 19 of American Chemistry Council, Biocides Panel comments, PDF docket 

ID EPA-HQ- OPP-2008-0110-0088]) recognized that evaluating actual residues in some of the uses 

(such as flat work surfaces and belts) is extremely difficult to evaluate but also concluded that any 

such residues "do not contribute significantly in comparison with residues from CIP treatment." As 

such, FDA modeled the CIP (clean-in-place) potential residues only. Attachment 3 [See attachment 

3 on page 19 of American Chemistry Council, Biocides Panel comments, PDF docket ID EPA-HQOPP-2008-0110-0088] discusses that FDA developed a model to estimate exposure to sanitizer 

components from use of sanitizers for Clean-in-Place (CIP) applications. It references FDA 1988 

(Attachment 4 [See Attachements 4A and 4B on page 23 of American Chemistry Council, Biocides 

Panel comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088]) to illustrate that milk 

processing and other CIP applications represent the major exposures for consumers from CIP 

applications. 

FDA identified mean and eaters only consumption from their Market Research Corporation of 

America (MRCA) data from Menu Census IV [FN#2:FDA elsewhere (FDA 2006) notes that it used 

the Market Research Corporation of America (MRCA) 14- day Menu Census data for many years 

for most of its intake estimates but typically uses other sources currently, including CSFII, 

NHANES or an integrate CSFII/NHANES approach, although FDA’s approach is proprietary. It 

does still use the MRCA data to confirm its estimates from other approaches.]. This 1985 

memorandum (Attachment 4) identifies an update to consumption based on the most recent MRCA 

data. FDA grouped foods into the categories identified 21 CFR 170.3(n), which still is current. From 

the 43 possible food categories at 21 CFR 170.3(n), FDA selected 15 which, in their professional 

judgment, were "foods processed in a manner where CIP sanitizing might be employed." FDA then 

identified the average and 90th percentile food intake (grams/person/day) for each of those 

categories for eaters only. Those intake values formed the basis for estimating the intake of the 

component of a food contact sanitizing solution for calculating the estimated dietary intake (EDI). 

FDA further points out that the resulting EDI is highly conservative in that it assumes consumers at 

90th percentile consumers in all food categories. Attachment 5 provides updated MRCA 

consumption data. 

In this memorandum (Attachment 4 [See Attachements 4A and 4B on page 23 of American 

Chemistry Council, Biocides Panel comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088]), 

FDA identifies the calculation of potential exposure to a component of a food contact sanitizing 

solution in the following manner: 

EDI = ((At use concentration in ug/in2) / (weight of food/surface area in g/in2)) x food intake in 

g/p/day 

Food intake values are identified for the mean and 90th percentile. Consumption at the 90th 

percentile is considered to be twice the mean, which FDA 2006 (at IV.E) reconfirms. 

The weight of food in grams per square inch of surface area is identified in (Attachment 3 [See 

attachment 3 on page 19 of American Chemistry Council, Biocides Panel comments, PDF docket 

ID EPA-HQ- OPP-2008-0110-0088]) for the critical food types that may be contacted in typical 

CIP applications. For beer/beverages it is 968, for egg/mayonnaise products it is 413, and for milk 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 775 

(dairy) it is 43 grams/in2. Exposure is dominated by the use of sanitizers to treat milk-processing 

equipment because it represents the highest potential exposure. Attachment 2 [See attachment 2 on 

page 14 of American Chemistry Council, Biocides Panel comments, PDF docket ID EPA-HQOPP-2008-0110-0088] also is referenced as the basis for the amount of food contacting the surfaces 

of equipment. 

To convert from EDI to a concentration in the total daily diet, the EDI is divided by amount of 

food eaten (3000 g or 3 kg) and then converted appropriately (e.g., 1 mg of sanitizer in 1 kg of food 

is 1 ppm). 

Thus, in its review of FAP 2B4301, FDA (Attachment 5D [See attachment 5D on page 49 of 

American Chemistry Council, Biocides Panel comments, PDF docket ID EPA-HQ- OPP-2008-

0110-0088]) calculates the EDI for components of the formulation for use on food processing 

surfaces and utensils including dairy, assuming a residue of 1 mg sanitizer solution/cm2 (6.4 

mg/in2) remains on sanitized surfaces (worst-case assumption), all of which migrates to food, and a 

maximum use level of 35,000 ppm for the entire formulation. By this time (1994), FDA wass 

estimating exposures only for the food categories of greatest interest/greatest contribution from 

uses in food processing/dairy uses. 

[See table on page 7-8 of American Chemistry Council, Biocides Panel comments, PDF docket ID 

EPA-HQ-OPP-2008-0110-0088] Based on MRCA Menu Census Survay, 14 day average. All ages 

included in eaters only. Total sample mean = eaters=only mean food intake x % eaters 

The following calculation is for the component Citric Acid (CA), which is 94% w/w of the 

formulated sanitizer solution: 

(6.4 mg sanitizer solution/in2) x (35 ug Formulation/1 mg san. sol) x (32.9 ug CA/35 ug 

Formulation) x (in2/ 968 g Beverage/p/d) = 6.5 ug CA/p/d 

Thus the following is the calculated EDI for each component and each food category, as shown in 

Attachment 5D [See attachment 5D on page 49 of American Chemistry Council, Biocides Panel 

comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088], where the % after the component is 

its level in formulation. 

[See table Calculation of EDI for Mean (Total Sample) Intake on page 8 of American Chemistry 

Council, Biocides Panel comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088] 

FDA further stated that the percent eaters of all the foods listed in the above tables is 99.3. Since the 

percentage of eaters approaches 100%, the eaters-only and total sample cumulative exposures may 

be considered the same. Further "as an individual is likely to eat from each of the above food groups 

on a regular basis, we may assume that the eaters-only EDIs for individual sanitizer components are 

equal to the total sample values." 

FDA Attachment 5D [See attachment 5D on page 49 of American Chemistry Council, Biocides 

Panel comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088] calculated the 90th percentile 

EDIs, based on its assessment that these are approximately twice the mean levels. The following are 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 776 

FDA’s exposure estimates for components of the formulation when used on food processing 

equipment, including dairy 

[See table on page 8 of American Chemistry Council, Biocides Panel comments, PDF docket ID 

EPA-HQ-OPP-2008-0110-0088] Dietary concentration assumes a diet of 3 kg per person/day 

FDA (Attachment 5D [See attachment 5D on page 49 of American Chemistry Council, Biocides 

Panel comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088]) stated "The above values 

represent more than a 100-fold decrease over the exposure estimated calculated in our 12-17-02 

memorandum, reflecting the elimination of sanitizer use in public-eating establishments." 

On the basis of these exposure estimates and that there was very little increase in overall cumulative 

exposure to all of these already-regulated compounds (as direct and indirect additives), FDA 

established a regulation stating "in addition to use on food processing equipment and utensils, this 

solution may be used on dairy-processing equipment." (21 CFR.1010(b)(44), 60 FR 18739, April 13, 

1995). It should be noted that while FDA 1993 Guidance includes a method to estimate exposure 

for dairy uses, a separate calculation is not conducted for modeling exposure for this category. 

In its review of FAP 1B4245 (Attachment 8 [See attachment 8 on page 74 of American Chemistry 

Council, Biocides Panel comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088]), FDA 

evaluated a sanitizing solution for use on all food processing equipment and utensils, including dairy, 

using the same model as described above for estimating worst-case dietary exposure from the 

proposed uses. The potential exposure in the same 5 food categories was determined, in this case 

using a maximum residue determined by analytical methods. This memorandum clearly confirms 

that this is the appropriate model for estimating exposure to sanitizers used in all food processing 

area applications, including milk processing, brewery, beverage, and others. It references the prior 

FDA memoranda (Attachment 2 [See attachment 2 on page 14 of American Chemistry Council, 

Biocides Panel comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088], 4 [See attachments 4A 

and 4B on page 24 of American Chemistry Council, Biocides Panel comments, PDF docket ID 

EPA-HQ- OPP-2008-0110-0088]) for the basis of determination of dietary exposures for these uses, 

similar to what is discussed above in reference to FAP 2B4301. In this case, however, the 90th 

percentile consumption is based on a factor of 2.5 compared to the mean consumption value. On 

the basis of these exposure estimates, FDA established a regulation stating "in addition to on food 

processing equipment and utensils, this solution may be used on dairy-processing equipment." (21 

CFR.1010(b)(43), 58 FR 57554, October 26, 1993). 

Model 3: "All food processing equipment and utensils, excluding dairy". 

There are very few instances where FDA established regulations permitting use of a sanitizing 

solution on all food processing equipment, excluding dairy. In both available examples, however, the 

regulation also included use in public eating facilities. As described above, the model for use in 

public eating facilities results in exposures more than 100X those from even food processing 

equipment with dairy. While FDA could add exposures from Model 2 or Model 3 to those from 

Model 1, the effect of doing so is insignificant. Therefore, it was not done in the available examples 

(Attachments 1 [See attachment 1 on page 12 of American Chemistry Council, Biocides Panel 

comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088], 6 [See attachment 6 on page 56 of 

American Chemistry Council, Biocides Panel comments, PDF docket ID EPA-HQ- OPP-2008-
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 777 

0110-0088]; 7A [See attachment 7A on page 59 of American Chemistry Council, Biocides Panel 

comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088], 7B [See attachment 7B on page 71 of 

American Chemistry Council, Biocides Panel comments, PDF docket ID EPA-HQ- OPP-2008-

0110-0088] in part for some concentrations). 

When petitioners requested approval only for highly specialized uses, FDA estimated exposures only 

for those specialized uses, rather than one of the worst-case models identified above. For example, 

when use only on dairy processing equipment is of interest, FDA used the model identified in FDA 

1993. FDA 1993 also states: 

"The same type of calculations would be performed for residues on food processing equipment and 

utensils in other food processing plants (e.g. breweries)" 

Thus, when the petitioner was interested in obtaining only limited clearances, either model 1 nor 

model 2 was used. For example, in its evaluation of FAP 2B3547 (Attachment 9), FDA calculated 

the amount of potential sanitizer residue in a dairy processing system and worst-case assumptions to 

estimate the potential concentration in milk of the component as 23 ppb. FDA (Attachment 9 [See 

attachment 9 on page 82 of American Chemistry Council, Biocides Panel comments, PDF docket 

ID EPA-HQ- OPP-2008-0110-0088]) identified that the dietary concentration of 23 ppb would be 

the contribution to diet (EDI) if milk were 100% of the diet (such as for an infant) but stated that 

the dietary contribution (EDI) would be considerably less if milk were not 100% of the diet. This 

same memorandum contrasts their calculation for EDI from the very limited use in dairy processing 

equipment to how EDI would be calculated for the broadest use of sanitizing solutions. In 

discussing its model for the broadest use of sanitizing solutions (in public eating facilities), FDA 

(Attachment 9 [See attachment 9 on page 82 of American Chemistry Council, Biocides Panel 

comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088]) states: 

"This is a very conservative estimate since it assumes that all food consumed by a person contained 

traces of this one sanitizing solution. In reality, exposure would probably be at least an order of 

magnitude smaller, but this cannot be easily documented. Thus, we are suggesting a maximum EDI 

...of 200 ppb of the total daily diet, but we point out that in reality the EDI could be well below the 

50 ppb mark. This is probably also true of sanitizers in general." 

Several years after review of FAP 2B3547 (Attachment 9 [See attachment 9 on page 82 of American 

Chemistry Council, Biocides Panel comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088]), 

FDA (Attachment 10 [See attachment 10 on page 87 of American Chemistry Council, Biocides 

Panel comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088]) considered a petition (FAP 

3H3756) to revise the clearances for that sanitizing solution, this time to address a different 

surfactant and expand use more broadly to food processing equipment in general. FDA (Attachment 

10 [See attachment 10 on page 87 of American Chemistry Council, Biocides Panel comments, PDF 

docket ID EPA-HQ- OPP-2008-0110-0088]) estimated dietary exposures for the expanded 

application using model 2, described above. 

FDA then also considered the expansion of the original sanitizing solution considered under FAP 

2B3547 (Attachment 9 [See attachment 9 on page 82 of American Chemistry Council, Biocides 

Panel comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088]) to include use on additional 

food processing equipment, specifically for the brewery, beverage, egg and mayonnaise industries. In 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 778 

this case (Attachment 4B [See attachment 4B on page 28 of American Chemistry Council, Biocides 

Panel comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088]), FDA estimated the potential 

residual concentration and then estimated the contribution to the diet (EDI) based on the 

consumption of those commodities. The supporting documents identify how the potential dietary 

concentrations were determined. FDA (Attachment 4A [See attachment 4A on page 24 of American 

Chemistry Council, Biocides Panel comments, PDF docket ID EPA-HQ- OPP-2008-0110-0088]) 

later expanded its calculations of dietary contribution (EDI) for all food processing uses, including 

dairy. That calculation is described above in association with model 2. 

Thus, in the case of very limited uses in processing areas, FDA would calculate potential exposure 

and a resulting dietary contribution based on the specific uses, combining those uses. However, this 

is done extremely rarely, with FDA largely using model 2 to include all food processing areas, 

including dairy, without separately modeling the individual use scenarios. 

Concluding Comments 

FDA had clearly well-documented bases for how it estimated exposures to components of sanitizing 

solutions, which varied depending on whether the broadest worst-case use covering public eating 

facilities and all processing areas was being considered or whether the petitioned uses were more 

limited. In practice, only models 1 or 2 were used except in rare instances. In all cases, however, 

FDA used its model and highly conservative assumptions about the "worst case" scenario to 

establish regulations for sanitizing solutions for the broader uses that the specific model was 

designed to represent. 

References 

FDA. 1993. Sanitizing Solutions: Chemistry Guidance for Food Additive Petitions. Version 1.1. 

http://www.cfsan.fda.gov/~dms/opa-cg3a.html 

FDA. 2006. Estimating Dietary Intake of Substances in Food. Guidance for Industry. August 2006. 

http://www.cfsan.fda.gov/~dms/opa2cg8.html 

Attachments: 

[See table on page 11 of American Chemistry Council, Biocides Panel comments, PDF docket ID 

EPA-HQ- OPP-2008-0110-0088] 

Response: see response 110.37 

Comment Code: 119300 Commenter's Concept of Residue Chemistry Data Requirements Table 

Revisions 

Comment Summary: As part of their comments, the commenter provided an alternate 

Antimicrobial Residue Chemistry Data Requirements Table with testnotes. EPA’s response is for 

the entire alternate testing scheme and not the individual parts. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 779 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25619 

Comment Code: 119300 

Comment: (e) and (f) - Table/Footnotes, see attachment 1.[See Table - Antimicrobial Residue 

Chemistry Data Requirements on P.21 of EPA-HQ- OPP-2008-0110-0086.PDF] 

Response: See response 110.36. 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25656 

Comment Code: 119300 

Comment: 

Table – Antimicrobial Residue Chemistry Data Requirements 

Testing 

Guideline 

Number 

Data Requirement 

Food Use Pattern 

Test Substance Footnote

Aquatic 

Use for 

Antifouling 

& 

Aquaculture 

Production 

- Indoor/ 

Outdoor 

Raw 

Agricultural 

Commodities 

- Indoor/ 

Outdoor 

Commercial &

Institutional 

Hard Surfaces 

- Indoor 

Residential

Hard 

Surfaces*-

Indoor 

NonExempt 

Treated 

Articles 

- 

Indoor 

Supporting Information 

860.1100 Chemical 

Identity R R R R R TGAI 

860.1200 Directions for 

Use R R R R R ---- 

860.1550 Proposed 

tolerance R R R NR R PAI & residueof concern 

860-

1560 

Reasonable 

grounds in 

support of 

petition for 

tolerance or 

exemption 

R R R NR R ---- 

860.1650 

Submittal of 

analytical 

reference 

standards 

CR CR CR NR CR PAI & residue 

of concern 1 

Tier 1 

Screening level 

dietary 

exposure 

assessment 

R R R CR R ---- 2, 7, 8 

Tier 2
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 780 

Testing 

Guideline 

Number 

Data Requirement 

Food Use Pattern 

Test Substance Footnote

Aquatic 

Use for 

Antifouling 

& 

Aquaculture 

Production 

- Indoor/ 

Outdoor 

Raw 

Agricultural 

Commodities 

- Indoor/ 

Outdoor 

Commercial &

Institutional 

Hard Surfaces 

- Indoor 

Residential

Hard 

Surfaces*-

Indoor 

NonExempt 

Treated 

Articles 

- 

Indoor 

Refined dietary 

exposure 

assessment 

CR CR CR CR CR TEP 2, 4, 9 

Tier 3 

Nature of 

residue on 

surface 

NR CR CR NR CR PAIRA or 

TGAI 1, 4, 6 

 Bioaccumulation CR CR NR NR NR TGAI, PAI, 

degradate 1, 4 

Magnitude of 

residue CR CR CR NR CR TEP 1, 3, 4, 

5 

860.1340 

Residue 

analytical 

method 

CR CR CR NR CR Residue of 

concern 1, 4 

860.1380 Storage Stability CR CR CR NR CR 

TEP or 

residue of 

concern 

1, 3, 4 

 * A 408 Tolerance Assessment is NOT required for residential food use patterns. The applicability 

of a dietary assessment for residential use products will be determined on a case by case basis by the 

1 Not Required if exempt from tolerance provided the dietary exposure is not needed due to low 

toxicity or the theoretical estimates of exposure are adequate to assess dietary risk. 

2 Use Appropriate models to estimates exposure by ingestion. 

3 Use Appropriate protocols for residue determination. 

4 Consult with Agency before conducting Tier 2 or Tier 3 Testing 

5 For hard surfaces in commercial, institutional, residential and treated articles this would be a 

migration study. 

6 For aquatic use, nature of residue is determined in the bioaccumulation test. 

7 The residue estimate is for the amount leached from the treated surface. 

8 Assessment conducted using estimated surface residues. 

9 Assessment conducted using measured surface residues from TEP. 

Response: See response 110.36. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27230 

Comment Code: 119300 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 781 

Comment: Proposed 158.2290(c) should be eliminated in its entirety and proposed sections (d) and 

(e) renumbered as (c) and (d). 

The Panel proposes that paragraph (e) be replaced with the following tables and associated test 

notes. 

Because of the dissimilar nature of the potential residue chemistry data requirements for applications 

as rinses or to water (livestock drinking water and non-municipal water treatment) and those for less 

direct application, the Panel proposes separating the table into two parts to improve clarity and 

understanding as described below: [The Panel proposes that paragraph (e) be replaced with the 

following tables and associated test notes.] 

Table – Antimicrobial Residue Chemistry Data Requirements 

Part 1 – Aquatic Food and Commercial & Institutional Indoor Food Uses Other than Rinses 

or Applications to Water 

Testing 

Guideline 

Number 

Data Requirement Aquatic 

Food 

Commercial 

& 

Institutional 

Indoor Food 

Non-food 

Use Pattern 

Residential 

Indoor 

Test 

Substance Footnote 

Supporting Information 

860.1100 Chemical Identity R R R TGAI 

860.1200 Directions for Use R R R ---- 

860.1550 Proposed tolerance or 

exemption R R NR 

PAI & 

residue of 

concern 

860.1560 

Reasonable grounds 

in support of petition 

for tolerance or 

exemption 

R R NR ---- 

860.1650 

Submittal of 

analytical reference 

standards 

CR CR NR 

PAI & 

residue of 

concern 

1 

Tier 1 

None 

Screening level 

dietary exposure 

assessment 

R R CR ---- 2, 7, 8, 9 

Tier 2 

None Refined dietary 

exposure assessment CR CR CR TEP 2, 4, 8, 10 

Tier 3 

None Nature of residue on 

surface NR CR NR PAIRA or TGAI 1, 4, 6 

None Bioaccumulation CR NR NR 

TGAI, 

PAI, 

degradate 

1, 4 

None Magnitude of residue CR CR NR TEP 1, 3, 4, 5 

860.1340 

Residue analytical 

method CR CR NR 

Residue 

of 

concern 

1, 4 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 782 

860.1380 Storage stability CR CR NR 

TEP or 

residue of 

concern 

1,3, 4 

1 Not required for an exemption from tolerance provided the dietary exposure estimates are not 

needed due to low toxicity or the theoretical estimates of exposure are adequate to assess dietary 

risk. 

2 Use appropriate models to estimate exposure. 

3 Use appropriate protocols for residue determination. 

4 Consult with Agency before conducting Tier 2 or Tier 3 Testing may be appropriate. 

5 For hard surfaces in commercial, institutional, residential and treated articles this may be a 

migration study. 

6 For aquatic use, nature of residue is determined in the bioaccumulation test. 

7 For aquatic use, the residue estimate is for the amount leached from the treated surface. 

8 If the use is covered by a tolerance/tolerance exemption for the commercial use, an exposure 

assessment for the residential use is not required (NR). 

9 Assessment conducted using estimated surface residues. 

10 Assessment conducted using measured surface residues from TEP and transfer factors if 

relevant. 

Part 2: Fruit and Vegetable Rinses and Water Treatment Uses 

 Commercial & Institutional Indoor Food 

Testing 

Guideline 

Number 

Data Requirement 

NonMunicipal 

Water* 

Fruit & 

Vegetable 

Rinses** 

Livestock 

Drinking 

Water 

Test 

Substance Footnote 

Supporting Information

860.1100 Chemical Identity R R R TGAI 

860.1200 Directions for Use R R R ---- 

860.1550 Proposed tolerance or 

exemption R R R 

PAI & 

residue of 

concern 

860.1560 

Reasonable grounds 

in support of petition 

for tolerance or 

exemption 

R R R ---- 

860.1650 

Submittal of 

analytical reference 

standards 

CR CR R 

PAI & 

residue of 

concern 

1 

Tier 1 – Estimate of Dietary Exposures

None Estimate of dietary 

exposure 

R R R PAI or 

TGAI 2 

Tier 2

Nature of the Residue

None Nature of the residue 

in commodity NR CR NR PAI or 

TGAI 3 

None Nature of the residue 

in livestock NR CR CR PAI or 

TGAI 3 

None 

Residue analytical 

methods for 

enforcement of 

tolerances 

CR CR CR Residue of 

concern 

1 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Residue Chemistry Section (110) Page 783 

 Commercial & Institutional Indoor Food 

Testing 

Guideline 

Number 

Data Requirement 

NonMunicipal 

Water* 

Fruit & 

Vegetable 

Rinses** 

Livestock 

Drinking 

Water 

Test 

Substance Footnote 

None Multiresidue 

analytical method CR CR CR Residue of 

concern 

1 

Magnitude of the Residue

None In commodities NR CR NR TGAI or 

TEP 1, 4 

None Meat/milk/poultry/ 

eggs 

NR NR CR TGAI or 

TEP 1, 4 

None In water CR NR NR TGAI or 

TEP 1, 4 

None Storage stability CR CR CR TGAI 1, 4 

Anticipated Residues

None Anticipated residues CR CR CR Residue of 

Concern 1 

[The Panel proposes that paragraph (e) be replaced with the following tables and associated test 

notes.] 

1 Not required for an exemption from tolerance provided the dietary exposure estimates are not 

needed due to low toxicity or the theoretical estimates of exposure are adequate to assess dietary 

risk. 

2 Use appropriate models to estimate exposure 

3 Required when assumption of degradation or transformation is appropriate 

4 Required when refinement of exposure estimates is needed 

*Includes antimicrobials applied to process water contacting food 

**Post harvest treatment in the field, in transporation, or in a washing/packing facility where 

processing does not occur. 

Response: See response 110.36. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27653 

Comment Code: 119300 

Comment: Proposed 158.2290(c) should be eliminated in its entirety and proposed sections (d) and 

(e) renumbered as (c) and (d). 

LANXESS proposes that paragraph (e) be replaced with the following tables and associated test 

notes. 

Because of the dissimilar nature of the potential residue chemistry data requirements for applications 

as rinses or to water (livestock drinking water and non-municipal water treatment) and those for less 

direct application, LANXESS proposes separating the table into two parts to improve clarity and 

understanding. 
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Comments and Response References: 

Residue Chemistry Section (110) Page 784 

[See Table "Antimicrobial Residue Chemistry Data Requirements Part 1 - Aquatic Food and 

Commercial & Institutional Indoor Food Uses Other than Rinses or Applications to Water" in PDF 

docket ID EPA-HQ-OPP-2008-0110-0064] 

[LANXESS proposes that paragraph (e) be replaced with the following tables and associated test 

notes.] 1 Not required for an exemption from tolerance provided the dietary exposure estimates are 

not needed due to low toxicity or the theoretical estimates of exposure are adequate to assess dietary 

risk. 

[LANXESS proposes that paragraph (e) be replaced with the following tables and associated test 

notes.] 2 Use appropriate models to estimate exposure. 3 Use appropriate protocols for residue 

determination. 4 Consult with Agency before conducting Tier 2 or Tier 3 Testing may be 

appropriate. 5 For hard surfaces in commercial, institutional, residential and treated articles this may 

be a migration study. 6 For aquatic use, nature of residue is determined in the bioaccumulation test. 

7 For aquatic use, the residue estimate is for the amount leached from the treated surface. 8 If the 

use is covered by a tolerance/tolerance exemption for the commercial use, an exposure assessment 

for the residential use is not required (NR). 9 Assessment conducted using estimated surface 

residues. 10 Assessment conducted using measured surface residues from TEP and transfer factors 

if relevant. 

[LANXESS proposes that paragraph (e) be replaced with the following tables and associated test 

notes.] [See Table "Antimicrobial Residue Chemistry Data Requirements Part 2 - Fruit and 

Vegetable Rinses and Water Treatment Uses" in PDF docket ID EPA-HQ- OPP-2008-0110-0064] 

[LANXESS proposes that paragraph (e) be replaced with the following tables and associated test 

notes.] 1 Not required for an exemption from tolerance provided the dietary exposure estimates are 

not needed due to low toxicity or the theoretical estimates of exposure are adquate to assess dietary 

risk. 2 Use appropriate models to estimate exposure 3 Required when assumption of degradation or 

transformation is appropriate 4 Required when refinement of exposure estimates is needed 

Response: See response 110.36. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Risk Assessment Section (120) Page 785 

Environmental Risk Assessment (120) 

Verbatim Comments and Response References for the Environmental Risk 

Assessment Section 

Comment Code: 120000 Environmental risk assessment 

Commenter Name: Ray S. McAlister 

Commenter Organization: CropLife America 

Letter ID: 0079 

Comment ID: 25469 

Comment Code: 120000 

Comment: With respect to environmental risk assessment, CLA recommends that the 

Antimicrobial Division consider the PBT approach proposed by EFED and evaluated by the FIFRA 

Science Advisory Panel in October 2008, before a wholesale list of new data requirements are 

approved for antimicrobial pesticides. (See 

http://www.epa.gov/scipoly/sap/meetings/2008/102808_mtg.htm.) 

Response: see response 120.6 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26200 

Comment Code: 120000 

Comment: Environmental Fate/Effects: 

P&G has been in the business of providing consumers with disinfecting products for many years. 

We have our own environmental safety assessment process which includes an environmental effects 

analysis and an environmental exposure analysis. The basis of the exposure analysis is a wastewater 

treatment plant model (ASTREAT). Our approach has been applied to all of the active and inactive 

ingredients in our products and has demonstrated their safety in the environment. Proof of this is 

the fact that none of our ingredients has ever been implicated as causing a risk in the environment. 

This level of safety is provided despite the fact that our approach involves the use of significantly 

fewer animals when compared with the EPA’s recommended program. Further, our approach is 

more closely aligned with safety programs recommended by governments around the world. P&G’s 

approach has been published in peer reviewed journals, has withstood the test of time and scientific 

scrutiny, and was shared with EPA in a private meeting. P&G’s model was made available to EPA 

for its use. We recommend that EPA reconsider the number and variety of animal studies it is 

considering in support of the risk assessment of disinfectants disposed down the drain. 

Response: see response 134.10 
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Comments and Response References: 

Environmental Risk Assessment Section (120) Page 786 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26398 

Comment Code: 120000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * EPA assumes product misuse with environmental exposure.[FN#8: (page 59405)] This is 

not a valid justification to require data to support a registration decision. 

Response: see response 120.4 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26402 

Comment Code: 120000 

Comment: EPA’s Proposal also improperly assumes that all wood preservative antimicrobial 

products will result in "high environmental exposures." To the extent that wood preserved with an 

antimicrobial might come into either ground or aquatic contact, there is a potential for exposure. In 

the case of soil, this exposure is likely to be highly localized but in the case of aquatic environments, 

possibly less so. In either event, the Proposal does not contain data requirements that are useful to 

determining when environmental exposure could occur or for generating reliable estimates of such 

exposure. The Proposal subjects all wood preservatives to leach rate testing, without regard to 

whether the use would result in any environmental exposure. Of even greater concern, the Proposal 

would require submission of data generated by leach rate test methods that are not useful for 

estimating environmental exposures, would seriously overestimate potential environmental 

exposures, and would lead to the regulation of wood preservatives in a manner entirely inconsistent 

with potential environmental risk.[FN#59:American Wood Preservers’ Association Methods E11-97 

and E20-04.] 

Response: see response 120.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26456 

Comment Code: 120000 

Comment: Equally significant, the 1997 discussions on environmental risk assessment issues are not 

sufficient to support the Proposal in its current form. As EPA points out, it has in the last few years 

adopted a number of the SAP recommendations with regard to environmental fate testing for 

antimicrobials where use may result in release down-the-drain. Nonetheless, as discussed in 

Appendix E, EPA has not provided useful criteria for determining appropriate uses for triggering 

such requirements.[FN#84:Similarly, EPA has not addressed the 1997 SAP recommendation that it 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Risk Assessment Section (120) Page 787 

consider "where testing from one [EPA] Office may be substituted for the requirements of the 

Office of Pesticide Programs." Id. at 14.] 

Response: see response 120.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26719 

Comment Code: 120000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * EPA assumes product misuse with environmental 

exposure.[FN#4:Page 59405.] This is not a valid justification to require data to support a registration 

decision. 

Response: see response 120.4 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26993 

Comment Code: 120000 

Comment: EPA’s Proposal also improperly assumes that all wood preservative antimicrobial 

products will result in "high environmental exposures." To the extent that wood preserved with an 

antimicrobial might come into either ground or aquatic contact, there is a potential for exposure. In 

the case of soil, this exposure is likely to be highly localized but in the case of aquatic environments, 

possibly less so. In either event, the Proposal does not contain data requirements that are useful to 

determining when environmental exposure could occur or for generating reliable estimates of such 

exposure. The Proposal subjects all wood preservatives to leach rate testing, without regard to 

whether the use would result in any environmental exposure. Of even greater concern, the Proposal 

would require submission of data generated by a leach rate test methods that are not useful for 

estimating environmental exposures, would seriously overestimate potential environmental 

exposure, and would lead to the regulation of wood preservatives in a manner entirely inconsistent 

with potential environmental risk.[FN59: American Wood Preservers’ Association Methods E11-97 

and E20-04.] 

Response: see response 120.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27206 

Comment Code: 120000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Risk Assessment Section (120) Page 788 

Comment: Equally significant, the 1997 discussions on environmental risk assessment issues are not 

sufficient to support the Proposal in its current form. As EPA points out, it has in the last few years 

adopted a number of the SAP recommendations with regard to environmental fate testing for 

antimicrobials where use may result in release down-the-drain. Nonetheless, as discussed in 

Appendix E, EPA has not provided useful criteria for determining appropriate uses for triggering 

such requirements.[FN86: Similarly, EPA has not addressed the 1997 SAP recommendation that it 

consider "where testing from one [EPA] Office may be substituted for the requirements of the 

Office of Pesticide Programs." Id. at 14.] 

Response: see response 120.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27398 

Comment Code: 120000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * EPA assumes product misuse with environmental 

exposure.[FN#4:Page 59405.] This is not a valid justification to require data to support a registration 

decision. 

Response: see response 120.4 

Comment Code: 121000 Factors considered in determining the high/low exposure groupings 

Commenter Name: Abigail Trueblood 

Commenter Organization: Dow Chemical Company 

Letter ID: 0082 

Comment ID: 25475 

Comment Code: 121000 

Comment: The classification of "high" and "low" exposures is troubling because the very broad 

categorizations potentially include all antimicrobials, rendering the classifications to be without 

meaning. For example, the attempt to categorize biocide products as "high" or "low" environment 

exposure based on product types alone is questionable. The physical and chemical properties of 

products, in addition to the use patterns, are necessary to determine actual environmental exposures. 

Response: see response 140.3 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25606 

Comment Code: 121000 
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Comments and Response References: 

Environmental Risk Assessment Section (120) Page 789 

Comment: Section Number XI. 

Title B. Determination of the Two groupings: Low and High Environmental Exposure 

Paragraph p. 59405 

Excerpt from Federal Register General comment 

HC Comment The PMRA does not differentiate antimicrobial pesticides into a low or high 

environmental exposure group, but rather,pesticides are categorized under specific USCs. The 

minimum set of data requirements for each particular use site is identified with "R" or required data. 

These studies must be addressed by data/information or with an acceptable scientifically valid 

rationale supporting its waiver. The "R" data are augmented by further data requirements designated 

as "CR" or conditionally required. These data are required based on potential exposure and other 

criteria dependent on the results of the "R" studies. The applicant is able to provide a scientifically 

valid rationale to waive an "R" data requirement when the potential for environmental exposure is 

low. This often results in a similar categorization of antimicrobial pesticides as the EPA, but without 

the division of antimicrobial pesticides into a low or high environmental exposure groups. 

Response: see response 140.3 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26213 

Comment Code: 121000 

Comment: D. Identification of Areas of Specific Concern 

The following are some of the problems identified in the proposed rule: 1) Dividing antimicrobials 

into two groups, low and high environmental exposure, for determining environmental and 

ecotoxicity data requirements is arbitrary and does not accurately represent the potential 

environmental exposures associated with the use of the products. Use Patterns descriptions provide 

a better alternative with a more realistic representation of environmental exposure with antimicrobial 

use. 

Response: see response 140.3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27005 

Comment Code: 121000 

Comment: D. Identification of Areas of Specific Concern 

The following are some of the problems identified in the proposed rule: 
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Comments and Response References: 

Environmental Risk Assessment Section (120) Page 790 

1) Dividing antimicrobials into two groups, low and high environmental exposure, for determining 

environmental and ecotoxicity data requirements is arbitrary and does not accurately represent the 

potential environmental exposures associated with the use of the products. Use Patterns descriptions 

provide a better alternative with a more realistic representation of environmental exposure with 

antimicrobial use. 

Response: see response 140.3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27514 

Comment Code: 121000 

Comment: D. Identification of Areas of Specific Concern 

The following are some of the problems identified in the proposed rule: 

1) Dividing antimicrobials into two groups, low and high environmental exposure, for determining 

environmental and ecotoxicity data requirements is arbitrary and does not accurately represent the 

potential environmental exposures associated with the use of the products. Use Patterns descriptions 

provide a better alternative with a more realistic representation of environmental exposure with 

antimicrobial use. 

Response: see response 140.3 

Comment Code: 122000 High environmental exposure 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26990 

Comment Code: 122000 

Comment: For example, any release from a once-through water treatment system is a point- source 

discharge regulated under the Clean Water Act.[FN56: Clean Water Act, sections 301 et seq., creates 

standards and permit obligations for point source discharges. It is illegal to discharge any pollutant 

from a point source without a permit. The National Pollutant Discharge Elimination System 

(NPDES) permit program controls point source discharges. EPA defines point source discharges as 

"discrete conveyances such as pipes or man- made ditches." Industrial, municipal, and other facilities 

must obtain NPDES permits if their discharges go directly to surface waters. See 40 CFR Parts 100-

135 for NPDES and related regulations; see also 40 CFR 400-471 for industry- specific effluent 

guidelines and standards, which cover the vast majority of industrial and institutional users of 

antimicrobials, e.g., pulp, paper and paperboard mills (40 CFR Part 430) and painting formulators 

(40 CFR Part 446).] This is in direct contrast to the extensive non-point source discharges of 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Risk Assessment Section (120) Page 791 

conventional pesticides.[FN57: In contrast to the extensive regulation of point source discharges, 

non-point source discharges are regulated under CWA sections 208 and 319. These sections require 

states to develop watershed management plans to impede non-point source discharges and to 

identify waters damaged or threatened by runoff. There are no equivalent permit requirements or 

regulations to effectively control environmental exposures for the vast majority of non-point source 

discharges.] The ability to regulate and control point source discharges is far greater than for nonpoint discharges and the regulatory requirements are concomitantly more comprehensive. 

Response: See response 30.25. 

Comment Code: 124000 Wood preservatives being regulated differently based on use patterns 

(land use vs. Aquatic use) 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25603 

Comment Code: 124000 

Comment: *An outstanding issue is how the risk assessment for wood preservatives is conducted 

between the PMRA and EPA. The EPA’s risk assessment is based on the treated wood when used 

at the final use site, while the PMRA’s risk assessment is based at the site where the wood is treated. 

The PMRA also does not distinguish between terrestrial-only or aquatic-only use for anti-sapstains 

and heavy-duty wood preservatives. 

Response: see response 120.5 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25607 

Comment Code: 124000 

Comment: Section Number XI. 

Title D. Data Requirements for Wood Preservatives 

Paragraph 1; p. 59405 

Excerpt from Federal Register The data required to register a wood preservative product depend on 

the use site of the treated wood, which can be land-only, aquatic-only or both. 

HC Comment The focus of the EPA’s evaluation of the risk of wood preservatives is on the use of 

treated wood at the actual site of use, with in-use exposure potentially being minimized by label 

restrictions. In contrast, the PMRA assesses the risk of wood preservatives at the site of treatment of 

the wood and considers potential exposure of neighbouring aquatic systems. The PMRA recognizes 
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Comments and Response References: 

Environmental Risk Assessment Section (120) Page 792 

that not all types of wood preservatives will result in the same degree of risk, with antisapstains and 

heavy duty wood preservatives having a greater potential for impacting the environment than readyto-use wood stains and coatings. The PMRA does not make any differentiation in data requirements 

between land-only versus aquatic-only use of treated wood, as potential environmental impact on 

freshwater and estuarine systems adjacent to antisapstain and heavy-duty treatment facilities is the 

primary concern. Many wood preservative treatment facilities in Canada are located within close 

proximity to sensitive salmon bearing streams and rivers and the leaching of the wood preservative 

product would be greatest from treated wood at the treatment facility rather than at the actual site of 

use of the wood. To protect these sensitive aquatic habitats in Canada, aquatic fate and aquatic 

toxicology data are, therefore, required for all wood preservatives other than ready-to-use wood 

stains and coatings. 

 Section Number XI. 

Title D. Data Requirements for Wood Preservatives 

Paragraph 2; p. 59405 

Excerpt from Federal Register Therefore, if a product specifies that wood that has been treated with 

that product cannot be used in areas with the potential for that wood coming into contact with 

water, then EPA believes that the potential for exposure is decreased. Accordingly, it is current EPA 

practice to require fewer environmental fate and ecological effects studies for such products. 

HC Comment The US EPA should take into consideration that the potential for the leaching of 

wood preservative products is highest from freshly treated wood at the treatment facility rather than 

from treated wood at the actual site of service. This exposure scenario should be used to conduct 

the risk assessment for wood preservatives, as leaching at the site of use will be minimized after 

fixation into the wood at the treatment facility. 

Response: see response 120.5 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25632 

Comment Code: 124000 

Comment: The remaining differences in data requirements between the two agencies are: *The 

PMRA requirement for an incineration/thermal decomposition study at high and low temperatures 

for wood preservatives. The remaining differences in data requirements between the two agencies 

are: *Because the PMRA does not distinguish data requirements between terrestrial- only versus 

aquaticonly use for anti-sapstains and heavy-duty wood preservatives, several of the environmental 

fate and environmental toxicology studies for wood preservatives are required by the PMRA, while 

these same studies are only conditionally required by the EPA. 

Response: see response 120.5 
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Comments and Response References: 

Environmental Risk Assessment Section (120) Page 793 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27691 

Comment Code: 124000 

Comment: 20. Proposed Regulation # [Section] 158.2240(a)(4) 

Text of the Proposed Regulation (emphasis added) Nontarget organisms: General. "For wood 

preservatives, the Agency may require data on both the parent compound, which is incorporated 

into wood, and on transformation/degradation products which occur as dislodgeable residues (such 

as hand contact with treated wood) or leachate residues (such as from soil or water contact with 

treated wood). 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated on what grounds the Agency will require data on the both the parent compound and the on 

transformation/degradation products for wood preservatives. 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 29000 

Comment Code: 124000 

Comment: 20. Proposed Regulation # [Section] 158.2240(a)(4) 

Text of the Proposed Regulation (emphasis added) Nontarget organisms: General. "For wood 

preservatives, the Agency may require data on both the parent compound, which is incorporated 

into wood, and on transformation/degradation products which occur as dislodgeable residues (such 

as hand contact with treated wood) or leachate residues (such as from soil or water contact with 

treated wood). 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated on what grounds the Agency will require data on the both the parent compound and the on 

transformation/degradation products for wood preservatives. 

Response: see response 3
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Comments and Response References: 

Letter from Environmental Working Group Section (125) Page 794 

Letter from Environmental Working Group (125) 

Verbatim Comments and Response Reference for the Letter from 

Environmental Working Group 

Comment Code: 125000 Letter from Environmental Working Group 

Commenter Name: Olga V. Naidenko 

Commenter Organization: Environmental Working Group 

Letter ID: 0077 

Comment ID: 31439 

Comment Code: 125000 

Comment: April 6, 2009 

EPA needs to protect people and the environment from contamination with antimicrobial pesticides 

Office of Pesticide Programs Environmental Protection Agency 1200 Pennsylvania Ave, NW, 

Washington DC 20460-0001 

Regarding: Proposed Rule for Data Requirements for Antimicrobial Pesticides Docket EPA-HQOPP-2008-0110 

Environmental Working Group (EWG) is a non-profit public health and environmental research 

and advocacy organization based in Washington, DC. We focus much of our research on potential 

health risks from chemical contamination of food, water, consumer products, and the environment. 

With this letter, we urge the Environmental Protection Agency (EPA) to address the health and 

safety gaps in its proposed rule on antimicrobial pesticides in order to protect human and 

environmental health from excessive exposures to these potent chemicals. 

Antimicrobial pesticides and preservatives serve a useful public health function, especially in 

medical, commercial, and industrial applications. But their increasing and unnecessary use in a wide 

range of consumer products has been associated with environmental pollution, potential human 

health risks, and toxicity to ecosystems (Aiello 2007; Focazio 2008; James 2009). With the proposed 

rule, EPA revises and updates the existing data requirements for information that manufacturers 

need to submit to the Agency during the pesticide registration process. The new data requirements 

should allow EPA to make regulatory decisions so as to protect human health and the environment 

from potentially harmful, unintended effects of antimicrobial pesticide products, many of which are 

powerful toxicants. 

EWG supports the overall approach the Agency has taken with the proposed data rule that 

incorporates tiered toxicology, exposure, and environmental fate studies. However, several 

shortcomings of the draft rule threaten to undermine its future regulatory effectiveness, since it 

allows pesticide manufacturers to avoid responsibility for the full scope of environmental health 

risks due to antimicrobial pesticide pollution. Furthermore, the final EPA rule needs to account for 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Letter from Environmental Working Group Section (125) Page 795 

the overall presence of antimicrobial products in commerce, whatever their original mode of 

registration. EWG urges EPA to strengthen the new rule in three key areas that should: 

* Protect human health from cumulative exposure to antimicrobial pesticides; * Require monitoring 

of pesticide contamination in the environment and in people, including in cord blood and 

statistically representative samples from other vulnerable populations; * Ensure that aquatic and 

terrestrial ecosystems are protected from chronic pesticide toxicity. Details and supporting 

information for these recommendations are described below. 

1. Protect human health from cumulative exposure to antimicrobial pesticides 

Research by government scientists at the Centers for Disease Control and Prevention (CDC) and 

the U.S. Geological Survey, independent academic researchers, and public health advocacy groups 

demonstrated that already, the bodies of people and environment at large have been contaminated 

with antimicrobial pesticides and related chemicals used as preservatives, such as antibacterial soap 

ingredients triclosan and triclocarcban, agricultural antimicrobial pesticide ortho-phenylphenol, and 

wood deck preservative arsenic (Caldwell 2008; CDC 2005; Chu 2007; Coogan 2008; EWG 2008a; 

Focazio 2008; Halden 2005; Kingsbury 2008; Kolpin 2002). For example, the bodies of nearly 75% 

of Americans are polluted with triclosan (Calafat 2008). The reason for this extensive contamination 

is clear: present system of pesticide registration creates an ambiguous and dangerous situation 

whereby antimicrobial pesticide manufacturers can produce and include these toxic chemicals in a 

wide variety of consumer products without any scrutiny from EPA. Simply by avoiding the use of 

the word "pesticide" on the product label, manufacturers can add antimicrobial chemicals to any 

consumer product they choose. As a result, people may be exposed to multiple sources of 

antimicrobial pesticides in their own homes, often without their knowledge and without a chance to 

make an informed decision (EWG 2008b). This loophole must be closed so as to protect the health 

of American families. 

Hand soap ingredients triclosan and triclocarban illustrate the unacceptable weakness of the current 

EPA approach to antimicrobial pesticide regulation. Triclosan and triclocarban share a common 

pattern of household usage, heavy disposal into wastewater plants, accumulation in wastewater 

sludge, and contamination of effluent, which eventually leads to contamination of ambient water 

bodies and drinking water with these pesticides (Halden 2005; Young 2008). Once released into the 

environment, they pose grave risks to aquatic life (Coogan 2008; Lawrence 2009; Oliveira 2009; 

Orvos 2002; Tatarazako 2004; Yang 2008). Additionally, these antimicrobials have been associated 

with adverse effects on thyroid, estrogen, and testosterone hormone function (Ahn 2008; Chen 

2008; James 2009; Kumar 2008; Zorrilla 2008); 

Despite these well-documented risks, the majority of triclosan and triclocarban- containing products, 

such as household cleaners and hand soaps, completely evade EPA oversight since they officially fall 

under FDA’s jurisdiction. In the case of triclosan, some of its’ antimicrobial uses (excluding handsoaps and cleaners) are reviewed by EPA. In contrast, triclocarban effectively slips under the radar 

of regulatory agencies. Although previously triclocarban has been registered with EPA for use as a 

pesticide, triclocarban registration has been later cancelled (NPIRS 2008), but its use in commerce 

has continued. Triclocarban is still found in numerous antibacterial bar soaps on the market. EWG’s 

Cosmetic Safety database lists 55 different products containing triclocarban, including 51 different 

bar soaps (EWG 2009) and the actual numbers are likely to be higher (Perencevich 2001). 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Letter from Environmental Working Group Section (125) Page 796 

From both scientific and health perspectives, it is completely irrelevant whether exposure to an 

antimicrobial pesticide is due to the presence of this chemical in a product that is regulated by EPA, 

FDA, or any other government agency - what matters is whether or not the overall exposures are 

safe over life-time. The proposed rule fails to remedy the current regulatory impasse whereby EPA 

cannot enforce manufacturer responsibility for the full range of antimicrobial pesticide exposures 

faced by people and the environment. The final EPA rule needs to account for the overall presence 

of antimicrobial products in commerce, whatever their original mode of registration. So long as 

potent pesticide compounds appear in consumer products with little or no review from EPA, public 

health remains at risk. 

Antimicrobial pesticides and preservatives serve a useful public health function, especially in medical 

applications where they can prevent the spread of life-threatening diseases. In contrast, 

antimicrobials do not bring additional health benefits for residential indoor and consumer product 

applications; instead, they may contribute to potential development of antimicrobial resistance 

(Birosova 2009; Cottell 2009; Levy 2001). Increasing and unnecessary use of antimicrobials in a wide 

range of consumer products raises concerns, because of the prospect of reduced medical usefulness 

due to antimicrobial resistance. Spread of triclosan- and triclocarban-tolerant bacterial strains could 

result in these chemicals becoming ineffective in their important medical applications (Aiello 2007). 

As summarized in a recent review, "of major concern is the possibility that triclosan resistance may 

contribute to reduced susceptibility to clinically important antimicrobials, due to either crossresistance or co-resistance mechanisms...thus, widespread use of triclosan may represent a potential 

public health risk in regard to development of concomitant resistance to clinically important 

antimicrobials"(Yazdankhah 2006). Ensuring EPA oversight over the full use of an antimicrobial 

compound is the first step towards avoiding potential development of antimicrobial resistance in 

future. 

Environmental and human health risks of antimicrobial pesticides should be addressed with a 

comprehensive health and safety assessment that would not hide behind the artificial separation of 

pesticide regulation between FDA and EPA. This divided responsibility for the same pesticide 

between separate government agencies does not serve the public interest since it allows a large 

percentage of products containing antimicrobial chemicals to be manufactured and used with no 

effective health and safety controls. The only solution that would protect the health of people and 

the environment is for EPA to enforce pesticide manufacturers’ accountability for all uses of their 

products in commerce. 

EPA would be able to protect public health and the environment from antimicrobials only if the 

Agency would consider aggregate risks and exposures. Furthermore, since there are so many uses of 

the same pesticide that EPA currently has no way to track, long-term downstream monitoring of 

people and the environment is critical. 

2. Require monitoring of pesticide contamination in the environment and in people, including in 

cord blood and statistically representative samples from other vulnerable populations 

Assessing human and environmental health risks due to antimicrobial pesticides requires both 

toxicity and exposure data. The proposed rule includes a solid and reliable panel of tests that would 

produce information about the pesticide’s potential for mammalian toxicity. In contrast, the draft 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Letter from Environmental Working Group Section (125) Page 797 

rule has only minimal and woefully insufficient data requirements for monitoring pesticide 

contamination of people and the environment. As a result, both EPA and the general public would 

lack information on cumulative pesticide exposures which leaves at risk potentially vulnerable 

populations such as pregnant women, the developing fetus, and young children, as well as certain 

groups of workers who may be exposed to high levels of antimicrobial pesticides in their workplace. 

While acknowledging the importance of real-life biomonitoring of human and environmental 

exposure to antimicrobial pesticides, the proposed rule does not actually require manufacturers to 

conduct these studies as a part of pesticide registration process. For some antimicrobials, such as 

triclosan, biomonitoring data may be availble thanks to the work of the CDC, government- and 

university- funded academic scientists, and non-profit organization. These studies clearly 

demonstrate the widespread triclosan contamination of water, soils, aquatic life and the bodies of 

people (Calafat 2008; Cha 2009; Coogan 2008; EWG 2008c; Halden 2005). For other pesticides, 

such as triclocarban, data on environmental contamination are available, but no human 

biomonitoring studies have been conducted as yet (Cha 2009; Coogan 2007; Coogan 2008; Sapkota 

2007)}. Moreover, as new antimicrobial pesticides are developed and introduced into consumer 

products, the same story repeats itself, with both EPA and public health researchers constantly 

forced to play catch up and do detective work so as to discover which antimicrobials are becoming 

new, emergent contaminants and polluting bodies of people and the environment. 

To address these glaring data gaps, manufacturers should be responsible for conducting 

biomonitoring studies on an ongoing basis. Understandably, such data would not be available for a 

recently discovered antimicrobial going through its first registration at EPA. However, collection of 

biomonitoring data should be a mandatory condition for a pesticide to remain in commerce. These 

data must be publicly available, allowing all concerned stakeholders--water utilities, health agencies, 

researchers, and parents--to make informed, data-driven decisions on risk mitigation. 

In the proposed rule, monitoring of representative U.S. waters and monitoring of pesticide body 

burden in people in residential and occupational settings are both included as a "conditional 

requirement," meaning that there is less than 50% chance for biomonitoring to be required during a 

pesticide registration process. This weak condition creates a convenient loophole that allows 

manufacturers to continue using persistent polluting antimicrobial pesticides in consumer products 

so long as environmental contamination studies have not been conducted or made publicly available. 

To resolve this problem and to avoid present and future contamination, EPA should require 

manufactures to monitor and publicly release all data for pesticide contamination in soils, aquatic 

life, ambient waters, and wastewater sludge and effluent. EPA should also require mandatory 

monitoring of antimicrobial pesticide levels in umbilical cord blood, so as to detect any risks to the 

developing fetus, and in statistically representative samples from other vulnerable populations. 

3. Ensure that aquatic and terrestrial ecosystems are protected from chronic pesticide toxicity 

By their very design, antimicrobial pesticides are meant to kill. In most situations, these pesticides 

provide beneficial features such as decreasing potential spread of infections in medical, food storage 

and processing, and food-preparation settings; protecting equipment and building materials from 

mold and rotting; controlling wood degradation; avoiding bacterial growth in public water systems, 

swimming pools, and aquatic areas as well as many other applications. Yet, whether used in flowthrough water systems that flush high volumes of pesticides down the drain or included as 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Letter from Environmental Working Group Section (125) Page 798 

preservatives in a material that slowly leaches pesticides over time, a significant portion of 

antimicrobial pesticides eventually ends up in wastewater plants. Following wastewater treatment, 

these pesticides pollute sludge, water, sediment, and soils, where they pose direct toxicity to aquatic 

life, and, with food and water, risks to human health as well. 

EWG applauds EPA for working towards a system of tiered toxicology, exposure, and 

environmental fate studies that, ideally, would provide necessary information for human and 

ecosystem risk assessment. EWG supports the overall approach of the Agency that ranks the need 

for test data based on the toxicity and persistence of the antimicrobial pesticide. 

However, EWG is very concerned that in the proposed rule, ecological toxicity assessments 

("nontarget organism data requirements") are primarily based on acute toxicity studies. Although the 

proposed rule considers a "conditional requirement" for studies that would provide chronic toxicity 

information, high- production volume pesticides that are used in consumer products would fall 

outside of this requirement. This would allow environmental contamination to continue and leave 

aquatic and terrestrial ecosystems unprotected from chronic pesticide toxicity. 

In order to assure environmental safety of pesticides, EPA should require manufacturers to provide 

to the Agency data on both environmental exposure and chronic ecotoxicity of antimicrobial 

pesticides. As discussed in the previous section, EPA needs to have access to up-to-date 

environmental monitoring results as a key first step for protecting water, soils, and wildlife from 

toxic pollutants. 

Second, environmental risk assessment needs to consider chronic exposure of aquatic life to 

antimicrobial pesticides. For example, triclosan and triclocarban have been shown to accumulate in 

algae three orders of magnitude above the ambient levels (Coogan 2007). Triclocarban and triclosan 

also accumulate in snails (Coogan 2008). Bioaccumulation of triclosan metabolites in fish five orders 

of magnitude above the ambient levels has been reported (Balmer 2004). Triclocarban is even more 

persistent than triclosan and thus may pose greater chronic toxicity risks (Cha 2009; Heidler 2006; 

Miller 2008). Triclosan and triclocarban associate with sludge in wastewater treatment plants and 

with sediment in the water column. Sediment may serve as a constant-release delivery mechanism 

for high doses of antimicrobials, especially for bottom-dwelling organisms such as worms, mussels 

and clams, crabs, and some herbivorous fish species (Binelli 2009; Miller 2008). Furthermore, larvae 

of many aquatic organisms are filter-feeding. Thus, during the early, most sensitive stage of their life 

cycle, they may be exposed to levels of antimicrobial pesticides that have been associated with 

embryotoxicity, teratogenic developmental changes, and hatching delay (Oliveira 2009). 

Due to their toxicity towards a wide spectrum of microbial and algal species, antimicrobials may 

disrupt critical ecological processes performed by beneficial microorganisms in nature (Dokianakis 

2004; Johnson 2009; Lawrence 2009; Miller 2008; Neumegen 2005; Waller 2009). Especially 

worrisome are recent reports that indicate significant presence of antimicrobial pesticides in 

agricultural soils, due to soil application of triclosan- and triclocarban-containing sludge and 

biosolids from wastewater treatment plants (Cha 2009). EPA’s latest Targeted National Sewage 

Sludge Survey found triclosan in 92.4 % of public wastewater treatment plants tested nationwide; 

triclocarban was found in 100% of wastewater plants (U.S. EPA 2009). In some cases, triclocarban 

levels in dried wastewater sludge were as high as 441 microgram/kilogram (parts per million, ppm), 

while triclosan levels reached 133 ppm (U.S. EPA 2009). These findings are of great concern 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Letter from Environmental Working Group Section (125) Page 799 

because triclosan and triclocarban can inhibits soil respiration and nitrification processes that are 

essential for preserving soil fertility (Waller 2009). They can also disrupt oxygen-producing algal 

communities in waterways and form toxic degradation byproducts (Aranami 2007; Lawrence 2009). 

All of these harmful effects pose chronic toxicity risks. Acute toxicity studies alone are insufficient 

for addressing the damaging effects of longterm environmental contamination with antibacterial 

pesticides. 

EPA should develop a data-based approach for comprehensive assessment and mitigation of 

chronic ecotoxicity risks. These studies should be driven by the real-life findings of pesticide levels 

in the environment and their effects on the ecosystems. Simply carrying chronic toxicity tests on 

laboratory organisms would not be sufficient to answer this question; instead, ecosystem health 

monitoring should be used as a key parameter for addressing ecological risks of antimicrobial 

pesticides. EPA should stand by its mandate as Environmental Protection Agency and ensure that 

chronic exposures to antimicrobial pesticides would not pose a risk to long-term survival and 

stability of aquatic and terrestrial ecosystems and productivity of agricultural soils. 

In conclusion, EWG strongly urges EPA to strengthen the proposed data requirements for 

antimicrobial pesticides so as to address outstanding gaps in key areas such as cumulative human 

and environmental exposures, potential risks to human health, and chronic ecosystem toxicity. 

Future decisions on the use of antimicrobial pesticides should be based on extensive research and 

data collection that would provide necessary information for risk assessment and mitigation. We 

look forward to working with the Agency on the issues of pesticide safety for humans and the 

environment and we will be happy to provide our feedback and comments as EPA continues to 

assess toxicity data for antimicrobial pesticides. We are certain that with concerted effort and 

involvement of multiple stakeholders, many of the present risks of indoor pesticide use would be 

avoided and better health protection implemented, while preserving the use of antibacterials in the 

settings where they are truly needed. 

 With best regards, Olga V. Naidenko, Ph.D. Senior Scientist Environmental Working Group 

 References 

Ahn KC, Zhao B, Chen J, Cherednichenko G, Sanmarti E, Denison MS, et al. 2008. In vitro 

biologic activities of the antimicrobials triclocarban, its analogs, and triclosan in bioassay screens: 

receptor-based bioassay screens. Environ Health Perspect 116(9): 1203-10. 

Aiello AE, Larson EL, Levy SB. 2007. Consumer antibacterial soaps: effective or just risky? Clin 

Infect Dis 45 Suppl 2: S137-47. 

Aranami K, Readman JW. 2007. Photolytic degradation of triclosan in freshwater and seawater. 

Chemosphere 66(6): 1052-6. 

Balmer ME, Poiger T, Droz C, Romanin K, Bergqvist PA, Muller MD, et al. 2004. Occurrence of 

methyl triclosan, a transformation product of the bactericide triclosan, in fish from various lakes in 

Switzerland. Environ Sci Technol 38(2): 390-5. 
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Comments and Response References: 

Letter from Environmental Working Group Section (125) Page 800 

Binelli A, Cogni D, Parolini M, Riva C, Provini A. 2009. Cytotoxic and genotoxic effects of in vitro 

exposure to Triclosan and Trimethoprim on zebra mussel (Dreissena polymorpha) hemocytes. 

Comp Biochem Physiol C Toxicol Pharmacol. 

Birosova L, Mikulasova M. 2009. Development of triclosan and antibiotic resistance in Salmonella 

enterica serovar Typhimurium. J Med Microbiol 58(Pt 4): 436-41. 

Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL. 2008. Urinary concentrations of triclosan in 

the U.S. population: 2003-2004. Environ Health Perspect 116(3): 303-7. 

Caldwell KL, Jones RL, Verdon CP, Jarrett JM, Caudill SP, Osterloh JD. 2008. Levels of urinary 

total and speciated arsenic in the US population: National Health and Nutrition Examination Survey 

2003-2004. J Expo Sci Environ Epidemiol. 

CDC. 2005. Centers for Disease Control and Prevention. Third National Report on Human 

Exposure to Environmental Chemicals. NCEH Pub. No. 05-0570 Available: 

http://www.cdc.gov/exposurereport/ [accessed December 17 2008]. 

Cha J, Cupples AM. 2009. Detection of the antimicrobials triclocarban and triclosan in agricultural 

soils following land application of municipal biosolids. Water Res. 

Chen J, Ahn KC, Gee NA, Ahmed MI, Duleba AJ, Zhao L, et al. 2008. Triclocarban enhances 

testosterone action: a new type of endocrine disruptor? Endocrinology 149(3): 1173-9. 

Chu S, Metcalfe CD. 2007. Simultaneous determination of triclocarban and triclosan in municipal 

biosolids by liquid chromatography tandem mass spectrometry. J Chromatogr A 1164(1-2): 212- 8. 

Coogan MA, Edziyie RE, La Point TW, Venables BJ. 2007. Algal bioaccumulation of triclocarban, 

triclosan, and methyl-triclosan in a North Texas wastewater treatment plant receiving stream. 

Chemosphere 67(10): 1911-8. 

Coogan MA, La Point TW. 2008. Snail bioaccumulation of triclocarban, triclosan, and 

methyltriclosan in a North Texas, USA, stream affected by wastewater treatment plant runoff. 

Environ Toxicol Chem 27(8): 1788-93. 

Cottell A, Denyer SP, Hanlon GW, Ochs D, Maillard JY. 2009. Triclosan-tolerant bacteria: changes 

in susceptibility to antibiotics. J Hosp Infect. 

Dokianakis SN, Kornaros ME, Lyberatos G. 2004. On the effect of pharmaceuticals on bacterial 

nitrite oxidation. Water Sci Technol 50(5): 341-6. 

EWG. 2008a. Environmental Working Group Human Toxome Project: Triclosan. Available: 

http://www.ewg.org/sites/humantoxome/chemicals/chemical.php?chemid=100376 [accessed 

December 19 2008]. 

EWG. 2008b. Pesticide in Soap, Toothpaste and Breast Milk - Is It Kid-Safe? Available: 

http://www.ewg.org/reports/triclosan [accessed July 23 2008]. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Letter from Environmental Working Group Section (125) Page 801 

EWG. 2008c. Teen Girls' Body Burden of Hormone-Altering Cosmetics Chemicals. Available: 

http://www.ewg.org/reports/teens [accessed December 18 2008]. 

EWG. 2009. Environmental Working Group's Skin Deep cosmetic safety database. Ingredient 

report: triclocarban. Available: http://skindeep.ewg.org/ingredient.php?ingred06=706622 [accessed 

April 6 2009]. 

Focazio MJ, Kolpin DW, Barnes KK, Furlong ET, Meyer MT, Zaugg SD, et al. 2008. A national 

reconnaissance for pharmaceuticals and other organic wastewater contaminants in the United States 

- II) Untreated drinking water sources. Sci Total Environ 402(2-3): 201-16. 

Halden RU, Paull DH. 2005. Co-occurrence of triclocarban and triclosan in U.S. water resources. 

Environ Sci Technol 39(6): 1420-6. 

Heidler J, Sapkota A, Halden RU. 2006. Partitioning, persistence, and accumulation in digested 

sludge of the topical antiseptic triclocarban during wastewater treatment. Environ Sci Technol 

40(11): 3634-9. 

James MO, Li W, Summerlot DP, Rowland-Faux L, Wood CE. 2009. Triclosan is a potent inhibitor 

of estradiol and estrone sulfonation in sheep placenta. Environ Int: in press. 

Johnson DR, Czechowska K, Chevre N, van der Meer JR. 2009. Toxicity of triclosan, penconazole 

and metalaxyl on Caulobacter crescentus and a freshwater microbial community as assessed by flow 

cytometry. Environ Microbiol. 

Kingsbury JA, Delzer GC, Hopple JA. 2008. Anthropogenic Organic Compounds in Source Water 

of Nine Community Water Systems that Withdraw from Streams, 2002-05. U.S. Geological Survey 

Scientific Investigations Report 2008-5208. Available: http://pubs.usgs.gov/sir/2008/5208/ 

[accessed December 10 2008]. 

Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, et al. 2002. 

Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999- 2000: 

a national reconnaissance. Environ Sci Technol 36(6): 1202-11. 

Kumar V, Balomajumder C, Roy P. 2008. Disruption of LH-induced testosterone biosynthesis in 

testicular Leydig cells by triclosan: probable mechanism of action. Toxicology 250(2-3): 124-31. 

Lawrence JR, Zhu B, Swerhone GD, Roy J, Wassenaar LI, Topp E, et al. 2009. Comparative 

microscale analysis of the effects of triclosan and triclocarban on the structure and function of river 

biofilm communities. Sci Total Environ: in press. 

Levy SB. 2001. Antibacterial household products: cause for concern. Emerg Infect Dis 7(3 Suppl): 

512-5. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Letter from Environmental Working Group Section (125) Page 802 

Miller TR, Heidler J, Chillrud SN, DeLaquil A, Ritchie JC, Mihalic JN, et al. 2008. Fate of triclosan 

and evidence for reductive dechlorination of triclocarban in estuarine sediments. Environ Sci 

Technol 42(12): 4570-6. 

Neumegen RA, Fernandez-Alba AR, Chisti Y. 2005. Toxicities of triclosan, phenol, and copper 

sulfate in activated sludge. Environ Toxicol 20(2): 160-4. 

NPIRS. 2008. National Pesticide Information Retrieval System Available: 

http://ppis.ceris.purdue.edu/ [accessed June 13 2008]. 

Oliveira R, Domingues I, Koppe Grisolia C, Soares AM. 2009. Effects of triclosan on zebrafish 

early-life stages and adults. Environ Sci Pollut Res Int: in press. 

Orvos DR, Versteeg DJ, Inauen J, Capdevielle M, Rothenstein A, Cunningham V. 2002. Aquatic 

toxicity of triclosan. Environ Toxicol Chem 21(7): 1338-49. 

Perencevich EN, Wong MT, Harris AD. 2001. National and regional assessment of the antibacterial 

soap market: a step toward determining the impact of prevalent antibacterial soaps. Am J Infect 

Control 29(5): 281-3. 

Sapkota A, Heidler J, Halden RU. 2007. Detection of triclocarban and two co- contaminating 

chlorocarbanilides in US aquatic environments using isotope dilution liquid chromatography tandem 

mass spectrometry. Environ Res 103(1): 21-9. 

Tatarazako N, Ishibashi H, Teshima K, Kishi K, Arizono K. 2004. Effects of triclosan on various 

aquatic organisms. Environ Sci 11(2): 133-40. 

U.S. EPA. 2009. Targeted National Sewage Sludge Survey: Sampling and Analysis Technical Report. 

Statistical Analysis Report. Available: http://www.epa.gov/waterscience/biosolids/tnsssoverview. 

html#results [accessed February 17, 2009]. 

Waller NJ, Kookana RS. 2009. Effect of triclosan on microbiological activity in Australian soils. 

Environ Toxicol Chem: in press. 

Yang LH, Ying GG, Su HC, Stauber JL, Adams MS, Binet MT. 2008. Growth-inhibiting effects of 

12 antibacterial agents and their mixtures on the freshwater microalga Pseudokirchneriella 

subcapitata. Environ Toxicol Chem 27(5): 1201-8. 

Yazdankhah SP, Scheie AA, Hoiby EA, Lunestad BT, Heir E, Fotland TO, et al. 2006. Triclosan 

and antimicrobial resistance in bacteria: an overview. Microb Drug Resist 12(2): 83-90. 

Young TA, Heidler J, Matos-Perez CR, Sapkota A, Toler T, Gibson KE, et al. 2008. Ab initio and in 

situ comparison of caffeine, triclosan, and triclocarban as indicators of sewage-derived microbes in 

surface waters. Environ Sci Technol 42(9): 3335-40. 

Zorrilla LM, Gibson EK, Jeffay SC, Crofton KM, Setzer WR, Cooper RL, et al. 2008. The Effects 

of Triclosan on Puberty and Thyroid Hormones in Male Wistar Rats. Toxicol Sci: in press. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Letter from Environmental Working Group Section (125) Page 803 

Response: See responses 125.1, 125.3, 125.4, 125.5, 125.6, 125.7, and 125.8. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 804 

Down-the-Drain (130) 

Verbatim Comments and Response References for the Down-the-Drain 

Section 

Comment Code: 130000 Down-the-drain 

Commenter Name: Jamie S. Heisig-Mitchell 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 

Comment ID: 25438 

Comment Code: 130000 

Comment: Further, as it is now well documented, the potential for these compounds to pass 

through treatment systems and reach surface waters is great, demanding increased testing to ensure 

adequate protection of wildlife. In light of this, it is not acceptable to continue allowing new 

compounds to be manufactured or distributed in commercial products before the full extent of 

impact is understood. It is more effective both in terms of cost and in terms of results to control 

these items before they are allowed to be manufactured or used in commercial products. 

Response: see response 130.3 

Commenter Name: Jamie S. Heisig-Mitchell 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 

Comment ID: 25441 

Comment Code: 130000 

Comment: POTW Protection 

*HRSD has reservations about the current Experimental Use Permit (EUP) guidelines. EUPs are 

issued for controlled uses in the support of the data collection efforts required for product 

registration. While it is surmised that many of the discharges resulting from such activities will be 

relatively small in volume, the potential does exist for large volumes to reach local POTWs. EPA 

should propose mechanisms to adequately protect POTWs from these discharges. 

Response: see response 30.19 

Commenter Name: Jamie S. Heisig-Mitchell 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 

Comment ID: 25453 

Comment Code: 130000 

Comment: *It is critical to ensure that these toxicity tests are rigorous and capable of defining a 

level of effect. Defensible test methods capable of producing reliable data are key to the protection 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 805 

of the environment as well as human health. As a nation, we cannot continue to introduce new, 

potentially harmful chemicals into our environment without carefully scrutiny. Once these chemicals 

are in the environment, removal can be costly and ineffective. Keeping potentially harmful chemicals 

out of the environment is the only way to ensure protection. 

Response: see responses 121.1, 121.8, and 130.3 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25660 

Comment Code: 130000 

Comment: Support EPA’s approach to evaluating impacts on municipal wastewater treatment 

plants 

The proposed rule acknowledges that many antimicrobial pesticides are typically washed "down the 

drain" and that these products have the potential to impact municipal wastewater treatment 

operations and the quality of discharges from municipal wastewater treatment plants. EPA has 

proposed four new data requirements for use in a screening-level assessment to evaluate the fate of 

antimicrobials that reach municipal wastewater treatment plants. 

EPA has also proposed a tiered approach to conducting "down-the-drain assessments." SFE and the 

SFPUC support these revisions to the data requirements, however we are concerned that some of 

the assumptions used in the "Down-the-Drain" modeling will not provide the sufficient protection 

from potential impacts to aquatic organisms. 

San Francisco is a member of the California Association of Sanitation Agencies (CASA) and its 

technical support group TriTAC, as well as the National Association of Clean Water Agencies 

(NACWA), and by reference supports the detailed comments related to antimicrobial pesticides 

disposal and the potential impacts to sewage treatment agencies and the aquatic environment by 

these organizations. 

Response: EPA acknowledges San Francisco Environment's support for the down-the-drain 

revisions to the data requirements. See also 134.3. 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25682 

Comment Code: 130000 

Comment: ECOTOXICITY DATA REQUIREMENTS 

Aquatic exposures -"high" and "low" exposure use pattern classifications 
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Comments and Response References: 

Down-the-Drain Section (130) Page 806 

SFE and the SPFUC concur with U.S. EPA’s analysis that the antimicrobial use patterns that can 

result in discharge to municipal wastewater treatment plants include: food-handling/storage 

establishments, premises, and equipment; commercial, institutional, and industrial premises and 

equipment; agricultural premises and equipment; residential and public access premises; medical 

premises and equipment; human drinking water systems; recirculating industrial processes and water 

systems; materials preservatives; and swimming pools. SFE and the SFPUC also concur with EPA’s 

classification of antifoulant coatings and paints, once-through industrial water systems, wood 

preservatives, and aquatic area applications as "high environmental exposure" use patterns that may 

involve direct release of antimicrobial pesticides into aquatic environments. 

Response: EPA acknowledges SFE's and SPFUC's concurrence that antimicrobial use patterns can 

result in discharges to municipal wastewater treatment plants. 

Commenter Name: Jay Feldman 

Commenter Organization: Beyond Pesticides 

Letter ID: 0067 

Comment ID: 25704 

Comment Code: 130000 

Comment: We applaud EPA’s decision to go forward with these new rules and support the new 

revisions and inclusion of nine new data requirements. 

We also appreciate the agency’s recognition that many antimicrobial pesticides are indeed washed 

down the drain and discharged into wastewater treatment plants (WWTPs). With this, we support 

EPA’s incorporation of modeling techniques, e.g. the Down the Drain Model, to assist in the 

evaluation of the environmental fate and impact of antimicrobials, their impact on WWTP 

processes, and the long-term improvement of the agency’s hazard analyses. 

Response: EPA acknowledges Beyond Pesticides' support for the down-the-drain revisions to the 

data requirements. 

Commenter Name: Jay Feldman 

Commenter Organization: Beyond Pesticides 

Letter ID: 0067 

Comment ID: 25715 

Comment Code: 130000 

Comment: Down the Drain Model 

This model proposed by the agency to estimate concentrations of chemicals in surface waters, as a 

result of disposal of consumer products into wastewaters, is a useful tool to assist wastewater 

treatment agencies with the wastewater treatment process, and to monitor the fate and effects of 

these chemicals once in the waterways. This, along with the new environmental fate studies to 

identify potential harm to the microbial treatment processes at WWTPs, would provide data on the 

fate and effects of these chemicals in sewage sludge. This is important since sewage sludge is often 

recycled on agricultural lands and can potentially contaminate the food supply. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 807 

Response: EPA acknowledges Beyond Pesticide's support for the down-the-drain revisions to the 

data requirements. 

Commenter Name: Jay Feldman 

Commenter Organization: Beyond Pesticides 

Letter ID: 0067 

Comment ID: 25717 

Comment Code: 130000 

Comment: We recommend that when using the model, the agency also takes into account 

transformation and degradation products of the antimicrobial substances under review, and their 

impacts on surface waters, microbial communities in WWTPs, as well as in sewage sludge. For 

example, a study investigating triclosan in WWTPs found that high concentrations of its metabolite 

methyl triclosan were found to be emitted from the plants as a result of biological methylation of 

triclosan occurring within the plants.[FN5: 5 Balmer, M.E., T. Poiger, C. Droz, K. Romanin et al. 

2004. Occurrence of methyl triclosan, a transformation product of the bactericide triclosan, in fish 

from various lakes in Switzerland. Environmental Science and Technology 2004. 38: p. 390-395.] 

Methyl triclosan is however, much more persistent and bio-accumulative than its parent. 

Response: see response 130.4 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25736 

Comment Code: 130000 

Comment: In addition, Part 158 addresses the issue of "down the drain" by proposing 4 new data 

requirements for use in screening level assessment of the fate of antimicrobials that reach 

Wastewater treatment plants ryvwTP's). However, 158W lacks a risk assessment procedure to 

determine the true fate of down-the-drain products. 

Response: see response 130.5 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25777 

Comment Code: 130000 

Comment: Sewerage agencies need U.S. EPA's assistance to protect water from contamination by 

pesticides. Properly implemented, U.S. EPA's pesticide registration process can help ensure that 

water quality and biosolids standards and objectives are met, and aquatic and terrestrial habitats are 

protected. The proposed rule acknowledges that many antimicrobial pesticides are typically rinsed 

down the drain and that these products have the potential to impact POTWs. To consider the 

potential impacts of pesticides discharged to POTWs, U.S. EPA has proposed four new data 

requirements for use in a screening-level assessment to evaluate the fate of antimicrobials that reach 
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Comments and Response References: 

Down-the-Drain Section (130) Page 808 

POTWs. The Agency has also proposed a tiered methodology to conduct down-the-drain 

assessments. Tri-TAC supports these revisions to the data requirements. 

Response: EPA acknowledges Tri-TAC's support for the down-the-drain revisions to the data 

requirements. 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25780 

Comment Code: 130000 

Comment: Water Quality Risks From Pesticides 

POTWs are not designed to treat pesticides. However, pesticides may be discharged to POTWs in 

conjunction with both indoor and outdoor pesticide applications. Pesticides can potentially interfere 

with treatment plant operation, ability to recycle reclaimed water and biosolids, and compliance with 

National Pollutant Discharge Elimination System (NPDES) permit effluent limits. 

Response: OPP appreciates receiving this information. 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25782 

Comment Code: 130000 

Comment: When a pesticide is used indoors, it can be discharged to a sewer, either because the use 

produces wastewater, or because an indirect pathway for sewer discharge exists (e.g., the treated 

surface is eventually cleaned with water or a pesticide-impregnated garment is laundered). Since 

POTWs are not designed to treat pesticides, treatment plant effluent and biosolids may contain the 

pesticide. Such pesticide releases may cause aquatic toxicity and exceedances of permit effluent 

limits. 

Response: OPP appreciates receiving this information. 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25783 

Comment Code: 130000 

Comment: The proposed rule recognizes that antimicrobial pesticide uses can involve water quality 

risks and proposes data requirements to assess those risks. Tri-TAC concurs with U.S. EPA's 

analysis that the antimicrobial use patterns resulting in discharge typically rinsed down the drain are: 

agricultural premises and equipment, food-handling/storage establishments, premises, and 

equipment, commercial, institutional, and industrial premises and equipment, residential and public 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 809 

access premises, medical premises and equipment, industrial processes and water systems, and 

swimming pools. Tri-TAC supports U.S. EPA's conclusion that environmental fate, biodegradation, 

and microbial data are needed to evaluate the risks associated with these uses. 

Response: EPA acknowledges the Districts' support for requiring environmental fate, 

biodegradation, and microbial data to evaluate down-the-drain uses. 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25799 

Comment Code: 130000 

Comment: POTWs Testing Costs 

NPDES discharges are required to conduct regularly scheduled acute and chronic toxicity bioassays. 

The frequency of routine bioassay testing varies from permit to permit, but they are generally 

conducted at approximately monthly intervals with an average cost of $500 and $1,000 for each 

acute and chronic test respectively. These toxicity tests are conducted in addition to chemicalspecific monitoring to assess potential aquatic life impacts associated with unregulated chemicals, 

chemical combinations, and substances that do not have established water quality criteria thresholds. 

If toxicity is observed during routine testing, dischargers are typically required to conduct accelerated 

tests weekly for a minimum of six weeks at an additional cost of approximately $3,000 to $6,000 

depending on the test. If toxicity is observed in two or more of the weekly accelerated tests, the 

discharger would be required to implement a toxicity identification evaluation (TIE). TIEs consist of 

multiple toxicity tests conducted with multiple sample manipulations in order to characterize and 

eventually identify the toxicity causing constituent(s). The cost of a TIE can vary widely from 

$10,000 to well over $100,000 depending on complexity and persistence of the toxicant. Once 

identified the cost to treat or remove the toxicity causing compound(s) can vary dramatically. 

Response: OPP appreciates receiving this information. 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25872 

Comment Code: 130000 

Comment: Sewerage agencies need U.S. EPA's assistance to protect water from contamination by 

pesticides. Properly implemented, U.S. EPA's pesticide registration process can help ensure that 

water quality and biosolids standards and objectives are met, and aquatic and terrestrial habitats are 

protected. 

The proposed rule acknowledges that many antimicrobial pesticides are typically rinsed down the 

drain and that these products have the potential to impact POTWs. To consider the potential 

impacts of pesticides discharged to POTWs, U.S. EPA has proposed four new data requirements for 

use in a screening-level assessment to evaluate the fate of antimicrobials that reach POTWs. The 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 810 

Agency has also proposed a tiered methodology to conduct down-the-drain assessments. CASA 

supports these revisions to the data requirements. 

Response: EPA acknowledges CASA's support for the down-the-drain revisions to the data 

requirements. 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25875 

Comment Code: 130000 

Comment: Water Quality Risks From Pesticides 

POTWs are not designed to treat pesticides. However, pesticides may be discharged to POTWs in 

conjunction with both indoor and outdoor pesticide applications. Pesticides can potentially interfere 

with treatment plant operation, ability to recycle reclaimed water and biosolids, and compliance with 

National Pollutant Discharge Elimination System (NPDES) permit effluent limits. 

Response: OPP appreciates receiving this information. 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25877 

Comment Code: 130000 

Comment: When a pesticide is used indoors, it can be discharged to a sewer, either because the use 

produces wastewater, or because an indirect pathway for sewer discharge exists (e.g., the treated 

surface is eventually cleaned with water or a pesticide-impregnated garment is laundered). Since 

POTWs are not designed to treat pesticides, treatment plant effluent and biosolids may contain the 

pesticide. Such pesticide releases may cause aquatic toxicity and exceedances of permit effluent 

limits. 

Response: OPP appreciates receiving this information. 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25878 

Comment Code: 130000 

Comment: The proposed rule recognizes that antimicrobial pesticide uses can involve water quality 

risks and proposes data requirements to assess those risks. CASA concurs with U.S. EPA's analysis 

that the antimicrobial use patterns resulting in discharge typically rinsed down the drain are: 

agricultural premises and equipment, food-handling/storage establishments, premises, and 

equipment, commercial, institutional, and industrial premises and equipment, residential and public 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 811 

access premises, medical premises and equipment, industrial processes and water systems, and 

swimming pools. CASA supports U.S. EPA's conclusion that environmental fate, biodegradation, 

and microbial data are needed to evaluate the risks associated with these uses. 

Response: EPA acknowledge's CASA's support for requiring data to understand discharges 

typically rinsed down-the-drain. 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25895 

Comment Code: 130000 

Comment: POTWs Testing Costs 

NPDES discharges are required to conduct regularly scheduled acute and chronic toxicity bioassays. 

The frequency of routine bioassay testing varies from permit to permit, but they are generally 

conducted at approximately monthly intervals with an average cost of $500 and $1,000 for each 

acute and chronic test respectively. These toxicity tests are conducted in addition to chemicalspecific monitoring to assess potential aquatic life impacts associated with unregulated chemicals, 

chemical combinations, and substances that do not have established water quality criteria thresholds. 

If toxicity is observed during routine testing, dischargers are typically required to conduct accelerated 

tests weekly for a minimum of six weeks at an additional cost of approximately $3,000 to $6,000 

depending on the test. If toxicity is observed in two or more of the weekly accelerated tests, the 

discharger would be required to implement a toxicity identification evaluation (TIE). TIEs consist of 

multiple toxicity tests conducted with multiple sample manipulations in order to characterize and 

eventually identify the toxicity causing constituent(s). The cost of a TIE can vary widely from 

$10,000 to well over $100,000 depending on complexity and persistence of the toxicant. Once 

identified the cost to treat or remove the toxicity causing compound(s) can vary dramatically. 

Response: OPP appreciates receiving this information. 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25971 

Comment Code: 130000 

Comment: Consistent with its past comments on the registration process and the need to better 

understand a chemical’s full range of impacts before it is used in commercial products, NACWA 

strongly supports the proposed data requirements. 

In October 2005, NACWA provided comments on the Office of Pesticide Programs’ general review 

of its registration requirements (July 13, 2005; 70 Fed. Reg. 40251). At that time, NACWA noted the 

need for the pesticide registration process to better predict true environmental concentrations of 

pesticide residues and the potential impacts on the wastewater treatment process and to put in place 

the necessary controls to limit those impacts. POTWs are not designed to remove pesticides and 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 812 

treatment plant effluent and biosolids have been found to contain pesticide residues. Source control 

for discharges of harmful substances is the best option for ensuring that adverse environmental 

impacts are avoided. NACWA believes that effective evaluation of the true impacts of pesticides 

during the registration process is necessary to assess whether the manufacture and use of these 

substances will negatively affect the environment and the wastewater treatment process at our 

country’s POTWs. The proposed data requirements for antimicrobial pesticides are a major step 

toward achieving this goal. 

Response: EPA acknowledges NACWA's support for the down-the-drain data requirements. 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25980 

Comment Code: 130000 

Comment: * National Pollutant Discharge Elimination System (NPDES) permits require POTWs 

to conduct regularly scheduled acute and chronic toxicity tests. These tests are very sensitive, even to 

minute quantities of toxic pollutants. The frequency of routine toxicity testing varies from permit to 

permit, but they are generally conducted at approximately monthly intervals with an average cost of 

$500 and $1,000 for each acute and chronic test respectively. These toxicity tests are conducted in 

addition to chemical- specific monitoring to assess potential aquatic life impacts associated with 

unregulated chemicals, chemical combinations, and substances that do not have established water 

quality criteria thresholds. If toxicity is observed during routine testing, dischargers are typically 

required to conduct accelerated tests weekly for a minimum of six weeks at an additional cost of 

approximately $3,000 to $6,000 per test depending on nature of the test. If toxicity is observed in a 

certain number of tests, the discharger may be required to implement a toxicity identification 

evaluation (TIE), consisting of multiple toxicity tests in the hopes of identifying the toxicity causing 

constituent(s). The cost of a TIE can vary widely from $10,000 to well over $100,000 depending on 

complexity and persistence of the toxicant. Once identified the cost to treat or remove the toxicity 

causing compound(s) can vary dramatically. Failure of these tests for some CWA permittees also 

results in a violation of their permit conditions, leading to possible enforcement actions and 

monetary penalties. 

Response: OPP appreciates receiving this information. 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26098 

Comment Code: 130000 

Comment: The Districts would benefit from U.S. EPA's assistance in protecting water from 

contamination by pesticides. Properly implemented, U.S. EPA's pesticide registration process can 

help ensure that water quality and biosolids standards and objectives are met, and aquatic and 

terrestrial habitats are protected. The proposed rule acknowledges that many antimicrobial pesticides 

are typically rinsed down the drain and that these products have the potential to impact Publicly 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 813 

Owned Treatment Works (POTWs). To consider the potential impacts of pesticides discharged to 

POTWs, U.S. EPA has proposed four new data requirements for use in a screening-level assessment 

to evaluate the fate of antimicrobials that reach POTWs. The Agency has also proposed a tiered 

methodology to conduct down-the-drain assessments. The Districts support these revisions to the 

data requirements. 

Response: EPA acknowledges the Sanitation Districts of Los Angeles County's support for the 

down-the-drain revisions to the data requirements. 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26101 

Comment Code: 130000 

Comment: Water Quality Risks From Pesticides 

POTWs are not designed to treat pesticides. However, pesticides may be discharged to POTWs in 

conjunction with both indoor and outdoor pesticide applications. Pesticides can potentially interfere 

with treatment plant operation, ability to recycle reclaimed water and biosolids, and compliance with 

National Pollutant Discharge Elimination System (NPDES) permit effluent limits. 

Response: OPP appreciates receiving this information. 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26103 

Comment Code: 130000 

Comment: When a pesticide is used indoors, it can be discharged to a sewer, either because the use 

produces wastewater, or because an indirect pathway for sewer discharge exists (e.g., the treated 

surface is eventually cleaned with water or a pesticide-impregnated garment is laundered). Since 

POTWs are not designed to treat pesticides, treatment plant effluent and biosolids may contain the 

pesticide. Such pesticide releases may cause aquatic toxicity and exceedances of permit effluent 

limits. 

Response: OPP appreciates receiving this information. 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26104 

Comment Code: 130000 

Comment: The proposed rule recognizes that antimicrobial pesticide uses can involve water quality 

risks and proposes data requirements to assess those risks. The Districts concur with U.S. EPA's 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 814 

analysis that the antimicrobial use patterns resulting in discharge typically rinsed down the drain are: 

agricultural premises and equipment, food-handling/storage establishments, premises, and 

equipment, commercial, institutional, and industrial premises and equipment, residential and public 

access premises, medical premises and equipment, industrial processes and water systems, and 

swimming pools. The Districts support U.S. EPA's conclusion that environmental fate, 

biodegradation, and microbial data are needed to evaluate the risks associated with these uses. 

Response: EPA acknowledges the Districts' support for requiring environmental fate, 

biodegradation, and microbial data to evaluate down-the-drain uses. 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26120 

Comment Code: 130000 

Comment: POTWs Testing Costs 

NPDES dischargers are required to conduct regularly scheduled acute and chronic toxicity 

bioassays. The frequency of routine bioassay testing varies from permit to permit, but they are 

generally conducted at approximately monthly intervals with an average cost of $500 and $1,000 for 

each acute and chronic test respectively. These toxicity tests are conducted in addition to chemicalspecific monitoring to assess potential aquatic life impacts associated with unregulated chemicals, 

chemical combinations, and substances that do not have established water quality criteria thresholds. 

If toxicity is observed during routine testing, dischargers are typically required to conduct accelerated 

tests weekly for a minimum of six weeks at an additional cost of approximately $3,000 to $6,000 

depending on the test. If toxicity is observed in two or more of the weekly accelerated tests, the 

discharger would be required to implement a toxicity identification evaluation (TIE). TIEs consist of 

multiple toxicity tests conducted with multiple sample manipulations in order to characterize and 

eventually identify the toxicity causing constituent(s). The cost of a TIE can vary widely from 

$10,000 to well over $100,000 depending on complexity and persistence of the toxicant. Once 

identified the cost to treat or remove the toxicity causing compound(s) can vary dramatically. 

Recent incidences of diazinon contamination in surface waters and final effluents operated by 

several Districts' water reclamation facilities have resulted in NPDES permit mandated accelerated 

toxicity monitoring, implementation of TIEs, and eventually required receiving water and final 

effluent chemical monitoring for diazinon. The chemical monitoring alone is costing the Districts 

over $16,000 per year with diazinon-associated accelerated toxicity monitoring and TIEs conducted 

from 1995 through 2005 estimated at over $100,000. 

Response: OPP appreciates receiving this information. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26190 

Comment Code: 130000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 815 

Comment: First, the Proposal does not adequately "differentiate the types of review undertaken for 

antimicrobial pesticides."[FN#4:Id.] The Proposal does not provide the tools to enable applicants or 

registrants to ascertain the requirements for the varying antimicrobial product types in the 

regulation. The Proposal instead would establish a system under which the types of review that 

would be required for particular products could only be determined by case-by- case consultation 

with the Agency. 

Response: see response 3 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26229 

Comment Code: 130000 

Comment: 8) Down the drain models may not be suitable or practical for some antimicrobials, 

including oxidizers, reactive substances, and certain inorganics and volatile substances. Also, 

estimates of indoor products that are destined down the drain may be excessive if they do not take 

into account volatility (air), or post-application wipe-up (trash disposal) or other relevant activities 

and characteristics. 

Response: see response 130.1 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26487 

Comment Code: 130000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * At page 59,413 the EPA should explain ecological effects data are required for low 

exposure compounds if nothing passes through the DtD modeling for WWTP. 

Response: see response 134.20 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26531 

Comment Code: 130000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * The EPA should explain how the DTD assessment affects the need for non-target plant 

testing, and what the triggers and criteria are. 

Response: see responses 130.3 and 134.20 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 816 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26763 

Comment Code: 130000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * At page 59,413 the EPA should explain ecological effects 

data are required for low exposure compounds if nothing passes through the Down the Drain 

(DtD) model for WWTP. 

Response: see response 134.20 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26821 

Comment Code: 130000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * The EPA should explain how the DTD assessment affects 

the need for non-target plant testing, and what the triggers and criteria are. 

Response: see responses 130.3 and 134.20 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27025 

Comment Code: 130000 

Comment: [The following are some of the problems identified in the proposed rule:] 

8) Down the drain (DtD) models may not be suitable or practical for some antimicrobials, including 

oxidizers, reactive substances, certain inorganics, and volatile substances. Also, estimates of indoor 

products that are destined down the drain may be excessive if they do not take into account volatility 

(air), or post-application wipe-up (trash disposal) or other relevant activities and characteristics. 

Response: see response 130.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27424 

Comment Code: 130000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 817 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * At page 59,413 the EPA should explain ecological effects 

data are required for low exposure compounds if nothing passes through the Down the Drain 

(DtD) model for WWTP. 

Response: see response 134.20 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27467 

Comment Code: 130000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * The EPA should explain how the DTD assessment affects 

the need for non-target plant testing, and what the triggers and criteria are. 

Response: see responses 130.3 and 134.20 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27529 

Comment Code: 130000 

Comment: 8) Down the drain (DtD) models may not be suitable or practical for some 

antimicrobials, including oxidizers, reactive substances, certain inorganics, and volatile substances. 

Also, estimates of indoor products that are destined down the drain may be excessive if they do not 

take into account volatility (air), or post-application wipe-up (trash disposal) or other relevant 

activities and characteristics. 

Response: see response 130.1 

Comment Code: 132000 Biosolids 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25793 

Comment Code: 132000 

Comment: The potential environmental impacts of the cross- media transfers of pesticides needs to 

be addressed in U.S. EPA's environmental risk assessments. Tri-TAC supports higher-tiered 

environmental studies in cases where the screening-level assessment indicates that the pesticide 

would partition to biosolids or into the air. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 818 

Response: EPA acknowledges Tri-TAC's support for higher-tiered environmental studies. Also see 

response 134.22. 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25794 

Comment Code: 132000 

Comment: Biosolids Land Application Assessment 

Roughly fifty percent of the total cost of wastewater treatment is expended on solids handling and 

land application is a frequently used method for recycling biosolids. The Targeted National Sewage 

Sludge Survey released by U.S. EPA's Office of Science and Technology in January 2009 reported 

the presence of triclocarban in 100 percent and triclosan in 94 percent of its biosolids samples, 

confirming that these antimicrobials readily partition into the solids phase during wastewater 

treatment. It is essential that U.S. EPA be able to ensure adequate protection in the terrestrial 

environment from the use of antimicrobial pesticides. 

Response: OPP appreciates receiving the information about biosolids land application assessment. 

See responses 132.1 and 134.22. 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25796 

Comment Code: 132000 

Comment: Tri-TAC suggests that U.S. EPA's Office of Pesticide Programs and Wastewater 

Management work together to develop a methodology to evaluate potential impacts from the use of 

antimicrobial pesticides to biosolids land application in cases where down-the-drain assessments 

indicate that pesticides would partition into biosolids. The existing Office of Pesticide Programs' 

guidelines for the study of chemicals in the terrestrial environment could be modified to address 

biosolids amended soil systems. In addition, the evaluation should include an analysis of 

bioaccumulation, toxicity to microbes, and toxicity to worms, all of which have Office of Pesticide 

Programs' guidelines. Such studies are important to accurately quantify fate, exposure, and risk from 

the use of antimicrobial pesticides discharged to POTWs that partition into biosolids during 

wastewater treatment. 

Response: see response 132.1 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25890 

Comment Code: 132000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 819 

Comment: The potential environmental impacts of the cross- media transfers of pesticides needs to 

be addressed in U.S. EPA's environmental risk assessments. CASA supports higher-tiered 

environmental studies in cases where the screening-level assessment indicates that the pesticide 

would partition to biosolids or into the air. 

Biosolids Land Application Assessment 

Roughly fifty percent of the total cost of wastewater treatment is expended on solids handling and 

land application is a frequently used method for recycling biosolids. The Targeted National Sewage 

Sludge Survey ( http://wwww.epa.gov/waterscience/biosolids/) released by U.S. EPA's Office of 

Science and Technology in January 2009 reported the presence of triclocarban in 100 percent and 

triclosan in 94 percent of its biosolids samples, confirming that these antimicrobials readily partition 

into the solids phase during wastewater treatment. It is essential that U.S. EPA be able to ensure 

adequate protection in the terrestrial environment from the use of antimicrobial pesticides. 

Response: EPA acknowledges CASA's support for higher-tiered environmental studies. OPP 

appreciates receiving the information about biosolids land application assessment. Also see 

responses 132.1 and 134.22. 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25892 

Comment Code: 132000 

Comment: CASA suggests that U.S. EPA's Office of Pesticide Programs and Wastewater 

Management work together to develop a methodology to evaluate potential impacts from the use of 

antimicrobial pesticides to biosolids land application in cases where down-the-drain assessments 

indicate that pesticides would partition into biosolids. The existing Office of Pesticide Programs' 

guidelines for the study of chemicals in the terrestrial environment could be modified to address 

biosolids amended soil systems. In addition, the evaluation should include an analysis of 

bioaccumulation, toxicity to microbes, and toxicity to worms, all of which have Office of Pesticide 

Programs' guidelines. Such studies are important to accurately quantify fate, exposure, and risk from 

the use of antimicrobial pesticides discharged to POTWs that partition into biosolids during 

wastewater treatment. 

Response: see response 132.1 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25978 

Comment Code: 132000 

Comment: * EPA considers partitioning to the biosolids as ‘removal’ in some of its outreach 

materials for the proposal. Pesticide residuals that are adsorbed to the sludge should not be 

considered removed, but instead transferred to another medium. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 820 

* NACWA strongly supports higher-tiered environmental studies in cases where the screening level 

assessment indicates partitioning to biosolids. Roughly fifty percent of the total cost of wastewater 

treatment is expended on solids handling and land application is a frequently used method for 

recycling biosolids. The Targeted National Sewage Sludge Survey (TNSSS) released by EPA in 

January 2009, reported the presence of triclocarban in 100%, and triclosan in 94% of its biosolids 

samples, confirming the ready partitioning of these antimicrobials to the solids phase. It is essential 

that EPA be able to ensure adequate protection in the terrestrial environment from the use of these 

antimicrobial pesticides. 

Response: EPA acknowledges NACWA's support for higher-tiered environmental studies. 

Also see responses 132.1 and 134.22. 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26115 

Comment Code: 132000 

Comment: The potential environmental impacts of the cross- media transfers of pesticides needs to 

be addressed in U.S. EPA's environmental risk assessments. The Districts support higher-tiered 

environmental studies in cases where the screening-level assessment indicates that the pesticide 

would partition to biosolids or into the air. 

Biosolids Land Application Assessment 

Roughly fifty percent of the total cost of wastewater treatment is expended on solids handling and 

land application is a frequently used method for recycling biosolids. The Targeted National Sewage 

Sludge Survey released by U.S. EPA's Office of Science and Technology in January 2009 reported 

the presence of triclocarban in 100 percent and triclosan in 94 percent of its biosolids samples, 

confirming that these antimicrobials readily partition into the solids phase during wastewater 

treatment. It is essential that U.S. EPA be able to ensure adequate protection in the terrestrial 

environment from the use of antimicrobial pesticides. 

Response: EPA acknowledges Sanitation Districts of Los Angeles County's support for highertiered environmental studies. OPP appreciates receiving the information about biosolids land 

application assessment. See also response 134.22. 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26117 

Comment Code: 132000 

Comment: The Districts suggest that U.S. EPA's Offices of Pesticide Programs and Wastewater 

Management work together to develop a methodology to evaluate potential impacts from the use of 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 821 

antimicrobial pesticides to biosolids land application in cases where down-the-drain assessments 

indicate that pesticides would partition into biosolids. The existing Office of Pesticide Programs' 

guidelines for the study of chemicals in the terrestrial environment could be modified to address 

biosolids amended soil systems. In addition, the evaluation should include an analysis of 

bioaccumulation, toxicity to microbes, and toxicity to worms, all of which have Office of Pesticide 

Programs' guidelines. Such studies are important to accurately quantify fate, exposure, and risk from 

the use of antimicrobial pesticides discharged to POTWs that partition into biosolids during 

wastewater treatment. 

Response: see response 132.1 

Comment Code: 134000 Proposed approach for evaluating the potential impact of antimicrobial 

pesticide chemicals on waste water treatment plants and non-target organisms in receiving water 

bodies 

Commenter Name: Jamie S. Heisig-Mitchell 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 

Comment ID: 25440 

Comment Code: 134000 

Comment: The proposed changes for the down-the-drain antimicrobials are technically sound, 

necessary improvements which will not only provide additional protections to POTWs and our 

nation's waters, but will also provide consistency and clarity to the data collection process. 

Implementation of these new requirements must not be delayed. HRSD offers the following 

comments on potential improvements to the guidance which will further protect POTWs and 

aquatic life. 

Response: EPA acknowledges Hampton Roads Sanitation District's support for the down-thedrain revisions to the data requirements. 

Commenter Name: Jamie S. Heisig-Mitchell 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 

Comment ID: 25443 

Comment Code: 134000 

Comment: *HRSD is concerned with the decision to exclude antifoulants and wood preservatives 

from testing designed to protect POTWs and the aquatic environment. It is possible that these 

compounds may reach POTWs through sources such as hull blast water, landfill leachate 

*and centralized waste treatment facilities. EPA should revisit this assumption to verify its accuracy. 

Response: see response 134.1 

Commenter Name: Jamie S. Heisig-Mitchell 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 822 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 

Comment ID: 25444 

Comment Code: 134000 

Comment: *The Down-the-Drain model recommends modifying production volume to account 

for the percentage expected to go down the drain. HRSD agrees with this conceptually but believes 

that the values associated with various forms of usage and range of volatilities must be standardized 

to ensure consistency among exposure evaluations. 

Response: see response 134.3 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25687 

Comment Code: 134000 

Comment: Proposed approach to modeling discharges to municipal wastewater treatment plants 

EPA has proposed to use the Exposure and Fate Assessment Screening Tool (E-FAST) model with 

the Probabilistic Dilution Model (PDM) option to conduct screening- level assessments. During the 

workshop on the proposed rule on November 6, 2008, EPA staff implied that the model had certain 

limitations that we do not believe actually exist, based on the sources of the data sets used by EPA 

in development of the model. We request a careful evaluation of the model’s capabilities and its 

capacity to address all types of discharge locations (e.g., including salt water). 

We believe the model’s capabilities are much broader than indicated at the workshop. For example: 

* EPA staff indicated that the E-FAST model may have been based on municipal wastewater 

treatment plants that only received "residential" discharges. This is very unlikely. According to the 

E-FAST manual, the model was based on data from actual U.S. municipal wastewater treatment 

plants. Nearly every municipal wastewater treatment plant receives discharges from many types of 

non- residential sources, like commercial facilities, medical facilities, institutions, and cooling water 

systems (which are common on commercial buildings). Most municipal wastewater treatment plants 

also receive both process and non-process discharges from industrial facilities. 

* EPA staff indicated that chronic aquatic toxicity endpoints might not be used to evaluate 

antimicrobials discharges from municipal wastewater treatment plants. Our review of the E-FAST 

model does not show any reason that such an evaluation could not be conducted. Since EPA 

requires municipal wastewater treatment plants to conduct both acute and chronic aquatic toxicity 

tests regularly as conditions of Clean Water Act-regulated NPDES permits, both acute and chronic 

endpoints should be evaluated by EPA to ensure that antimicrobials discharges will not cause 

toxicity in municipal wastewater treatment plant effluent. 

* EPA staff suggested that "expert judgment" would be needed to estimate metals removal at 

municipal wastewater treatment plants. The EPA Office of Water has datasets suitable for this 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 823 

purpose-"expert judgment" is not needed. Whenever possible, actual data should be used (instead of 

estimates) to model removal efficiencies for all pollutants. Since removal efficiencies are input 

parameters into E-FAST, we do not see any reason why actual data could not be used for modeling 

discharges of well-characterized substances like copper and silver. 

* EPA staff indicated that evaluation of discharges to still water and to salt water would be 

challenging. Again, our review of the E-FAST model manual suggests that these discharges can be 

readily evaluated with appropriate input data and elimination of the PDM option. 

We understand that EPA is seeking to use existing, peer-reviewed models to evaluate reasonable 

worst case scenarios when it reviews pesticides. We believe that the E-FAST model is likely 

appropriate for EPA’s use; however, it needs to be appropriately parameterized. We encourage EPA 

to work with the Office of Water and technical experts from California’s Tri-TAC and the National 

Association of Clean Water Agencies (NACWA) to clarify how the E- FAST model should be 

parameterized for realistic scenarios for discharges of antimicrobial pesticides to municipal 

wastewater treatment plants-and for characterizing releases of water, air, and biosolids from those 

plants into the environment. 

Response: see responses 134.4, 134.11, 134.18, 134.21, and 134.23 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25792 

Comment Code: 134000 

Comment: Down-the-Drain Modeling 

U.S. EPA has proposed to use the E-FAST model with the Probabilistic Dilution Model (PDM) 

option to conduct screening-level assessments. Tri-TAC has previously submitted general comments 

to U.S. EPA regarding our concerns with E- FAST Version 2.0. In our comments, Tri-TAC has 

requested the technical basis for assuming the surface water concentrations obtained from the 10th 

and 50th percentile stream dilution factors as acute and chronic concentrations in national downthe-drain assessments. Some POTWs discharge to effluent dominated receiving waters, providing 

essentially the only source of water to a surface water body during dry periods, and NPDES permits 

for these facilities do not include a stream dilution factor. In addition, other facilities in the country 

do not have dilution credits in their NPDES permits for other environmental reasons. Therefore, 

U.S. EPA should not include stream dilution factors in national down-the-drain assessments for 

pesticides. 

For down-the-drain assessments, U.S. EPA should use E-FAST to calculate a median surface water 

concentration without a stream dilution factor for use as the chronic estimated environmental 

concentration in the risk analysis. For the acute estimated environmental concentrations, U.S. EPA 

should calculate a surface water concentration assuming a local high-end scenario appropriate for 

the pesticide. The surface water concentration from the high-end scenario, without a stream dilution 

factor, should be used as an acute estimated environmental concentration in the risk analysis. These 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 824 

simple modifications to the procedures for down-the-drain assessments would result in better 

assessments of the potential impacts to aquatic organisms. 

In the presentation entitled "158W Antimicrobial Data Requirements Workshop: Down-the-Drain 

Model" given by Pat Jennings on November 6, 2008, U.S. EPA states on slide number 99 that the 

down-the drain model "assumes all wastewaters entering a WWTP are from residential sources." It is 

unclear for the basis of this limitation. POTWs receive a combination of wastewater from 

residential, commercial, and industrial sources. It would be rare for a POTW to receive only 

residential wastewater. Even in smaller communities, POTWs receive wastewater from residential 

and commercial (e.g. schools, stores, restaurants, hotels/motels, and/or medical facilities) sources. 

Tri-TAC believes that the E- FAST model is applicable as a screening-level model for all 

antimicrobial use patterns resulting in discharge typically rinsed down the drain including agricultural 

premises and equipment, food-handling/storage establishments, premises, and equipment, 

commercial, institutional, and industrial premises and equipment, residential and public access 

premises, medical premises and equipment, industrial processes and water systems, and swimming 

pools. 

Tri-TAC would like to work with U.S. EPA's Office of Pesticide Programs and Wastewater 

Management to develop an improved wastewater discharge methodology to evaluate the potential 

impacts to aquatic organisms from pesticides discharged to POTWs utilizing E-FAST Version 2.0. 

This methodology would include an analysis of the input parameters and scenarios needed to 

generate representative surface water concentrations from the use of pesticides discharged to 

POTWs. Development of a methodology would be beneficial to both U.S. EPA and POTWs to 

evaluate the impacts of pesticides. 

Pesticide Removal Versus Cross-Media Transfer 

Tri-TAC would like to clarify the difference between pesticide removal during wastewater treatment 

and cross-media transfer of a pesticide. In the presentation entitled "158W Antimicrobial Data 

Requirements Workshop: Down-the- Drain Model" given by Pat Jennings on November 6, 2008, 

U.S. EPA states on slide number 106 that "removal of a chemical during wastewater treatment can 

occur by processes such as: biodegradation by wastewater treatment plant microorganisms, 

adsorption to sludge and bio-solids, volatilization/stripping, and hydrolysis." Adsorption to 

biosolids and volatilization/stripping are cross-media transfers of pesticides from wastewater to 

solids or air, respectively, and are not pesticide removal mechanisms. 

Response: see responses 134.15, 134.22, and 134.4 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25803 

Comment Code: 134000 

Comment: In the presentation entitled "158W Antimicrobial Data Requirements Workshop: 

Down-the-Drain Model" given by Pat Jennings on November 6, 2008, U.S. EPA states on slide 

number 110 that "when evaluating potential risks from effects to aquatic invertebrates and fish 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 825 

exceedance of the chronic COC for 20 or more days triggers potential for concern, exceedance of 

the acute COC for 4 or more days triggers potential for concern, and exceedance of COC for algae 

for 4 days or less may trigger a concern and is evaluated on a case-by-case basis." It is unclear the 

justification for these exceedance levels. U.S. EPA has a responsibility to ensure that pesticides are 

used in such a manner that mitigation under the Clean Water Act is minimal or unnecessary. Since 

the Clean Water Act prevents discharging "toxics in toxic amounts," a higher-tier analysis should be 

perform if the down-the-drain model results in one exceedance of the concentrations of concern. If 

the higher-tier analysis results in an exceedance of the concentration of concern, U.S. EPA should 

impose mitigation measures to ensure that water quality is protected. As detailed above, the 

California Clean Water Enforcement Act requires the Regional Boards to assess penalties for each 

NPDES permit exceedance, whether or not the POTW has the authority to prevent the violation. 

Response: see response 134.5 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25889 

Comment Code: 134000 

Comment: Down-the-Drain Modeling 

U.S. EPA has proposed to use the E-FAST model with the Probabilistic Dilution Model (PDM) 

option to conduct screening-level assessments. CASA requests the technical basis for assuming the 

surface water concentrations obtained from the 10th and 50th percentile stream dilution factors as 

acute and chronic concentrations in national down-the-drain assessments. Some POTWs discharge 

to effluent dominated receiving waters, providing essentially the only source of water to a surface 

water body during dry periods, and NPDES permits for these facilities do not include a stream 

dilution factor. In addition, other facilities in the country do not have dilution credits in their 

NPDES permits for other environmental reasons. Therefore, U.S. EPA should not include stream 

dilution factors in national down-the-drain assessments for pesticides. 

For down-the-drain assessments, U.S. EPA should use E-FAST to calculate a median surface water 

concentration without a stream dilution factor for use as the chronic estimated environmental 

concentration in the risk analysis. For the acute estimated environmental concentrations, U.S. EPA 

should calculate a surface water concentration assuming a local high-end scenario appropriate for 

the pesticide. The surface water concentration from the high-end scenario, without a stream dilution 

factor, should be used as an acute estimated environmental concentration in the risk analysis. These 

simple modifications to the procedures for down-the-drain assessments would result in better 

assessments of the potential impacts to aquatic organisms. 

In the presentation entitled "158W Antimicrobial Data Requirements Workshop: Down-the-Drain 

Model" given by Pat Jennings on November 6, 2008, U.S. EPA states on slide number 99 that the 

down-the drain model "assumes all wastewaters entering a WWTP are from residential sources." It is 

unclear for the basis of this limitation. POTWs receive a combination of wastewater from 

residential, commercial, and industrial sources. It would be rare for a POTW to receive only 

residential wastewater. Even in smaller communities, POTWs receive wastewater from residential 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 826 

and commercial (e.g. schools, stores, restaurants, hotels/motels, and/or medical facilities) sources. 

CASA believes that the E-FAST model is applicable as a screening-level model for all antimicrobial 

use patterns resulting in discharge typically rinsed down the drain including agricultural premises and 

equipment, food-handling/storage establishments, premises, and equipment, commercial, 

institutional, and industrial premises and equipment, residential and public access premises, medical 

premises and equipment, industrial processes and water systems, and swimming pools. 

CASA would like to work with U.S. EPA's Office of Pesticide Programs and Wastewater 

Management to develop an improved wastewater discharge methodology to evaluate the potential 

impacts to aquatic organisms from pesticides discharged to POTWs utilizing E-FAST Version 2.0. 

This methodology would include an analysis of the input parameters and scenarios needed to 

generate representative surface water concentrations from the use of pesticides discharged to 

POTWs. Development of a methodology would be beneficial to both U.S. EPA and POTWs to 

evaluate the impacts of pesticides. 

Pesticide Removal Versus Cross-Media Transfer 

CASA would like to clarify the difference between pesticide removal during wastewater treatment 

and cross-media transfer of a pesticide. In the presentation entitled "158W Antimicrobial Data 

Requirements Workshop: Down-the- Drain Model" given by Pat Jennings on November 6, 2008, 

U.S. EPA states on slide number 106 that "removal of a chemical during wastewater treatment can 

occur by processes such as: biodegradation by wastewater treatment plant microorganisms, 

adsorption to sludge and bio-solids, volatilization/stripping, and hydrolysis." Adsorption to 

biosolids and volatilization/stripping are cross-media transfers of pesticides from wastewater to 

solids or air, respectively, and are not pesticide removal mechanisms. 

Response: see responses 134.15, 134.22, and 134.4 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25901 

Comment Code: 134000 

Comment: In the presentation entitled "158W Antimicrobial Data Requirements Workshop: 

Down-the-Drain Model" given by Pat Jennings on November 6, 2008, U.S. EPA states on slide 

number 110 that "when evaluating potential risks from effects to aquatic invertebrates and fish 

exceedance of the chronic COC for 20 or more days triggers potential for concern, exceedance of 

the acute COC for 4 or more days triggers potential for concern, and exceedance of COC for algae 

for 4 days or less may trigger a concern and is evaluated on a case-by-case basis." It is unclear the 

justification for these exceedance levels. U.S. EPA has a responsibility to ensure that pesticides are 

used in such a manner that mitigation under the Clean Water Act is minimal or unnecessary. Since 

the Clean Water Act prevents discharging "toxics in toxic amounts," a higher-tier analysis should be 

perform if the down-the-drain model results in one exceedance of the concentrations of concern. If 

the higher-tier analysis results in an exceedance of the concentration of concern, U.S. EPA should 

impose mitigation measures to ensure that water quality is protected. As detailed above, the 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 827 

California Clean Water Enforcement Act requires the Regional Boards to assess penalties for each 

NPDES permit exceedance, whether or not the POTW has the authority to prevent the violation. 

Response: see response 134.5 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25976 

Comment Code: 134000 

Comment: General Comments 

* Coordination among EPA offices in reviewing pesticide data is essential to effective CWA 

implementation. NACWA believes that more coordination with the Office of Water is needed. 

There appears to be a lack of understanding in the proposal regarding the municipal wastewater 

treatment process (including an erroneous assumption that municipal plants only receive wastewater 

from households) and existing regulatory programs like the National Pretreatment Program and the 

role it plays in keeping pollutants out of the sewer system. 

Response: see responses 20.3 and 134.4 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25982 

Comment Code: 134000 

Comment: Specific Comments 

* NACWA is concerned with the decision to exclude antifoulants and wood preservatives from 

testing designed to protect POTWs and the aquatic environment. It is possible that these 

compounds may reach POTWs through sources such as hull blast water, landfill leachate and 

centralized waste treatment facilities. EPA should revisit this assumption to verify its accuracy. 

Response: see response 134.1 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25988 

Comment Code: 134000 

Comment: * Some POTWs discharge to effluent-dominated or effluent-dependent receiving waters 

(where the effluent is the only source of water during dry periods). NPDES permits for these 

facilities do not include a stream dilution factor. In addition, other facilities in the country do not 

have dilution credits in their NPDES permits for other environmental reasons. These conditions 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 828 

make compliance with acute and chronic toxicity tests even more complicated. EPA should consider 

the lack of dilution credits for many POTWs as it determines whether to include stream dilution 

factors in national down-the- drain assessments for pesticides. 

Response: see response 134.15 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26114 

Comment Code: 134000 

Comment: Down-the-Drain Modeling 

U.S. EPA has proposed to use the E-FAST model with the Probabilistic Dilution Model (PDM) 

option to conduct screening-level assessments. The Districts have previously submitted general 

comments to U.S. EPA regarding our concerns with E- FAST Version 2.0. In our comments, the 

Districts have requested the technical basis for assuming the surface water concentrations obtained 

from the lOth and 50th percentile stream dilution factors as acute and chronic concentrations in 

national down-the-drain assessments. Some POTWs discharge to effluent dominated receiving 

waters, providing essentially the only source of water to a surface water body during dry periods, and 

NPDES permits for these facilities do not include a stream dilution factor. In addition, other 

facilities in the country do not have dilution credits in their NPDES permits for other environmental 

reasons. Therefore, U.S. EPA should not include stream dilution factors in national down-the-drain 

assessments for pesticides. 

For down-the-drain assessments, U.S. EPA should use E-FAST to calculate a median surface water 

concentration without a stream dilution factor for use as the chronic estimated environmental 

concentration in the risk analysis. For the acute estimated environmental concentration, U.S. EPA 

should calculate a surface water concentration assuming a local high-end scenario appropriate for 

the pesticide. The surface water concentration from the high-end scenario, without a stream dilution 

factor, should be used as an acute estimated environmental concentration in the risk analysis. These 

simple modifications to the procedures for down-the-drain assessments would result in better 

assessments of the potential impacts to aquatic organisms. 

In the presentation entitled "158W Antimicrobial Data Requirements Workshop: Down-the-Drain 

Model" given by Pat Jennings on November 6,2008, U.S. EPA states on slide number 99 that the 

down- the-drain model "assumes all wastewaters entering a WWTP are from residential sources." It 

is unclear for the basis of this limitation. POTWs receive a combination of wastewater from 

residential, commercial, and industrial sources. It would be rare for a POTW to receive only 

residential wastewater. Even in smaller communities, POTWs receive wastewater from residential 

and commercial (e.g., schools, stores, restaurants, hotels/motels, and/or medical facilities) sources. 

The Districts believe that the E-FAST model is applicable as a screening-level model for all 

antimicrobial use patterns resulting in discharge typically rinsed down the drain including agricultural 

premises and equipment, food-handling/storage establishments, premises, and equipment, 

commercial, institutional, and industrial premises and equipment, residential and public access 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 829 

premises, medical premises and equipment, industrial processes and water systems, and swimming 

pools. 

The Districts would like to work with U.S. EPA's Offices of Pesticide Programs and Wastewater 

Management to develop an improved wastewater discharge methodology to evaluate the potential 

impacts to aquatic organisms from pesticides discharged to POTWs utilizing E-FAST Version 2.0. 

This methodology would include an analysis of the input parameters and scenarios needed to 

generate representative surface water concentrations from the use of pesticides discharged to 

POTWs. Development of a methodology would be beneficial to both U.S. EPA and POTWs to 

evaluate the impacts of pesticides. 

Pesticide Removal Versus Cross-Media Transfer 

The Districts would like to clarify the difference between pesticide removal during wastewater 

treatment and cross-media transfer of a pesticide. In the presentation entitled "158W Antimicrobial 

Data Requirements Workshop: Down-the- Drain Model" given by Pat Jennings on November 6, 

2008, U.S. EPA states on slide number 106 that "removal of a chemical during wastewater treatment 

can occur by processes such as: biodegradation by wastewater treatment plant microorganisms, 

adsorption to sludge and bio-solids, volatilization/stripping, and hydrolysis." Adsorption to 

biosolids and volatilization/stripping are cross-media transfers of pesticides from wastewater to 

solids or air, respectively, and are not pesticide removal mechanisms. 

Response: see responses 134.15, 134.22, and 134.4 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26124 

Comment Code: 134000 

Comment: In the presentation entitled "158W Antimicrobial Data Requirements Workshop: 

Down-the-Drain Model" given by Pat Jennings on November 6, 2008, U.S. EPA states on slide 

number 110 that "when evaluating potential risk from effects to aquatic invertebrates and fish 

exceedance of the chronic COC for 20 or more days triggers potential for concern, exceedance of 

the acute COC for 4 or more days triggers potential for concern, and exceedance of COC for algae 

for 4 days or less may trigger a concern and is evaluated on a case-by-case basis." It is unclear the 

justification for these exceedance levels. U.S. EPA has a responsibility to ensure that pesticides are 

used in such a manner that mitigation under the Clean Water Act is minimal or unnecessary. Since 

the Clean Water Act prevents discharging "toxics in toxic amounts," a higher-tier analysis should be 

performed if the down the- drain model results in one exceedance of the concentrations of concern. 

If the higher-tier analysis results in an exceedance of the concentration of concern, U.S. EPA should 

impose mitigation measures to ensure that water quality is protected. As detailed above, the 

California Clean Water Enforcement Act requires the Regional Boards to assess penalties for each 

NPDES permit exceedance, whether or not the POTW has the authority to prevent the violation. 

Response: see response 134.5 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 830 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26343 

Comment Code: 134000 

Comment: A. DtD Modeling is Site Specific 

Down-the-drain (DtD) modeling is highly site specific due to its reliance on a single WWTP removal 

value to model the entire United States, and would be very difficult, to obtain meaningful 

environmental exposure estimates for generic use. If results from this model exceed environmental 

levels or concentrations of concern, data needs are identified and additional testing triggered. 

Neither the amount disposed down the drain, the removal, or the concentration of concern (COC), 

the key input parameters affecting DtD, are clearly defined or explained. For example, the Agency 

should address whether the COC is an acute value, a chronic value, or the lowest value in all cases, 

and why. The most relevant values should be explained. 

The Agency fails to explain several aspects of the requirements built into the model, from product 

use to transport of the WWTP. These are as follows: 

* The Agency must explain how to determine how much substance actually goes down the drain as 

opposed to an estimate based on annual production volumes. 

* There is a critical need to identify how factors such as reactivity, degradation of the active 

ingredient in the sewer, volatilization in the sewer, and adsorption to wastes affect how much 

reaches the WWTP. 

* Model results are highly dependent on streamflow (dilution). There is no guidance on what value 

should be used. In addition, 1Q10, 7Q10 and 30Q5 are extremely conservative values that are 

unrealistic. Even the Harmonic Mean flow is lower than EPA has used in the past. 

* The Agency should clarify the dilution factor at WWTP (flow rates, population served, industrial 

contributions to WWTP, seasonal variations, geographic differences, etc.). 

* The Agency should address which percentile to use for highly variable modeling assumptions (e.g. 

average surface water concentration, stream dilution factor for streams to which wastewater 

treatment facilities discharge). 

* There is no clear definition for how "Days exceeding COC" will be used in decision making. What 

are the regulatory implications of "failing" the model? The Agency should provide more explanation 

as to the intended use of the model and results. 

Overall the DtD model is given too much weight in this process -- it should be cited as an 

"example" of a model, not the definitive answer. Finally, the guidance supporting the use of the 

model, as for any model, needs to be improved such that the model can be understood by an 

applicant simply by reading it. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 831 

Response: see responses 130.1, 134.3, 134.10, 134.11, 134.14, 134.15, 134.17, and 134.19 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26350 

Comment Code: 134000 

Comment: B. Is the Substance Suitable for DtD Modeling? 

Many endpoints for substances can be estimated via EpiWin or other software, and estimates via 

accepted models should be acceptable to use in place of data. The DtD is really just a dilution 

model, based on the input and assumptions selected, and therefore should be appropriate for many 

substances including metals, quaternary ammonium compounds, triclosan, and inorganic chemicals. 

Hypochlorite, however, may react during use, in the sewer or in the WWTP. Thus, a simple removal 

factor at the WWTP is likely insufficient to fully account for hypochlorite fate after use. Any 

compound that would volatilize in the home or sewer would also give poor results. Second, 

uncertainty in estimating the down the drain volume of the substance is an issue. Many antibacterial 

compounds are used with a wipe that is then disposed in solid waste. However, accurately estimating 

the down the drain volume and allowing for loss in the sewer/distribution system are essential 

factors for the reliability of this model. Here, good monitoring data is beneficial. 

Finally, there are more modern approaches available to estimate surface water concentrations of 

chemicals. GIS based tools such as the P&G developed GIS-ROUT allow estimation of surface 

water concentrations on a site specific basis. This would facilitate site specific evaluations of risk due 

to these materials. These tools directly address some of the limitations in the DtD model and should 

be further investigated. 

EPA’s approach for down the drain chemicals separates the exposure and the effects phases of the 

assessments and subjects chemicals to similar testing requirements regardless of the mass of 

chemical disposed to the environment. The fact that EPA does not guide testing by the extent of 

environmental exposure is wasteful for ingredients which will reach the environment at low levels. 

Even for chemicals which are used at greater volume, there is no proof that EPA’s program will 

achieve its goal without being wasteful and P&G believes the EPA approach will likely result in 

significant, unwarranted costs in animals, time, and dollars. This will result in unnecessary loss of 

animals, increased costs to the consumer and will negatively affect product innovation as new 

product development will be slowed due to the extra regulatory burden. The benefit to the 

environment of the EPA approach is likely to be small and not commensurate with its costs. 

Further, we recommend EPA consider the use of ASTREAT for predicting removal of disinfecting 

compounds during wastewater treatment. 

C. Uncertainty in Application of DtD Model Results 

It is unclear how results from DtD modeling will be interpreted, and how results will be applied, 

including use in environmental risk assessment and triggering additional environmental and 

ecotoxicity data needs. In fact, if EPA is relying on DtD modeling results, the Agency must indicate 

criteria to use in the model. Furthermore, DtD modeling assumes that some ecotoxicity information 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 832 

is available (i.e. LOC/COC values) to estimate risk quotients or RQs (i.e. Exposure/Toxicity), which 

could trigger additional testing. In the new proposal, based on Use Patterns to trigger data 

requirements, these data may not be available or necessary to run the DtD model. In addition, it is 

unclear how generic DtD modeling would be applied for acceptable use of products in different 

geographic regions, like desert or water restricted areas. 

Other validated models and means to estimate potential environmental exposures should be 

acceptable, including the use of EpiWin and EpiSuites, SAR/QSAR, and open literature references 

as a testing alternative to estimate endpoints for use in environmental modeling. For example, the 

removal value entered for modeling can be estimated from the biodegradability rate constant, 

volatility, and the Koc using a variety of models, a lab scale WWTP, or monitoring data. Models 

used to do this include STP and ASTREAT. In relevant part, the Canadian government evaluated a 

range of models and concluded that ASTREAT was superior to OPPTs model STP. In fact, it 

should be acceptable to run an environmental risk assessment screen using means other than DtD 

and conduct fate testing only if there is a need to show a loss during WWTP. Thus, if assuming 

100% of the substance goes into effluent and is still regarded as safe, there is no need for 

environmental fate or ecotoxicity testing. 

Finally, guidance is needed on standard test methods which can be used to estimate input 

parameters for the model. This guidance should specify how volatilization, hydrolysis, and 

biodegradation during product use, disposal, and transport to the WWTP (i.e., in sewer) are to be 

estimated and incorporated into the DtD model. Where possible, other modeling approaches should 

also be discussed and allowed. 

D. Summary Comments on the Use of DtD Modeling 

The DtD model should not be part of the regulation as a requirement, but only serve as an example 

of environmental modeling for products in those relevant Use Patterns. It should be used only in 

relation to very limited use patterns for antimicrobial pesticides, be used only with appropriate 

chemistries, and must fully identify the significant limitations associated with the use of this model in 

any regulatory decision. 

The Agency has not identified how the output from this model would be used in a regulatory 

decision. P&G asserts that no decisions should be made on the basis of the results of this modeling 

until the model has been fully and appropriately reviewed for such purposes and the Agency has 

clarified how the information will be used. Ideally, the Agency will further investigate GIS based 

tools to predict surface water concentrations due to their ability to include a range of dilution 

factors, wastewater treatment types, and integrate releases from commercial, industrial, and domestic 

sectors. 

Response: see responses 130.1, 134.9, 134.10, 134.11, 134.14, 134.19, and 134.20 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27172 

Comment Code: 134000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 833 

Comment: A. DtD Modeling is Site Specific 

Down-the-drain (DtD) modeling is highly site specific due to its reliance on a single WWTP removal 

value to model the entire United States, and would be very difficult to obtain meaningful 

environmental exposure estimates for generic use. If results from this model exceed environmental 

levels or concentrations of concern, data needs are identified and additional testing triggered. 

Neither the amount disposed down the drain, the removal, or the concentration of concern (COC) , 

the key input parameters affecting DtD, are clearly defined or explained. For example, the Agency 

should address whether the COC is an acute value, a chronic value, or the lowest value in all cases, 

and why. The most relevant values should be explained. 

The Agency fails to explain several aspects of the requirements built into the model, from product 

use through transport to the WWTP, and beyond. These are as follows: 

* The Agency must explain how to determine how much substance actually goes down the drain as 

opposed to an estimate based on annual production volumes. 

* There is a critical need to identify how factors such as reactivity, degradation of the active 

ingredient, volatility, adsorption to wastes affect how much reaches the WWTP. 

* Model results are highly dependent on stream flow (dilution). There is no guidance on what value 

should be used. In addition, 1Q10, 7Q10 and 30Q5 are extremely conservative values that are 

unrealistic. Even the Harmonic Mean flow is lower than EPA has used in the past. 

* The Agency should clarify the dilution factor at WWTP (flow rates, population served, industrial 

contributions to WWTP, seasonal variations, geographic differences, etc.). 

* The Agency should address which percentile to use for highly variable modeling assumptions (e.g., 

average surface water concentrtion, stream dilution factor for streams to which wastewater 

treatment facilities discharge). 

• There is no clear definition for how "Days exceeding COC" will be used in decision making. What 

are the regulatory implications of "failing" the model? The Agency should provide more explanation 

as to the intended use of the model and results. 

Overall the DtD model is given too much weight in this process - it should be cited as an "example" 

of a model, not the definitive answer. Finally, the guidance supporting the use of the model, as for 

any model, needs to be improved such that the model can be understood by an applicant simply by 

reading it. 

Response: see responses 130.1, 134.3, 134.10, 134.11, 134.14, 134.15, 134.17, and 134.19 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27173 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 834 

Comment Code: 134000 

Comment: B. Is the Substance Suitable for DtD Modeling? 

Many endpoints for substances can be estimated via EpiWin or other software, and estimates via 

accepted models should be acceptable to use in place of data. The DtD is really just a dilution 

model, based on the input and assumptions selected, and therefore should be appropriate for many 

substances including metals, quaternary ammonium compounds, triclosan, and inorganic chemicals. 

Hypochlorite, however, may react during use, in the sewer or in the WWTP. Thus, a simple removal 

factor at the WWTP is likely insufficient to fully account for hypochlorite fate after use. Any 

compound that would volatilize in the home or sewer would also give poor results. Second, 

uncertainty in estimating the down the drain volume of the substance is an issue. Many antibacterial 

compounds are used with a wipe that is then disposed in solid waste. However, accurately estimating 

the down the drain volume and allowing for loss in the sewer/distribution system are essential 

factors for the reliability of this model. Here, good monitoring data is beneficial. 

C. Uncertainty in Application of DtD Model Results 

It is unclear how results from DtD modeling will be interpreted, and how results will be applied, 

including use in environmental risk assessment and triggering additional environmental and 

ecotoxicity data needs. In fact, if EPA is relying on DtD modeling results, to the Agency must 

indicate criteria to use in the model. Furthermore, DtD modeling assumes that some ecotoxicity 

information is available (i.e., LOC/COC values) to estimate risk quotients or RQs (i.e., 

Exposure/Toxicity), which could trigger additional testing. In the new proposal, based on Use 

Patterns to trigger data requirements, these data may not be available or necessary to run the DtD 

model. In addition, it is unclear how generic DtD modeling would be applied for acceptable use of 

products in different geographic regions, like desert or water restricted areas. 

Other validated models and means to estimate potential environmental exposures should be 

acceptable, including the use of EpiWin and EpiSuites, SAR/QSAR, and open literature references 

as a testing alternative to estimate endpoints for use in environmental modeling. For example, the 

removal value entered for modeling can be estimated from the biodegradability rate constant, 

volatility, and the Koc using a variety of models, a lab scale WWTP, or monitoring data. Models 

used to do this include STP and ASTREAT. In relevant part, the Canadian government evaluated a 

range of models and concluded that ASTREAT was superior to OPPTs model STP. In fact, it 

should be acceptable to run an environmental risk assessment screen using means other than DtD 

and conduct fate testing only if there is a need to show a loss during WWTP. Thus, if assuming 

100% of the substance goes into effluent and is still regarded as safe, there is no need for 

environmental or ecotoxicity testing. 

Finally, guidance is needed on standard test methods which can be used to estimate input 

parameters for the model. This guidance should specify how volatilization, hydrolysis, and 

biodegradation during product use, disposal, and transport to the WWTP (i.e., in sewer) are to be 

estimated and incorporated into the DtD model. Where possible, other modeling approaches should 

also be discussed and allowed. 

D. Summary Comments on the Use of DtD Modeling 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 835 

The DtD model should not be part of the regulation as a requirement, but only serve as an example 

of environmental modeling for products in those relevant Use Patterns. It should be used only in 

relation to very limited use patterns for antimicrobial pesticides, be used only with appropriate 

chemistries, and must fully identify the significant limitations associated with the use of this model in 

any regulatory decision. 

The Agency has not identified how the output from this model would be used in a regulatory 

decision. The Panel asserts that no decisions should be made on the basis of the results of this 

modeling until the model has been fully and appropriately reviewed for such purposes and the 

Agency has clarified how the information will be used. 

Response: see responses 130.1, 134.9, 134.10, 134.11, 134.14, 134.19, and 134.20 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27608 

Comment Code: 134000 

Comment: A. DtD Modeling is Site Specific 

Down-the-drain (DtD) modeling is highly site specific due to its reliance on a single WWTP removal 

value to model the entire United States, and would be very difficult to obtain meaningful 

environmental exposure estimates for generic use. If results from this model exceed environmental 

levels or concentrations of concern, data needs are identified and additional testing triggered. 

Neither the amount disposed down the drain, the removal, or the concentration of concern (COC) , 

the key input parameters affecting DtD, are clearly defined or explained. For example, the Agency 

should address whether the COC is an acute value, a chronic value, or the lowest value in all cases, 

and why. The most relevant values should be explained 

The Agency fails to explain several aspects of the requirements built into the model, from product 

use through transport to the WWTP, and beyond. These are as follows: 

* The Agency must explain how to determine how much substance actually goes down the drain as 

opposed to an estimate based on annual production volumes. 

* There is a critical need to identify how factors such as reactivity, degradation of the active 

ingredient, volatility, adsorption to wastes affect how much reaches the WWTP. 

* Model results are highly dependent on streamflow (dilution). There is no guidance on what value 

should be used. In addition, 1Q10, 7Q10 and 30Q5 are extremely conservative values that are 

unrealistic. Even the Harmonic Mean flow is lower than EPA has used in the past. 

* The Agency should clarify the dilution factor at WWTP (flow rates, population served, industrial 

contributions to WWTP, seasonal variations, geographic differences, etc.). 
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Comments and Response References: 

Down-the-Drain Section (130) Page 836 

* The Agency should address which percentile to use for highly variable modeling assumptions (e.g. 

average surface water concentration, stream dilution factor for streams to which wastewater 

treatment facilities discharge). 

* There is no clear definition for how "Days exceeding COC" will be used in decision making. What 

are the regulatory implications of "failing" the model? The Agency should provide more explanation 

as to the intended use of the model and results. 

Overall the DtD model is given too much weight in this process - it should be cited as an "example" 

of a model, not the definitive answer. Finally, the guidance supporting the use of the model, as for 

any model, needs to be improved such that the model can be understood by an applicant simply by 

reading it. 

Response: see responses 130.1, 134.3, 134.10, 134.11, 134.14, 134.15, 134.17, and 134.19 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27610 

Comment Code: 134000 

Comment: B. Is the Substance Suitable for DtD Modeling? 

Many endpoints for substances can be estimated via EpiWin or other software, and estimates via 

accepted models should be acceptable to use in place of data. The DtD is really just a dilution 

model, based on the input and assumptions selected, and therefore should be appropriate for many 

substances including metals, quaternary ammonium compounds, triclosan, and inorganic chemicals. 

Hypochlorite, however, may react during use, in the sewer or in the WWTP. Thus, a simple removal 

factor at the WWTP is likely insufficient to fully account for hypochlorite fate after use. Any 

compound that would volatilize in the home or sewer would also give poor results. Second, 

uncertainty in estimating the down the drain volume of the substance is an issue. Many antibacterial 

compounds are used with a wipe that is then disposed in solid waste. However, accurately estimating 

the down the drain volume and allowing for loss in the sewer/distribution system are essential 

factors for the reliability of this model. Here, good monitoring data is beneficial. 

C. Uncertainty in Application of DtD Model Results It is unclear how results from DtD modeling 

will be interpreted, and how results will be applied, including use in environmental risk assessment 

and triggering additional environmental and ecotoxicity data needs. In fact, if EPA is relying on DtD 

modeling results, to the Agency must indicate criteria to use in the model. Furthermore, DtD 

modeling assumes that some ecotoxicity information is available (i.e. LOC/COC values) to estimate 

risk quotients or RQs (i.e. Exposure/Toxicity), which could trigger additional testing. In the new 

proposal, based on Use Patterns to trigger data requirements, these data may not be available or 

necessary to run the DtD model. In addition, it is unclear how generic DtD modeling would be 

applied for acceptable use of products in different geographic regions, like desert or water restricted 

areas. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 837 

Other validated models and means to estimate potential environmental exposures should be 

acceptable, including the use of EpiWin and EpiSuites, SAR/QSAR, and open literature references 

as a testing alternative to estimate endpoints for use in environmental modeling. For example, the 

removal value entered for modeling can be estimated from the biodegradability rate constant, 

volatility, and the Koc using a variety of models, a lab scale WWTP, or monitoring data. Models 

used to do this include STP and ASTREAT. In relevant part, the Canadian government evaluated a 

range of models and concluded that ASTREAT was superior to OPPTs model STP. In fact, it 

should be acceptable to run an environmental risk assessment screen using means other than DtD 

and conduct fate testing only if there is a need to show a loss during WWTP. Thus, if assuming 

100% of the substance goes into effluent and is still regarded as safe, there is no need for 

environmental or ecotoxicity testing. 

Finally, guidance is needed on standard test methods which can be used to estimate input 

parameters for the model. This guidance should specify how volatilization, hydrolysis, and 

biodegradation during product use, disposal, and transport to the WWTP (i.e., in sewer) are to be 

estimated and incorporated into the DtD model. Where possible, other modeling approaches should 

also be discussed and allowed. 

D. Summary Comments on the Use of DtD Modeling 

The DtD model should not be part of the regulation as a requirement, but only serve as an example 

of environmental modeling for products in those relevant Use Patterns. It should be used only in 

relation to very limited use patterns for antimicrobial pesticides, be used only with appropriate 

chemistries, and must fully identify the significant limitations associated with the use of this model in 

any regulatory decision. 

The Agency has not identified how the output from this model would be used in a regulatory 

decision. LANXESS asserts that no decisions should be made on the basis of the results of this 

modeling until the model has been fully and appropriately reviewed for such purposes and the 

Agency has clarified how the information will be used. 

Response: see responses 130.1, 134.9, 134.10, 134.11, 134.14, 134.19, and 134.20 

Comment Code: 137000 Screening assessment on down-the-drain antimicrobial uses 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25686 

Comment Code: 137000 

Comment: Biosolids and air emissions from municipal wastewater treatment plants 

The municipal wastewater treatment plant-related elements of the proposed rule focus on data 

requirements to allow EPA to identify the potential for an antimicrobial pesticide to interfere with 

operations of a municipal wastewater treatment plant and to evaluate whether the antimicrobial 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 838 

pesticide may appear in wastewater effluent. The rule does not specifically address the potential for 

an antimicrobial pesticide to be transferred to air or biosolids (sewage sludge). Although such crossmedia transfers can remove an antimicrobial pesticide from water, they do not remove it from the 

environment. The potential environmental impacts of the crossmedia transfers of pesticides need to 

be addressed in EPA’s environmental risk assessments. SFE and the SFPUC request that EPA 

modify the proposed rule to clarify that higher-tiered environmental studies will be required in cases 

where the screening-level assessment indicates that the pesticide would partition to biosolids or into 

the air at a municipal wastewater treatment plant. This is especially important as San Francisco 

beneficially reuses 100% of its biosolids in land application, compost, and landfill beneficial reuse 

applications. Again, SFE and the SFPUC reference technical comments submitted by CASA, 

TriTAC and NACWA on this issue. 

Response: see responses 132.1 and 134.22 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25795 

Comment Code: 137000 

Comment: Tri-TAC supports higher-tiered environmental studies in cases where the screening-level 

down-the-drain assessment indicates that the pesticide would partition into biosolids. 

Response: EPA acknowledges Tri-TAC's support for requiring higher-tiered environmental studies 

under particular circumstances. Also see response 134.22. 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25891 

Comment Code: 137000 

Comment: CASA supports higher-tiered environmental studies in cases where the screening- level 

down-the-drain assessment indicates that the pesticide would partition into biosolids. 

Response: EPA acknowledges CASA's support for requiring higher-tiered environmental studies 

under particular circumstances. 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26068 

Comment Code: 137000 

Comment: Detailed Comments on Proposed Aquatic Toxicity, Chemistry, and Environmental Fate 

Data Requirements 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 839 

We support the following proposed data requirements, most of which reflect current USEPA 

practice for new registrations. These requirements should be applied to pesticides in Registration 

Review as well as to new antimicrobial pesticide registrations. 

* Requirement for minimum aquatic toxicity and environmental fate data sets for all antimicrobials. 

We support USEPA’s proposals to require a minimum set of aquatic toxicity and environmental fate 

data for all antimicrobials. The paucity of aquatic toxicity data for antimicrobials has interfered with 

government’s ability to ensure that their outdoor use does not adversely impact urban creeks, rivers, 

estuaries and near-shore ocean waters. 

Response: EPA acknowledges CASQA's support for requiring a minimum set of aquatic toxicity 

and environmental fate data for all antimicrobials. 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26081 

Comment Code: 137000 

Comment: Minimum aquatic toxicity data sets should be required for all degradates with long 

environmental half-lives. The approach for antimicrobial degradates ("metabolites") that USEPA has 

proposed is not workable. Data on degradates are only proposed to be required if USEPA makes a 

determination "that the transformation products of the parent compound are more toxic, persistent, 

bioaccumulative, or have been shown to cause adverse effects in mammalian or aquatic reproductive 

studies." If the registrant is not required to provide data characterizing degradates to USEPA, how 

can USEPA make this determination? Instead, USEPA should require minimum environmental fate 

and aquatic toxicity data sets for all antimicrobials degradates with long half-lives. 

Response: see responses 140.5 and 160.3 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26116 

Comment Code: 137000 

Comment: The Districts support higher-tiered environmental studies in cases where the screeninglevel down-the-drain assessment indicates that the pesticide would partition into biosolids. 

Response: EPA acknowledges the District's support for requiring higher-tiered environmental 

studies under particular circumstances. Also see response 134.22 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26342 

Comment Code: 137000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 840 

Comment: III. Comments on the Use of the "Down the Drain" Screening Assessment and on the 

"Case Study" White Paper 

In the proposed 158W environmental fate data requirements, "EPA specifically requests comments 

on the Agency’s rationale for requiring data to perform a screening assessment on down-the-drain 

antimicrobial uses, the potential for performing higher-tiered studies based on the results of the 

screening assessment, and the cost and burden of performing the studies."(FR pages 59406-7, 

Section XII. B. History of Environmental Fate Data Requirements for Antimicrobials). As discussed 

above, P&G asserts that there are only limited situations under which any assessment of 

environmental exposure is relevant for antimicrobial pesticides. The Agency previously has 

recognized limitations in providing meaningful estimates of environmental exposures with the use of 

this model. "The ‘Down-the-Drain’ model has uncertainties as follows: the model does not address 

the possibility of degradation of the parent, does not estimate the concentration of any degradants, 

and does not address actions to be taken to avoid contamination of POTWs when a chemical 

remains in the water and does not biodegrade."(OIT E-Fate Appendix, in EPA E-Fate Assessment 

of Octhilinone, Mar 30, 2007). 

Response: see responses 140.1, 140.4, and 134.16 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27171 

Comment Code: 137000 

Comment: IV. Comments on the Use of the "Down the Drain" Screening Assessment and on the 

"Case Study" White Paper 

In the proposed 158W environmental fate data requirements, "EPA specifically requests comments 

on the Agency’s rationale for requiring data to perform a screening assessment on down- the-drain 

antimicrobial uses, the potential for performing higher-tiered studies based on the results of the 

screening assessment, and the cost and burden of performing the studies."(FR pages 59406-7, 

Section XII. B. History of Environmental Fate Data Requirements for Antimicrobials). As discussed 

above, the Panel asserts that there are only limited situations under which any assessment of 

environmental exposure is relevant for antimicrobial pesticides. The Agency previously has 

recognized limitations in providing meaningful estimates of environmental exposures with the use of 

this model. "The ‘Down-the- Drain’ model has uncertainties as follows: the model does not address 

the possibility of degradation of the parent, does not estimate the concentration of any degradants, 

and does not address actions to be taken to avoid contamination of POTWs when a chemical 

remains in the water and does not biodegrade."(OIT E- Fate Appendix, in EPA E- Fate Assessment 

of Octhilinone, Mar 30, 2007). 

Response: see responses 140.1, 140.4, and 134.16 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Down-the-Drain Section (130) Page 841 

Letter ID: 0064 

Comment ID: 27607 

Comment Code: 137000 

Comment: IV. Comments on the Use of the "Down the Drain" Screening Assessment and on the 

"Case Study" White Paper 

In the proposed 158W environmental fate data requirements, "EPA specifically requests comments 

on the Agency’s rationale for requiring data to perform a screening assessment on down- the-drain 

antimicrobial uses, the potential for performing higher-tiered studies based on the results of the 

screening assessment, and the cost and burden of performing the studies."(FR pages 59406-7, 

Section XII. B. History of Environmental Fate Data Requirements for Antimicrobials). As discussed 

above, LANXESS asserts that there are only limited situations under which any assessment of 

environmental exposure is relevant for antimicrobial pesticides. The Agency previously has 

recognized limitations in providing meaningful estimates of environmental exposures with the use of 

this model. "The ‘Down-the- Drain’ model has uncertainties as follows: the model does not address 

the possibility of degradation of the parent, does not estimate the concentration of any degradants, 

and does not address actions to be taken to avoid contamination of POTWs when a chemical 

remains in the water and does not biodegrade."(OIT E- Fate Appendix, in EPA E-Fate Assessment 

of Octhilinone, Mar 30, 2007). 

Response: see responses 140.1, 140.4, and 134.16 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 842 

Environmental Fate (140)

Verbatim Comments and Response References for the Environmental Fate 

Section 

Comment Code: 140000 Environmental fate 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25608 

Comment Code: 140000 

Comment: Section Number XII. 

Title B. History of Environmental Fate Data Requirements for Antimicrobials 

Paragraph p. 59407 

Excerpt from Federal Register General comment 

HC Comment The PMRA has not, in the past, required data on antimicrobial pesticides that move 

from the area of application to a waste water treatment plant (WWTP). The PMRA agrees with the 

EPA that antimicrobial pesticides could pose a risk to biological treatment processes in WWTPs and 

will evaluate these down-the-drain environmental fate data (activated sludge sorption isotherm, 

ready biodegradability, porous pot test, and modified activated sludge, respiration inhibition test) 

should they be submitted to the PMRA. The PMRA also agrees that wood preservatives, 

antifoulants, and aquatic use sites do not fall under the down-the-drain use patterns. 

Response: EPA acknowledges' PMRA's support for the down-the-drain approach. 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25662 

Comment Code: 140000 

Comment: Ecotoxicity and environmental fate minimum data requirements 

SFE and the SFPUC support EPA’s proposal to require a minimum ecotoxicity and environmental 

fate data set for all antimicrobial pesticides. The paucity of aquatic toxicity data for antimicrobials 

has interfered with government’s ability to ensure that antimicrobials use does not adversely impact 

humans, wildlife, and aquatic organisms. In our own work, we have found the lack of basic 

ecotoxicity and environmental fate data for antimicrobials to be a major barrier to evaluating and 

comparing alternative products; these comparative evaluations are a key step in the implementation 

of our pest management, chemical product selection, and green building programs. This deficiency 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 843 

in EPA regulatory protection costs our City considerable amounts of money, because we must pay 

consultants to conduct these evaluations. There are many other public agencies nationwide who find 

themselves in a similar position. 

Response: EPA acknowledges SFE and SFPUC's support for EPA's proposal to require a 

minimum ecotoxicity and environmental fate data set for all antimicrobial pesticides. 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25685 

Comment Code: 140000 

Comment: Biosolids and air emissions from municipal wastewater treatment plants 

The municipal wastewater treatment plant-related elements of the proposed rule focus on data 

requirements to allow EPA to identify the potential for an antimicrobial pesticide to interfere with 

operations of a municipal wastewater treatment plant and to evaluate whether the antimicrobial 

pesticide may appear in wastewater effluent. The rule does not specifically address the potential for 

an antimicrobial pesticide to be transferred to air or biosolids (sewage sludge). Although such crossmedia transfers can remove an antimicrobial pesticide from water, they do not remove it from the 

environment. The potential environmental impacts of the crossmedia transfers of pesticides need to 

be addressed in EPA’s environmental risk assessments. SFE and the SFPUC request that EPA 

modify the proposed rule to clarify that higher-tiered environmental studies will be required in cases 

where the screening-level assessment indicates that the pesticide would partition to biosolids or into 

the air at a municipal wastewater treatment plant. This is especially important as San Francisco 

beneficially reuses 100% of its biosolids in land application, compost, and landfill beneficial reuse 

applications. Again, SFE and the SFPUC reference technical comments submitted by CASA, 

TriTAC and NACWA on this issue. 

Response: see response 140.8 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25696 

Comment Code: 140000 

Comment: Saltwater aquatic toxicity data 

Since both municipal wastewater treatment plant discharges and urban runoff routinely carry 

antimicrobials from urban areas into saltwater (in our case San Francisco Bay and the Pacific 

Ocean), salt water species aquatic toxicity data need to be required-rather than conditionally 

required-for all urban use patterns that may involve outdoor applications, applications or discharges 

directly to surface waters, or discharges to municipal wastewater treatment plants (i.e., food 

handling/storage establishments, premises, and equipment; commercial, institutional and industrial 

premises and equipment; residential and public access premises; medical premises, human drinking 
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Comments and Response References: 

Environmental Fate Section (140) Page 844 

water systems, materials preservatives, industrial processes and water systems, antifoulant paints and 

coatings, wood preservatives, swimming pools, and aquatic areas). Although we believe that 

additional aquatic toxicity data are necessary for proper evaluation of the water quality impacts of 

antimicrobial pesticides, at a minimum, EPA needs to require at least one marine/estuarine 

invertebrate, one vertebrate, and one plant species to properly assess the potential impacts to 

municipal wastewater treatment plants and receiving waters. 

Response: see response 140.9 

Commenter Name: Jay Feldman 

Commenter Organization: Beyond Pesticides 

Letter ID: 0067 

Comment ID: 25720 

Comment Code: 140000 

Comment: Other Issues of Concern 

We also recommend that the agency take a closer look at chemical mixtures currently found in the 

nation’s waterways and their possible synergistic effects. Several studies exist that detail the presence 

of varied concentrations of pharmaceuticals in surfaces waters, including several 

antimicrobials.[FN6: Kolpin, D.W., E.T. Furlong, M.T. Meyer, E.M. Thurman, et al. 2002. 

Pharmaceuticals, Hormones, and other organic wastewater contaminants in U. S. streams, 1999-

2000: A National Reconnaissance. Environ. Sci. Technol. 36, 1202-1211.] However, little to no 

effort has been made toward investigating how these chemicals interact with each other in the 

environment, or their combined effects on human and environmental health. Recent studies have 

found that mixtures of pesticides in surface water, especially at low doses, have a dramatic adverse 

impact on aquatic species compared to the individual chemical.[FN7: Relyea, RA. 2009. A cocktail of 

contaminants: how mixtures of pesticides at low concentrations affect aquatic communities. 

Oecologia. 159(2):363-76; Laetz, C,A et al. 2009. The Synergistic Toxicity of Pesticide Mixtures: 

Implications for Risk Assessment and the Conservation of Endangered Pacific Salmon. Environ. 

Health Perspec. 117 (3); Tierney et al. 2008. Salmon Olfaction is Impaired by an Environmentally 

Realistic Pesticide Mixture. Environ. Sci. Technol. 42 (13): 4996-5001.] The agency cannot rule out 

that antimicrobial mixtures occurring in the environment have an added impact on environmental 

health. As such, the agency must allocate resources to look at this phenomenon which has so far 

been ignored in risk analyses. 

Response: see response 140.7 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25940 

Comment Code: 140000 

Comment: Efate - Emphasis should be placed on the importance of the fate assessment, 

particularly for antimicrobials that can be classified in the "Lower environmental" exposure groups. 

The Predicted Environmental Concentration from the environmental fate assessment should be 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 845 

used and compared to existing test results already generated for the listed species to determine if 

sufficient safety margins are available. If so, these antimicrobials should be exempt from higher tier 

testing. 

E-Fate assessment should be considered when higher tier testing is suggested. For example, 

hypochlorite breaks down very rapidly in the environment. Continuous test exposure of species to 

hypochlorite is not appropriate. 

Response: see response 140.10 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25954 

Comment Code: 140000 

Comment: In the case of addressing the ecotoxicity and environmental fate it would be more useful 

to utilize the European approach for addressing wood products and their environmental exposure. 

This approach is provided below: 

[Table 1. European approach for addressing wood products and their environmental exposure -- see 

PDF docket ID EPA-HQ-OPP-2008-0110-0091] 

Based on this table, classes 3-5 would be subject to the more extensive data requirements to assess 

ecotoxicity and environmental fate. 

Response: see response 140.29 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25994 

Comment Code: 140000 

Comment: * To the extent possible, EPA should make publicly available the results of its 

assessments and the methodologies used. These materials would be helpful to POTWs conducting 

toxicity evaluations. 

Response: see response 140.32 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26036 

Comment Code: 140000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 846 

Comment: Since 1999, CASQA has provided comments on selected USEPA pesticide registration 

and reregistration actions, including proposed changes in policies and regulations, and actions 

involving specific active ingredients that appear in urban runoff (e.g., polyhexamethylene 

biguanadine, copper, metam sodium, diazinon, chlorpyrifos, permethrin, cypermethrin). Our focus 

on pesticide registration issues is the result of numerous scientific studies conducted in California by 

stormwater programs, wastewater treatment plants, the University of California, California Regional 

Water Quality Control Boards, United States Geological Survey, and USEPA showing widespread 

toxicity in local creeks and rivers, urban runoff, and wastewater treatment plant effluent from 

pesticide residues. These studies have demonstrated that the use of some pesticides registered under 

the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) can and does adversely affect water 

bodies in California. Ironically, as a result of discharges of pesticides registered for use by USEPA 

under FIFRA, the State Water Board and USEPA have found many waters in urban areas of 

California to be impaired in accordance with Clean Water Act [Section] 303(d). 

Response: EPA appreciates receiving this information. 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26038 

Comment Code: 140000 

Comment: Consequently, expensive programs have been required of many cities and counties, 

through municipal stormwater NPDES permits, to restore the designated beneficial uses of 

pesticide-impaired waters. Through this process, CASQA has recognized the need for USEPA to be 

more proactive in its implementation of its FIFRA authority to reduce the potential for registered 

pesticides to impair surface water quality. 

Response: see responses 20.3 and 30.12 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26063 

Comment Code: 140000 

Comment: Recirculating Cooling Water Systems 

The proposed antimicrobials data rule appears to be based on an inaccurate assessment of the fate 

of biocides in recirculating (non-single-pass) cooling water systems. On page 59389, USEPA notes 

that it has assumed that any biocide in recirculating cooling water systems will be degraded prior to 

discharge. This assumption is incorrect. Low biocide concentrations are not the basis for initiating 

discharges from cooling water systems. Discharges are usually triggered by increased concentration 

of ions and other chemicals in the water. Discharging allows the system to be refilled with water and 

thereby diluted. Due to evaporative losses, biocide concentrations in discharges from recirculating 

cooling water systems are often higher than the starting biocide concentrations. We have enclosed 

[See attachments in PDF docket ID EPA-HQ- OPP-2008-0110-0089] cooling water systems 
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Comments and Response References: 

Environmental Fate Section (140) Page 847 

management guidelines that explain this phenomenon and provide additional background on 

cooling water systems operations. 

Although these discharges seem small, they can be environmentally significant. For example, in the 

service area of the Palo Alto, California regional wastewater treatment plant (population about 

200,000), a survey identified more than 100 cooling water systems, about half at large industries and 

about half in commercial and residential buildings. In the 1990s, that wastewater treatment plant 

experienced a tributyltin discharge problem that was linked to use of tributyltin as a cooling water 

system biocide. Tributyltin was used in fewer than 5% of the cooling towers in the region served by 

the wastewater treatment plant (all of which were recirculating cooling water systems). In working to 

address the problem, wastewater treatment plant staff discovered many recirculating cooling towersincluding one treated with tributyltin-that discharged directly to storm drains and flowed untreated 

into local creeks.[FN7:Moran, K. (2009), former Manager of Environmental Control Programs, City 

of Palo Alto. Personal communication, March 2009.] While Palo Alto identified and redirected these 

discharges, most U.S. municipalities do not have regulatory programs that comprehensively address 

discharge points for recirculating cooling water systems. USEPA should restructure the rule to 

reflect that recirculating cooling water systems discharge biocides to both municipal wastewater 

treatment plants and directly to surface waters via storm drains. 

Recognizing the adverse environmental impacts of tributyltin discharges from recirculating cooling 

water systems, the California Department of Pesticide Regulation (DPR) prohibited their use in the 

San Francisco Bay Area in the mid-1990s. Two short fact sheets describing this case study and a 

copy of the DPR report that provided the scientific basis for its regulations are enclosed [See 

attachments in PDF docket ID EPA-HQ- OPP-2008-0110-0089]. 

Response: see response 140.11 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26202 

Comment Code: 140000 

Comment: The proposed regulations for indoor antimicrobial pesticides are inconsistent with 

indoor conventional pesticides which are conditionally required to submit only hydrolysis data and 

are not required to conduct any other environmental fate data. Contrast this to the requirements for 

"low environmental exposure" antimicrobials, where without any explanation or rationale, five 

environmental fate studies are required for ALL antimicrobials. Moreover, higher tiered testing is 

conditionally required for all antimicrobials, without regard to whether they are indoor or outdoor, 

or have no potential for environmental exposure.[FN#5: Compare 40 CFR 158.1100 with Proposed 

§158.2280. See pages 59442-443 for list of guidelines under "low environmental exposure" as R and 

CR.] As highlighted earlier, P&G strongly encourages the Agency to consider a tiered approach to 

risk assessment versus the proposed high/low approach. 

Response: see responses 1, 140.1, 140.3, and 140.10 

Commenter Name: Janice L. Dhonau 
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Comments and Response References: 

Environmental Fate Section (140) Page 848 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26205 

Comment Code: 140000 

Comment: Data requirements for environmental fate are necessary to assess the risks of potential 

environmental exposure and the related potential to cause adverse effects on humans or nontarget 

organisms in the environment. The majority of antimicrobial pesticide uses is indoor and/or 

environmentally contained and presents little potential for environmental exposure. As a result, it is 

important to clearly identify when potential environmental exposures may be relevant to avoid 

unnecessary testing. 

Any proposed requirement for environmental fate data for antimicrobial pesticides must clearly 

identify what antimicrobial pesticides are and what uses of those pesticides pose sufficient potential 

for environmental exposure that assessment under FIFRA is needed. Next, in proposing these data 

requirements for antimicrobial pesticides, the Agency must take into consideration the requirements 

of FIFRA Section 3(h)(3)(A)(ii), which mandates that EPA "differentiate the types of review 

undertaken for antimicrobial pesticides,...conform[ing] the degree and type of review to the risks and 

benefits presented,...[and] considering the use patterns of the product, toxicity, expected exposure 

and product type." 

The proposed rule arbitrarily assigns product types to ‘high’ or ‘low’ exposure groups. However, the 

Agency has not explained those assignments, and has not defined what is meant by these terms or 

how those terms relate to risk assessments for antimicrobial pesticides. The Agency must eliminate 

the use of these arbitrary categorizations. 

The proposed rule should reflect accurately how these requirements apply to the uses and how they 

are relevant to antimicrobial pesticides rather than to conventional chemicals. 

Response: see responses 1, 140.1, and 140.3 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26207 

Comment Code: 140000 

Comment: A. Environmental Data Are Not Required for Indoor Uses for Other Pesticides 

Given that neither 158.1300 nor 158.2060 require environmental fate data for indoor use 

conventional or biochemical pesticides, it is unclear why the Agency asserts that extensive data are 

required for indoor uses of antimicrobials. The proposed rule is inconsistent with the requirements 

for other types of pesticides, without any clear explanation or justification. While P&G agrees that 

the Agency may wish to consider different types of assessments for antimicrobials than for other 

types of pesticides, P&G believes that the Agency can do so only when a need has been publicly 

discussed and well justified and the appropriate methodology for the assessment developed through 

a transparent process with scientific peer review. 
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Comments and Response References: 

Environmental Fate Section (140) Page 849 

Response: see responses 1 and 140.1 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26211 

Comment Code: 140000 

Comment: The requirements for environmental fate within the proposed regulation must be limited 

to those use patterns that potentially could result in environmental exposure relevant to assessment 

under FIFRA. There are limited uses of antimicrobial pesticides that may have a potential to affect 

the environment through dissipation after use (as contrasted with disposal), or where the actual use 

of the pesticide may result in the potential for environmental contamination. P&G supports the 

proposal offered by the ACC Biocides Panel which clearly identifies those few uses. 

Response: see response 140.1 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26232 

Comment Code: 140000 

Comment: 11) The substance(s) to test for each requirement is not always clear. If a transformation 

product (e.g, metabolite or degradate) is identified, but is quickly degraded, the EPA should clarify 

whether it should be isolated for testing. In its discussion of the SAP review, the Agency agrees with 

SAP and states that it proposes to clarify the need for testing metabolites when the available data 

suggest they are more toxic. This clarification needs to be made more apparent in the proposed rule. 

Response: see response 140.5 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26304 

Comment Code: 140000 

Comment: Exposure assumptions must be scientifically justified based on the use of the specific 

product. Any such assumptions used to support a regulation or proposal should be disclosed and 

explained, and subject to independent scientific review. At a minimum, comments and input should 

be solicited on the assumptions in the Proposal. The Proposal falls short because none of these 

steps has been taken with respect to exposure categorization. 

The Panel believes that the two categories are inadequately supported based on the current record. 
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Comments and Response References: 

Environmental Fate Section (140) Page 850 

The Panel’s position is bolstered by the Proposal itself, which includes many data requirements for 

the determination of exposures, acknowledging that specific product use data are required in order 

to understand the potential level of exposure involved with that specific product use. 

Assumptions that product types and/or uses relate to levels of exposure and should be a basis for 

determining data requirements are insupportable and should be removed from the Proposal. 

Instead, requirements should be tiered based on pertinent factors such as the chemical and/or 

physical characteristics of the compound being assessed, routes of exposure, hazard as related to the 

routes of exposure, and the results of initial testing. The proper tiering of data depends upon these 

considerations, not arbitrary assignment of "high" or "low" exposure. Further, the approach to 

satisfying data requirements must incorporate current science and allow for future improvements in 

risk assessment, including use of integrated approaches to determining potential data requirements, 

hazard characterization, and risk assessment. 

Assuming the Agency continues to be interested in pursuing "high" and "low" exposure categories 

as a vehicle for tiering data requirements, additional issues must be addressed. 

Response: see response 140.3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26334 

Comment Code: 140000 

Comment: Manufacturers of conventional indoor pesticides are conditionally required to submit 

only hydrolysis data and are not required to conduct any other environmental fate data. Contrast this 

to the requirements for "low environmental exposure" antimicrobials, where without any 

explanation or rationale; five environmental fate studies are required for all antimicrobials. 

Moreover, higher tiered testing is conditionally required for all antimicrobials, without regard to 

whether they are indoor or outdoor, or have any potential for environmental 

exposure.[FN#40:Compare 40 CFR 158.1100 with Proposed [Section]158.2280. See pages 59442-

443 for list of guidelines under "low environmental exposure" as R and CR.] 

Response: see responses 1 and 140.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26392 

Comment Code: 140000 

Comment: VI. Potential Exposures to Antimicrobials Differ from Other Pesticides and Require 

Different Approaches Instead of conforming the regulation to the degree of risk posed by various 

antimicrobial uses as required by FIFRA [Section] 3(h), the Proposal’s data requirements are based 

upon unsubstantiated and often overstated assumptions about exposure. See the discussions in 

Appendices G and H for greater detail on the types of review that must be incorporated into the 
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Comments and Response References: 

Environmental Fate Section (140) Page 851 

data requirements to conform the review to reasonable worst case assumptions regarding human 

and environmental risk. 

Response: see response 1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26394 

Comment Code: 140000 

Comment: Unlike conventional pesticides, antimicrobials are not intended to be broadcast directly 

into the environment. Even in the case of antimicrobials that EPA has categorized, without 

explanation, as "high" exposure (once-through industrial water systems, wood preservatives and 

antifoulants), the potential introduction to the environment differs profoundly from that of 

conventional pesticides. 

Response: see response 140.1 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26538 

Comment Code: 140000 

Comment: Moreover, disposal of antimicrobial pesticides is outside of the scope of FIFRA, and 

should not be assessed unless the product disposal is not covered under a relevant federal, state, or 

local statute or regulation for hazardous wastes or the product label for a nonhazardous waste does 

not restrict against disposal of product down a sanitary sewer following a use that could result in 

such exposure. The regulation must provide adequate and appropriate direction as to when 

environmental exposure is potentially of concern and then tier the data requirements for ecological 

effects to be relevant to the risk assessment needed for that exposure. Similar to the closely-related 

data requirements for environmental fate, there are only a few circumstances where certain 

ecological effects data are relevant for antimicrobial pesticides. 

Response: see responses 30.2 and 160.32 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26861 

Comment Code: 140000 

Comment: A. Environmental Fate Data Requirements 

Manufacturers of conventional indoor pesticides are conditionally required to submit only hydrolysis 

data and are not required to conduct any other environmental fate data. Contrast this to the 
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Comments and Response References: 

Environmental Fate Section (140) Page 852 

requirements for "low environmental exposure" antimicrobials, where without any explanation or 

rationale; five environmental fate studies are required for all antimicrobials. Moreover, higher tiered 

testing is conditionally required for all antimicrobials, without regard to whether they are indoor or 

outdoor, or have any potential for environmental exposure.[FN40: Compare 40 CFR 158.1100 with 

Proposed §158.2280. See pages 59442-443 for list of guidelines under "low environmental exposure" 

as R and CR.] 

Response: see response 140.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26970 

Comment Code: 140000 

Comment: I. Introduction 

Data requirements for environmental fate are necessary to assess the risks of potential 

environmental exposure and the related potential to cause adverse effects on humans or nontarget 

organisms in the environment. The majority of antimicrobial pesticide uses is indoor and/or 

environmentally contained, and presents little potential for environmental exposure. As a result, it is 

important to clearly identify when potential environmental exposures may be relevant in order to 

avoid unnecessary testing. 

First, any proposed requirement for environmental fate data for antimicrobial pesticides must clearly 

identify what antimicrobial pesticides are and which uses of those pesticides pose sufficient potential 

for environmental exposure that assessment under FIFRA is needed. In both cases, the proposed 

rule is lacking. Next, in proposing these data requirements for antimicrobial pesticides, the Agency 

must take into consideration the requirements of FIFRA Section 3(h)(3)(A)(ii), which mandates that 

EPA "differentiate the types of review undertaken for antimicrobial pesticides, . . . conform[ing] the 

degree and type of review to the risks and benefits presented, . . . [and] considering the use patterns 

of the product, toxicity, expected exposure and product type." 

Response: see responses 1 and 140.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26974 

Comment Code: 140000 

Comment: VI. Potential Exposures are Different for Antimicrobials and Require Different 

Approaches 

Instead of conforming the regulation to the degree of risk posed by various antimicrobial uses as 

required by FIFRA §3(h), the Proposal’s data requirements are based upon unsubstantiated and 

often overstated assumptions about exposure. See the discussions in Appendices G and H for 
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Comments and Response References: 

Environmental Fate Section (140) Page 853 

greater detail on the types of review that must be incorporated into the data requirements to 

conform the review to reasonable worst case assumptions regarding human and environmental risk. 

Response: see response 1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26976 

Comment Code: 140000 

Comment: Unlike conventional pesticides, antimicrobials are not intended for being directly 

broadcast into the environment. Even in the case of antimicrobials that EPA has categorized, 

without explanation, as "high" exposure (once-through industrial water systems, wood preservatives 

and antifoulants), the potential introduction to the environment differs profoundly from that of 

conventional pesticides. 

Response: see response 140.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26985 

Comment Code: 140000 

Comment: The proposed rule arbitrarily assigns product types to ‘high’ or ‘low’ exposure groups. 

However, the Agency has not explained those assignments, and has not defined what is meant by 

these terms or how those terms relate to risk assessments for antimicrobial pesticides. As discussed 

elsewhere in these comments, the Agency must eliminate the use of these arbitrary categorizations 

(Refer to Panel’s General Comments at Sections I and III). Those groupings are unrelated to any 

clear need for environmental risk assessment. 

II. Comments on Proposed Rule (pages 59406-12; section 158.2280), Data Requirements for 

Environmental Fate The Panel provides the following comments on the rule as proposed. In a 

subsequent section, the Panel offers an alternative proposal that it believes is consistent with the 

statutory requirements and the intent for identification of potential environmental fate data 

requirements for antimicrobial pesticides. As explained in further detail below, the proposed rule 

should reflect accurately how these requirements apply to the uses and how they are relevant to 

antimicrobial pesticides rather than to conventional chemicals. 

Response: see responses 140.3 and 140.35 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26987 

Comment Code: 140000 
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Comments and Response References: 

Environmental Fate Section (140) Page 854 

Comment: A. Environmental Data Are Not Required for Indoor Uses for Other Pesticides 

Given that neither 158.1300 nor 158.2060 require environmental fate data for indoor use 

conventional nor biochemical pesticides, it is unclear why the Agency asserts that extensive data are 

required for indoor uses of antimicrobials. The proposed rule is inconsistent with the requirements 

for other types of pesticides, without any clear explanation or justification. While the Panel agrees 

that the Agency may wish to consider different types of assessments for antimicrobials than for 

other types of pesticides, the Panel strongly believes that the Agency can do so only when a need has 

been publicly discussed and well justified and the appropriate methodology for the assessment 

developed through a transparent process with scientific peer review. 

Response: see responses 1 and 140.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27002 

Comment Code: 140000 

Comment: The requirements for environmental fate data within the proposed regulation must be 

limited to those use patterns that potentially could result in environmental exposure relevant to 

assessment under FIFRA. There are limited uses of antimicrobial pesticides that may have a 

potential to affect the environment through dissipation after use (as contrasted with disposal), or 

where the actual use of the pesticide may result in the potential for environmental contamination. 

The Panel below offers a proposal which clearly identifies those few uses. 

Response: see response 140.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27028 

Comment Code: 140000 

Comment: [The following are some of the problems identified in the proposed rule:] 

11) The substance(s) to test for each requirement is not always clear. If a transformation product 

(e.g., metabolite or degradate) is identified, but is quickly degraded, the EPA should clarify whether 

it should be isolated for testing. In its discussion of the SAP review, the Agency agrees with SAP 

and states that it proposes to clarify the need for testing metabolites when the available data suggest 

they are more toxic. No such clarity is apparent in this proposed rule. 

Response: see response 140.5 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 
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Comments and Response References: 

Environmental Fate Section (140) Page 855 

Letter ID: 0088 

Comment ID: 27053 

Comment Code: 140000 

Comment: 31. Proposed Regulation # [Section] 158.2280(a)(2) 

Text of the Proposed Regulation (emphasis added) Environmental fate: General. "If the Agency 

believes that the transformation products of the parent compound are more toxic, persistent, or 

bioaccumulative than the parent compound, or have been shown to cause adverse effects in 

mammalian or aquatic reproductive studies, then data on those transformation products are also 

required to support registration." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether the "transformation products of the parent compound 

are more toxic, persistent, or bioaccumulative than the parent compound, or have been shown to 

cause adverse effects in mammalian or aquatic reproductive studies." 

32. Proposed Regulation # [Section] 158.2280(a)(3) 

Text of the Proposed Regulation (emphasis added) Environmental fate: General. "For wood 

preservatives, the Agency may require data on both the parent compound that is incorporated into 

the wood, and on transformation/degradation products that occur in wood post-treatment or occur 

as dislodgeable residues (such as hand contact with treated wood) or leachate residues (such as from 

soil or water contact with treated wood). 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether the Agency will require data or not. 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27061 

Comment Code: 140000 

Comment: As proposed, the environmental fate data requirements for antimicrobial pesticides are 

not sufficiently clear to enable a registrant to determine the kinds of data and information EPA 

requires to make a regulatory decision and thus are inconsistent with the stated purpose of a data 

requirement regulation (40 CFR 158.1(a)). (See Panel’s General Comments at Section I.) The 

proposed requirements also do not recognize the very major differences between the uses of 

antimicrobial pesticides and other pesticides with regard to environmental exposure potential. 

Response: see responses 3 and 140.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
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Comments and Response References: 

Environmental Fate Section (140) Page 856 

Letter ID: 0064 

Comment ID: 27496 

Comment Code: 140000 

Comment: APPENDIX H 

COMMENTS ON PROPOSED DATA REQUIREMENTS FOR ENVIRONMENTAL FATE 

 I.Introduction.............................................................1 

II. Comments on Proposed Rule (pages 59406-12; section 158.2280), Data Requirements for 

Environmental Fate...................................2 

A. Environmental Data Are Not Required for Indoor Uses for Other 

Pesticides...........................................2 

B. Pesticide Disposal Is Not Regulated Under FIFRA.........................3 

C. Testing Guidelines Are Not Available to Provide Guidance................3 

D. Identification of Areas of Specific Concern.............................3 

III. Alternative Approach for Environmental Fate Data Requirements.........8 

A. Environmental Exposure Estimates Drive Data Needs by Tiered Testing.....8 

B. Specific Alternative Proposal for Environmental Fate Data Requirements..9 

IV. Comments on the Use of the "Down the Drain" Screening Assessment and on the "Case Study" 

White Paper..................13 

A. DtD Modeling is Site Specific..........................................14 

B. Is the Substance Suitable for DtD Modeling?............................15 

C. Uncertainty in Application of DtD Model Results........................15 

D. Summary Comments on the Use of DtD Modeling............................16 

 I. Introduction 

Data requirements for environmental fate are necessary to assess the risks of potential 

environmental exposure and the related potential to cause adverse effects on humans or nontarget 

organisms in the environment. The majority of antimicrobial pesticide uses is indoor and/or 

environmentally contained, and presents little potential for environmental exposure. As a result, it is 

important to clearly identify when potential environmental exposures may be relevant in order to 

avoid unnecessary testing. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 857 

First, any proposed requirement for environmental fate data for antimicrobial pesticides must clearly 

identify what antimicrobial pesticides are and which uses of those pesticides pose sufficient potential 

for environmental exposure that assessment under FIFRA is needed. In both cases, the proposed 

rule is lacking. Next, in proposing these data requirements for antimicrobial pesticides, the Agency 

must take into consideration the requirements of FIFRA Section 3(h)(3)(A)(ii), which mandates that 

EPA "differentiate the types of review undertaken for antimicrobial pesticides, . . . conform[ing] the 

degree and type of review to the risks and benefits presented, . . . [and] considering the use patterns 

of the product, toxicity, expected exposure and product type." 

Response: see responses 1 and 140.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27500 

Comment Code: 140000 

Comment: The proposed rule arbitrarily assigns product types to ‘high’ or ‘low’ exposure groups. 

However, the Agency has not explained those assignments, and has not defined what is meant by 

these terms or how those terms relate to risk assessments for antimicrobial pesticides. As discussed 

elsewhere in these comments, the Agency must eliminate the use of these arbitrary categorizations 

(Refer to Panel’s General Comments at Sections I and III). Those groupings are unrelated to any 

clear need for environmental risk assessment. 

II. Comments on Proposed Rule (pages 59406-12; section 158.2280), Data Requirements for 

Environmental Fate 

LANXESS provides the following comments on the rule as proposed. In a subsequent section, 

LANXESS offers an alternative proposal that it believes is consistent with the statutory 

requirements and the intent for identification of potential environmental fate data requirements for 

antimicrobial pesticides. As explained in further detail below, the proposed rule should reflect 

accurately how these requirements apply to the uses and how they are relevant to antimicrobial 

pesticides rather than to conventional chemicals. 

Response: see responses 140.3 and 140.35 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27502 

Comment Code: 140000 

Comment: A. Environmental Data Are Not Required for Indoor Uses for Other Pesticides 

Given that neither 158.1300 nor 158.2060 require environmental fate data for indoor use 

conventional nor biochemical pesticides, it is unclear why the Agency asserts that extensive data are 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 858 

required for indoor uses of antimicrobials. The proposed rule is inconsistent with the requirements 

for other types of pesticides, without any clear explanation or justification. While LANXESS agrees 

that the Agency may wish to consider different types of assessments for antimicrobials than for 

other types of pesticides, LANXESS strongly believes that the Agency can do so only when a need 

has been publicly discussed and well justified and the appropriate methodology for the assessment 

developed through a transparent process with scientific peer review. 

Response: see response 140.1 and 1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27506 

Comment Code: 140000 

Comment: The requirements for environmental fate data within the proposed regulation must be 

limited to those use patterns that potentially could result in environmental exposure relevant to 

assessment under FIFRA. There are limited uses of antimicrobial pesticides that may have a 

potential to affect the environment through dissipation after use (as contrasted with disposal), or 

where the actual use of the pesticide may result in the potential for environmental contamination. 

LANXESS below offers a proposal which clearly identifies those few uses. 

Response: see response 140.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27538 

Comment Code: 140000 

Comment: 11) The substance(s) to test for each requirement is not always clear. If a transformation 

product (e.g., metabolite or degradate) is identified, but is quickly degraded, the EPA should clarify 

whether it should be isolated for testing. In its discussion of the SAP review, the Agency agrees with 

SAP and states that it proposes to clarify the need for testing metabolites when the available data 

suggest they are more toxic. No such clarity is apparent in this proposed rule. 

Response: see response 140.5 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27555 

Comment Code: 140000 

Comment: As proposed, the environmental fate data requirements for antimicrobial pesticides are 

not sufficiently clear to enable a registrant to determine the kinds of data and information EPA 

requires to make a regulatory decision and thus are inconsistent with the stated purpose of a data 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 859 

requirement regulation (40 CFR 158.1(a)). (See Panel’s General Comments at Section I.) The 

proposed requirements also do not recognize the very major differences between the uses of 

antimicrobial pesticides and other pesticides with regard to environmental exposure potential. 

Response: see responses 1, 3, and 140.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27710 

Comment Code: 140000 

Comment: 31. Proposed Regulation # [Section] 158.2280(a)(2) 

Text of the Proposed Regulation (emphasis added) Environmental fate: General. "If the Agency 

believes that the transformation products of the parent compound are more toxic, persistent, or 

bioaccumulative than the parent compound, or have been shown to cause adverse effects in 

mammalian or aquatic reproductive studies, then data on those transformation products are also 

required to support registration." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether the "transformation products of the parent compound 

are more toxic, persistent, or bioaccumulative than the parent compound, or have been shown to 

cause adverse effects in mammalian or aquatic reproductive studies." 

32. Proposed Regulation # [Section] 158.2280(a)(3) 

Text of the Proposed Regulation (emphasis added) Environmental fate: General. "For wood 

preservatives, the Agency may require data on both the parent compound that is incorporated into 

the wood, and on transformation/degradation products that occur in wood post-treatment or occur 

as dislodgeable residues (such as hand contact with treated wood) or leachate residues (such as from 

soil or water contact with treated wood). 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether the Agency will require data or not. 

Response: see response 3 

Comment Code: 143000 Photodegradation in water study 

Commenter Name: Jamie S. Heisig-Mitchell 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 

Comment ID: 25449 

Comment Code: 143000 
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Comments and Response References: 

Environmental Fate Section (140) Page 860 

Comment: *One of the Tier I screenings considers photodegradation. If a compound is shown to 

readily degrade in sunlight, then higher tiered testing may not be required since it is believed that the 

chemical will not persist in the environment. While this may be appropriate for chemicals that have 

intermittent inputs, it would not be appropriate for those that have chronic inputs through treated 

wastewater effluent. Chronic inputs create a "pseudopersistence", necessitating higher tier testing for 

aquatic life effects. EPA must consider these chronic inputs when deciding if higher tier testing is 

required. 

Response: see response 140.12 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25989 

Comment Code: 143000 

Comment: * One of the Tier I screenings considers photodegradation. If a compound is shown to 

readily degrade in sunlight, then higher tiered testing may not be required since it is believed that the 

chemical will not persist in the environment. While this may be appropriate for chemicals that are 

intermittently discharged to surface waters, it would not be appropriate for treated wastewater 

effluent where the discharge is continuous. Continuous discharges can create "pseudopersistence", 

necessitating higher tier testing for aquatic life effects. EPA should consider these chronic inputs 

when deciding if higher tier testing is required. 

Response: see response 140.12 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26233 

Comment Code: 143000 

Comment: 12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below. 

a) Photodegradation in water. The Agency should explain why this endpoint is important for DtD 

substances that travel to water treatment plants (WWTPs) and do not pass through; whether for a 

substance that is "readily photodegradable" in water other E-Fate tests be waived; and what 

"shallow" and water turbidity mean if a study that is conducted to determine photodegradation 

occurs in shallow water. 

Response: see response 140.12 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27029 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 861 

Comment Code: 143000 

Comment: 12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below. 

a) Photodegradation in water. The Agency should explain why this endpoint is important for DtD 

substances that travel to waste water treatment plants (WWTPs) and do not pass through; whether 

for a substance that is "readily photodegradable" in water other E-Fate tests be waived; and what 

"shallow" and water turbidity mean if a study that is conducted to determine photodegradation 

occurs in shallow water. 

Response: see response 140.12 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27539 

Comment Code: 143000 

Comment: 12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below. 

a) Photodegradation in water. The Agency should explain why this endpoint is important for DtD 

substances that travel to waste water treatment plants (WWTPs) and do not pass through; whether 

for a substance that is "readily photodegradable" in water other E-Fate tests be waived; and what 

"shallow" and water turbidity mean if a study that is conducted to determine photodegradation 

occurs in shallow water. 

Response: see response 140.12 

Comment Code: 144000 Photodegradation in soil study 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26234 

Comment Code: 144000 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] b) Photodegradation in soil. The 

Agency should explain what additional information a photodegradation study offers if a substance 

hydrolyzes and its behavior is known from its soil profile. 

Response: see response 140.13 

Commenter Name: Hasmukh C. Shah 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 862 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27042 

Comment Code: 144000 

Comment: [Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] 

b) Photodegradation in soil. The Agency should explain what additional information a 

photodegradation study offers if a substance hydrolyzes and its behavior is known from its soil 

profile. 

Response: see response 140.13 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27540 

Comment Code: 144000 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] b) Photodegradation in soil. The 

Agency should explain what additional information a photodegradation study offers if a substance 

hydrolyzes and its behavior is known from its soil profile. 

Response: see response 140.13 

Comment Code: 145000 Activated sludge sorption isotherm study 

Commenter Name: Jamie S. Heisig-Mitchell 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 

Comment ID: 25445 

Comment Code: 145000 

Comment: *HRSD agrees with the new requirement to collect data on the aerobic respiration 

process of the microorganisms present in activated sludge. However, the potential for impacts on 

microbial activity in the wastewater treatment process is not limited to effects on aerobic respiration. 

Microorganisms play a critical role in nutrient removal, therefore, additional consideration must be 

given to effects on biological nutrient removal efficiencies. Nutrient removal is or will soon be 

required of many POTWs nationwide. The aerobic respiration test will not provide sufficient data to 

assess the potential for impact on these sensitive biological processes. Testing needs to be conducted 

on a compound's potential to affect the nitrification and phosphorus removal processes. Data on 

inhibition of these processes is necessary to protect treatment plant nutrient removal efficiencies. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 863 

Response: see response 140.14 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25983 

Comment Code: 145000 

Comment: * NACWA agrees with the new requirement to collect data on the aerobic respiration 

process of the microorganisms present in activated sludge. However, the potential for impacts on 

microbial activity in the wastewater treatment process is not limited to effects on aerobic respiration. 

Additional consideration must be given to effects of antimicrobial agents on biological nutrient 

removal efficiencies. Nutrient removal is or will soon be required of many POTWs that discharge to 

impaired water bodies. The aerobic respiration test is insufficient to evaluate the impact of 

antimicrobial agents on nutrient removal efficiency. Testing needs to be conducted on a compound’s 

potential to affect the nitrification and phosphorus removal processes, which will vary from plant to 

plant. Data on inhibition of these processes is necessary to protect treatment plant nutrient removal 

efficiencies. 

Response: see response 140.14 

Comment Code: 146000 Ready biodegradability study 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26222 

Comment Code: 146000 

Comment: 7) Certain required studies may not be suitable or practical for antimicrobial testing, 

including biodegradability testing with inorganic chemicals. Also, at the dosing level necessary to see 

CO2 evolution caused by the compound above background evolution, many biocides will be toxic 

to the microbial community. 

Response: see responses 140.15 and 140.34 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26248 

Comment Code: 146000 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] c) Ready biodegradability. Testing 

may not be suitable for certain antimicrobials, including inorganics. Also, at the dosing level 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 864 

necessary to see CO2 evolution caused by the compound above background evolution, many 

biocides will be toxic to the microbial community. 

Response: see responses 140.15 and 140.34 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27024 

Comment Code: 146000 

Comment: [The following are some of the problems identified in the proposed rule:] 

7) Certain required studies may not be suitable or practical for antimicrobial testing, including 

biodegradability testing with inorganic chemicals. Also, at the dosing level necessary to see CO2 

evolution caused by the compound above background evolution, many biocides will be toxic to the 

microbial community. 

Response: see responses 140.15 and 140.34 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27043 

Comment Code: 146000 

Comment: [Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] 

c) Ready biodegradability. Testing may not be suitable for certain antimicrobials, including 

inorganics. Also, at the dosing level necessary to see CO2 evolution caused by the compound above 

background evolution, many biocides will be toxic to the microbial community. 

Response: see responses 140.15 and 140.34 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27528 

Comment Code: 146000 

Comment: 7) Certain required studies may not be suitable or practical for antimicrobial testing, 

including biodegradability testing with inorganic chemicals. Also, at the dosing level necessary to see 

CO2 evolution caused by the compound above background evolution, many biocides will be toxic 

to the microbial community. 

Response: see responses 140.15 and 140.34 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 865 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27541 

Comment Code: 146000 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] c) Ready biodegradability. Testing 

may not be suitable for certain antimicrobials, including inorganics. Also, at the dosing level 

necessary to see CO2 evolution caused by the compound above background evolution, many 

biocides will be toxic to the microbial community. 

Response: see responses 140.15 and 140.34 

Comment Code: 147000 Porous pot test 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27044 

Comment Code: 147000 

Comment: [Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] 

d) Porous Pot Test. The Agency should clarify whether other factors may be considered (e.g. based 

on P/C properties, inorganics, sludge adsorption and removal), or studies that simulate WWTPs 

substitute for this test (e.g. bioreactor test, OECD 303). 

Response: see response 140.16 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27542 

Comment Code: 147000 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] d) Porous Pot Test. The Agency 

should clarify whether other factors may be considered (e.g. based on P/C properties, inorganics, 

sludge adsorption and removal), or studies that simulate WWTPs substitute for this test (e.g. 

bioreactor test, OECD 303). 

Response: see response 140.16 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 866 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 28976 

Comment Code: 147000 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] d) Porous Pot Test The Agency 

should clarify whether other factors may be considered (e.g. based on P/C properties, inorganics, 

sludge adsorption and removal), or studies that simulate WWTPs substitute for this test (e.g. 

bioreactor test, OECD 303). 

Response: see response 140.16 

Comment Code: 148000 Modified activated sludge, respiration inhibition test 

Commenter Name: Jamie S. Heisig-Mitchell 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 

Comment ID: 25446 

Comment Code: 148000 

Comment: *HRSD agrees with the new requirement to collect data on the aerobic respiration 

process of the microorganisms present in activated sludge. However, the potential for impacts on 

microbial activity in the wastewater treatment process is not limited to effects on aerobic respiration. 

Microorganisms play a critical role in nutrient removal, therefore, additional consideration must be 

given to effects on biological nutrient removal efficiencies. Nutrient removal is or will soon be 

required of many POTWs nationwide. The aerobic respiration test will not provide sufficient data to 

assess the potential for impact on these sensitive biological processes. Testing needs to be conducted 

on a compound's potential to affect the nitrification and phosphorus removal processes. Data on 

inhibition of these processes is necessary to protect treatment plant nutrient removal efficiencies. 

Response: see response 140.14 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25984 

Comment Code: 148000 

Comment: * NACWA agrees with the new requirement to collect data on the aerobic respiration 

process of the microorganisms present in activated sludge. However, the potential for impacts on 

microbial activity in the wastewater treatment process is not limited to effects on aerobic respiration. 

Additional consideration must be given to effects of antimicrobial agents on biological nutrient 

removal efficiencies. Nutrient removal is or will soon be required of many POTWs that discharge to 

impaired water bodies. The aerobic respiration test is insufficient to evaluate the impact of 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 867 

antimicrobial agents on nutrient removal efficiency. Testing needs to be conducted on a compound’s 

potential to affect the nitrification and phosphorus removal processes, which will vary from plant to 

plant. Data on inhibition of these processes is necessary to protect treatment plant nutrient removal 

efficiencies. 

Response: see response 140.14 

Comment Code: 149100 Aerobic soil metabolism study 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26249 

Comment Code: 149100 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] e) Aerobic soil metabolism. It is not 

clear what "intermittently dry" means for aquatic areas, and the Agency should define "chemicals 

that degrade quickly in soil." 

Response: see responses 140.17 and 140.30 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27045 

Comment Code: 149100 

Comment: [Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] 

e) Aerobic soil metabolism. It is not clear what "intermittently dry" means for aquatic areas, and the 

Agency also should define "chemicals that degrade quickly in soil." 

Response: see responses 140.17 and 140.30 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27549 

Comment Code: 149100 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] e) Aerobic soil metabolism. It is not 

clear what "intermittently dry" means for aquatic areas, and the Agency also should define 

"chemicals that degrade quickly in soil." 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 868 

Response: see responses 140.17 and 140.30 

Comment Code: 149110 Anaerobic soil metabolism study 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26250 

Comment Code: 149110 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] f) Anaerobic soil metabolism. For 

treated wood, the expression "in soils which may become flooded or waterlogged" is unclear. The 

EPA should clarify what is meant by "chemicals that degrade quickly in soil." 

Response: see responses 140.18 and 140.30 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27046 

Comment Code: 149110 

Comment: [Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] 

f) Anaerobic soil metabolism. For treated wood, the expression "in soils which may become flooded 

or waterlogged" is unclear. Again, EPA should clarify what is meant by "chemicals that degrade 

quickly in soil." 

Response: see responses 140.18 and 140.30 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27550 

Comment Code: 149110 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] f) Anaerobic soil metabolism. For 

treated wood, the expression "in soils which may become flooded or waterlogged" is unclear. Again, 

EPA should clarify what is meant by "chemicals that degrade quickly in soil." 

Response: see responses 140.18 and 140.30 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 869 

Comment Code: 149120 Aerobic and anaerobic aquatic metabolism 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25709 

Comment Code: 149120 

Comment: Aquatic fate requirements 

SFE and the SFPUC agree with EPA’s proposal to require aerobic and anaerobic aquatic 

metabolism studies and aquatic sediment studies for pesticides likely to appear in surface waters 

and/or aquatic sediments. These data can provide useful indications of the fate of pesticides in 

surface waters. 

Response: EPA acknowledges SF Environment's support for requiring aerobic and anaerobic 

aquatic metabolism studies and aquatic sediment for pesticides likely to appear in surface waters 

and/or sediments. 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26072 

Comment Code: 149120 

Comment: * Requirements for aerobic and anaerobic aquatic metabolism studies and aquatic 

sediment for pesticides likely to appear in surface waters and/or aquatic sediments. These data can 

provide useful indications of the fate of pesticides in surface waters. 

Response: EPA acknowledges CASQA's support for requiring aerobic and anaerobic aquatic 

metabolism studies and aquatic sediment for pesticides likely to appear in surface waters and/or 

sediments. 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26251 

Comment Code: 149120 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] g) Aerobic and anaerobic aquatic 

metabolism; It is not clear what WOE evaluation and test results trigger this data requirement, and 

what is an acceptable D1/2. The Agency statement that the dissipation pathway in aquatic 

environments are "almost always" different than in terrestrial is too ambiguous, and there are 

examples of antimicrobials where this is not the case. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 870 

Response: see responses 140.19 and 140.20 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27047 

Comment Code: 149120 

Comment: [Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] 

g) Aerobic and anaerobic aquatic metabolism. It is not clear what WOE evaluation and test results 

trigger this data requirement, and what is an acceptable D1/2. The Agency statement that the 

dissipation pathway in aquatic environments are "almost always" different than in terrestrial is too 

ambiguous, and there are examples of antimicrobials where this is not the case. 

Response: see responses 140.19 and 140.20 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27551 

Comment Code: 149120 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] g) Aerobic and anaerobic aquatic 

metabolism. It is not clear what WOE evaluation and test results trigger this data requirement, and 

what is an acceptable D1/2. The Agency statement that the dissipation pathway in aquatic 

environments are "almost always" different than in terrestrial is too ambiguous, and there are 

examples of antimicrobials where this is not the case. 

Response: see responses 140.19 and 140.20 

Comment Code: 149130 Aquatic sediment studies 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25699 

Comment Code: 149130 

Comment: Sediment toxicity testing 

SFE and the SFPUC support proposed requirements for acute and chronic sediment toxicity tests. 

These data are essential to the evaluation of the surface water impacts of pesticides that may 

partition into sediments in fresh water or salt water. We would prefer if the rule recognized that 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 871 

because of the generally anaerobic environment presented by sediments, many pesticides and inert 

ingredients in the sediments will only slowly degrade and may build up over time. Thus, exemption 

from whole sediment toxicity testing should only be considered if there is strong evidence that 

pesticides would not make their way into sediments or be toxic to sediment-dwelling organisms. 

Response: EPA acknowledges SFE and SFPUC's support for acute and chronic sediment toxicity 

tests. 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25798 

Comment Code: 149130 

Comment: Whole Sediment Toxicity Testing 

Tri-TAC supports the addition of whole sediment acute and chronic toxicity testing for freshwater 

and marine/estuarine invertebrates. Tri-TAC supports the conditional requirement based on 

antimicrobial presence in the water column, potential to sorb to sediment, and the persistence of the 

antimicrobial. 

Response: EPA acknowledges the Tri-TAC's support for conditionally requiring whole sediment 

acute and chronic toxicity testing for freshwater and marine/estuarine invertebrates 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25894 

Comment Code: 149130 

Comment: Whole Sediment Toxicity Testing 

CASA supports the addition of whole sediment acute and chronic toxicity testing for freshwater and 

marine/estuarine invertebrates. CASA supports the conditional requirement based on antimicrobial 

presence in the water column, potential to sorb to sediment, and the persistence of the 

antimicrobial. 

Response: EPA acknowledges CASA's support for conditionally requiring whole sediment acute 

and chronic toxicity testing for freshwater and marine/estuarine invertebrates. 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26076 

Comment Code: 149130 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 872 

Comment: * Conditional requirement for acute and chronic sediment toxicity testing. These data 

are essential to the evaluation of the surface water impacts of pesticides that may partition into 

sediments in fresh water or salt water. 

Response: EPA acknowledges CASQA's support for acute and chronic sediment toxicity tests. 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26119 

Comment Code: 149130 

Comment: Whole Sediment Toxicity Testing 

The Districts support the addition of whole sediment acute and chronic toxicity testing for 

freshwater and marine/estuarine invertebrates. The Districts support the conditional requirement 

based on antimicrobial presence in the water column, potential to sorb to sediment, and the 

persistence of the antimicrobial. 

Response: EPA acknowledges the District's support for conditionally requiring whole sediment 

acute and chronic toxicity testing for freshwater and marine/estuarine invertebrates 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27058 

Comment Code: 149130 

Comment: [Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] 

h) Aquatic sediment studies. Again, it is unclear what results will likely trigger this requirement. 

Aquatic field dissipation study is discussed in this section, likely a throw-back from Conventional 

Pesticides since "a terrestrial applied pesticide that has high potential to enter aquatic waterways" for 

antimicrobial use pattern is likely very limited, and it is not clear what is intended. The Agency 

should explain how DtD modeling affects the need for this test. 

Response: see response 140.21 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27552 

Comment Code: 149130 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] h) Aquatic sediment studies; Again, it 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 873 

is unclear what results will likely trigger this requirement. Aquatic field dissipation study is discussed 

in this section, likely a throw-back from Conventional Pesticides since "a terrestrial applied pesticide 

that has high potential to enter aquatic waterways" for antimicrobial use pattern is likely very limited, 

and it is not clear what is intended. The Agency should explain how DtD modeling affects the need 

for this test. 

Response: see response 140.21 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 28977 

Comment Code: 149130 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] h) Aquatic sediment studies; Again, it 

is unclear what results will likely trigger this requirement. Aquatic field dissipation study is discussed 

in this section, likely cited from Conventional Pesticides since "a terrestrial applied pesticide that has 

high potential to enter aquatic waterways" for antimicrobial use pattern is likely very limited, and it is 

not clear what is intended. The Agency should explain how DtD modeling affects the need for this 

test. 

Response: see response 140.21 

Comment Code: 149140 Monitoring of representative U.S. waters 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25711 

Comment Code: 149140 

Comment: Surface water monitoring 

The conditional requirement for monitoring of representative U.S. waters should be required for all 

pesticides that are estimated by EPA to potentially appear at concentrations within a factor of 10 of 

aquatic life benchmarks, water quality criteria, or drinking water criteria after any mitigation imposed 

as part of registration. In our view, monitoring has been required much too infrequently. 

Response: see response 140.24 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26073 

Comment Code: 149140 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 874 

Comment: * Conditional requirement for monitoring of representative U.S. waters. Monitoring 

appropriate to use patterns should be required for all pesticides that are estimated by USEPA to 

potentially occur at environmentally relevant concentrations after any mitigation imposed as part of 

registration. In our view, monitoring has been required much too infrequently. 

Response: see response 140.24 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26203 

Comment Code: 149140 

Comment: Also there is a requirement for "monitoring of representative U.S. waters" that is 

conditionally required for all "high environmental exposure" antimicrobial uses. However, there is 

no guideline requirement for this, it has never been vetted by an EPA SAP, and there is no apparent 

plan to generate such guidance. 

Response: see responses 140.22 and 191.3 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26252 

Comment Code: 149140 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] i) Monitoring of representative U.S. 

waterways. Again, the Agency must provide criteria that trigger this requirement. Since 

antimicrobials are not broadcast into the environment, the criteria for toxicity and persistence must 

be substantially high for a biocide to trigger a requirement of this sort. The Agency also should 

define "likely to occur in non-target organisms." 

Response: see responses 140.22 and 140.31 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26336 

Comment Code: 149140 

Comment: Also, there is a requirement for "monitoring of representative U.S. waters" that is 

conditionally required for all "high environmental exposure" antimicrobial uses. However, there is 

no guideline requirement for this, it has never been reviewed by an EPA SAP, and there is no 

apparent plan to generate such guidance. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 875 

Response: see responses 140.22 and 191.3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26862 

Comment Code: 149140 

Comment: Also, there is a requirement for "monitoring of representative U.S. waters" that is 

conditionally required for all "high environmental exposure" antimicrobial uses. However, there is 

no guideline requirement for this, it has never been reviewed by an EPA SAP, and there is no 

apparent plan to generate such guidance. 

Response: see responses 140.22 and 191.3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27059 

Comment Code: 149140 

Comment: [Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] 

i) Monitoring of representative U.S. waterways. Again, the Agency must provide criteria that trigger 

this requirement. Since antimicrobials are not broadcast into the environment, the criteria for 

toxicity and persistence must be substantially high for a biocide to trigger a requirement of this sort. 

The Agency also should define "likely to occur in non- target organisms." 

Response: see responses 140.22 and 140.31 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27553 

Comment Code: 149140 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] i) Monitoring of representative U.S. 

waterways. Again, the Agency must provide criteria that trigger this requirement. Since 

antimicrobials are not broadcast into the environment, the criteria for toxicity and persistence must 

be substantially high for a biocide to trigger a requirement of this sort. The Agency also should 

define "likely to occur in non- target organisms." 

Response: see responses 140.22 and 140.31 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 876 

Comment Code: 149150 Special leaching studies 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26404 

Comment Code: 149150 

Comment: The situation with the proposed regulation of antifoulant coatings is similar. EPA has 

assumed high environmental exposure without any consideration of the behavior of the particular 

antifoulant active ingredient in the aquatic environment. The Proposal also requires use of a leach 

rate test methodology that specifically states it is not to be used for estimating environmental 

exposures.[FN#60:See Standard Test Method for Determination of Copper Released from 

Antifoulant Coatings in Substitute Ocean Water, ASTM Method Designation D6442-06 (ASTM, 

2006). (This method replaces the ASTM method currently designated in the proposed regulation, 

D5108-90, published in 1990.) At section 1.4., ASTM states The results of this test method do not 

reflect environmental copper release rates for antifoulant products and are not suitable for direct use 

in the process of generating environmental risk assessments, environmental loading estimates, or for 

estimating release rate limits for regulation purposes The method goes on to state at section 4.4 that 

Where the results of this test methods are used in the process of generating environmental risk 

assessments . . . it is most strongly recommended that the relationship between laboratory release 

rates and actual environmental inputs is taken into account to allow a more accurate approximation 

of the . . . release rates from antifoulant coatings under real- life conditions. This can be 

accomplished through the application of appropriate correction factors. The Panel recently has been 

informed that the Agency intends to use data results from this test method without a correction 

factor. Such use will result in unrealistic estimation of risk, even when a more realistic assessment 

could be easily done. This is an example of the problem with not only the data that are being 

required, but with how those data are used for risk assessment purposes. Both issues are 

fundamental to the antimicrobial pesticide regulatory program and have to be addressed 

transparently and in a scientifically sound manner.] EPA has not met the mandate of FIFRA 3(h) to 

conform the degree and type of review of these antimicrobial use types to their actual risks. 

Response: see response 140.25 and testnote 140.15 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27008 

Comment Code: 149150 

Comment: The situation with the proposed regulation of antifoulant coatings is similar. EPA has 

assumed high environmental exposure without any consideration of the behavior of the particular 

antifoulant active ingredient in the aquatic environment. The Proposal also requires use of a leach 

rate test methodology that specifically states it is not to be used for estimating environmental 

exposures.[FN60: See Standard Test Method for Determination of Copper Released from 

Antifoulant Coatings in Substitute Ocean Water, ASTM Method Designation D6442-06 (ASTM, 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 877 

2006). (This method replaces the ASTM method currently designated in the proposed regulation, 

D5108-90, published in 1990.) At section 1.4., ASTM states 

The results of this test method do not reflect environmental copper release rates for antifoulant 

products and are not suitable for direct use in the process of generating environmental risk 

assessments, environmental loading estimates, or for estimating release rate limits for regulation 

purposes 

The method goes on to state at section 4.4 that 

Where the results of this test methods are used in the process of generating environmental risk 

assessments . . . it is most strongly recommended that the relationship between laboratory release 

rates and actual environmental inputs is taken into account to allow a more accurate approximation 

of the . . . release rates from antifoulant coatings under real- life conditions. This can be 

accomplished through the application of appropriate correction factors. 

LANXESS recently has been informed that the Agency intends to use data results from this test 

method without a correction factor. Such use will result in unrealistic estimation of risk, even when a 

more realistic assessment could be easily done. This is an example of the problem with not only the 

data that are being required, but how those data are used for risk assessment purposes. Both issues 

are fundamental to the antimicrobial pesticide regulatory program and have to be addressed 

transparently and in a scientifically sound manner.] EPA has not met the mandate of FIFRA 3(h) to 

conform the degree and type of review of these antimicrobial use types to their actual risks. 

Response: see response 140.25 and testnote 140.15 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27056 

Comment Code: 149150 

Comment: 34. Proposed Regulation # [Section] 158.2280(f)(15) 

Text of the Proposed Regulation (emphasis added) Environmental fate: Test notes. "For wood 

preservatives, an aquatic leaching study is required. A soil leaching study is required if human or 

environmental exposures are likely to occur from leachates that contain the active ingredient or 

principal transformation products from wood treated with a preservative product. For those studies, 

the Agency accepts the following methods or their equivalents: America Wood Preservers’ 

Association (AWPA) Method E11-97 (aquatic leaching), and AWPA Method E20-04 (soil leaching). 

Prior approval of studies conducted according to E11-97 is not required. All other protocols must 

be approved by the Agency prior to the initiation of the study. Details for developing protocols are 

available from the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether the protocol will be approved. These required private 

negotiations are a procedure for the development of later tests. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 878 

Response: see responses 3 and 30.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27060 

Comment Code: 149150 

Comment: [Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] 

j) Special leaching studies. According to footnote 15, EPA is requiring any wood preservative to 

meet the special leaching study requirement, yet not all wood is in direct contact with water. The 

EPA should consider using the EWPA and EU criteria for wood preservatives that looks at five 

criteria. The first three criteria do not involve contact with water. The following are the EU criteria 

for wood preservatives, as an example of descriptions of use conditions that could be considered as 

separately developed guidance for understanding potential exposures. This type of explanation and 

guidance would be helpful and would need to be expanded to address uses of other unregulated 

articles treated with material preservatives. See the chart below. 

Class Service conditions Description Typical uses 

1 Interior, dry Situation in which wood or wood-based 

product is under cover, fully protected from 

the weather and not exposed to wetting. 

Framing, roof 

timbers 

2 Interior, damp Situation in which wood or wood-based 

product is under cover, fully protected from 

the weather but where high environmental 

humidity can lead to occasional but not 

persistent wetting. 

Framing, roof 

timbers 

3 A Protected exterior Situation in which wood or wood product is 

not covered and not in contact with the 

ground. It is either continually exposed to the 

weather or is protected from the weather but 

subject to frequent wetting. 

Exterior joinery 

3 B Unprotected 

exterior 

Deck boards 

4 A In-ground Situation in which wood or wood product is 

permanently in contact with the ground or 

fresh water and thus is permanently exposed 

to wetting. 

Fence posts 

4 B In-ground, severe, 

fresh water 

Cooling tower 

5 Marine Situation in which wood or wood-based 

product is permanently exposed to salt water. 

Piles 

EPA references transformation products on degradation in the leachate. The Agency should 

consider how the requirements would apply if the transformation products are immediately 

degraded. No criteria are identified for the amount leached from the wood or the amount of 

leachate considered harmful to the environment. Also, the Agency should consider the same for 

preservatives that are used for millwork or joinery. Here there is no direct contact with water or an 

aqueous environment, yet as written, the proposed rule would require this study. 
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Comments and Response References: 

Environmental Fate Section (140) Page 879 

Lastly, EPA for wood preservatives references AWPA method E11-97 or E20-04 and for 

antifoulants ASTM Method D5108-90 "or their equivalents" as preferred methods. However, these 

methods are of limited or no relevance to estimating environmental exposures resulting from inservice articles treated with material preservative products or antifoulants, respectively. These 

methods are known to significantly overestimate leach rates and are not intended for use in risk 

assessments. EPA needs to explain how it would use these data in a manner that would be 

consistent with sound regulatory decision-making. Otherwise, alternate methods must be identified 

that are appropriate for use in regulatory decision- making. 

Response: see responses 140.25 and 140.29, and testnotes 140.15 and 140.16 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27064 

Comment Code: 149150 

Comment: 35. Proposed Regulation # [Section] 158.2280(f)(16) 

Text of the Proposed Regulation (emphasis added) Environmental fate: Test notes. "For antifoulant 

paints and coatings, a leaching study is required. The Agency accepts the following method or its 

equivalent: American Society for Testing and Materials (ASTM) Method D5108-90. Prior approval 

of studies conducted according to D5108-90 is not required. All other protocols must be approved 

by the Agency prior to the initiation of the study. Details for developing protocols are available from 

the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether the protocol will be approved. These required private 

negotiations are a procedure for the development of later tests. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27554 

Comment Code: 149150 

Comment: [12) Comments where certain required studies may not be suitable or practical for 

antimicrobial testing for specific data requirements are below.] j) Special leaching studies. According 

to footnote 15, EPA is requiring any wood preservative to meet the special leaching study 

requirement, yet not all wood is in direct contact with water. The EPA should consider using the 

EWPA and EU criteria for wood preservatives that looks at five criteria. The first three criteria do 

not involve contact with water. The following are the EU criteria for wood preservatives, as an 

example of descriptions of use conditions that could be considered as separately developed guidance 

for understanding potential exposures. This type of explanation and guidance would be helpful and 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 880 

would need to be expanded to address uses of other unregulated articles treated with material 

preservatives. See the chart below. 

[See table on page 7 of appendix H, PDF docket ID EPA-HQ-OPP-2008-0110-0064] 

EPA references transformation products on degradation in the leachate. The Agency should 

consider how the requirements would apply if the transformation products are immediately 

degraded. No criteria are identified for the amount leached from the wood or the amount of 

leachate considered harmful to the environment. Also, the Agency should consider the same for 

preservatives that are used for millwork or joinery. Here there is no direct contact with water or an 

aqueous environment, yet as written, the proposed rule would require this study., 

Lastly, EPA for wood preservatives references AWPA method E11-97 or E20-04 and for 

antifoulants ASTM Method D5108-90 "or their equivalents" as preferred methods. However, these 

methods are of limited or no relevance to estimating environmental exposures resulting from inservice articles treated with material preservative products or antifoulants, respectively. These 

methods are known to significantly overestimate leach rates and are not intended for use in risk 

assessments. EPA needs to explain how it would use these data in a manner that would be 

consistent with sound regulatory decision-making. Otherwise, alternate methods must be identified 

that are appropriate for use in regulatory decision- making. 

Response: see response 140.25, 140.29, and testnotes 140.15 and 140.16 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27714 

Comment Code: 149150 

Comment: 34. Proposed Regulation # [Section] 158.2280(f)(15) 

Text of the Proposed Regulation (emphasis added) Environmental fate: Test notes. "For wood 

preservatives, an aquatic leaching study is required. A soil leaching study is required if human or 

environmental exposures are likely to occur from leachates that contain the active ingredient or 

principal transformation products from wood treated with a preservative product. For those studies, 

the Agency accepts the following methods or their equivalents: America Wood Preservers’ 

Association (AWPA) Method E11-97 (aquatic leaching), and AWPA Method E20-04 (soil leaching). 

Prior approval of studies conducted according to E11-97 is not required. All other protocols must 

be approved by the Agency prior to the initiation of the study. Details for developing protocols are 

available from the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether the protocol will be approved. These required private 

negotiations are a procedure for the development of later tests. 

35. Proposed Regulation # [Section] 158.2280(f)(16) 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 881 

Text of the Proposed Regulation (emphasis added) Environmental fate: Test notes. "For antifoulant 

paints and coatings, a leaching study is required. The Agency accepts the following method or its 

equivalent: American Society for Testing and Materials (ASTM) Method D5108-90. Prior approval 

of studies conducted according to D5108-90 is not required. All other protocols must be approved 

by the Agency prior to the initiation of the study. Details for developing protocols are available from 

the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether the protocol will be approved. These required private 

negotiations are a procedure for the development of later tests. 

Response: see response 3 

Comment Code: 149160 Tiered approach to environmental fate studies 

Commenter Name: Abigail Trueblood 

Commenter Organization: Dow Chemical Company 

Letter ID: 0082 

Comment ID: 25480 

Comment Code: 149160 

Comment: With respect to the Environmental Fate data requirements, a recurring theme in this 

Proposal is a lack of details on the triggers and weight of evidence criteria which would result in 

higher tiered testing. The process appears to be a "black box" into which there is initial input, 

including results of lower tier testing, which is then evaluated by the Agency with a potential output 

of higher tier data requirements. The difficulty is that the criteria for the testing endpoints which 

would trigger additional testing have not been communicated. The Agency needs to include in this 

Proposal specific criteria for these testing endpoints. Without that information available, it is unclear 

how a registrant would be able to review or challenge Agency findings. In addition, there is no clear 

indication of how the Agency will process the results/endpoints from the higher tiered testing. 

Response: see response 140.26 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25604 

Comment Code: 149160 

Comment: Detailed Considerations: 

 

Section Number IV. 

Title E. The Nature of Changes to Requirements F. Tiered Data Requirements 
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Comments and Response References: 

Environmental Fate Section (140) Page 882 

Paragraph 5 & 6; p. 59387 4; p. 59388 

Excerpt from Federal Register Most screening-level environmental fate assessments would be 

performed.........to the end of paragraph 6. The need for higher tiered data depends on the frequency, 

duration, or magnitude of the exposure, but also on the results of the first tier of the data 

HC Comment The PMRA agrees that data requirements depend on use patterns, but does not 

formally require data on a tiered basis. The PMRA believes that, prior to the submission of an 

application for the registration of a pesticidal product, an applicant should be completely aware of 

the behaviour of their pesticidal product in the environment. It is, therefore, expected that all 

appropriate studies are submitted to the PMRA for review together with the application to register 

the product. If an applicant has reason to believe that a study is not required, they may submit a 

science based rationale for a data waiver. In addition, PMRA requires data on major transformation 

products, i.e., transformation products greater than 10% of the initial concentration of the pesticide 

at any time during a study. Transformation products that have not attained 10% (e.g., 8 - 9%), but 

show a continuous increase in concentration up until the termination of the study is considered to 

be major. Further, a transformation product that is toxic would be considered major. Failing to 

submit the appropriate data or acceptable waiver request could result in an incomplete assessment 

and the inability to complete the risk assessment, which could in turn result in a delay or an inability 

to provide a registration decision for the proposed product. 

Response: EPA agrees with PMRA that all appropriate studies should be submitted for review as 

part of the application to register the product. 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25761 

Comment Code: 149160 

Comment: Section 158,2280 - Environmental Fate Ecolab agrees with the ACC Biocides Panel in 

its proposed elimination of the low exposure use pattern. As stated previously, this is arbitrary and 

meaningless. 

Response: see response 140.3 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25762 

Comment Code: 149160 

Comment: Indoor conventional pesticides are conditionally required to submit only hydrolysis data 

and are not required to conduct any other environmental fate data. Without any explanation or 

rational, five environmental fate studies are required for all "low" exposure antimicrobials. In 

addition, higher tier testing is required for all antimicrobials without regard as to whether they are 
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Comments and Response References: 

Environmental Fate Section (140) Page 883 

indoor or outdoor or have no potential for environmental exposure. Section 158.220 also 

conditionally requires monitoring of representative US waters for all "high" exposure antimicrobials 

uses. Again the Agency is imposing a data requirement in the absence a guideline which has not 

been reviewed by the SAP. 

As described previously, Ecolab proposes a tiered testing approach that is triggered for each use 

pattern through a deterministic or risk quotient methodology. Ecolab reminds the Agency that it 

currently uses RQ approaches for assessing pesticide risks to terrestrial and aquatic animals and 

plants. Such an approach provides an objective guidance for each additional data requirement, saves 

applicant and Agency resources, and provides a more scientifically based foundation for evaluating 

hazard, exposure and risk for each use pattern. 

Response: see responses 140.1, 140.27, and 140.22 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25958 

Comment Code: 149160 

Comment: While the Agency has indicated its desire to include four additional biodegradation 

screening studies under environmental fate, it is still unclear why these studies are necessary 

especially for low exposure products. If these studies are being requested to meet concerns over the 

Down the Drain (DTD) issue, we note that the basis for this regulatory thrust is the California UP3 

project. This project was focused on the use of Pest Control Operator (PCO) applied pesticides for 

insecticidal use in and around the home. Aside from one Clorox product reference, no 

measurements were made or reported for biocides in California urban runoff. DTD issues also do 

not address the fact that other regulatory statutes (NPDES, Sewage permitting) will pertain to 

biocides in wastewater streams. Nonetheless, the need for data requirements over and beyond those 

already required for conventional chemicals requires additional review and re- proposal. 

Response: see responses 1, 2, and 140.1 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25962 

Comment Code: 149160 

Comment: Secondly, as indicated, a tiered approach provides a methodical means to address the 

need for exposure information as in environmental fate. For example, simple leaching tests from 

treated wood (e.g. composite wood) could be used to determine initial residues of concern. If 

residues were substantial additional environmental fate testing would be triggered. Similarly, if 

neurotoxicity or immunotoxicity- enhanced subchronic oral feeding studies resulted in concerns, 

additional higher tiered testing would be required. 

Response: see response 140.10 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 884 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26214 

Comment Code: 149160 

Comment: 2) A tiered approach for environmental fate testing is supported. First tier testing should 

be conducted if the Use Pattern and appropriate modeling or leaching studies indicate 

environmental exposures of concern, unless the testing is not appropriate for the substance. If 

estimates of environmental exposures are of concern, higher tier testing may be required to 

complete an acceptable environmental risk assessment. However, test results that trigger additional 

testing and weight-of-evidence considerations are not clear or not specified in the Agency’s 

proposed rule. 

3) The EPA must provide more details on the triggers and weight-of-evidence criteria that will result 

in higher tiered testing. EPA should provide more specific criteria for testing endpoints that can 

trigger additional testing. Moreover, the industry should have the opportunity to review and 

comment on the EPA’s assessment. Lastly, EPA should explain how it will process the results and 

endpoints from the higher tiered testing. 

Response: see response 140.26 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26303 

Comment Code: 149160 

Comment: For example, for environmental fate data requirements, "low" environmental exposure 

includes indoor residential or institutional, and indoor industrial product uses; while "high" 

environmental exposure categories include industrial process water (once- through), antifoulants, 

wood preservatives, and aquatic areas product uses. 73 Fed. Reg. at 59442-43. 

The Agency fails to provide any explanation for its decision to include certain uses in one or another 

category, justify the basis for the two broad exposure categories or to explain how the 

characterizations as "high" or "low" justify different data requirements. Exposure levels cannot 

simply be assumed based on product types, yet it appears that is what EPA has done. 

The fact that two products are used in a similar manner does not mean the types or magnitudes of 

exposures are similar. One product could be highly volatile and result in an inhalation exposure, 

whereas another product with a similar use involves no inhalation risk. 

Response: see response 140.3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 885 

Letter ID: 0064 

Comment ID: 26818 

Comment Code: 149160 

Comment: In the Proposal for antimicrobials, however, the Agency has eliminated any potential for 

effective tiering of data requirements by the unsubstantiated assignment of exposure categories and 

by the conditions under which data requirements must be addressed. In the Proposal, the Agency 

claims that it proposes to "tier" the data requirements by assigning certain categories of 

antimicrobial products to "high" or "low" exposure categories. For example, for environmental fate 

data requirements, "low" environmental exposure includes indoor residential or institutional, indoor 

industrial product uses; while "high" environmental exposure categories include industrial process 

water (once- through), antifoulants, wood preservatives, and aquatic areas product uses. 73 Fed. Reg. 

at 59442-43. 

The Agency fails to provide any explanation for its decision to include certain uses in one or another 

category, justify the basis for the two broad exposure categories or to explain how the 

characterizations as "high" or "low" justify different data requirements. Exposure levels cannot 

simply be assumed based on product types, yet it appears that is what EPA has done. 

The fact that two products are used in a similar manner does not mean the types or magnitudes of 

exposures are similar. One product could be highly volatile and result in an inhalation exposure, 

whereas another product with a similar use involves no inhalation risk. Exposure assumptions must 

be scientifically justified based on the use of the specific product. Any such assumptions used to 

support a regulation or proposal should be disclosed and explained, and subject to independent 

scientific review. At a minimum, comments and input should be solicited on the assumptions in the 

Proposal. The Proposal falls short because none of these steps has been taken with respect to 

exposure categorization. LANXESS believes that the two categories are inadequately supported 

based on the current record. LANXESS’s position is bolstered by the Proposal itself, which includes 

many data requirements for the determination of exposures, acknowledging that specific product use 

data are required in order to understand the potential level of exposure involved with that specific 

product use. 

Response: see response 140.3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27006 

Comment Code: 149160 

Comment: [The following are some of the problems identified in the proposed rule:] 

2) A tiered approach for environmental fate testing is supported. First tier testing should be 

conducted if the Use Pattern and appropriate modeling or leaching studies indicate environmental 

exposures of concern, unless the testing is not appropriate for the substance. If estimates of 

environmental exposures are of concern, higher tier testing may be required to complete an 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 886 

acceptable environmental risk assessment. However, test results that trigger additional testing and 

weight-of-evidence considerations are not clear or not specified in the Agency’s proposed rule. 

3) The EPA must provide more details on the triggers and weight-of-evidence criteria that will result 

in higher tiered testing, including more specific criteria for testing endpoints that can trigger 

additional testing. Moreover, the industry should have the opportunity to review and comment on 

the EPA’s assessment. Lastly, EPA should explain how it will process the results and endpoints 

from the higher tiered testing. 

Response: see response 140.26 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27515 

Comment Code: 149160 

Comment: 2) A tiered approach for environmental fate testing is supported. First tier testing should 

be conducted if the Use Pattern and appropriate modeling or leaching studies indicate 

environmental exposures of concern, unless the testing is not appropriate for the substance. If 

estimates of environmental exposures are of concern, higher tier testing may be required to 

complete an acceptable environmental risk assessment. However, test results that trigger additional 

testing and weight-of-evidence considerations are not clear or not specified in the Agency’s 

proposed rule. 

3) The EPA must provide more details on the triggers and weight-of-evidence criteria that will result 

in higher tiered testing, including more specific criteria for testing endpoints that can trigger 

additional testing. Moreover, the industry should have the opportunity to review and comment on 

the EPA’s assessment. Lastly, EPA should explain how it will process the results and endpoints 

from the higher tiered testing. 

Response: see response 140.26 

Comment Code: 149161 High exposure uses 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26065 

Comment Code: 149161 

Comment: Antifoulant coatings and paints, wood preservatives, and aquatic area applications 

We support classification of antifoulant coatings and paints, wood preservatives, and aquatic area 

applications as "high environmental exposure" use patterns. The environmental fate and non-target 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 887 

organism data requirements for these use patterns are generally appropriate and will ensure that 

USEPA continues to receive data necessary for its environmental risk assessments. 

USEPA requested comments on the environmental fate data requirements for wood preservative 

products. Since these products are commonly used outdoors in urban areas, it is essential that 

USEPA require all data necessary to estimate their transfer to urban runoff. The leaching test 

required for aquatic uses may be adequate for this purpose. 

Response: EPA acknowledges CASQA's support for classifying antifoulant coatings and paints, 

wood preservatives, and aquatic area application as high environmental exposure. 

Comment Code: 149170 Data and reporting requirements table for environmental fate (suggested 

additions, deletions, etc.) 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25666 

Comment Code: 149170 

Comment: Approach to data requirements for metabolites needs to be redesigned 

EPA has proposed an approach that inherently denies it the data necessary to evaluate pesticide 

metabolites. Data on metabolites would only be required if EPA makes a determination "that the 

transformation products of the parent compound are more toxic, persistent, bioaccumulative, or 

have been shown to cause adverse effects in mammalian or aquatic reproductive studies." If the 

registrant is not required to provide data characterizing these properties of metabolites, it will be 

impossible for EPA to make this determination. EPA should require minimum data sets for all 

metabolites with long half-lives. 

Response: see response 140.5 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26067 

Comment Code: 149170 

Comment: Detailed Comments on Proposed Aquatic Toxicity, Chemistry, and Environmental Fate 

Data Requirements 

We support the following proposed data requirements, most of which reflect current USEPA 

practice for new registrations. These requirements should be applied to pesticides in Registration 

Review as well as to new antimicrobial pesticide registrations. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 888 

* Requirement for minimum aquatic toxicity and environmental fate data sets for all antimicrobials. 

We support USEPA’s proposals to require a minimum set of aquatic toxicity and environmental fate 

data for all antimicrobials. The paucity of aquatic toxicity data for antimicrobials has interfered with 

government’s ability to ensure that their outdoor use does not adversely impact urban creeks, rivers, 

estuaries and near-shore ocean waters. 

Response: EPA acknowledges CASQA's support for minimum aquatic toxicity and environmental 

fate data sets for all antimicrobials 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26082 

Comment Code: 149170 

Comment: Minimum aquatic toxicity data sets should be required for all degradates with long 

environmental half-lives. The approach for antimicrobial degradates ("metabolites") that USEPA has 

proposed is not workable. Data on degradates are only proposed to be required if USEPA makes a 

determination "that the transformation products of the parent compound are more toxic, persistent, 

bioaccumulative, or have been shown to cause adverse effects in mammalian or aquatic reproductive 

studies." If the registrant is not required to provide data characterizing degradates to USEPA, how 

can USEPA make this determination? Instead, USEPA should require minimum environmental fate 

and aquatic toxicity data sets for all antimicrobials degradates with long half-lives. 

Response: see response 140.5 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26253 

Comment Code: 149170 

Comment: As proposed, the environmental fate data requirements for antimicrobial pesticides are 

not sufficiently clear to enable a registrant to determine the kinds of data and information EPA 

requires to make a regulatory decision and thus are inconsistent with the stated purpose of a data 

requirement regulation (40 CFR 158.1(a)). They also do not recognize the very major differences 

between the uses of antimicrobial pesticides and other pesticides with regard to environmental 

exposure potential. 

Response: see responses 1 and 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27055 

Comment Code: 149170 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 889 

Comment: 33. Proposed Regulation # [Section] 158.2280(f)(12) 

Text of the Proposed Regulation (emphasis added) Environmental fate: Test notes. "Protocols must 

be approved by the Agency prior to the initiation of the study. Details for developing protocols are 

available from the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether the protocol will be approved. These required private 

negotiations are a procedure for the development of later tests. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27712 

Comment Code: 149170 

Comment: 33. Proposed Regulation # [Section] 158.2280(f)(12) 

Text of the Proposed Regulation (emphasis added) Environmental fate: Test notes. "Protocols must 

be approved by the Agency prior to the initiation of the study. Details for developing protocols are 

available from the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the criteria used to determine whether the protocol will be approved. These required private 

negotiations are a procedure for the development of later tests. 

Response: see response 3 

Comment Code: 149180 Screening-level of fate assessments (three pronged-approach) 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25609 

Comment Code: 149180 

Comment: Section Number XII. 

Title C. Today’s Proposal for Low Environmental Exposure Antimicrobials 

Paragraph p. 59407 

Excerpt from Federal Register General comment 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 890 

HC Comment Although the PMRA does not have any previous experience with the Down-TheDrain and STPWIN models, the agency will evaluate these data if and when they are submitted for 

review for acceptability on a case-by-case basis. Similar to the proposed three prong approach, the 

PMRA will use this information, combined with the down-the-drain environmental fate data and the 

required data submitted for review for the particular USC to conduct the risk of the pesticide to the 

environment. However, unlike the three prong approach proposed by the EPA, the PMRA expects 

the applicant to submit all required data or acceptable science based waiver requests, whether they 

are lower or higher tiered studies, together with their application to register their product. Please 

refer to comments for Section IV, E and F, for details. 

Response: EPA acknowledges PMRA's support for the "three-pronged approach." 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25784 

Comment Code: 149180 

Comment: In addition, Tri-TAC agrees with U.S. EPA's proposed tiered analysis approach of 

conducting screening-level environmental fate assessments, which can then indicate the need for 

higher- tiered fate and ecotoxicity studies and higher- tiered environmental assessments. 

Response: EPA acknowledges Tri-TAC's support for the proposed tiered analysis approach for 

conducting screening-level environmental fate assessments. 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25879 

Comment Code: 149180 

Comment: In addition, CASA agrees with U.S. EPA's proposed tiered analysis approach of 

conducting screening-level environmental fate assessments, which can then indicate the need for 

higher-tiered fate and ecotoxicity studies and higher- tiered environmental assessments. 

Response: EPA acknowledges CASA's support for the proposed tiered analysis approach for 

conducting screening-level environmental fate assessments. 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26105 

Comment Code: 149180 

Comment: In addition, the Districts agree with U.S. EPA's proposed tiered analysis approach of 

conducting screening-level environmental fate assessments, which can then indicate the need for 

higher-tiered fate and ecotoxicity studies and higher- tiered environmental assessments. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 891 

Response: EPA acknowledges the Districts' support for the proposed tiered analysis approach for 

conducting screening-level environmental fate assessments. 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26230 

Comment Code: 149180 

Comment: 9) The Agency proposes a "three-pronged approach" for DtD environmental exposure 

modeling. The EPA should clarify (a) if the modeling approach is appropriate for all DtD uses, or 

alternatives acceptable; (b) if hydrolysis or photodegradation in water demonstrates rapid and 

complete conversion of the antimicrobial, what value do the other three biodegradability studies 

add; (c) whether there is a threshold or de minimus exposure estimate where the study results are 

not significant for risk assessment; and (d) if a degradate was readily biodegradable, whether that 

would satisfy the criteria of both environmental chemistry and aquatic toxicity. 

Response: see response 140.33 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27026 

Comment Code: 149180 

Comment: [The following are some of the problems identified in the proposed rule:] 

9) The Agency proposes a "three-pronged approach" for DtD environmental exposure modeling. 

The EPA should clarify (a) if the modeling approach is appropriate for all DtD uses, and if 

alternatives are acceptable; (b) if hydrolysis or photodegradation in water demonstrates rapid and 

complete conversion of the antimicrobial, what value do the other three biodegradability studies 

add; (c) whether there is a threshold or de minimus exposure estimate where the study results are 

not significant for risk assessment; and (d) if a degradate was readily biodegradable, whether that 

would satisfy the criteria of both environmental chemistry and aquatic toxicity. 

Response: see response 140.33 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27530 

Comment Code: 149180 

Comment: 9) The Agency proposes a "three-pronged approach" for DtD environmental exposure 

modeling. The EPA should clarify (a) if the modeling approach is appropriate for all DtD uses, and 

if alternatives are acceptable; (b) if hydrolysis or phodegradation in water demonstrates rapid and 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 892 

complete conversion of the antimicrobial, what value do the other three biodegradability studies 

add; (c) whether there is a threshold or de minimus exposure estimate where the study results are 

not significant for risk assessment; and (d) if a degradate was readily biodegradable, whether that 

would satisfy the criteria of both environmental chemistry and aquatic toxicity. 

Response: see response 140.33 

Comment Code: 149200 Commenter's Concept of Environmental Fate Data Requirements Table 

Revisions 

Comment Summary: As part of their comments, the commenter provided an alternate 

Antimicrobial Environmental Fate Data Requirements Table with testnotes. EPA’s response is for 

the entire alternate testing scheme and not the individual parts. 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26261 

Comment Code: 149200 

Comment: II. Alternative Proposal for Environmental Fate Data Requirements 

Assessment of environmental exposure for antimicrobial pesticides is relevant under very limited 

circumstances. Uses that occur indoors should not be subject to environmental exposure assessment 

any more than such an assessment would be relevant for conventional or biochemical pesticides. 

The imposition of these requirements on indoor antimicrobial uses is all the more troubling because, 

to the extent that environmental exposure occurs, such occurrences are regulated under other 

environmental statutes. As such, the potential need to address environmental fate data requirements 

is limited to only a few antimicrobial use patterns. Data are not required when disposal is not subject 

to FIFRA, including areas such as any product where disposal is regulated as a hazardous waste, 

where NPDES permits are required for disposal, where labeling prohibits disposal without 

appropriate permitting or prohibits disposal down sanitary sewers. As a result, Indoor applications 

should not be subject to these data requirements, 

The Biocide Panel’s proposal for environmental fate data requirements is based on proposed new 

Use Pattern categories that are relevant, clear and applicable to antimicrobial pesticides. P&G 

supports the Biocides Panel’s use pattern proposal. Please refer to the Panel’s proposed use patterns. 

This alternative proposal incorporates those new Use Pattern categories. Where a use is excluded 

from the definition of an antimicrobial pesticide or from the definition of a pesticide chemical, it 

should be excluded from this section. For uses which are pesticidal but not within the scope of the 

definition of antimicrobial pesticides, a reference should be made to the appropriate sections of the 

data requirements for conventional or biochemical pesticides. 

Estimating environmental exposure is an essential prelude to determination of environmental fate 

data requirements. By the use of appropriate modeling, environmental exposure can be estimated for 

products based on Use Pattern. For instance, environmental exposure models are available for 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 893 

estimating whether indoor institutional, residential, and commercial products would likely be present 

in WWTP effluent at levels of concern. There are many different models or other approaches to 

estimating exposures. Since none have as yet been fully vetted for antimicrobial pesticides, P&G 

supports the Panel recommendation that the Agency initiate the appropriate scientific review 

process to evaluate the potential utility and limitations of the various approaches and to do so in a 

way that allows for public participation and comment. 

A tiered testing approach is recommended to fulfill environmental fate data requirements for 

antimicrobials when needed for risk assessment. In determining an acceptable environmental risk 

assessment, other data may be considered to supplement or replace environmental fate data. Some 

examples of these are listed below. 

*Physical chemistry data and SAR/QSAR information are helpful for predicting environmental 

partitioning and estimating environmental fate endpoints. 

*Along with the predicted environmental concentration resulting from use of the product estimated 

by modeling, ecotoxicity data may be used to determine environmental no effect concentrations and 

an acceptable environmental risk assessment target. 

The Agency should select an appropriate exposure model, and supplement with measured data as 

needed to reduced uncertainty and avoid use of default assumptions. The selection and use of 

exposure models and risk assessment methods must be relevant, clearly defined, and developed in a 

manner that is both scientifically valid and open for public comment. Specifying exposure 

methodology is not appropriate within this regulation and all such references should be eliminated. 

The following is the Panel’s specific alternative proposal. As a member of the Panel, P&G welcomes 

an opportunity to discuss these alternatives. 

If antimicrobial use pattern categories are described in regulations apart from Section 158.100, 

specific reference to the identification and description must be incorporated into the following 

paragraph. 158.2280(a) should be completely rewritten as follows. (a) General . Sections 158.100 

through 158.130 describe how to use this table to determine the environmental fate data 

requirements for a particular pesticide product. Notes that apply to an individual test and include 

specific conditions, qualifications, or exceptions to the designated test are listed in paragraph (e) of 

this section. The existing paragraphs (b) and (c) should be replaced with the following: (b) Use 

Patterns. (1) The general use patterns for antimicrobial environmental fate data requirements are 

‘Indoor Institutional, Residential, and Commercial,’ Aquatic, and Material Preservatives, where these 

are identified as follows 1. Indoor institutional, residential and commercial includes the use of 

sanitizers, disinfectants, viricides and similar products for the following: on hard surfaces; on soft 

surfaces; in the air; as laundry disinfectants and sanitizers; as swimming pool disinfectants or 

algaecides (public or private, including pool, hot tubs, and spas); on medical equipment; use in any 

of the types of facilities that fall within these definitions. This use pattern is included only when the 

product is not a hazardous waste and when the label does not restrict against disposal or rinsing 

down a sanitary sewer for a use that could result in such an exposure. 2. Aquatic areas involve uses 

that result in the potential for direct exposure of natural bodies of water to antimicrobials, although 

the exposure likely is limited and is not a direct application to aquatic sites. These include 

oncethrough cooling systems (where no pretreatment of the treated discharge occurs), antifoulant 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 894 

coatings, and ballast water treatments. 3. Material Preservatives for Exempt Treated Articles include 

wood preservatives as well as any other type of preservative where the final article is used outdoors 

on a significant basis and there is reliable evidence that the article, under anticipated conditions of 

use, will release the antimicrobial preservative in sufficient quantities to produce environmental 

exposures of concern (c) Use of products as aquatic herbicides or agricultural fungicides are outside 

of the scope of these data requirements. Registrants of such uses should refer to Subpart N or to 

sec. 158.2060 of this Part. 

The table of data requirements at paragraph (e) should be replaced by the following. (The definition 

of ROC as residue of concern should be added to paragraph (d). 

[See Table on pages 16 and 17, PDF docket ID EPA-HQ-OPP-2008-0110-0081.pdf] 

(a) Test notes. The following test notes apply to the data requirements in the table in paragraph (d) 

of this section: 1 Data are required for Indoor Institutional, Residential, and Commercial uses in 

cases where significant environmental exposure is likely to occur as a result of use, based on 

modeling or other appropriate estimation methods. This use pattern is included only when the 

product is not a hazardous waste and when the label does not restrict against disposal or rinsing 

down a sanitary sewer for a use that could result in such an exposure. 

2 For testing antifoulant paints and coatings, testing is to be performed with both sterile buffered 

distilled water and sterile synthetic seawater at pHs 5, 7, and 9. 

3 Data are required 1) when the use pattern is aquatic; or 2) when the Indoor Institutional, 

Residential, and Commercial uses identify that exposure to waterways is likely to occur based on 

modeling or other appropriate estimation methods; or 3) when unregulated articles containing a 

material preservative are used in a terrestrial setting and leaching studies or modeling estimates 

suggest that residues are likely to result in exposure to waterways. Screening level risk assessment 

using physical chemical properties of the active ingredient and appropriate exposure modeling is 

advisable. 

4 Information is required when unregulated article containing a material preservative is used in a 

terrestrial setting and leaching studies or modeling estimates suggest that residues are likely to result 

in exposure to soil. Screening level risk assessment using physical chemical properties of the active 

ingredient and appropriate exposure modeling is advisable. 

5 Data are not required when the electronic absorption spectra, measured at pHs 5, 7, and 9, of the 

active ingredient and its hydrolytic products, if any, show no absorption or tailing between 290 and 

800 nm. 

 6 Data are not required for active ingredients that are not biodegradable (e.g., inorganic chemicals, 

chemical elements). The selection of the particular biodegradation study depends on the physical 

and chemical properties of the test substance, a pre-screen exposure estimate based on appropriate 

modeling and, if available, the results of the activated sludge isotherm and the modified activated 

sludge respiration inhibition studies. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 895 

7 Required if the pass criteria for the ready biodegradability study are not met. This means 70% or 

greater removal of dissolved organic carbon and 60% or greater of theoretical oxygen demand or 

theoretical carbon dioxide production. These pass values must be reached in a 10-day window 

within the 28-day period of the test. This may not be suitable for inorganic substances, volatile 

materials or other types of antimicrobials. Other studies or information on the active ingredient 

should be considered. 

8 Data are required if results from hydrolysis, photodegradation in water (or soil), biodegradation 

tests, or other reliable weight-of-evidence information indicates environmental exposure of concern 

for the active ingredient. 

9 Adsorption and desorption using a batch equilibrium method is preferred. In some cases, as when 

the antimicrobial pesticide degrades rapidly, soil column leaching with un-aged or aged columns may 

be more appropriate to fully characterize the potential mobility of the parent compound and major 

transformation products. 

10 The environmental media (soil, water, hydrosoil, sediment, and biota) to be utilized in these tests 

must be representative of potential use sites. 

11 For unregulated articles treated with a material preservative, the need to conduct soil or aquatic 

metabolism studies will depend upon where the article is to be used (i.e., anticipated exposure 

conditions) and whether leaching studies identify either a residue level of concern or residue 

composition of concern for which additional assessment may be needed. 

12 Environmental analytical chemistry methods used to generate data associated with this study 

must include results of a successful confirmatory method trial by an independent laboratory. 

13 Registrants should consult with the Agency on appropriate test protocol. 

14 Data are required if weight-of- evidence indicates the potential for aquatic exposure, and if the 

active ingredient or its transformation products are likely to have the potential for persistence, 

mobility, nontarget aquatic toxicity, or bioaccumulation; i.e., the half-life of the active ingredient in 

the sediment is estimated to be [<=] 10 days from modeling programs or the aerobic soil or aquatic 

metabolism studies, and if any of the following conditions exist: - The soil partition coefficient (Kd) 

is >= 50; - The log Kow is >= 3; -The Koc is >= 1000. Registrants should consult with the Agency 

on appropriate test protocol prior to conducting the study. 

15 Data are required if the weight-of-evidence indicates that the active ingredient or principal 

transformation products are likely to occur in nontarget freshwater, estuarine, or marine waters such 

that human or environmental exposures are likely to occur. The Agency takes into account other 

factors such as the toxicity of the chemical(s), available monitoring data and the vulnerability of the 

freshwater, estuarine, or marine water resources in the area where exposure could occur. 

16 For unregulated articles treated with a material preservative, an aquatic leaching study is required 

if aquatic environmental exposure is anticipated or determined from the use of the article. A soil 

leaching study is required if terrestrial environmental exposures are anticipated or are determined 

from the use of the article. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 896 

17 For antifoulant paints and coatings, a leaching study is required. 

Response: see response 140.35 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27063 

Comment Code: 149200 

Comment: III. Alternative Approach for Environmental Fate Data Requirements 

Assessment of environmental exposure for antimicrobial pesticides is relevant under very limited 

circumstances. Uses that occur indoors should not be subject to environmental exposure assessment 

any more than such an assessment would be relevant for conventional or biochemical pesticides. 

The imposition of these requirements on indoor antimicrobial uses is all the more troubling because, 

to the extent that environmental exposure occurs, such occurrences are regulated under other 

environmental statutes. As such, the potential need to address environmental fate data requirements 

is limited to only a few antimicrobial use patterns. Data are not required when disposal is not subject 

to FIFRA, including areas such as any product where disposal is regulated as a solid waste, as a 

hazardous waste, where NPDES permits are required for disposal, or where labeling prohibits 

disposal without appropriate permitting or prohibits disposal down sanitary sewers. As a result, 

indoor applications should not be subject to these data requirements. 

The Panel elsewhere has proposed new Use Pattern categories that are relevant, clear and applicable 

to antimicrobial pesticides (See Appendix B). This alternative proposal incorporates those new Use 

Pattern categories. Where a use is excluded from the definition of an antimicrobial pesticide or from 

the definition of a pesticide chemical, it should be excluded from this section. For uses that are 

pesticidal but not within the scope of the definition of antimicrobial pesticides, a reference should 

be made to the appropriate sections of the data requirements for conventional or biochemical 

pesticides. 

A. Environmental Exposure Estimates Drive Data Needs by Tiered Testing Estimating 

environmental exposure is an essential prelude to determination of environmental fate data 

requirements. By the use of appropriate modeling, environmental exposure can be estimated for 

products based on Use Pattern. For instance, environmental exposure models are available for 

estimating whether indoor institutional, residential, and commercial products would likely be present 

in WWTP effluent at levels of concern. Appropriately designed and validated leaching studies are 

useful to determine the rate and extent of residue released to the environment from antifoulant 

paints and coatings and from articles treated with material preservatives exposed to the environment 

(e.g., preservatives in treated wood or in other treated articles). If modeling or reliable leaching data 

indicate exposure to the environment at levels of concern, additional environmental testing is 

needed to confirm and/or refine the exposure estimates. There are many different models or other 

approaches to estimating exposures. Since none have as yet been fully vetted for antimicrobial 

pesticides, the Panel recommends that the Agency initiate the appropriate scientific review process 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 897 

to evaluate the potential utility and limitations of the various approaches and to do so in a way that 

allows for public participation and comment. 

A tiered testing approach is recommended to fulfill environmental fate data requirements for 

antimicrobials when needed for risk assessment. In determining an acceptable environmental risk 

assessment, other data may be considered to supplement or replace environmental fate data. The 

Panel has provided a list of some of these below. 

* Physical chemistry data and SAR/QSAR information are helpful for predicting environmental 

partitioning and estimating environmental fate endpoints. 

* Along with the predicted environmental concentration resulting from use of the product estimated 

by modeling, ecotoxicity data may be used to determine environmental no effect concentrations and 

an acceptable environmental risk assessment target. 

An appropriate exposure model, supplemented with measured data as needed to reduce uncertainty 

and avoid use of default assumptions, provides more realistic environmental exposure estimates to 

use in risk assessment. As discussed elsewhere (See Panel’s General Comments at Section I), the 

selection and use of exposure models and risk assessment methods must be relevant, clearly defined, 

and developed in a transparent manner that is both scientifically valid and open for public comment. 

Yet the Panel does not believe that specifying exposure methodology is appropriate within this 

regulation and recommends that all such references be eliminated. 

B. Specific Alternative Proposal for Environmental Fate Data Requirements 

The following is the Panel’s specific alternative proposal. The Panel welcomes an opportunity to 

discuss these alternatives. 

If antimicrobial use pattern categories are described in regulations apart from Section 158.100, 

specific reference to the identification and description must be incorporated into the following 

paragraph. 158.2280(a) should be completely rewritten as follows. 

(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the 

environmental fate data requirements for a particular pesticide product. Notes that apply to an 

individual test and include specific conditions, qualifications, or exceptions to the designated test are 

listed in paragraph (e) of this section. 

The existing paragraphs (b) and (c) should be replaced with the following: 

(b) Use Patterns. (1) The general use patterns for antimicrobial environmental fate data requirements 

are ‘Indoor Institutional, Residential, and Commercial,’ ‘Aquatic,’ and ‘Material Preservatives,’ where 

these are identified as follows 

1. Indoor Institutional, Residential and Commercial includes the use of sanitizers, disinfectants, 

virucides and similar products for the following: on hard surfaces; on soft surfaces; in the air; as 

laundry disinfectants and sanitizers; as swimming pool disinfectants or algaecides (public or private, 

including pool, hot tubs, and spas); on medical equipment; use in any of the types of facilities that 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 898 

fall within these definitions. This use pattern is included only when the product is not a hazardous 

waste and when the label does not restrict against disposal or rinsing down a sanitary sewer for a use 

that could result in such an exposure. 

2. Aquatic areas involve uses that result in the potential for direct exposure of natural bodies of 

water to antimicrobials, although the exposure likely is limited and is not a direct application to 

aquatic sites. These include once- through cooling systems (where no pretreatment of the treated 

discharge occurs), antifoulant coatings, and ballast water treatments. 

3. Material Preservatives for Exempt Treated Articles include wood preservatives as well as any 

other type of preservative where the final article is used outdoors on a significant basis and there is 

reliable evidence that the article, under anticipated conditions of use, will release the antimicrobial 

preservative in sufficient quantities to produce environmental exposures of concern 

(c) Use of products as aquatic herbicides or agricultural fungicides are outside of the scope of these 

data requirements. Registrants of such uses should refer to Subpart N or to sec. 158.2060 of this 

Part. 

The table of data requirements at paragraph (e) should be replaced by the following. The definition 

of ROC as residue of concern should be added to paragraph (d). 

Testing 

Guideline 

Number 

Data Requirement Antimicrobial Use Pattern Test Substance to 

Support 

Test Note 

Number 

Indoor 

Institutional, 

Residential, 

Commercial 

Aquatic Material 

Preservative 

for Treated 

Article 

MP EP 

Degradation Studies – Laboratory 

None Hydrolysis CR R R TGAI or 

PAIRA 

TGAI or 

PAIRA 

1,2 

None Photodegradation in 

water 

CR R CR TGAI or 

PAIRA 

TGAI or 

PAIRA 

1,2,3,5 

None Photodegradation in 

soil 

NR NR CR TGAI or 

PAIRA 

TGAI or 

PAIRA 

1,4,5 

Biodegradation Studies -Laboratory 

835.1110 Activated Sludge 

Sorption Isotherm 

CR NR NR TGAI or 

ROC 

TGAI or 

ROC 

1 

835.3110 Ready 

Biodegradability 

CR NR NR TGAI or 

ROC 

TGAI or 

ROC 

1,6 

Testing 

Guideline 

Number 

Data Requirement Antimicrobial Use Pattern Test Substance to 

Support 

Test Note 

Number 

Indoor 

Institutional, 

Residential, 

Commercial 

Aquatic Material 

Preservativ

e for 

Treated 

Article 

MP EP 

850.6800 Modified Activated 

Sludge, Respiration 

Inhibition Test 

CR NR NR TGAI or 

ROC 

TGAI or 

ROC 

1 

835.3220 Simulated WWTP; 

e.g., Porous Pot Study 

CR NR NR TGAI or 

ROC 

TGAI or 

ROC 

1,7 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 899 

Testing 

Guideline 

Number 

Data Requirement Antimicrobial Use Pattern Test Substance to 

Support 

Test Note 

Number 

Indoor 

Institutional, 

Residential, 

Commercial 

Aquatic Material 

Preservative 

for Treated 

Article 

MP EP 

Mobility Studies – Laboratory 

None Leaching and 

adsorption/desorption 

NR CR CR TGAI or 

ROC 

TGAI or 

ROC 

8,9 

Metabolism Studies – Laboratory 

None Aerobic soil 

metabolism 

NR CR CR TGAI or 

ROC 

TGAI or 

ROC 

8,10,11 

None Anaerobic soil 

metabolism 

NR NR CR TGAI or 

ROC 

TGAI or 

ROC 

8,10,11 

None Aerobic aquatic 

metabolism 

NR CR CR TGAI or 

ROC 

TGAI or 

ROC 

8,10,11 

None Anaerobic aquatic 

metabolism 

NR CR CR TGAI or 

ROC 

TGAI or 

ROC 

8,10,11 

Dissipation Studies – Field 

None Aquatic (sediment) NR CR CR ROC ROC 8,12, 

13,14 

Ground and Surface Water Monitoring 

None Monitoring of U.S. 

representative waters 

NR CR CR TEP or 

ROC 

TEP or 

ROC 

12, 13, 15 

Special Studies 

None Special leaching NR CR CR TEP TEP 16,17 

 (a) Test notes. The following test notes apply to the data requirements in the table in paragraph (d) 

of this section: 

1 Data are required for Indoor Institutional, Residential, and Commercial uses in cases where 

significant environmental exposure is likely to occur as a result of use, based on modeling or other 

appropriate estimation methods. This use pattern is included only when the product is not a 

hazardous waste and when the label does not restrict against disposal or rinsing down a sanitary 

sewer for a use that could result in such an exposure. 

 2 For testing antifoulant paints and coatings, testing is to be performed with both sterile buffered 

distilled water and sterile synthetic seawater at pHs 5, 7, and 9. 

 3 Data are required 1) when the Indoor Institutional, Residential, and Commercial uses identify that 

exposure to waterways is likely to occur based on modeling or other appropriate estimation 

methods; or 2) when the use pattern is aquatic; or 3) when unregulated articles containing a material 

preservative are used in a terrestrial setting and leaching studies or modeling estimates suggest that 

residues are likely to result in exposure to waterways Screening level risk assessment using physical 

chemical properties of the active ingredient and appropriate exposure modeling is advisable. 

 4 Information is required when unregulated article containing a material preservative is used in a 

terrestrial setting and leaching studies or modeling estimates suggest that residues are likely to result 

in exposure to soil. Screening level risk assessment using physical chemical properties of the active 

ingredient and appropriate exposure modeling is advisable. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 900 

 5 Data are not required when the electronic absorption spectra, measured at pHs 5, 7, and 9, of the 

active ingredient and its hydrolytic products, if any, show no absorption or tailing between 290 and 

800 nm. 

 6 Data are not required for active ingredients that are not biodegradable (e.g., inorganic chemicals, 

chemical elements). The selection of the particular biodegradation study depends on the physical 

and chemical properties of the test substance, a pre-screen exposure estimate based on appropriate 

modeling and, if available, the results of the activated sludge isotherm and the modified activated 

sludge respiration inhibition studies. 

 7 Required if the pass criteria for the ready biodegradability study are not met. This means 70% or 

greater removal of dissolved organic carbon and 60% or greater of theoretical oxygen demand or 

theoretical carbon dioxide production. These pass values must be reached in a 10-day window 

within the 28-day period of the test. These may not be suitable for inorganic substances, volatile 

materials or other types of antimicrobials. Other studies or information on the active ingredient 

should be considered. 

 8 Data are required if results from hydrolysis, photodegradation in water (or soil), biodegradation 

tests, or other reliable weight-of-evidence information indicates environmental exposure of concern 

for the active ingredient. 

 9 Adsorption and desorption using a batch equilibrium method is preferred. In some cases, as when 

the antimicrobial pesticide degrades rapidly, soil column leaching with un-aged or aged columns may 

be more appropriate to fully characterize the potential mobility of the parent compound and major 

transformation products. 

 10 The environmental media (soil, water, hydrosoil, sediment, and biota) to be utilized in these tests 

must be representative of potential use sites. 

 11 For unregulated articles treated with a material preservative, the need to conduct soil or aquatic 

metabolism studies will depend upon where the article is to be used (i.e., anticipated exposure 

conditions) and whether leaching studies identify either a residue level of concern or residue 

composition of concern for which additional assessment may be needed. 

 12 Environmental analytical chemistry methods used to generate data associated with this study 

must include results of a successful confirmatory method trial by an independent laboratory. 

 13 Registrants should consult with the Agency on appropriate test protocol. 

 14 Data are required if weight-of-evidence indicates the potential for aquatic exposure, and if the 

active ingredient or its transformation products are likely to have the potential for persistence, 

mobility, nontarget aquatic toxicity, or bioaccumulation; i.e., the half-life of the active ingredient in 

the sediment is estimated to be >10 days from modeling programs or the aerobic soil or aquatic 

metabolism studies, and if any of the following conditions exist: 

- The soil partition coefficient (Kd) is [>=] 50; - The log Kow is [>=] 3; - The Koc is [>=] 1000. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 901 

Registrants should consult with the Agency on appropriate test protocol prior to conducting the 

study. 

 15 Data are required if the weight-of-evidence indicates that the active ingredient or principal 

transformation products are likely to occur at levels that would indicate potential toxicity to 

nontarget organisms in freshwater, estuarine, or marine waters, or if there is the potential for 

persistence, mobility or bioaccumulation. The Agency takes into account other factors such as the 

toxicity of the chemical(s), available monitoring data and the vulnerability of the freshwater, 

estuarine, or marine water resources in the area where exposure could occur. 

 16 For unregulated articles treated with a material preservative, an aquatic leaching study is required 

using a representative treated article if aquatic environmental exposure is anticipated or determined 

from the use of the article. A soil leaching study using a representative treated article is required if 

terrestrial environmental exposures are anticipated or are determined from the use of the article. 

17 For antifoulant paints and coatings, a leaching study is required. 

Response: see response 140.35 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27558 

Comment Code: 149200 

Comment: III. Alternative Approach for Environmental Fate Data Requirements 

Assessment of environmental exposure for antimicrobial pesticides is relevant under very limited 

circumstances. Uses that occur indoors should not be subject to environmental exposure assessment 

any more than such an assessment would be relevant for conventional or biochemical pesticides. 

The imposition of these requirements on indoor antimicrobial uses is all the more troubling because, 

to the extent that environmental exposure occurs, such occurrences are regulated under other 

environmental statutes. As such, the potential need to address environmental fate data requirements 

is limited to only a few antimicrobial use patterns. Data are not required when disposal is not subject 

to FIFRA, including areas such as any product where disposal is regulated as a solid waste, as a 

hazardous waste, where NPDES permits are required for disposal, or where labeling prohibits 

disposal without appropriate permitting or prohibits disposal down sanitary sewers. As a result, 

indoor applications should not be subject to these data requirements. 

LANXESS elsewhere has proposed new Use Pattern categories that are relevant, clear and 

applicable to antimicrobial pesticides (See Appendix B). This alternative proposal incorporates those 

new Use Pattern categories. Where a use is excluded from the definition of an antimicrobial 

pesticide or from the definition of a pesticide chemical, it should be excluded from this section. For 

uses that are pesticidal but not within the scope of the definition of antimicrobial pesticides, a 

reference should be made to the appropriate sections of the data requirements for conventional or 

biochemical pesticides. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 902 

A. Environmental Exposure Estimates Drive Data Needs by Tiered Testing 

Estimating environmental exposure is an essential prelude to determination of environmental fate 

data requirements. By the use of appropriate modeling, environmental exposure can be estimated for 

products based on Use Pattern. For instance, environmental exposure models are available for 

estimating whether indoor institutional, residential, and commercial products would likely be present 

in WWTP effluent at levels of concern. Appropriately designed and validated leaching studies are 

useful to determine the rate and extent of residue released to the environment from antifoulant 

paints and coatings and from articles treated with material preservatives exposed to the environment 

(e.g., preservatives in treated wood or in other treated articles). If modeling or reliable leaching data 

indicate exposure to the environment at levels of concern, additional environmental testing is 

needed to confirm and/or refine the exposure estimates. There are many different models or other 

approaches to estimating exposures. Since none have as yet been fully vetted for antimicrobial 

pesticides, LANXESS recommends that the Agency initiate the appropriate scientific review process 

to evaluate the potential utility and limitations of the various approaches and to do so in a way that 

allows for public participation and comment. 

A tiered testing approach is recommended to fulfill environmental fate data requirements for 

antimicrobials when needed for risk assessment. In determining an acceptable environmental risk 

assessment, other data may be considered to supplement or replace environmental fate data. 

LANXESS has provided a list of some of these below. 

* Physical chemistry data and SAR/QSAR information are helpful for predicting environmental 

partitioning and estimating environmental fate endpoints. 

* Along with the predicted environmental concentration resulting from use of the product estimated 

by modeling, ecotoxicity data may be used to determine environmental no effect concentrations and 

an acceptable environmental risk assessment target. 

An appropriate exposure model, supplemented with measured data as needed to reduce uncertainty 

and avoid use of default assumptions, provides more realistic environmental exposure estimates to 

use in risk assessment. As discussed elsewhere (See Panel’s General Comments at Section I), the 

selection and use of exposure models and risk assessment methods must be relevant, clearly defined, 

and developed in a transparent manner that is both scientifically valid and open for public comment. 

Yet LANXESS does not believe that specifying exposure methodology is appropriate within this 

regulation and recommends that all such references be eliminated. 

B. Specific Alternative Proposal for Environmental Fate Data Requirements 

The following is LANXESS’s specific alternative proposal. LANXESS welcomes an opportunity to 

discuss these alternatives. 

If antimicrobial use pattern categories are described in regulations apart from Section 158.100, 

specific reference to the identification and description must be incorporated into the following 

paragraph. 158.2280(a) should be completely rewritten as follows. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 903 

(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the 

environmental fate data requirements for a particular pesticide product. Notes that apply to an 

individual test and include specific conditions, qualifications, or exceptions to the designated test are 

listed in paragraph (e) of this section. 

The existing paragraphs (b) and (c) should be replaced with the following: 

(b) Use Patterns. 

(1) The general use patterns for antimicrobial environmental fate data requirements are ‘Indoor 

Institutional, Residential, and Commercial,’ ‘Aquatic,’ and ‘Material Preservatives,’ where these are 

identified as follows 

1. Indoor Institutional, Residential and Commercial includes the use of sanitizers, disinfectants, 

virucides and similar products for the following: on hard surfaces; on soft surfaces; in the air; as 

laundry disinfectants and sanitizers; as swimming pool disinfectants or algaecides (public or private, 

including pool, hot tubs, and spas); on medical equipment; use in any of the types of facilities that 

fall within these definitions. This use pattern is included only when the product is not a hazardous 

waste and when the label does not restrict against disposal or rinsing down a sanitary sewer for a use 

that could result in such an exposure. 

2. Aquatic areas involve uses that result in the potential for direct exposure of natural bodies of 

water to antimicrobials, although the exposure likely is limited and is not a direct application to 

aquatic sites. These include once- through cooling systems (where no pretreatment of the treated 

discharge occurs), antifoulant coatings, and ballast water treatments. 

3. Material Preservatives for Exempt Treated Articles include wood preservatives as well as any 

other type of preservative where the final article is used outdoors on a significant basis and there is 

reliable evidence that the article, under anticipated conditions of use, will release the antimicrobial 

preservative in sufficient quantities to produce environmental exposures of concern 

(c) Use of products as aquatic herbicides or agricultural fungicides are outside of the scope of these 

data requirements. Registrants of such uses should refer to Subpart N or to sec. 158.2060 of this 

Part. 

The table of data requirements at paragraph (e) should be replaced by the following. The definition 

of ROC as residue of concern should be added to paragraph (d). 

[See table on pages 10-11 of appendix H, PDF docket ID EPA-HQ-OPP-2008-0110-0064] 

(a) Test notes. The following test notes apply to the data requirements in the table in paragraph (d) 

of this section: 

1 Data are required for Indoor Institutional, Residential, and Commercial uses in cases where 

significant environmental exposure is likely to occur as a result of use, based on modeling or other 

appropriate estimation methods. This use pattern is included only when the product is not a 

hazardous waste and when the label does not restrict against disposal or rinsing down a sanitary 

sewer for a use that could result in such an exposure. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 904 

2 For testing antifoulant paints and coatings, testing is to be performed with both sterile buffered 

distilled water and sterile synthetic seawater at pHs 5, 7, and 9. 

3 Data are required 1) when the Indoor Institutional, Residential, and Commercial uses identify that 

exposure to waterways is likely to occur based on modeling or other appropriate estimation 

methods; or 2) when the use pattern is aquatic; or 3) when unregulated articles containing a material 

preservative are used in a terrestrial setting and leaching studies or modeling estimates suggest that 

residues are likely to result in exposure to waterways Screening level risk assessment using physical 

chemical properties of the active ingredient and appropriate exposure modeling is advisable. 

4 Information is required when unregulated article containing a material preservative is used in a 

terrestrial setting and leaching studies or modeling estimates suggest that residues are likely to result 

in exposure to soil. Screening level risk assessment using physical chemical properties of the active 

ingredient and appropriate exposure modeling is advisable. 

5 Data are not required when the electronic absorption spectra, measured at pHs 5, 7, and 9, of the 

active ingredient and its hydrolytic products, if any, show no absorption or tailing between 290 and 

800 nm. 

6 Data are not required for active ingredients that are not biodegradable (e.g., inorganic chemicals, 

chemical elements). The selection of the particular biodegradation study depends on the physical 

and chemical properties of the test substance, a pre-screen exposure estimate based on appropriate 

modeling and, if available, the results of the activated sludge isotherm and the modified activated 

sludge respiration inhibition studies. 

7 Required if the pass criteria for the ready biodegradability study are not met. This means 70% or 

greater removal of dissolved organic carbon and 60% or greater of theoretical oxygen demand or 

theoretical carbon dioxide production. These pass values must be reached in a 10-day window 

within the 28-day period of the test. These may not be suitable for inorganic substances, volatile 

materials or other types of antimicrobials. Other studies or information on the active ingredient 

should be considered. 

8 Data are required if results from hydrolysis, photodegradation in water (or soil), biodegradation 

tests, or other reliable weight-of-evidence information indicates environmental exposure of concern 

for the active ingredient. 

9 Adsorption and desorption using a batch equilibrium method is preferred. In some cases, as when 

the antimicrobial pesticide degrades rapidly, soil column leaching with un-aged or aged columns may 

be more appropriate to fully characterize the potential mobility of the parent compound and major 

transformation products. 

10 The environmental media (soil, water, hydrosoil, sediment, and biota) to be utilized in these tests 

must be representative of potential use sites. 

11 For unregulated articles treated with a material preservative, the need to conduct soil or aquatic 

metabolism studies will depend upon where the article is to be used (i.e., anticipated exposure 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Environmental Fate Section (140) Page 905 

conditions) and whether leaching studies identify either a residue level of concern or residue 

composition of concern for which additional assessment may be needed. 

12 Environmental analytical chemistry methods used to generate data associated with this study 

must include results of a successful confirmatory method trial by an independent laboratory. 

13 Registrants should consult with the Agency on appropriate test protocol. 

14 Data are required if weight-of-evidence indicates the potential for aquatic exposure, and if the 

active ingredient or its transformation products are likely to have the potential for persistence, 

mobility, nontarget aquatic toxicity, or bioaccumulation; i.e., the half-life of the active ingredient in 

the sediment is estimated to be >10 days from modeling programs or the aerobic soil or aquatic 

metabolism studies, and if any of the following conditions exist: - The soil partition coefficient (Kd) 

is [>=] 50; - Thelog Kow is [>=] 3; - The Koc is [>=] 1000. Registrants should consult with the 

Agency on appropriate test protocol prior to conducting the study. 

15 Data are required if the weight-of-evidence indicates that the active ingredient or principal 

transformation products are likely to occur at levels that would indicate potential toxicity to 

nontarget organsims in freshwater, estuarine, or marine waters, or if there is the potential for 

persistence, mobility or bioaccumulation. The Agency takes into account other factors such as the 

toxicity of the chemical(s), available monitoring data and the vulnerability of the freshwater, 

estuarine, or marine water resources in the area where exposure could occur. 

16 For unregulated articles treated with a material preservative, an aquatic leaching study is required 

using a representative treated article if aquatic environmental exposure is anticipated or determined 

from the use of the article. A soil leaching study using a representative treated article is required if 

terrestrial environmental exposures are anticipated or are determined from the use of the article. 

17 For antifoulant paints and coatings, a leaching study is required. 

Response: see response 140.35 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Plant Protection Section (150) Page 906 

Non-Target Plant Protection (150) 

Verbatim Comments and Response References for the Non-Target Plant 

Protection Section 

Comment Code: 151000 Seedling emergence (Tier II - dose-response) 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26532 

Comment Code: 151000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * For higher-tiered studies, CR for low exposure grouping based on algal studies, the 

proposal acknowledges that many antimicrobials are algaecides, but should also explain the criteria 

that will be applied to trigger higher-tiered studies based on results from algal studies. 

Response: see response 151.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26822 

Comment Code: 151000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * For higher-tiered studies, CR for low exposure grouping 

based on algal studies, the proposal acknowledges that many antimicrobials are algaecides, but 

should also explain the criteria that will be applied to trigger higher-tiered studies based on results 

from algal studies. 

Response: see response 151.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27468 

Comment Code: 151000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * For higher-tiered studies, CR for low exposure grouping 

based on algal studies, the proposal acknowledges that many antimicrobials are algaecides, but hould 

also explain the criteria that will be applied to trigger higher-tiered studies based on results from algal 

studies. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Plant Protection Section (150) Page 907 

Response: see response 151.1 

Comment Code: 152000 Vegetative vigor (Tier II dose-response) 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26527 

Comment Code: 152000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * Under footnote 3, the EPA addresses low environmental exposure and three criteria are 

again used to capture products. The hydrolysis here indicates half- life of greater than 4 days but 

now includes metabolites and/or transformation products. pH levels are not discussed and this 

differs from the earlier ecotox hydrolysis requirement whereby the active and/or metabolites are 

addressed if they persist greater than 5 days at pH’s 5,7, 9.[FN#14:footnote 13 page 59438.] The 

EPA should be consistent in this respect. 

Response: see response 152.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26812 

Comment Code: 152000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Under footnote 3, the EPA addresses low environmental 

exposure and three criteria are again used to capture products. The hydrolysis here indicates half- life 

of greater than 4 days but now includes metabolites and/or transformation products. pH levels are 

not discussed and this differs from the earlier ecotox hydrolysis requirement whereby the active 

and/or metabolites are addressed if they persist greater than 5 days at pH’s 5,7, 9.10 The EPA 

should be consistent in this respect. 

Response: see response 152.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27457 

Comment Code: 152000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Under footnote 3, the EPA addresses low environmental 

exposure and three criteria are again used to capture products. The hydrolysis here indicates half- life 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Plant Protection Section (150) Page 908 

of greater than 4 days but now includes metabolites and/or transformation products. pH levels are 

not discussed and this differs from the earlier ecotox hydrolysis requirement whereby the active 

and/or metabolites are addressed if they persist greater than 5 days at pH’s 5,7, 9. [FN#10:Page 

59438, note 13.] The EPA should be consistent in this respect. 

Response: see response 152.1 

Comment Code: 153000 Aquatic plant growth (Tier II dose-response) 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26529 

Comment Code: 153000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * Footnote 5[FN#15:Page 59439] references four different algal species but does not 

differentiate on the basis of freshwater versus saltwater species. If the active is not directly applied to 

salt water the footnote should indicate so. 

Response: see response 153.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26814 

Comment Code: 153000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Footnote 5[FN#11:Page 59439] references four different 

algal species but does not differentiate on the basis of freshwater versus saltwater species. If the 

active is not directly applied to salt water the footnote should indicate so. 

Response: see response 153.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27459 

Comment Code: 153000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Footnote 5[FN#11:Page 59439] references four different 

algal species but does not differentiate on the basis of freshwater versus saltwater species. If the 

active is not directly applied to salt water the footnote should indicate so. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Plant Protection Section (150) Page 909 

Response: see response 153.1 

Comment Code: 154000 Terrestrial and aquatic field studies 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26535 

Comment Code: 154000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * The EPA should explain how any of the terrestrial plant- related requirements are relevant 

to uses of antimicrobials and how any such data would be used in a relevant risk assessment. In 

addition, the EPA should address how potential effects on corn and tomatoes are related to 

antimicrobial pesticides. Antimicrobials are not applied directly in the environment. 

Response: see responses 154.1 and 154.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26825 

Comment Code: 154000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * The EPA should explain how any of the terrestrial plantrelated requirements are relevant to uses of antimicrobials and how any such data would be used in a 

relevant risk assessment. In addition, the EPA should address how potential effects on corn and 

tomatoes are related to antimicrobial pesticides. 

Response: see responses 154.1 and 154.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27471 

Comment Code: 154000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * The EPA should explain how any of the terrestrial plantrelated requirements are relevant to uses of antimicrobials and how any such data would be used in a 

relevant risk assessment. In addition, the EPA should address how potential effects on corn and 

tomatoes are related to antimicrobial pesticides. 

Response: see responses 154.1 and 154.2 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Plant Protection Section (150) Page 910 

Comment Code: 155000 Tiered approach to non-target plant protection studies 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26346 

Comment Code: 155000 

Comment: C. Non-Target Plant Data Requirements 

For conventional products, non-target plant data are required only for outdoor use patterns, that is, 

terrestrial, aquatic and forestry and residential outdoor. For these use patterns, Tier 1 phytotoxicity 

data are required. Upper tier data are conditionally required for these outdoor uses. For 

antimicrobials, all use patterns, including "low environmental exposure" uses, have Tier II data 

required or conditionally required. There are no requirements for lower tier data for antimicrobials, 

only Tier II and Tier III studies. Further, Tier II algal plant growth is required for all antimicrobial 

uses.[FN#43:Compare 40 CFR 158.700 with Proposed [Section] 158.2250. For a complete list of 

guideline numbers, see page 59439.] 

Response: see responses 155.1 and 155.2 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26525 

Comment Code: 155000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * Under the Non-Target Plant Protection section, the EPA should include Tier I or explain 

why only Tier II testing is required, in as much as this differs significantly from the regulation for 

conventional pesticides. 

Response: see response 155.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26810 

Comment Code: 155000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Under the Non-Target Plant Protection section, the EPA 

should include Tier I or explain why only Tier II testing is required, in as much as this differs 

significantly from the regulation for conventional pesticides. 

Response: see response 155.2 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Plant Protection Section (150) Page 911 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26872 

Comment Code: 155000 

Comment: C. Non-Target Plants Data Requirements 

For conventional products, non-target plant data requirements are required only for outdoor use 

patterns, terrestrial, aquatic and forestry and residential outdoor. For these use patterns, Tier 1 

phytotoxicity data are required. Upper tier data are conditionally required for these outdoor uses. 

For antimicrobials, all use patterns, including "low environmental exposure" uses, have Tier II data 

required or conditionally required. There are no requirements for lower tier data for antimicrobials, 

only Tier II and Tier III studies. Further, Tier II algal plant growth is required for ALL antimicrobial 

uses.[FN43: Compare 40 CFR 158.700 with Proposed [section]158.2250. For a complete list of 

guideline numbers, see page 59439.] 

Response: see responses 155.1 and 155.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27455 

Comment Code: 155000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Under the Non-Target Plant Protection section, the EPA 

should include Tier I or explain why only Tier II testing is required, in as much as this differs 

significantly from the regulation for conventional pesticides. 

Response: see response 155.2 

Comment Code: 157000 Commenter's Concept of Non-Target Plant Protection Data 

Requirements Table Revisions 

Comment Summary: As part of their comments, the commenter provided an alternate Non-Target 

Plant Protection Data Requirements Table with testnotes. EPA’s response is for the entire alternate 

testing scheme and not the individual parts. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27816 

Comment Code: 157000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Plant Protection Section (150) Page 912 

Comment: The LANXESS’s recommendations for revisions to data requirements at paragraph (e) 

are as follows, where the definition of ROC as residue of concern should be added to paragraph (d): 

[See table on page 14 of appendix F in PDF docket ID EPA-HQ-OPP-2008-0110-0064] 

1 Data are required only when environmental exposure is likely to result under normal usage 

conditions as determined by appropriate assessment methods. 

 2 Data are not required when the test organism is intended target species for the pesticide product. 

3 Data are required if a tested aquatic species exhibits a 25 percent or greater detrimental effect in 

the Tier 1 study. When Tier II testing is required, the test species should be the species that showed 

detrimental effects in the Tier 1 test. 

 4 Data are required if a tested terrestrial species exhibits a 25 percent or greater detrimental effect in 

the Tier 1 study. When Tier II testing is required, the test species should be the species that showed 

detrimental effects in the Tier 1 test. 

 5 Tests are required on a case-by-case basis based on the results of lower tier phytotoxicity studies, 

adverse incident reports, intended use pattern, and environmental fate characteristics that indicate 

potential exposure. 

6 Registrants must consult with the Agency on appropriate test protocols prior to designing the 

study. 

Response: see response 155.3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27817 

Comment Code: 157000 

Comment: The Panel’s recommendations for revisions to data requirements at paragraph (e) are as 

follows, where the definition of ROC as residue of concern should be added to paragraph (d): 

Testing 

Guideline 

Number 

Data Requirement Antimicrobial Use Pattern Test Substance to 

Support 

Footnote 

Test Note 

Number 

Indoor 

Institutional, 

Residential, 

Commercial 

Aquatic Material 

Preservative 

for Treated 

Article 

MP EP 

Tier 1 

None Seedling emergence 

(tier 1) 

CR CR CR ROC ROC 1 

None Vegetative vigor (tier 

1) 

CR CR CR ROC ROC 1 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Plant Protection Section (150) Page 913 

Testing 

Guideline 

Number 

Data Requirement Antimicrobial Use Pattern Test Substance to 

Support 

Footnote 

Test Note 

Number 

Indoor 

Institutional, 

Residential, 

Commercial 

Aquatic Material 

Preservative 

for Treated 

Article 

MP EP 

None Aquatic plant growth 

(tier 1, algae and 

vascular plants) 

CR CR CR ROC ROC 1, 2 

Tier 2 

None Aquatic plant growth 

(algae, dose 

response) 

NR CR CR ROC ROC 1, 2, 3 

None Aquatic plant growth 

(vascular plant, dose 

response) 

NR CR CR ROC ROC 1, 2, 3 

None Seedling emergence 

(tier 2) 

NR CR CR ROC ROC 1, 4 

None Vegetative vigor 

dose response 

NR CR CR ROC ROC 1, 4 

Tier 3 – Nontarget Area Phytotoxicity 

None Terrestrial field study NR CR CR ROC ROC 1, 5, 6 

None Aquatic field study NR CR CR ROC ROC 1, 5, 6 

1 Data are required only when environmental exposure is likely to result under normal usage 

conditions as determined by appropriate assessment methods. 

 2 Data are not required when the test organism is intended target species for the pesticide product. 

3 Data are required if a tested aquatic species exhibits a 25 percent or greater detrimental effect in 

the Tier 1 study. When Tier II testing is required, the test species should be the species that showed 

detrimental effects in the Tier 1 test. 

 4 Data are required if a tested terrestrial species exhibits a 25 percent or greater detrimental effect in 

the Tier 1 study. When Tier II testing is required, the test species should be the species that showed 

detrimental effects in the Tier 1 test. 

 5 Tests are required on a case-by-case basis based on the results of lower tier phytotoxicity studies, 

adverse incident reports, intended use pattern, and environmental fate characteristics that indicate 

potential exposure. 

6 Registrants must consult with the Agency on appropriate test protocols prior to designing the 

study. 

Response: see response 155.3 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 914 

Non-Target Organism Exposure (160) 

Verbatim Comments and Response References for the Non-Target Organism 

Exposure Section 

Comment Code: 160000 Non-Target Organism Exposure 

Commenter Name: Jamie S. Heisig-Mitchell 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 

Comment ID: 25451 

Comment Code: 160000 

Comment: *The toxicity tests for avians and aquatic life do not have endpoints designed to 

specifically measure the potential for endocrine disruption. Some of the endpoints of endocrine 

disruption are more sensitive than the traditional endpoints measured in the proposed toxicity tests 

and may produce adverse effects at much lower concentrations. 

Response: see response 160.4 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25949 

Comment Code: 160000 

Comment: In the case of addressing the ecotoxicity and environmental fate it would be more useful 

to utilize the European approach for addressing wood products and their environmental exposure. 

This approach is provided below: 

[Table 1. European approach for addressing wood products and their environmental exposure -- see 

PDF docket ID EPA-HQ-OPP-2008-0110-0091] 

Based on this table, classes 3-5 would be subject to the more extensive data requirements to assess 

ecotoxicity and environmental fate. 

Response: see response 160.39 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25991 

Comment Code: 160000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 915 

Comment: * The toxicity tests for avians and aquatic life do not have endpoints designed to 

specifically measure the potential for endocrine disruption. Some of the endpoints of endocrine 

disruption are more sensitive than the traditional endpoints measured in the proposed toxicity tests 

and may produce adverse effects at much lower concentrations. 

Response: see response 160.4 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26352 

Comment Code: 160000 

Comment: Ecological effects data requirements for nontarget organisms and plants are necessary to 

assess the potential for adverse effects resulting from potential environmental exposure. Most 

antimicrobial pesticide uses are indoor or environmentally contained, and therefore present little 

potential for environmental exposure. Consequently, they present little to no potential to adversely 

affect nontarget organisms and plants. Ultimately, it is important to clearly identify when potential 

environmental exposures may be relevant or not, and then to clearly identify what data are needed to 

assess the potential risks of such effects, avoiding unnecessary animal testing or development of 

unnecessary data. 

Response: see responses 1 and 160.1 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26354 

Comment Code: 160000 

Comment: First, any proposed requirement for non-target organism data for antimicrobial 

pesticides must be tailored to antimicrobial pesticides. Second, the requirement must dictate which 

uses of those pesticides pose sufficient potential for environmental exposure that assessment of 

effects on nontargets under FIFRA is needed. The proposed rule does not include either of these 

critical components. Further, in proposing these data requirements for antimicrobial pesticides, the 

Agency is required to take into consideration the requirements of FIFRA Section 3(h)(3)(A)(ii), 

which mandates that EPA "differentiate the types of review undertaken for antimicrobial 

pesticides,...conform[ing] the degree and type of review to the risks and benefits presented..., 

considering the use patterns of the product, toxicity, expected exposure and product type." There is 

no evidence in the Proposal that the Agency has done so. 

Response: see response 1 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26355 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 916 

Comment Code: 160000 

Comment: IV. Comments on Proposed Rule (pages 59412-17; section 158.2240 and 158.2250), 

Data Requirements for Nontarget Organisms and Nontarget Plants 

The need for data to assess potential effects on non-target species is predicated on those species 

being exposed in the environment to the compound in question. There are very few uses of 

antimicrobial pesticides that have any expectation of environmental exposure. Even where there 

might be environmental exposure, such exposure will be at very low levels. 

Response: see response 160.1 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26362 

Comment Code: 160000 

Comment: Given that neither Subpart G, at 158.630 and 158.660, nor 158.2060 require any 

ecological effects data for indoor use conventional or biochemical pesticides, it is unclear why 

extensive data are required for indoor uses of antimicrobials, which cover most of the uses. The 

proposed rule is inconsistent with the requirements for other types of pesticides, without any clear 

explanation or justification. While the Panel agrees that the Agency may wish to consider different 

types of assessments for antimicrobials than for other types of pesticides and that such an approach 

would be consistent with FIFRA 3(h), the Panel believes that the Agency should do so only when a 

need has been publicly discussed and well justified. An appropriate methodology for the assessment 

should be developed through a transparent process with scientific peer review. 

Response: see responses 1 and 160.1 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26365 

Comment Code: 160000 

Comment: The requirements for ecological effects data within the regulation should be limited to 

those use patterns which potentially could result in environmental exposure relevant to ecological 

effects assessment under FIFRA. There are limited uses of antimicrobial pesticides where ecological 

effects information may be relevant. This is because there are few antimicrobial pesticides uses that 

may have a potential to affect the environment through dissipation after use (as contrasted with 

disposal) or where the actual use of the pesticide may result in the potential for environmental 

contamination. . 

Response: see response 160.1 

Commenter Name: Janice L. Dhonau 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 917 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26375 

Comment Code: 160000 

Comment: The Agency asserts that certain tier 1 non-target organism acute toxicity data are needed 

"in case of unintended or coincident exposure to antimicrobials, such as a transportation 

accident."[FN#7: (page 59412)] However, there is no equivalent requirement for conventional or 

biochemical pesticides, and the Agency has not justified why this concern is applicable only to 

antimicrobial pesticides. 

Response: see response 160.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26700 

Comment Code: 160000 

Comment: I. INTRODUCTION 

Ecological effects data requirements for nontarget organisms and plants are necessary to assess the 

potential for adverse effects resulting from potential environmental exposure. Most antimicrobial 

pesticide uses are indoor or environmentally contained, and therefore present little potential for 

environmental exposure. Consequently, they present little to no potential to adversely affect 

nontarget organisms and plants. Ultimately, it is important to clearly identify when potential 

environmental exposures may be relevant or not, and then to clearly identify what data are needed to 

assess the potential risks of such effects, avoiding unnecessary animal testing or development of 

data. 

Response: see response 160.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26701 

Comment Code: 160000 

Comment: First, any proposed requirement for nontarget organism data for antimicrobial pesticides 

must be tailored to antimicrobial pesticides. Second, the requirement must dictate which uses of 

those pesticides pose sufficient potential for environmental exposure that assessment of effects on 

nontargets under FIFRA is needed. The proposed rule does not include either of these critical 

components. Further, in proposing these data requirements for antimicrobial pesticides, the Agency 

is required to take into consideration the requirements of FIFRA Section 3(h)(3)(A)(ii), which 

mandates that EPA "differentiate the types of review undertaken for antimicrobial pesticides, . . . 

conform[ing] the degree and type of review to the risks and benefits presented, . . . considering the 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 918 

use patterns of the product, toxicity, expected exposure and product type." There is no evidence in 

the Proposal that the Agency has done so. 

Response: see response 1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26702 

Comment Code: 160000 

Comment: II. COMMENTS ON PROPOSED RULE (PAGES 59412-17; SECTION 158.2240 

AND 158.2250), DATA REQUIREMENTS FOR NONTARGET ORGANISMS AND 

NONTARGET PLANTS 

In this section, the Panel provides the following comments on the rule as proposed. In a subsequent 

section, the Panel offers an alternative proposal that is consistent with the statutory requirements 

and the identification of potential environmental chemistry data requirements for antimicrobial 

pesticides. The Panel suggests that the proposed rule be rewritten and reproposed to accurately 

comply with the FIFRA requirements as applied to antimicrobial pesticides. 

The need for data to assess potential effects on nontarget species is predicated on those species 

being exposed in the environment to the compound in question. As discussed elsewhere in these 

comments (See Appendix H), there are very few uses of antimicrobial pesticides for which there is 

any expectation of environmental exposure. Even where there might be environmental exposure, 

such exposure will be at very low levels. For example, the Panel refers the Agency to its comments 

on environmental fate data requirements for material preservatives used to treat articles used in 

various outdoor environments (such as wood preservatives). These comments make 

recommendations on how to determine the appropriate environmental exposures and the need for 

ecological effects data 

Response: See responses 2 and 160.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26704 

Comment Code: 160000 

Comment: The requirements for ecological effects data within the regulation should be limited to 

those use patterns which potentially could result in environmental exposure relevant to ecological 

effects assessment under FIFRA. There are limited uses of antimicrobial pesticides where ecological 

effects information may be relevant. This is because there are few antimicrobial pesticides uses that 

may have a potential to affect the environment through dissipation after use (as contrasted with 

disposal) or where the actual use of the pesticide may result in the potential for environmental 

contamination. In the next section, the Panel offers a proposal that clearly identifies those few uses. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 919 

Response: see response 160.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26708 

Comment Code: 160000 

Comment: The Agency asserts that certain tier 1 nontarget organism acute toxicity data are needed 

"in case of unintended or coincident exposure to antimicrobials, such as a transportation 

accident."[FN#3:Page 59412.] However, there is no equivalent requirement for conventional or 

biochemical pesticides, and the Agency has not justified why this concern is applicable only to 

antimicrobial pesticides. 

Response: see response 160.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26721 

Comment Code: 160000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * EPA must specify how the Agency will determine if the 

transformation products are more toxic, persistent, bioaccumulative or have been shown to cause 

adverse effects in mammalian or aquatic reproductive studies.[FN#5:Section 1582240 NonTarget 

Organisms, Paragraph 3.] More transparency and the use of readily available and reviewed methods 

would help the registrant anticipate EPA’s needs and meet those needs accordingly. 

Response: see response 160.3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26833 

Comment Code: 160000 

Comment: As proposed, the ecological effects data requirements for antimicrobial pesticides are 

not sufficiently clear to enable a registrant to determine the kinds of data and information EPA 

requires to make a regulatory decision and thus are inconsistent with the stated purpose of a data 

requirement regulation.[FN#12:40 CFR 158.1(a).] They also do not recognize the very major 

differences between the uses of antimicrobial pesticides and other pesticides with regard to 

environmental exposure potential and the need for ecological effects data. For these reasons, the 

Proposal should be redrafted and reproposed. The Panel suggests EPA adopt the approach outlined 

below in that reproposal. 

Response: See Responses 1 and 2 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 920 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26982 

Comment Code: 160000 

Comment: 19. Proposed Regulation # [Section] 158.2240(a)(3) 

Text of the Proposed Regulation (emphasis added) Nontarget organisms: General. "If the Agency 

determines that the transformation products of the parent compound are more toxic, persistent, 

bioaccumulative, or have been shown to cause adverse effects in mammalian or aquatic reproductive 

studies, then data on those transformation products are required to support registration." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated how the Agency will determine if the transformation products of the parent compound are 

more toxic, persistent, bioaccumulative, or have been shown to cause adverse effects in mammalian 

or aquatic reproductive studies. 

Response: see response 3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27012 

Comment Code: 160000 

Comment: [The following are some of the problems identified in the proposed rule:] 

4) For certain Use Patterns, including Indoor Industrial, discharges to the environment from the 

facility are regulated by Agencies or Offices other than Office of Pesticide Programs (e.g., facility 

wastewater treatment, NPDES permits for effluent, RCRA for wastes, etc). For these Use Patterns, 

environmental fate and ecotoxicity data requirements should not be required for FIFRA registration. 

Response: see response 160.38 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27384 

Comment Code: 160000 

Comment: APPENDIX F COMMENTS ON PROPOSED DATA REQUIREMENTS FOR 

ECOLOGICAL EFFECTS 

I. Introduction...................................................................1 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 921 

II. Comments on Proposed Rule (pages 59412-17; section 158.2240 and 158.2250), Data 

Requirements for Nontarget Organisms and Nontarget Plants....................2 

III. Alternative Proposal for Ecological Effects Data Requirements................7 

A. Proposed Alternative Section 158.2240 Data Requirements for Nontarget 

Organisms...........................................................8 

B. Proposed Alternative Section 158.2250 Data Requirements for Nontarget Plant 

Protection........................12 

I. INTRODUCTION 

Ecological effects data requirements for nontarget organisms and plants are necessary to assess the 

potential for adverse effects resulting from potential environmental exposure. Most antimicrobial 

pesticide uses are indoor or environmentally contained, and therefore present little potential for 

environmental exposure. Consequently, they present little to no potential to adversely affect 

nontarget organisms and plants. Ultimately, it is important to clearly identify when potential 

environmental exposures may be relevant or not, and then to clearly identify what data are needed to 

assess the potential risks of such effects, avoiding unnecessary animal testing or development of 

data. 

First, any proposed requirement for nontarget organism data for antimicrobial pesticides must be 

tailored to antimicrobial pesticides. Second, the requirement must dictate which uses of those 

pesticides pose sufficient potential for environmental exposure that assessment of effects on 

nontargets under FIFRA is needed. The proposed rule does not include either of these critical 

components. Further, in proposing these data requirements for antimicrobial pesticides, the Agency 

is required to take into consideration the requirements of FIFRA Section 3(h)(3)(A)(ii), which 

mandates that EPA "differentiate the types of review undertaken for antimicrobial pesticides, . . . 

conform[ing] the degree and type of review to the risks and benefits presented, . . . considering the 

use patterns of the product, toxicity, expected exposure and product type." There is no evidence in 

the Proposal that the Agency has done so. 

Response: see responses 1 and 160.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27385 

Comment Code: 160000 

Comment: II. COMMENTS ON PROPOSED RULE (PAGES 59412-17; SECTION 158.2240 

AND 158.2250), DATA REQUIREMENTS FOR NONTARGET ORGANISMS AND 

NONTARGET PLANTS 

In this section, LANXESS provides the following comments on the rule as proposed. In a 

subsequent section, LANXESS offers an alternative proposal that is consistent with the statutory 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 922 

requirements and the identification of potential environmental chemistry data requirements for 

antimicrobial pesticides. LANXESS suggests that the proposed rule be rewritten and reproposed to 

accurately comply with the FIFRA requirements as applied to antimicrobial pesticides. 

The need for data to assess potential effects on nontarget species is predicated on those species 

being exposed in the environment to the compound in question. As discussed elsewhere in these 

comments (See Appendix H), there are very few uses of antimicrobial pesticides for which there is 

any expectation of environmental exposure. Even where there might be environmental exposure, 

such exposure will be at very low levels. For example, LANXESS refers the Agency to its comments 

on environmental fate data requirements for material preservatives used to treat articles used in 

various outdoor environments (such as wood preservatives). These comments make 

recommendations on how to determine the appropriate environmental exposures and the need for 

ecological effects data 

Response: see responses 2 and 160.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27387 

Comment Code: 160000 

Comment: Given that neither Subpart G, at 158.630 and 158.660, nor 158.2060 require any 

ecological effects data for indoor use conventional or biochemical pesticides, it is unclear why 

extensive data are required for indoor uses of antimicrobials. The proposed rule is inconsistent with 

the requirements for other types of pesticides, without any clear explanation or justification. While 

LANXESS agrees that the Agency may wish to consider different types of assessments for 

antimicrobials than for other types of pesticides and that such an approach would be consistent with 

FIFRA 3(h), LANXESS believes that the Agency should do so only when a need has been publicly 

discussed and well justified. An appropriate methodology for the assessment should be developed 

through a transparent process with scientific peer review. 

Response: See responses 1 and 160.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27389 

Comment Code: 160000 

Comment: The requirements for ecological effects data within the regulation should be limited to 

those use patterns which potentially could result in environmental exposure relevant to ecological 

effects assessment under FIFRA. There are limited uses of antimicrobial pesticides where ecological 

effects information may be relevant. This is because there are few antimicrobial pesticides uses that 

may have a potential to affect the environment through dissipation after use (as contrasted with 

disposal) or where the actual use of the pesticide may result in the potential for environmental 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 923 

contamination. In the next section, LANXESS offers a proposal that clearly identifies those few 

uses. 

Response: see response 160.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27393 

Comment Code: 160000 

Comment: The Agency asserts that certain tier 1 nontarget organism acute toxicity data are needed 

"in case of unintended or coincident exposure to antimicrobials, such as a transportation 

accident."[FN#3:Page 59412.] However, there is no equivalent requirement for conventional or 

biochemical pesticides, and the Agency has not justified why this concern is applicable only to 

antimicrobial pesticides. 

Response: see response 160.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27400 

Comment Code: 160000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] 

* EPA must specify how the Agency will determine if the transformation products are more toxic, 

persistent, bioaccumulative or have been shown to cause adverse effects in mammalian or aquatic 

reproductive studies.[FN#5:Section 1582240 NonTarget Organisms, Paragraph 3.] More 

transparency and the use of readily available and reviewed methods would help the registrant 

anticipate EPA’s needs and meet those needs accordingly. 

Response: see response 160.3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27478 

Comment Code: 160000 

Comment: As proposed, the ecological effects data requirements for antimicrobial pesticides are 

not sufficiently clear to enable a registrant to determine the kinds of data and information EPA 

requires to make a regulatory decision and thus are inconsistent with the stated purpose of a data 

requirement regulation.[FN#12:40 CFR 158.1(a).] They also do not recognize the very major 

differences between the uses of antimicrobial pesticides and other pesticides with regard to 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 924 

environmental exposure potential and the need for ecological effects data. For these reasons, the 

Proposal should be redrafted and reproposed. LANXESS suggests EPA adopt the approach 

outlined below in that reproposal. 

Response: see responses 1, 2, and 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27517 

Comment Code: 160000 

Comment: 4) For certain Use Patterns, including Indoor Industrial, discharges to the environment 

from the facility are regulated by Agencies or Offices other than Office of Pesticide Programs (e.g., 

facility wastewater treatment, NPDES permits for effluent, RCRA for wastes, etc). For these Use 

Patterns, environmental fate and ecotoxicity data requirements should not be required for FIFRA 

registration. 

Response: see response 160.38 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27688 

Comment Code: 160000 

Comment: 19. Proposed Regulation # [Section] 158.2240(a)(3) 

Text of the Proposed Regulation (emphasis added) Nontarget organisms: General. "If the Agency 

determines that the transformation products of the parent compound are more toxic, persistent, 

bioaccumulative, or have been shown to cause adverse effects in mammalian or aquatic reproductive 

studies, then data on those transformation products are required to support registration." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated how the Agency will determine if the transformation products of the parent compound are 

more toxic, persistent, bioaccumulative, or have been shown to cause adverse effects in mammalian 

or aquatic reproductive studies. 

Response: see response 3 

Comment Code: 161000 Acute avian oral toxicity 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26471 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 925 

Comment Code: 161000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * Under Acute Avian Toxicity, the species proposed in this proposal differ from those in 

requirements for conventional pesticides, but no justification is provided. If there is a reason for 

differences, it should be provided. 

Response: see response 160.5 and testnote 160.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26741 

Comment Code: 161000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Under Acute Avian Toxicity, the species proposed in this 

proposal differ from those in requirements for conventional pesticides, but no justification is 

provided. If there is a reason for differences, it should be provided. 

Response: see response 160.5 and testnote 160.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27408 

Comment Code: 161000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Under Acute Avian Toxicity, the species proposed in this 

proposal differ from those in requirements for conventional pesticides, but no justification is 

provided. If there is a reason for differences, it should be provided. 

Response: see response 160.5 and testnote 160.1 

Comment Code: 162000 Acute aquatic toxicity studies (LC50 fish and EC50 invertebrate) 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25787 

Comment Code: 162000 

Comment: Aquatic Toxicity Testing 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 926 

Water quality agencies have refined aquatic toxicity test methods and updated the organisms selected 

for these test methods since U.S. EPA originally adopted Part 158. The U.S. EPA Office of 

Pesticide Programs should take this opportunity to modernize its methods and to make its program 

consistent with Clean Water Act implementation by requiring the use of the same test species. For 

example, when Part 158 was first established, Daphnia magna was the preferred freshwater aquatic 

invertebrate test species. Since then, Ceriodaphnia dubia has become the preferred test species for 

water quality agencies on the West Coast. 

Response: see response 190.2 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25790 

Comment Code: 162000 

Comment: U.S. EPA has proposed requiring acute freshwater fish and acute freshwater 

invertebrate toxicity testing for all antimicrobial pesticides for the technical grade active ingredient. 

Higher-tiered data would be required when the appropriate trigger is met. U.S. EPA proposes that 

these two aquatic toxicity tests be used in combination with the screening-level environmental fate 

assessment to assess impacts of antimicrobial pesticides on POTWs. Tri-TAC strongly disagrees 

with this proposal. For antimicrobial pesticides with uses that discharge to POTWs, it is essential to 

have both acute and chronic toxicity test results for at least one freshwater invertebrate, vertebrate, 

and plant species and at least one marine/estuarine invertebrate, vertebrate, and plant species to 

properly assess the potential impacts to POTWs and receiving waters. U.S. EPA requires POTWs 

regularly conduct acute and chronic aquatic toxicity tests as conditions in NPDES permits; 

therefore, Tri-TAC believes that it is reasonable for U.S. EPA to require adequate aquatic toxicity 

testing before registering antimicrobial pesticides with uses that discharge to POTWs. 

Response: see response 160.8 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25882 

Comment Code: 162000 

Comment: Aquatic Toxicity Testing 

Water quality agencies have refined aquatic toxicity test methods and updated the organisms selected 

for these test methods since U.S. EPA originally adopted Part 158. The U.S. EPA Office of 

Pesticide Programs should take this opportunity to modernize its methods and to make its program 

consistent with Clean Water Act implementation by requiring the use of the same test species. For 

example, when Part 158 was first established, Daphnia magna was the preferred freshwater aquatic 

invertebrate test species. Since then, Ceriodaphnia dubia has become the preferred test species for 

water quality agencies on the West Coast. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 927 

Response: see response 190.2 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25886 

Comment Code: 162000 

Comment: U.S. EPA has proposed requiring acute freshwater fish and acute freshwater 

invertebrate toxicity testing for all antimicrobial pesticides for the technical grade active ingredient. 

Higher-tiered data would be required when the appropriate trigger is met. U.S. EPA proposes that 

these two aquatic toxicity tests be used in combination with the screening-level environmental fate 

assessment to assess impacts of antimicrobial pesticides on POTWs. CASA strongly disagrees with 

this proposal. For antimicrobial pesticides with uses that discharge to POTWs, it is essential to have 

both acute and chronic toxicity test results for at least one freshwater invertebrate, vertebrate, and 

plant species and at least one marine/estuarine invertebrate, vertebrate, and plant species to properly 

assess the potential impacts to POTWs and receiving waters. U.S. EPA requires POTWs regularly 

conduct acute and chronic aquatic toxicity tests as conditions in NPDES permits; therefore, CASA 

believes that it is reasonable for U.S. EPA to require adequate aquatic toxicity testing before 

registering antimicrobial pesticides with uses that discharge to POTWs. 

Response: see response 160.8 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25986 

Comment Code: 162000 

Comment: * EPA has proposed requiring acute freshwater fish and acute freshwater invertebrate 

toxicity testing for all antimicrobial pesticides for the technical grade active ingredient. Higher-tiered 

data would be required when the appropriate trigger is met. EPA proposes that these two aquatic 

toxicity tests be used in combination with the screening-level environmental fate assessment to 

assess impacts of antimicrobial pesticides on POTWs. NACWA believes it is essential to have both 

acute and chronic toxicity test results for at least one freshwater invertebrate, vertebrate, and plant 

species and at least one marine/estuarine invertebrate, vertebrate, and plant species to properly 

assess the potential impacts to POTWs and receiving waters. 

Response: see response 160.8 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26041 

Comment Code: 162000 

Comment: Proposed Data Requirements - Aquatic Toxicity 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 928 

We support USEPA’s proposal to require a minimum aquatic toxicity data set for all antimicrobial 

pesticides. The paucity of aquatic toxicity data for antimicrobials has interfered with government’s 

ability to ensure that outdoor antimicrobial pesticide use does not adversely impact urban creeks, 

rivers, estuaries and near-shore ocean waters. As explained below, USEPA should expand and 

modify the proposed requirements to harmonize with the aquatic toxicity testing methods used in 

USEPA’s implementation of the Clean Water Act. 

* Proposed requirement does not include sufficient species. The proposed rule requires only three 

aquatic toxicity data points as a minimum data set: acute toxicity for one fresh water fish (species 

unspecified), acute toxicity for one fresh water invertebrate (species unspecified), and chronic 

toxicity for one plant (green algae). These minimum data will be too few to meet USEPA’s 

environmental risk assessment needs. USEPA Office of Water requires data from eight families 

(taxa) of aquatic animals as the minimum data set for water quality criteria development (eight 

additional saltwater values and at least four chronic toxicity values would be needed to develop a full 

set of water quality criteria).[FN2:USEPA (1985). Guidelines for deriving numerical national water 

quality criteria for the protection of aquatic organisms and their uses. PB-85-227049.] The Office of 

Water insists on a more robust data set because interspecies variation can be significant. Variations 

of orders of magnitude are not uncommon.[FN3:Demonstrated by data in the USEPA database. 

Recent research specifically to this question has been conducted by NOAA Fisheries (e.g., Fulton, 

M. et al. (2008) Comparative Toxicity Assessments of Urban Pesticides in Estuarine Biota. 

Presentation at SETAC North America Conference, Tampa FL. November.)] Consider the 

following examples: 

- The chlorpyrifos LC50s for two species of freshwater fish (Fathead minnow and Bluegill) differ by 

a factor of 90. Two saltwater fish (Sheepshead minnow and Silverside [Menidia menidia]) have 

chlorpyrifos LC50s that differ by a factor of almost 400. 

- The diazinon LC50s for two species of freshwater fish (Fathead minnow and Rainbow trout) differ 

by a factor of 85. 

- The freshwater sediment bifenthrin LC50 of two invertebrates (Daphnia magna and Hyalella 

azteca) differs by a factor of 150. 

* Species should be specified to match requirements of Office of Water. Test notes should specify 

the same species and test methods as USEPA Office of Water requires for effluent toxicity testing, 

which are listed in 40 Code of Federal Regulations (CFR) Part 136.3, Table 1A (copy enclosed [See 

attachments in PDF docket ID EPA-HQ- OPP-2008-0110-0089]). Since the selection of standard 

test species used by the Office of Water for Clean Water Act implementation has been through 

scientific review, this addition would be appropriate and would facilitate both FIFRA and Clean 

Water Act compliance. Harmonization of requirements will help avoid the problematic regulatory 

gaps that have occurred with pesticides like diazinon and chlorpyrifos. 

* Salt water species aquatic toxicity data need to be included in the minimum data set for all 

antimicrobials that may be used outdoors in urban areas. Any pesticide used outdoors in coastal 

urban areas like the San Francisco, Los Angeles, and San Diego areas would be "likely to enter the 

estuarine/marine environment," thus meeting the condition for requiring these additional tests. If 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 929 

these data are not included among the minimum data set, the regulation should be revised to clarify 

that implementation of this requirement is expected to be quite common. 

* Aquatic organism testing guidelines should be updated to harmonize with Office of Water 

methods. We encourage OPP to update its aquatic toxicity testing Guidelines to harmonize them 

with Clean Water Act requirements. Since the Office of Water’s approved aquatic toxicity testing 

methods (which are listed in 40CFR136.3 Table 1A) [See PDF docket ID EPA-HQ-OPP-2008-110-

0089] have already been through scientific peer review, updates based on Office of Water’s 

approved methods should be relatively straightforward. 

Response: see response 190.2 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26108 

Comment Code: 162000 

Comment: Aquatic Toxicity Testing 

Water quality agencies have refined aquatic toxicity test methods and updated the organisms selected 

for these test methods since U.S. EPA originally adopted Part 158. The U.S. EPA Office of 

Pesticide Programs should take this opportunity to modernize its methods and to make its program 

consistent with Clean Water Act implementation by requiring the use of the same test species. For 

example, when Part 158 was first established, Daphnia magna was the preferred freshwater aquatic 

invertebrate test species. Since then, Ceriodaphnia dubia has become the preferred test species for 

water quality agencies on the West Coast. 

Response: see response 190.2 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26111 

Comment Code: 162000 

Comment: U.S. EPA has proposed requiring acute freshwater fish and acute freshwater 

invertebrate toxicity testing for all antimicrobial pesticides for the technical grade active ingredient. 

Higher-tiered data would be required when the appropriate trigger is met. U.S. EPA proposes that 

these two aquatic toxicity tests be used in combination with the screening-level environmental fate 

assessment to assess impacts of antimicrobial pesticides on POTWs. The Districts strongly disagree 

with this proposal. For antimicrobial pesticides with uses that discharge to POTWs, it is essential to 

have both acute and chronic toxicity test results for at least one freshwater invertebrate, vertebrate, 

and plant species and at least one marine/estuarine invertebrate, vertebrate, and plant species to 

properly assess the potential impacts to POTWs and receiving waters. U.S. EPA requires POTWs 

regularly conduct acute and chronic aquatic toxicity tests as conditions in NPDES permits; 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 930 

therefore, the Districts believe that it is reasonable for U.S. EPA to require adequate aquatic toxicity 

testing before registering antimicrobial pesticides with uses that discharge to POTWs. 

Response: see response 160.8 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26478 

Comment Code: 162000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * Under Acute Aquatic Toxicity, for low exposure, the proposed regulation states that 

"testing on a second species is required if the active ingredient or principal transformation products 

are stable in the environment or if the LC50 in the first species tested is greater that 1ppm." The 

EPA must explain what is considered "stable" in the environment, and how a registrant would 

determine if "transformation products" would need to be tested. EPA should justify its selection of 

1 mg/L to trigger additional testing and discuss its rationale for conducting additional testing on less 

toxic compounds. It would seem that more testing should be conducted on more toxic compounds. 

Response: see response 160.3 and testnote 160.3 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26488 

Comment Code: 162000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * The EPA should also explain what the basis is for the trigger point in footnote 7(i). 

Response: see response 160.9 and testnote 160.7 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26521 

Comment Code: 162000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * Guideline 850.1010 and 1075 are listed as "NR" for wood preservatives, but footnote 7 

then lists the criteria that trigger testing. If they are required, the difference between "CR" and "NR" 

is unclear. 

Response: see response 160.7 and testnote 160.7 

Commenter Name: Hasmukh C. Shah 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 931 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26760 

Comment Code: 162000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Under Acute Aquatic Toxicity, for low exposure, the 

proposed regulation states that "testing on a second species is required if the active ingredient or 

principal transformation products are stable in the environment or if the LC50 in the first species 

tested is greater that 1ppm." The EPA must explain what is considered "stable" in the environment, 

and how a registrant would determine if "transformation products" would need to be tested. 

Response: see response 160.3 and testnote 160.3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26787 

Comment Code: 162000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * The EPA should also explain what the basis is for the 

trigger point in footnote 7(i). 

Response: see response 160.9 and testnote 160.7 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26801 

Comment Code: 162000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Guideline 850.1010 and 1075 are listed as "NR" for wood 

preservatives, but footnote 7 then lists the criteria that trigger testing. If they are required, the 

difference between "CR" and "NR" is unclear. 

Response: see response 160.7 and testnote 160.7 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27421 

Comment Code: 162000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Under Acute Aquatic Toxicity, for low exposure, the 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 932 

proposed regulation states that "testing on a second species is required if the active ingredient or 

principal transformation products are stable in the environment or if the LC50 in the first species 

tested is greater that 1ppm." The EPA must explain what is considered "stable" in the environment, 

and how a registrant would determine if "transformation products" would need to be tested. 

Response: see response 160.3 and testnote 160.3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27425 

Comment Code: 162000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * The EPA should also explain what the basis is for the 

trigger point in footnote 7(i). 

Response: see response 160.9 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27445 

Comment Code: 162000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Guideline 850.1010 and 1075 are listed as "NR" for wood 

preservatives, but footnote 7 then lists the criteria that trigger testing. If they are required, the 

difference between "CR" and "NR" is unclear. 

Response: see response 160.7 and testnote 160.7 

Comment Code: 164000 Avian reproduction 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26459 

Comment Code: 164000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * Although the footnotes for avian reproduction studies indicate this is a requirement for 

low exposure actives, they do not explain why. The EPA also sets out four criteria, any one of which 

may trigger the need for a study; but fails to explain, for example, how that study relates to an in-can 

preservative. In addition, the EPA justifies the need for this study based on metabolites, and 

transformation products preceding or during the breeding season. While product use is year- round 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 933 

for antimicrobials, there is rarely any environmental exposure. The Agency also fails to explain how 

the metabolites or transformation products may persist in animal feed or how the environmental 

fate of a compound may affect this requirement. If a product hydrolyzes and is used as an in-can 

preservative, there should be no need a study of this type. 

* The EPA has not provided a definition of persistence and structural similarity to other 

compounds, which is used to capture as many compounds for testing as possible. 

Response: see response 160.36 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26461 

Comment Code: 164000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * If the EPA does not eliminate the testing requirement for avian reproduction or use a risk 

based trigger, the EPA needs to support its decision to use 100 mg a.i./kg as the trigger for 

additional testing. Selection of this concentration seems arbitrary when EPA could use exposure 

tools to conduct an initial assessment based on tier one data, and could trigger additional testing 

based on risk. 

Response: The commenter has confused the triggers for the avian dietary toxicity study and the 

avian reproduction study. see response 160.10 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26462 

Comment Code: 164000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * The likelihood of adverse effects on avian populations from the use of biocides is remote. 

Thus, any testing with avian species is not warranted because it requires unnecessary testing on 

animals, and cannot be supported on scientific grounds. EPA has failed to provide justification for 

this. All requirements-tier 1 and higher tiers-for avian testing of low exposure compounds should be 

reconsidered and eliminated as testing requirements. 

Response: see response 160.36 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26469 

Comment Code: 164000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 934 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * If avian testing is not eliminated, the EPA needs to support its selection of a log Kow of 

3.0 to trigger avian reproductive studies. 

Response: see response 160.11 and testnote 160.6 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26472 

Comment Code: 164000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * For avian reproduction, footnotes 1 and 6 seem to be contradictory. Footnote 1 requires a 

single avian reproduction study for all exposures and a second species for the high exposures, while 

footnote 6 stipulates conditions that trigger when a single study would be required. 

* Under footnote 6(i), the EPA does not specify whether it regards industrial process water systems 

(once through), and antifouling and wood preservatives (heavy duty and marine) as satisfying the 

criteria of repeated or continuous exposure. Testing is needed when there is conflicting information 

for footnote 6(iii), such that the Kow is < 1000 for the compound, but BCF data for a structurally 

similar molecule shows some bioaccumulative potential. The EPA should clarify these conflicting 

points as well. 

* The EPA also must clarify what is needed when a mammalian reproduction study indicates some 

adverse effects, but the study in the first avian species is negative. It is unclear whether a second 

study is required under footnote 6(iv). 

Response: see response 160.12, and testnotes 160.1 and 160.6 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26735 

Comment Code: 164000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Although the footnotes for avian reproduction studies 

indicate this is a requirement for low exposure actives, they do not explain why. The EPA also sets 

out four criteria, any one of which may trigger the need for a study; but fails to explain, for example, 

how that study relates to an in-can preservative. In addition, the EPA justifies the need for this study 

based on metabolites, and transformation products preceding or during the breeding season. While 

product use is year-round for antimicrobials, there is rarely any environmental exposure. The Agency 

also fails to explain how the metabolites or transformation products may persist in animal feed or 

how the environmental fate of a compound may affect this requirement. If a product hydrolyzes and 

is used as an in-can preservative, there should be no for need a study of this type. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 935 

[The Panel has listed the following points of contention in the proposed regulation for data 

requirements of ecological effects:] * The EPA has not provided a definition of persistence and 

structural similarity to other compounds, which is used to capture as many compounds for testing as 

possible. 

Response: see response 160.36 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26737 

Comment Code: 164000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * If the EPA does not eliminate the testing requirement for 

avian reproduction or use a risk based trigger, the EPA needs to support its decision to use 100 mg 

a.i./kg as the trigger for additional testing. Selection of this concentration seems arbitrary when EPA 

could use exposure tools to conduct an initial assessment based on tier one data, and could trigger 

additional testing based on risk 

Response: The commenter has confused the triggers for the avian dietary toxicity study and the 

avian reproduction study. see response 160.10 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26738 

Comment Code: 164000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * The likelihood of adverse effects on avian populations 

from the use of biocides is remote. Thus, any testing with avian species is not warranted because it 

requires unnecessary testing on animals, and cannot be supported on scientific grounds. Indeed the 

EPA has failed to provide justification for this. All requirements-tier 1 and higher tiers-for avian 

testing of low exposure compounds should be reconsidered and eliminated. 

Response: see response 160.36 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26740 

Comment Code: 164000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * If avian testing is not eliminated, the EPA needs to 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 936 

support its selection of a log Kow of 3.0 to trigger avian reproductive studies. 4 Page 59405. 5 

Section 1582240 NonTarget Organisms, Paragraph 3. 

Response: see response 160.11 and testnote 160.6 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26742 

Comment Code: 164000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * For avian reproduction, footnotes 1 and 6 seem to be 

contradictory. Footnote 1 requires a single avian reproduction study for all exposures and a second 

species for the high exposures, while footnote 6 stipulates conditions that trigger when a single study 

would be required. 

[The Panel has listed the following points of contention in the proposed regulation for data 

requirements of ecological effects:] * Under footnote 6(i), the EPA does not specify whether it 

regards industrial process water systems (once through), and antifouling and wood preservatives 

(heavy duty and marine) as meeting the criteria of repeated or continuous exposure. Testing is 

needed when there is conflicting information for footnote 6(iii), such that the Kow is < 1000 for the 

compound, but BCF data for a structurally similar molecule shows some bioaccumulative potential. 

The EPA should clarify these conflicting points as well. 

[The Panel has listed the following points of contention in the proposed regulation for data 

requirements of ecological effects:] * The EPA also must clarify what is needed when a mammalian 

reproduction study indicates some adverse effects, but the study in the first avian species is negative. 

It is unclear whether a second study required under footnote 6(iv). 

Response: see response 160.12, and testnotes 160.1 and 160.6 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27402 

Comment Code: 164000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Although the footnotes for avian reproduction studies 

indicate this is a requirement for low exposure actives, they do not explain why. The EPA also sets 

out four criteria, any one of which may trigger the need for a study; but fails to explain, for example, 

how that study relates to an in-can preservative. In addition, the EPA justifies the need for this study 

based on metabolites, and transformation products preceding or during the breeding season. While 

product use is year-round for antimicrobials, there is rarely any environmental exposure. The Agency 

also fails to explain how the metabolites or transformation products may persist in animal feed or 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 937 

how the environmental fate of a compound may affect this requirement. If a product hydrolyzes and 

is used as an in-can preservative, there should be no for need a study of this type. 

* The EPA has not provided a definition of persistence and structural similarity to other 

compounds, which is used to capture as many compounds for testing as possible. 

Response: see response 160.36, and testnotes 160.1 and 160.6 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27404 

Comment Code: 164000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * If the EPA does not eliminate the testing requirement for 

avian reproduction or use a risk based trigger, the EPA needs to support its decision to use 100 mg 

a.i./kg as the trigger for additional testing. Selection of this concentration seems arbitrary when EPA 

could use exposure tools to conduct an initial assessment based on tier one data, and could trigger 

additional testing based on risk 4 Page 59405. 5 Section 1582240 NonTarget Organisms, Paragraph 

3. 

Response: The commenter has confused the triggers for the avian dietary toxicity study and the 

avian reproduction study. see response 160.10 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27405 

Comment Code: 164000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * The likelihood of adverse effects on avian populations 

from the use of biocides is remote. Thus, any testing with avian species is not warranted because it 

requires unnecessary testing on animals, and cannot be supported on scientific grounds. Indeed the 

EPA has failed to provide justification for this. All requirements-tier 1 and higher tiers-for avian 

testing of low exposure compounds should be reconsidered and eliminated. 

Response: see response 160.36 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27406 

Comment Code: 164000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 938 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * If avian testing is not eliminated, the EPA needs to 

support its selection of a log Kow of 3.0 to trigger avian reproductive studies. 

Response: see response 160.11 and testnote 160.6 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27415 

Comment Code: 164000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * For avian reproduction, footnotes 1 and 6 seem to be 

contradictory. Footnote 1 requires a single avian reproduction study for all exposures and a second 

species for the high exposures, while footnote 6 stipulates conditions that trigger when a single study 

would be required. 

* Under footnote 6(i), the EPA does not specify whether it regards industrial process water systems 

(once through), and antifouling and wood preservatives (heavy duty and marine) as meeting the 

criteria of repeated or continuous exposure. Testing is needed when there is conflicting information 

for footnote 6(iii), such that the Kow is < 1000 for the compound, but BCF data for a structurally 

similar molecule shows some bioaccumulative potential. The EPA should clarify these conflicting 

points as well. 

* The EPA also must clarify what is needed when a mammalian reproduction study indicates some 

adverse effects, but the study in the first avian species is negative. It is unclear whether a second 

study is required under footnote 6(iv). 

Response: see response 160.12, and testnotes 160.1 and 160.6 

Comment Code: 165000 Acute estuarine and marine study 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26474 

Comment Code: 165000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * Aquatic Organism Testing: Footnotes 9/10 (Page 59438) Under the aquatic organism 

testing section, the term "as defined by the Agency" is vague, arbitrary and capricious because it 

does not provide any quantitative criteria to substantiate the need for a number of studies. For "low 

exposure" uses, a registrant’s fate is determined by the EPA and it is unclear what will be required 

next. The EPA should also define "toxicity to aquatic organisms," and whether there is a specific 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 939 

LC50 of an ingredient that would trigger TEP testing. How the level of this ingredient in a product 

relates to triggering TEP testing also must be explained. 

* Under the section, "Acute estuarine and marine organisms toxicity/Fish early lifestage testing," 

testing should be required only when an environmental risk assessment has been conducted with 

Tier I data and additional data are needed. 

Response: see responses 3, 160.13 and 160.14, and testnotes 160.9 and 160.10 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26508 

Comment Code: 165000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * Footnote 8 requires testing for each of estuarine/marine mollusk, invertebrate, and 

fish.[FN#10: GLN No.’s 850.1025, 1035, and 1075, respectively.] EPA should clarify why a Penaeid 

acute toxicity [FN#11: 850.1045.] and a bivalve acute toxicity - embryo larval [FN#12: 850.1055.] 

study are included. If these studies are optional or if the registrant can choose one, the EPA should 

clearly indicate as much. 

Response: see response 160.15 and testnote 160.8 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26745 

Comment Code: 165000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Aquatic Organism Testing: Footnotes 9/10 (Page 59438). 

Under the aquatic organism testing section, the term "as defined by the Agency" does not provide 

any quantitative criteria to substantiate the need for a number of studies. For "low exposure" uses, a 

registrant’s fate is determined by the EPA and it is unclear what will be required. The EPA should 

also define "toxicity to aquatic organisms," and whether there is a specific LC50 of an ingredient that 

would trigger TEP testing. How the level of this ingredient in a product relates to triggering TEP 

testing also must be explained. 

[The Panel has listed the following points of contention in the proposed regulation for data 

requirements of ecological effects:] * Under the section, "Acute estuarine and marine organisms 

toxicity/Fish early lifestage testing," testing should be required only when an environmental risk 

assessment has been conducted with Tier I data and additional data are needed. 

Response: see responses 3, 160.13 and 160.14, and testnotes 160.9 and 160.10 

Commenter Name: Hasmukh C. Shah 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 940 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26789 

Comment Code: 165000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Footnote 8 requires testing for each of estuarine/marine 

mollusk, invertebrate, and fish.[FN#6:GLN No.’s 850.1025, 1035, and 1075, respectively.] EPA 

should clarify why a Penaeid acute toxicity [FN#7:850.1045.] and a bivalve acute toxicity - embryo 

larval [FN#8:850.1055.] study are included. If these studies are optional or if the registrant can 

choose one, the EPA should clearly indicate as much. 

Response: see response 160.15 and testnote 160.8 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27417 

Comment Code: 165000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Aquatic Organism Testing: Footnotes 9/10 (Page 59438). 

Under the aquatic organism testing section, the term "as defined by the Agency" does not provide 

any quantitative criteria to substantiate the need for a number of studies. For "low exposure" uses, a 

registrant’s fate is determined by the EPA and it is unclear what will be required. The EPA should 

also define "toxicity to aquatic organisms," and whether there is a specific LC50 of an ingredient that 

would trigger TEP testing. How the level of this ingredient in a product relates to triggering TEP 

testing also must be explained. 

* Under the section, "Acute estuarine and marine organisms toxicity/Fish early lifestage testing," 

testing should be required only when an environmental risk assessment has been conducted with 

Tier I data and additional data are needed. 

Response: see responses 3, 160.13 and 160.14, and testnotes 160.9 and 160.10 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27433 

Comment Code: 165000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Footnote 8 requires testing for each of estuarine/marine 

mollusk, invertebrate, and fish.[FN#6:GLN No.’s 850.1025, 1035, and 1075, respectively.] EPA 

should clarify why a Penaeid acute toxicity [FN#7:850.1045.] and a bivalve acute toxicity - embryo 

larval [FN#8:850.1055.] study are included. If these studies are optional or if the registrant can 

choose one, the EPA should clearly indicate as much. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 941 

Response: see response 160.15 and testnote 160.8 

Comment Code: 166000 Fish early life stage and aquatic invertebrate life-cycle study 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26239 

Comment Code: 166000 

Comment: * The Agency has not set forth the criteria to determine whether, for low environmental 

exposures, pesticide residues from the parent compound or transformation products are likely to 

enter freshwater or estuarine/marine environments. In addition, the Agency failed to identify the 

factors to determine whether pesticide residues from the parent compound, transformation 

products, and/or leachates from preservative treated wood, are likely to enter freshwater or 

estuarine/marine environments. An applicant must consult with the Agency to determine if data are 

required for nontarget organisms in these circumstances, in the sole judgment of the 

Agency.[FN#10:Id. at [Section] 158.2240(f)(10).] 

Response: see response 160.13 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26485 

Comment Code: 166000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * Under the Fish ELS and Aquatic Invertebrate Life-Cycle requirements, the EPA should 

explain if these are for freshwater species, and how the Agency determines if treated wood residues 

would be likely to enter freshwater or estuarine/marine environments. 

Response: see responses 160.13 and 160.18 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26750 

Comment Code: 166000 

Comment: * The Agency has not set forth clearly the criteria it will use to determine whether, for 

low environmental exposures, pesticide residues from the parent compound or transformation 

products are likely to enter freshwater or estuarine/marine environments. In addition, the Agency 

failed to state the factors it will use to determine whether pesticide residues from the parent 

compound, transformation products, and/or leachates from preservative treated wood, are likely to 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 942 

enter freshwater or estuarine/marine environments. Without further clarification, an applicant must 

consult with the Agency to determine if data are required for nontarget organisms in these 

circumstances.[FN10: Id. at § 158.2240(f)(10).] 

Response: see response 160.13 and testnote 160.10 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26761 

Comment Code: 166000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Under the Fish Early Life Stage and Aquatic Invertebrate 

Life-Cycle requirements, the EPA should explain if these are for freshwater species, and how the 

Agency determines if treated wood residues would be likely to enter freshwater or estuarine/marine 

environments. 

Response: see responses 160.13 and 160.18 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26995 

Comment Code: 166000 

Comment: 21. Proposed Regulation # [Section] 158.2240(f)(10) 

Text of the Proposed Regulation (emphasis added) Nontarget organisms: Test notes. "For low 

environmental exposures, data are required if pesticide residues from the parent compound or 

transformation products are likely to enter freshwater or estuarine/marine environments, as 

determined by the Agency. For wood preservatives, data are required if pesticide residues from the 

parent compound, transformation products, and/or leachates from preservative-treated wood are 

likely to enter freshwater or estuarine/marine environments, as determined by the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the factors it will use to determine whether for low environmental exposures, pesticide 

residues from the parent compound or transformation products are likely to enter freshwater or 

estuarine/marine environments. In addition, the Agency not adequately stated the factors it will use 

to determine whether, for food preservatives, pesticide residues from the parent compound, 

transformation products, and/or leachates from preservative treated wood are likely to enter 

freshwater or estuarine/marine environments. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 943 

Letter ID: 0064 

Comment ID: 27422 

Comment Code: 166000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Under the Fish Early Life Stage and Aquatic Invertebrate 

Life-Cycle requirements, the EPA should explain if these are for freshwater species, and how the 

Agency determines if treated wood residues would be likely to enter freshwater or estuarine/marine 

environments. 

Response: see responses 160.13 and 160.18 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27693 

Comment Code: 166000 

Comment: 21. Proposed Regulation # [Section] 158.2240(f)(10) 

Text of the Proposed Regulation (emphasis added) Nontarget organisms: Test notes. "For low 

environmental exposures, data are required if pesticide residues from the parent compound or 

transformation products are likely to enter freshwater or estuarine/marine environments, as 

determined by the Agency. For wood preservatives, data are required if pesticide residues from the 

parent compound, transformation products, and/or leachates from preservative-treated wood are 

likely to enter freshwater or estuarine/marine environments, as determined by the Agency." 

The Proposed Regulations Are Vague for the Following Reasons The Agency has not adequately 

stated the factors it will use to determine whether for low environmental exposures, pesticide 

residues from the parent compound or transformation products are likely to enter freshwater or 

estuarine/marine environments. In addition, the Agency not adequately stated the factors it will use 

to determine whether, for food preservatives, pesticide residues from the parent compound, 

transformation products, and/or leachates from preservative treated wood are likely to enter 

freshwater or estuarine/marine environments. 

Response: see response 3 

Comment Code: 167000 Fish life cycle 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25698 

Comment Code: 167000 

Comment: Chronic aquatic toxicity 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 944 

SFE is pleased that EPA recognizes that acute toxicity studies are not a reliable indicator of chronic 

sensitivity, and that chronic data are therefore essential (FR Notice at p. 59414). SFE and the 

SFPUC support the additions to the rule to include chronic toxicity aquatic testing among the 

requirements for antimicrobials. Toxicity test results for sub-lethal end points other than growth and 

reproduction are also necessary. For example, effects on behavior, swimming performance (which 

affects a fish’s ability to maintain proper position in the water column, avoid predators, and capture 

food), and reproduction can be critical to the survival of a species. 

Aquatic toxicity reviews require data from additional species 

EPA currently requires pesticide toxicity data on a small number of aquatic species and for a limited 

number of chronic exposure endpoints. As a result, the Agency is unable to determine, for example, 

whether other pesticides may cause the kind of subtle, low concentration effects on fish behavior 

that diazinon does.[FN4: Scholz, N. L. et al. (2000). Diazinon disrupts antipredator and homing 

behaviors in Chinook salmon (Oncorhynchus tshawytscha). Can J Fish Aquat Sci 57:1911-1918.] In 

addition, it is difficult to extrapolate from one or two test species to predict the effects on additional 

species. The Agency would be in a much better position if it had available the range of aquatic test 

data required to calculate water quality criteria, which in fact exist for almost no modern pesticides 

except for a few widely used in agriculture. SFE and the SFPUC suggest that EPA conduct a 

thorough search of the scientific literature every time a pesticide is registered or reregistered. For any 

antimicrobial pesticide that has the potential to be discharged to surface water either directly (e.g., 

via direct application or stormwater runoff) or indirectly (e.g., via a municipal wastewater treatment 

plant), registrants should be required to supply any additional data needed to derive a water quality 

criterion for the pesticide in question. 

Response: EPA acknowledges SFE's and SFPUC's support for requiring higher-tiered chronic 

toxicity aquatic testing. see also 160.21 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26476 

Comment Code: 167000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * Under footnote 12.i of the fish life cycle requirement, exposure based risk assessment 

should be extended to point 12.ii. Identification is needed for organisms to be used in the 

assessment and concentrations are considered significant enough to trigger this requirement. 

Response: see response 160.19 and testnote 160.12 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26511 

Comment Code: 167000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 945 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * The EPA should clarify the basis for the trigger point in footnote 12(i). 

* Under footnote 12(ii), the EPA should clarify if the fish life cycle test would be triggered by 

mammalian and/or avian reproductive effects even if no effects on reproductive physiology were 

seen in the fish life cycle test. 

Response: see response 160.20 and testnote 160.12 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26758 

Comment Code: 167000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Under footnote 12.i of the fish life cycle requirement, 

exposure based risk assessment should be extended to point 12.ii. Identification is needed for 

organisms to be used in the assessment and concentrations are considered significant enough to 

trigger this requirement. 

Response: see response 160.19 and testnote 160.12 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26792 

Comment Code: 167000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * The EPA should clarify the basis for the trigger point in 

footnote 12(i). 

[The Panel has listed the following points of contention in the proposed regulation for data 

requirements of ecological effects:] * Under footnote 12(ii), the EPA should clarify if the fish life 

cycle test would be triggered by mammalian and/or avian reproductive effects even if no effects on 

reproductive physiology were seen in the fish life cycle test. 

Response: see response 160.20 and testnote 160.12 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27419 

Comment Code: 167000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 946 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Under footnote 12.i of the fish life cycle requirement, 

exposure based risk assessment should be extended to point 12.ii. Identification is needed for 

organisms to be used in the assessment and concentrations are considered significant enough to 

trigger this requirement. 

Response: see response 160.19 and testnote 160.12 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27435 

Comment Code: 167000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * The EPA should clarify the basis for the trigger point in 

footnote 12(i). 

* Under footnote 12(ii), the EPA should clarify if the fish life cycle test would be triggered by 

mammalian and/or avian reproductive effects even if no effects on reproductive physiology were 

seen in the fish life cycle test. 

Response: see response 160.20 and testnote 160.12 

Comment Code: 168000 Aquatic organisms, bioavailability, biomagnification toxicity tests 

Commenter Name: Jamie S. Heisig-Mitchell 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 

Comment ID: 25452 

Comment Code: 168000 

Comment: *Though higher tier tests for biomagnification are necessary to determine potential 

exposure levels throughout the food chain, this does not equate to a toxic effect. Additional studies 

would be necessary to determine the ecological impact of any biomagnification on the food web. 

Response: see response 160.23 

Commenter Name: Jamie S. Heisig-Mitchell 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 

Comment ID: 25454 

Comment Code: 168000 

Comment: Quality Assurance 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 947 

*Many of the aquatic toxicity methods fail to recommend adequate quality assurance procedures 

such as reference tests which assess the ability of the testing system to produce acceptable and 

reliable data. 

Response: see response 160.22 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25992 

Comment Code: 168000 

Comment: * Though higher tier tests for biomagnification are necessary to determine potential 

exposure levels throughout the food chain, this does not equate to a toxic effect. Additional studies 

would be necessary to determine the ecological impact of any biomagnification on the food web. 

Response: see response 160.23 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25993 

Comment Code: 168000 

Comment: * Many of the aquatic toxicity methods fail to recommend adequate quality ssurance 

procedures such as reference tests which assess the ability of the testing system to produce 

acceptable and reliable data. 

* EPA should consider the potential for these ingredients to impact air emissions from the POTW 

as they degrade in the treatment process. 

Response: see responses 160.22 and 160.24 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26519 

Comment Code: 168000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * Regarding footnote 13(iii), freshwater and marine waters are mostly in the pH 7 - 8.2 

range. Therefore, the hydrolytic effects at pH 5 are environmentally irrelevant. EPA should consider 

dropping the criteria for pH 5 and 9 and include marine water instead, so that the BCF test would 

not be required if the hydrolytic half-life is less than 5 days at pH 7 and in marine water. Also, the 

EPA should explain what the basis is for five days. 

Response: see response 160.37 and testnote 160.13 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 948 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26799 

Comment Code: 168000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Regarding footnote 13(iii), freshwater and marine waters 

are mostly in the pH 7 - 8.2 range. Therefore, the hydrolytic effects at pH 5 are environmentally 

irrelevant. EPA should consider dropping the criteria for pH 5 and 9 and include marine water 

instead, so that the BCF test would not be required if the hydrolytic half-life is less than 5 days at pH 

7 and in marine water. Also, the EPA should explain what the basis is for five days. 

Response: see response 160.37 and testnote 160.13 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27443 

Comment Code: 168000 

Comment: LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Regarding footnote 13(iii), freshwater and marine waters 

are mostly in the pH 7 - 8.2 range. Therefore, the hydrolytic effects at pH 5 are environmentally 

irrelevant. EPA should consider dropping the criteria for pH 5 and 9 and include marine water 

instead, so that the BCF test would not be required if the hydrolytic half-life is less than 5 days at pH 

7 and in marine water. Also, the EPA should explain what the basis is for five days. 

Response: see response 160.37 and testnote 160.13 

Comment Code: 169000 Simulated or actual field testing for aquatic organisms 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26400 

Comment Code: 169000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * EPA must specify how the Agency will determine if the transformation products are more 

toxic, persistent, bioaccumulative or have been shown to cause adverse effects in mammalian or 

aquatic reproductive studies.[FN#9: Section 1582240 Non- Target Organisms, Paragraph 3.] More 

transparency and the use of readily available and reviewed methods would help the registrant 

anticipate EPA’s needs and meet those needs accordingly. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 949 

Response: see response 160.3 and testnote 160.9 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26533 

Comment Code: 169000 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * Under guideline number 850.1950 low environmental exposure patterns should be "NR" 

for these requirements as the category itself implies exemption via footnote 17. 

Response: see response 160.26 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26823 

Comment Code: 169000 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Under guideline number 850.1950 low environmental 

exposure patterns should be "NR" for these requirements as the category itself implies exemption 

via footnote 17. 

Response: see response 160.26 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26997 

Comment Code: 169000 

Comment: 22. Proposed Regulation # [Section] 158.2240(f)(15) 

Text of the Proposed Regulation (emphasis added) Nontarget organisms: Test notes. "Protocols 

must be approved by the Agency prior to the initiation of the study. Details for developing 

protocols are available from the Agency." 

The Proposed Regulations Are Vague for the Following Reasons Although the Agency states that 

the details for developing protocols are available from the Agency, the Agency has not adequately 

explained what the protocols entail. These required private negotiations are a procedure for the 

development of later tests. 

Response: see response 3 

Commenter Name: Stanley Oslosky 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 950 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27470 

Comment Code: 169000 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * Under guideline number 850.1950 low environmental 

exposure patterns should be "NR" for these requirements as the category itself implies exemption 

via footnote 17. 

Response: see response 160.26 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27694 

Comment Code: 169000 

Comment: 22. Proposed Regulation # [Section] 158.2240(f)(15) 

Text of the Proposed Regulation (emphasis added) Nontarget organisms: Test notes. "Protocols 

must be approved by the Agency prior to the initiation of the study. Details for developing 

protocols are available from the Agency." 

The Proposed Regulations Are Vague for the Following Reasons Although the Agency states that 

the details for developing protocols are available from the Agency, the Agency has not adequately 

explained what the protocols entail. These required private negotiations are a procedure for the 

development of later tests. 

Response: see response 3 

Comment Code: 169100 Sediment testing 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26523 

Comment Code: 169100 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * There is no indication of the role that efate of a compound will play in the need for 

sediment testing as well as leaching. Use of a persistence criteria without further explanation of 

"persistence" is vague. The EPA states that only one of many criteria would need to be met, 

indicating that many products will fall into this category.[FN#13:page 59415] 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 951 

* The EPA should define "significant potential exposure" under the sediment testing section. 

Comments used for the conventional pesticides should be included here since they are the same. 

Again multiple criteria are being used in footnotes 17 and18 and it will difficult for simple actives to 

escape the need for doing these studies. In addition, the EPA should explain (1) the role of 

absorption/desorption and efate, aside from the current criteria; (2) which testing protocols are to 

be followed; (3) whether compounds that do not enter marine or brackish water would still be 

required to be tested; and (4) the role of earlier invertebrate tests and the use pattern of the product. 

Response: see responses 160.27, 160.28, 160.29, and 160.30, and testnotes 160.9, 160.17, and 

160.18 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26803 

Comment Code: 169100 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * There is no indication of the role that environmental fate 

of a compound will play in the need for sediment testing as well as leaching. Use of a persistence 

criterion without further explanation of "persistence" is vague. The EPA states that only one of 

many criteria would need to be met, indicating that many products will fall into this 

category.[FN#9:page 59415] 

[The Panel has listed the following points of contention in the proposed regulation for data 

requirements of ecological effects:] * The EPA should define "significant potential exposure" under 

the sediment testing section. Comments used for the conventional pesticides should be included 

here since they are the same. Again multiple criteria are being used in footnotes 17 and18 and it will 

difficult for simple actives to escape the need for doing these studies. In addition, the EPA should 

explain (1) the role of absorption/desorption and efate, aside from the current criteria; (2) which 

testing protocols are to be followed; (3) whether compounds that do not enter marine or brackish 

water would still be required to be tested; and (4) the role of earlier invertebrate tests and the use 

pattern of the product. 

Response: see responses 160.27, 160.28, 160.29, and 160.30, and testnotes 160.9, 160.17, and 

160.18 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27448 

Comment Code: 169100 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * There is no indication of the role that environmental fate 

of a compound will play in the need for sediment testing as well as leaching. Use of a persistence 

criteria without further explanation of "persistence" is vague. The EPA states that only one of many 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 952 

criteria would need to be met, indicating that many products will fall into this category.[FN#9:page 

59415] 

* The EPA should define "significant potential exposure" under the sediment testing section. 

Comments used for the conventional pesticides should be included here since they are the same. 

Again multiple criteria are being used in footnotes 17 and 18 and it will be difficult for simple actives 

to escape the need for doing these studies. In addition, the EPA should explain (1) the role of 

absorption/desorption and efate, aside from the current criteria; (2) which testing protocols are to 

be followed; (3) whether compounds that do not enter marine or brackish water would still be 

required to be tested; and (4) the role of earlier invertebrate tests and the use pattern of the product. 

Response: see responses 160.27, 160.28, 160.29, and 160.30, and testnotes 160.9, 160.17, and 

160.18 

Comment Code: 169110 Honeybee protection 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26399 

Comment Code: 169110 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * The degree of detail afforded for honeybee toxicity testing is excessive and unnecessary. It 

is not a major use and the Agency has not provided an explanation as to why it is relevant to 

antimicrobials. 

Response: see response 160.31 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26720 

Comment Code: 169110 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * The degree of detail afforded for honeybee toxicity testing 

is excessive and unnecessary. It is not a major use and the Agency has not provided an explanation 

as to why it is relevant to antimicrobials. 

Response: see response 160.31 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26999 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 953 

Comment Code: 169110 

Comment: 23. Proposed Regulation # [Section] 158.2240(f)(21) 

Text of the Proposed Regulation (emphasis added) Nontarget organisms: Test notes. "If beehives 

are constructed of treated wood a study similar to "Honey Bee Toxicity of Residues on Foliage" is 

required using treated wood instead of the foliage. Protocols must be approved by the Agency prior 

to the initiation of the study. Details for developing protocols are available from the Agency." 

The Proposed Regulations Are Vague for the Following Reasons Although the Agency states that 

the details for developing protocols are available from the Agency, the Agency has not adequately 

explained what the protocols entail. These required private negotiations are a procedure for the 

development of later tests. 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27399 

Comment Code: 169110 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * The degree of detail afforded for honeybee toxicity testing 

is excessive and unnecessary. It is not a major use and the Agency has not provided an explanation 

as to why it is relevant to antimicrobials. 

Response: see response 160.31 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27696 

Comment Code: 169110 

Comment: 23. Proposed Regulation # [Section] 158.2240(f)(21) 

Text of the Proposed Regulation (emphasis added) Nontarget organisms: Test notes. "If beehives 

are constructed of treated wood a study similar to "Honey Bee Toxicity of Residues on Foliage" is 

required using treated wood instead of the foliage. Protocols must be approved by the Agency prior 

to the initiation of the study. Details for developing protocols are available from the Agency." 

The Proposed Regulations Are Vague for the Following Reasons Although the Agency states that 

the details for developing protocols are available from the Agency, the Agency has not adequately 

explained what the protocols entail. These required private negotiations are a procedure for the 

development of later tests. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 954 

Response: see response 3 

Comment Code: 169120 Tiered approach to non-target organism studies 

Commenter Name: Jamie S. Heisig-Mitchell 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 

Comment ID: 25448 

Comment Code: 169120 

Comment: Toxicity Screening 

*The Tier I toxicity screening does not include data requirements for estuarine or marine organisms. 

This does not adequately protect the aquatic environment from discharges of these antimicrobial 

compounds. There are numerous instances in which the Water Quality Standard (WQS) for 

saltwater aquatic life is an order of magnitude or more lower for a pesticide than the freshwater 

aquatic life WQS. Modeling a need for additional Tier II exposure data based only on freshwater 

concentrations of concern fails to consider the potential for toxicity to saltwater organisms. 

Response: see response 160.8 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25985 

Comment Code: 169120 

Comment: * The Tier I toxicity screening does not include data requirements for estuarine or 

marine organisms. This does not adequately protect the aquatic environment from discharges of 

these antimicrobial compounds. There are numerous instances in which the Water Quality Standard 

(WQS) for saltwater aquatic life is an order of magnitude or more lower for a pesticide than the 

freshwater aquatic life WQS. Modeling a need for additional Tier II exposure data based only on 

freshwater concentrations of concern fails to consider the potential for toxicity to saltwater 

organisms. 

Response: see response 160.8 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26344 

Comment Code: 169120 

Comment: B. Non-Target Organism Data Requirements 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 955 

For indoor uses, "tier 1 testing" of terrestrial and aquatic organisms is conditionally required for 

conventional pesticides, but required for all antimicrobials, including those with indoor 

uses.[FN#41:Compare 40 CFR 158.400 with Proposed [Section] 158.2240.] For non-target 

terrestrial and aquatic organisms’ upper tier testing, it is difficult to make direct comparisons because 

the draft antimicrobial and final conventional use patterns differ. However, for greenhouse and 

indoor uses, upper tier data are not required for conventional pesticides; while for antimicrobials, the 

same upper tiered data are conditionally required for all "low environmental exposure" 

uses.[FN#42:Compare 40 CFR 158.400 with Proposed [Section] 158.2240.] 

Response: see responses 1 and 160.1 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26377 

Comment Code: 169120 

Comment: The Agency is proposing significant and costly testing of nontarget species for 

antimicrobials, without adequate consideration potential environmental exposure, promulgated 

regulations of other pesticide types, or a clear scientific justification. Further, the Agency must make 

clear how it will use the data generated on antimicrobial pesticides in a risk assessment and 

regulatory decision, since there are no clear risk assessment processes for antimicrobials. In addition, 

the Agency should readdress its levels of tiering, since little relief is provided from a reduction in the 

full suite of tests, leading to no meaningful difference between the tiers. 

Response: see responses 191.5 and 160.32 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26709 

Comment Code: 169120 

Comment: The Panel believes that the Agency is proposing significant and costly testing of 

nontarget species for antimicrobials, without adequate consideration of potential environmental 

exposure, promulgated regulations of other pesticide types, or a clear scientific justification. Further, 

the Agency must make clear how it will use the data generated on antimicrobial pesticides in a risk 

assessment and regulatory decision, since there are no clear risk assessment processes for 

antimicrobials (See Panel’s General Comments at Section I). In addition, the Agency should 

readdress its levels of tiering, since little relief is provided from a reduction in the full suite of tests, 

leading to no meaningful difference between the tiers. (See Panel’s General Comments at Sections I 

and III). 

Response: see responses 191.5 and 160.32 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 956 

Letter ID: 0088 

Comment ID: 26834 

Comment Code: 169120 

Comment: Moreover, disposal of antimicrobial pesticides is outside of the scope of FIFRA, and 

should not be assessed unless the product disposal is not covered under a relevant federal, state, or 

local statute or regulation for hazardous wastes or the product label for a nonhazardous waste does 

not restrict against disposal of product down a sanitary sewer following a use that could result in 

such exposure. The regulation must provide adequate and appropriate direction as to when 

environmental exposure is potentially of concern and then tier the data requirements for ecological 

effects to be relevant to the risk assessment needed for that exposure. Similar to the closely-related 

data requirements for environmental fate, there are only a few circumstances where certain 

ecological effects data are relevant for antimicrobial pesticides. 

Response: See responses 160.32 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26864 

Comment Code: 169120 

Comment: B. Non-Target Organism Data Requirements 

For indoor uses, "tier 1 testing" of terrestrial and aquatic organisms is conditionally required for 

conventional pesticides, but required for ALL antimicrobials, including those with indoor 

uses.[FN41: Compare 40 CFR 158.400 with Proposed [section]158.2240.] For non-target terrestrial 

and aquatic organisms’ upper tier testing, it is difficult to make direct comparisons because the draft 

antimicrobial and final conventional use patterns differ. However, for greenhouse and indoor uses, 

upper tier data requirements are not required for conventional pesticides; while for antimicrobials, 

the same upper tiered data requirements are conditionally required for all "low environmental 

exposure" uses.[FN42: For complete list of guideline numbers, see all CRs under "low 

environmental exposure" in the Proposal at 158.2240, under Higher Tier Testing (pages 59436-

437).] 

Response: see responses 1 and 160.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27395 

Comment Code: 169120 

Comment: LANXESS believes that the Agency is proposing significant and costly testing of 

nontarget species for antimicrobials, without adequate consideration of potential environmental 

exposure, promulgated regulations of other pesticide types, or a clear scientific justification. Further, 

the Agency must make clear how it will use the data generated on antimicrobial pesticides in a risk 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 957 

assessment and regulatory decision, since there are no clear risk assessment processes for 

antimicrobials (See LANXESS’s General Comments at Section I). In addition, the Agency should 

readdress its levels of tiering, since little relief is provided from a reduction in the full suite of tests, 

leading to no meaningful difference between the tiers. (See LANXESS’s General Comments at 

Sections I and III). 

Response: see responses 191.5 and 160.32 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27481 

Comment Code: 169120 

Comment: Moreover, disposal of antimicrobial pesticides is outside of the scope of FIFRA, and 

should not be assessed unless the product disposal is not covered under a relevant federal, state, or 

local statute or regulation for hazardous wastes or the product label for a nonhazardous waste does 

not restrict against disposal of product down a sanitary sewer following a use that could result in 

such exposure. The regulation must provide adequate and appropriate direction as to when 

environmental exposure is potentially of concern and then tier the data requirements for ecological 

effects to be relevant to the risk assessment needed for that exposure. Similar to the closely-related 

data requirements for environmental fate, there are only a few circumstances where certain 

ecological effects data are relevant for antimicrobial pesticides. 

Response: See response 160.32 

Comment Code: 169122 Low exposure uses 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25759 

Comment Code: 169122 

Comment: Section 158,2240 - Nontarget Organisms (Ecotox) As described previously, Ecolab 

proposes a tiered testing approach that is triggered for each use pattern through a deterministic or 

risk quotient methodology. The low exposure use pattern is subjective and arbitrary. 

Response: see responses 160.40 and 160.41 

Comment Code: 169130 Data and reporting requirements table for non-target organism (suggested 

additions, deletions, etc.) 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 958 

Letter ID: 0071 

Comment ID: 25665 

Comment Code: 169130 

Comment: Approach to data requirements for metabolites needs to be redesigned 

EPA has proposed an approach that inherently denies it the data necessary to evaluate pesticide 

metabolites. Data on metabolites would only be required if EPA makes a determination "that the 

transformation products of the parent compound are more toxic, persistent, bioaccumulative, or 

have been shown to cause adverse effects in mammalian or aquatic reproductive studies." If the 

registrant is not required to provide data characterizing these properties of metabolites, it will be 

impossible for EPA to make this determination. EPA should require minimum data sets for all 

metabolites with long half-lives. 

Response: see response 160.3 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26458 

Comment Code: 169130 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * The EPA should reconsider its use of TEP as a test article. Since TEPs vary greatly, 

validity of TEP testing is questionable. Also, non-target species will not be exposed to TEP because 

TEP is not applied in the environment. 

Response: see response 160.34 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26510 

Comment Code: 169130 

Comment: [Points of contention in the proposed regulation for data requirements of ecological 

effects:] * The use of "as determined by the Agency" as the criteria for testing (footnotes 10 and 11) 

gives no guidance to the registrant on how the Agency will make this decision. The Agency should 

provide clear criteria as to when the data requirements are applicable. 

Response: see response 3 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26540 

Comment Code: 169130 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 959 

Comment: Because all environmental exposure from the use of antimicrobial pesticides is indirect 

and will occur only after possible transformation, any data developed to assess the potential risk to 

nontarget organisms should be developed with the appropriate residue of concern (ROC) (i.e. 

degradation product or TGAI) rather than with the active ingredient. 

Response: see response 160.3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26734 

Comment Code: 169130 

Comment: [The Panel has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * The EPA should reconsider its use of TEP as a test 

article. Since TEPs vary greatly, validity of TEP testing is questionable. Also, nontarget species will 

not be exposed to TEP because TEP is not applied in the environment. 

Response: see response 160.34 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26836 

Comment Code: 169130 

Comment: Because all environmental exposure from the use of antimicrobial pesticides is indirect 

and will occur only after possible transformation, any data developed to assess the potential risk to 

nontarget organisms should be developed with the appropriate residue of concern (ROC) (i.e. 

degradation product or TGAI) rather than restricting testing to the TGAI which may not occur. 

Response: see response 160.3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27401 

Comment Code: 169130 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] * The EPA should reconsider its use of TEP as a test 

article. Since TEPs vary greatly, validity of TEP testing is questionable. Also, nontarget species will 

not be exposed to TEP because TEP is not applied in the environment. 

Response: see response 160.34 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 960 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27434 

Comment Code: 169130 

Comment: [LANXESS has listed the following points of contention in the proposed regulation for 

data requirements of ecological effects:] *The use of "as determined by the Agency" as the criteria 

for testing (footnotes 10 and 11) gives no guidance to the registrant on how the Agency will make 

this decision. The Agency should provide clear criteria as to when the data requirements are 

applicable. (See LANXESS’s General Comments at Section I) 

Response: see response 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27482 

Comment Code: 169130 

Comment: Because all environmental exposure from the use of antimicrobial pesticides is indirect 

and will frequently occur only after transformation, any data developed to assess the potential risk to 

nontarget organisms should be developed with the appropriate residue of concern (ROC) (i.e. 

degradation product or TGAI) rather than restricting testing to the TGAI which may not occur. 

Response: see response 160.3 

Comment Code: 169200 Commenter’s Concept of Data Requirements Table for Non-Target 

Organisms 

Comment Summary: As part of their comments, the commenters provided an alternate 

Antimicrobial Non-Target Organism Data Requirements Table with testnotes. EPA’s response is for 

the entire alternate testing scheme and not the individual parts. 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26537 

Comment Code: 169200 

Comment: As proposed, the ecological effects data requirements for antimicrobial pesticides are 

not sufficiently clear to enable a registrant to determine the kinds of data and information EPA 

requires to make a regulatory decision and thus are inconsistent with the stated purpose of a data 

requirement regulation.[FN#16:40 CFR 158.1(a)] They also do not recognize the very major 

differences between the uses of antimicrobial pesticides and other pesticides with regard to 

environmental exposure potential and the need for ecological effects data. For these reasons, the 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 961 

Proposal should be redrafted and reproposed. P&G supports the Panel’s suggestion that EPA adopt 

the approach outlined below in that reproposal. 

V. Alternative Proposal for Ecological Effects Data Requirements 

The assessment of potential risks to non-target species resulting from environmental exposure to 

antimicrobial pesticides is only relevant under limited circumstances. Any uses that occur indoors 

should not be subject to environmental exposure or non-target species risk assessments any more 

than such assessments would be relevant for conventional or biochemical pesticides. 

Response: see responses 2 and 160.41 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26548 

Comment Code: 169200 

Comment: The Panel’s alternative proposal is intended to provide clearer instructions to registrants, 

taking into account the specific considerations and applicability of these types of requirements for 

antimicrobial pesticides and to incorporate appropriate tiering to avoid unnecessary testing. This 

alternative proposal incorporates the new Use Pattern categories proposed in the Panel’s comments 

are relevant, clear and applicable to antimicrobial pesticides. A use is excluded from the definition of 

an antimicrobial pesticide or from the definition of a pesticide chemical, it should be excluded from 

this section. For uses which are pesticidal but not within the scope of the definition of antimicrobial 

pesticides, a reference should be to the appropriate sections of the data requirements for 

conventional or biochemical pesticides. For this reason, P&G supports the Biocides Panel’s 

alternative proposal. 

Proposed Alternative Section 158.2240 Data Requirements for Non-target Organisms. 

If antimicrobial use pattern categories are described elsewhere in the regulation besides Section 

158.100, specific reference to the identification and description must be incorporated into the 

following paragraph. P&G supports the Biocides Panel’s revisions to Section 158.2240(a) as follows: 

(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the 

environmental chemistry data requirements for a particular pesticide product. Notes that apply to an 

individual test and include specific conditions, qualifications, or exceptions to the designated test are 

listed in paragraph (e) of this section 

The existing paragraphs (b) and (c) should be replaced with the following: (b) Use Patterns. (1) The 

general use patterns for antimicrobial nontarget organism data requirements are ‘Indoor 

Institutional, Residential, and Commercial,’ Aquatic, and Material Preservatives, where these are 

identified as follows 

(a) Indoor institutional, residential and commercial includes the use of sanitizers, disinfectants, 

virucides and similar products for the following: on hard surfaces; on soft surfaces; in the air; as 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 962 

laundry disinfectants and sanitizers; as swimming pool disinfectants or algaecides (public or private, 

including pool, hot tubs, and spas); on medical equipment; and the use in any of the types of 

facilities that fall within these definitions. This use pattern is included only when the product is not a 

hazardous waste and when the label does not restrict against disposal or rinsing down a sanitary 

sewer for a use that could result in such an exposure. 

(b) Aquatic areas involve uses that result in the potential for direct exposure of natural bodies of 

water to antimicrobials, although the exposure likely is limited and is not a direct application to 

aquatic sites. These include once- through cooling systems (where no pretreatment of the treated 

discharge occurs), antifoulant coatings, and ballast 158.2060 of this Part. 

The table of data requirements at paragraph (e) should be replaced by the following, and the 

definition of ROC as residue of concern should be added to paragraph (d). 

[See Table of data requirements, page 28-31, PDF docket ID EPA-HQ-OPP-2008-0110-0081] 

Footnotes: 

1 Data are required only when environmental exposure is likely to result under normal usage 

conditions as determined by appropriate assessment methods. 

Data are required only when potential for exposure to avian species has been determined by 

appropriate assessment methods. Data are preferred on one waterfowl or one upland game bird 

species. 

3 Testing should be conducted either on a marine or a freshwater species based on the potential 

conditions of exposure 

 4 Data are required when the degree of environmental exposure and the environmental fate 

characteristics indicate the expected environmental concentration of the ROC in the aquatic 

environment is greater than or equal to 0.01 the EC50 or LC50 determined in any acute aquatic 

nontarget organism testing 

5 Data are required when one of the following conditions is met: 

i. The product or its degradates will be introduced directly into an aquatic environment (such as a 

ballast water treatment). ii Data on the TEP are required only when from scientifically valid models 

indicate the maximum expected environmental concentration (MEEC) or the estimated 

environmental concentration (EEC) is greater than or equal to the LC50 or EC50 of the LC50 or 

EC50 of the ROC when the end-product is used as directed. 

 6 Data are required for marine species if the potential exists for exposure to marine biota and either 

of the following criteria is met: 

i the octanol/water partition coefficient of the active ingredient and/or its major degradates is 

>1000, or ii the hydrolytic half life is greater than 5 days at pH 5, 7, or 9. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 963 

 7 Data are required for one waterfowl species if the avian acute oral toxicity for the active 

ingredient is less than or equal to 100 mg ai/kg and there is potential for exposure in avian feed 

items from the active ingredient or its degradates. Data on one upland game bird species are 

required if the avian dietary LC50 in the first species tested is less than or equal to 500 ppm ai in the 

diet. 

8 For aquatic use patterns, data are required on one waterfowl and one upland game bird species but 

only when results from the tier I acute avian oral toxicity study indicate an LD50 value that would be 

equivalent to a dietary concentration of greater than 0.20 ppm 

 9 Data are required if any of the following criteria is met: 

i. Birds may be subjected to repeated or continued exposure to the active ingredient or any of its 

transformation products especially preceding or during the breeding season. ii. The active ingredient 

or any of its metabolites or degradation products are stable in the environment to the extent that 

potentially toxic amounts may persist in the avian feed. iii. The active ingredient or any of its major 

metabolites or degradation products are stored or accumulated in plant or animal tissues as indicated 

by the octanol/water partition coefficient (Kow is greater than or equal to), accumulation studies, 

metabolic release and retention studies, or as indicated by structural similarity to known 

bioaccumulative chemicals. iv. Any other information such as that derived from mammalian 

reproduction studies that indicate reproduction in terrestrial vertebrates may be adversely affected by 

the anticipated use of the pesticide product. 

 10 Data are required when the product label permits construction of honeybee hives or use in the 

hives. 

 11 Data are required when results from the Tier 2 testing indicate a NOAEC of less than 0.5 ppm 

and environmental exposure is anticipated at levels of concern. 

 12 Data are required based on results of lower tier studies, intended use pattern and environmental 

fate characteristics, and adverse effects that indicate potential exposure. 

 13 Data are required if TGAI is organic and the half-life of the active ingredient in the sediment is 

estimated to be less than or equal to 10 days from aerobic soil metabolism study, aerobic aquatic soil 

metabolism study or other method of estimation and if any of the following conditions exist: 

i the soil partition coefficient (Kd) is greater than or equal to 50; ii the log Kow is greater than or 

equal to 3; or iii the Koc is greater than or equal to 1000. 

14 Data are required if the TGAI is organic and 

i Estimated Environmental Concentration water treatments. 

(c) Material Preservatives include wood preservatives as well as any other type of preservative where 

the final article is used outdoors on a significant basis and there is reliable evidence that the article, 

under anticipated conditions of use, will release the antimicrobial preservative in sufficient quantities 

to produce environmental exposures of concern 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 964 

(2) Data are not required if the end-use product is a gas, a highly volatile liquid, a highly reactive 

solid, or a highly corrosive material 

(c) Use of products as aquatic herbicides or agricultural fungicides is outside of the scope of these 

data requirements. Registrants of such uses should refer to Subpart G or to Section (EEC) either 

from testing or modeling is greater than 0.1 of the acute LC50/EC50 values of any tested 

invertebrate; and 

ii the half-life of the active ingredient in the sediment is estimated to be less than or equal to 10 days 

from aerobic soil metabolism study, aerobic aquatic soil metabolism study or other method of 

estimation and if any of the following conditions exist: a the soil partition coefficient (Kd) is greater 

than or equal to 50; b the log Kow is greater than or equal to 3; or c the Koc is greater than or equal 

to 1000. 

15 Sediment testing with estuarine/marine test species is required if the product is intended for 

direct application to the estuarine or marine environment or the product is expected to enter the 

environment in concentrations, which the Agency believes to be significant, either by runoff or 

erosion, because of its expected use or mobility patterns. 

 16 Data are required when the product label permits construction of honeybee hives or use in the 

hives and the LD50 is less than 11 micrograms per bee for one or more active ingredients in the 

formulated end-use product. 

Response: see response 160.41 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26837 

Comment Code: 169200 

Comment: The Panel’s alternative proposal is intended to provide clearer instructions to registrants, 

taking into account the specific considerations and applicability of these types of requirements for 

antimicrobial pesticides and to incorporate appropriate tiering to avoid unnecessary testing. This 

alternative proposal incorporates the new Use Pattern categories proposed in Appendix B that are 

relevant, clear and applicable to antimicrobial pesticides. Where a use is excluded from the definition 

of an antimicrobial pesticide or from the definition of a pesticide chemical, it should be excluded 

from this section. For uses which are pesticidal but not within the scope of the definition of 

antimicrobial pesticides, a reference should be to the appropriate sections of the data requirements 

for conventional or biochemical pesticides. \ 

A. Proposed Alternative Section 158.2240 Data Requirements for Nontarget Organisms 

If antimicrobial use pattern categories are described elsewhere in the regulation besides Section 

158.100, specific reference to the identification and description must be incorporated into the 

following paragraph. The Panel offers the following revisions to Section 158.2240(a). 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 965 

(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the 

environmental chemistry data requirements for a particular pesticide product. Notes that apply to an 

individual test and include specific conditions, qualifications, or exceptions to the designated test are 

listed in paragraph (e) of this section 

The existing paragraphs (b) and (c) should be replaced with the following: 

(b) Use Patterns. (1) The general use patterns for antimicrobial nontarget organism data 

requirements are ‘Indoor Institutional, Residential, and Commercial,’ Aquatic, and Material 

Preservatives, where these are identified as follows 

(a) Indoor institutional, residential and commercial includes the use of sanitizers, disinfectants, 

virucides and similar products for the following: on hard surfaces; on soft surfaces; in the air; as 

laundry disinfectants and sanitizers; as swimming pool disinfectants or algaecides (public or private, 

including pool, hot tubs, and spas); on medical equipment; and the use in any of the types of 

facilities that fall within these definitions. This use pattern is included only when the product is not a 

hazardous waste and when the label does not restrict against disposal or rinsing down a sanitary 

sewer for a use that could result in such an exposure. 

(b) Aquatic areas involve uses that result in the potential for direct exposure of natural bodies of 

water to antimicrobials, although the exposure likely is limited and is not a direct application to 

aquatic sites. These include once- through cooling systems (where no pretreatment of the treated 

discharge occurs), antifoulant coatings, and ballast water treatments. 

(c) Material Preservatives include wood preservatives as well as any other type of preservative where 

the final article is used outdoors on a significant basis and there is reliable evidence that the article, 

under anticipated conditions of use, will release the antimicrobial preservative in sufficient quantities 

to produce environmental exposures of concern 

(2) Data are not required if the end- use product is a gas, a highly volatile liquid, a highly reactive 

solid, or a highly corrosive material 

(c) Use of products as aquatic herbicides or agricultural fungicides is outside of the scope of these 

data requirements. Registrants of such uses should refer to Subpart G or to Section 158.2060 of this 

Part. 

The table of data requirements at paragraph (e) should be replaced by the following, and the 

definition of ROC as residue of concern should be added to paragraph (d). 

Testing 

Guideline 

Number 

Data Requirement Antimicrobial Use Pattern Test Substance to 

Support 

Footnote 

Test Note 

Number 

Indoor 

Institutional, 

Residential, 

Commercial 

Aquatic Material 

Preservative 

for Treated 

Article 

MP EP 

Tier 1 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 966 

Testing 

Guideline 

Number 

Data Requirement Antimicrobial Use Pattern Test Substance to 

Support 

Footnote 

Test Note 

Number 

Indoor 

Institutional, 

Residential, 

Commercial 

Aquatic Material 

Preservative 

for Treated 

Article 

MP EP 

None Acute freshwater 

invertebrate toxicity 

CR R CR TGAI TGAI 1 

None Acute freshwater fish 

toxicity 

CR R CR TGAI TGAI 1 

None Avian acute oral 

toxicity 

CR CR CR TGAI TGAI 1, 2 

Tier 2 

Aquatic Organisms 

None Aquatic Invertebrate 

Life Cycle 

NR CR CR ROC ROC or 

TEP 

1, 3, 4, 5 

None Fish early life-stage NR CR CR ROC ROC 1, 3, 4, 5 

None Acute toxicity to 

estuarine and marine 

organisms 

NR CR CR ROC ROC 1, 3, 4, 5 

Avian Testing 

None Avian Dietary 

Toxicity 

NR CR CR ROC ROC 1, 2, 7, 8 

None Avian Reproduction NR CR CR ROC ROC 1, 2, 9 

Other Terrestrial Organism Testing 

Testing 

Guideline 

Number 

Data Requirement Antimicrobial Use Pattern Test Substance to 

Support 

Footnote 

Test Note 

Number 

Indoor 

Institutional, 

Residential, 

Commercial 

Aquatic Material 

Preservative 

for Treated 

Article 

MP EP 

None Honeybee acute 

toxicity 

NR CR CR ROC ROC 1, 10 

Tier 3 

None Fish Life Cycle NR CR CR ROC ROC 1, 11 

None Aquatic organisms, 

bioavailability, 

biomagnification 

toxicity tests 

NR CR CR ROC ROC 1, 11 

None Simulated or actual 

field testing for 

aquatic organisms 

NR CR CR ROC ROC 1, 12 

None Whole sediment 

acute freshwater 

invertebrates 

NR CR CR ROC ROC 1, 3, 13 

None Whole sediment 

acute marine 

invertebrates 

NR CR CR ROC ROC 1, 3, 13 

None Toxicity of residues 

to honeybees 

NR CR CR ROC ROC 1, 16 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 967 

 Footnotes: 

1 Data are required only when environmental exposure is likely to result under normal usage 

conditions as determined by appropriate assessment methods. 

2 Data are required only when potential for exposure to avian species has been determined by 

appropriate assessment methods. Data are preferred on one waterfowl or one upland game bird 

species. 

3 Testing should be conducted either on a marine or a freshwater species based on the potential 

conditions of exposure. 

4 Data are required when the degree of environmental exposure and the environmental fate 

characteristics indicate the expected environmental concentration of the ROC in the aquatic 

environment is greater than or equal to 0.01 the EC50 or LC50 determined in any acute aquatic 

nontarget organism testing. 

5 Data are required when one of the following conditions is met: 

i. The product or its degradates will be introduced directly into an aquatic environment (such 

as a ballast water treatment). 

ii. ii Data on the TEP are required only when scientifically valid models indicate the maximum 

expected environmental concentration (MEEC) or the estimated environmental 

concentration (EEC) is greater than or equal to the LC50 or EC50 of the LC50 or EC50 of 

the ROC when the end-product is used as directed. 

6 Data are required for marine species if the potential exists for exposure to marine biota and either 

of the following criteria is met: i the octanol/water partition coefficient of the active ingredient 

and/or its major degradates is >1000, or ii the hydrolytic half life is greater than 5 days at pH 5, 7, or 

9. 

7 Data are required for one waterfowl species if the avian acute oral toxicity for the active ingredient 

is less than or equal to 100 mg a.i./kg and there is potential for exposure in avian feed items from 

the active ingredient or its degradates. Data on one upland game bird species are required if the 

avian dietary LC50 in the first species tested is less than or equal to 500 ppm a.i. in the diet. 

8 For aquatic use patterns, data are required on one waterfowl and one upland game bird species but 

only when results from the tier I acute avian oral toxicity study indicate an LD50 value that would be 

equivalent to a dietary concentration of greater than 0.20 ppm. 

9 Data are required if any of the following criteria is met: i. Birds may be subjected to repeated or 

continued exposure to the active ingredient or any of its transformation products especially 

preceding or during the breeding season. ii. The active ingredient or any of its metabolites or 

degradation products is stable in the environment to the extent that potentially toxic amounts may 

persist in the avian feed. iii. The active ingredient or any of its major metabolites or degradation 

products are stored or accumulated in plant or animal tissues as indicated by the octanol/water 

partition coefficient (Kow is greater than or equal to), accumulation studies, metabolic release and 

retention studies, or as indicated by structural similarity to known bioaccumulative chemicals. iv. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 968 

Any other information such as that derived from mammalian reproduction studies that indicate 

reproduction in terrestrial vertebrates may be adversely affected by the anticipated use of the 

pesticide product. 

10 Data are required when the product label permits construction of honeybee hives or use in the 

hives. 

11 Data are required when results from the Tier 2 testing indicate a NOAEC of less than 0.5 ppm 

and environmental exposure is anticipated at levels of concern. 

12 Data are required based on results of lower tier studies, intended use pattern and environmental 

fate characteristics, and adverse effects that indicate potential exposure. 

13 Data are required if TGAI is organic and the half-life of the active ingredient in the sediment is 

estimated to be greater than or equal to 10 days from aerobic soil metabolism study, aerobic aquatic 

soil metabolism study or other method of estimation and if any of the following conditions exist: i 

the soil partition coefficient (Kd) is greater than or equal to 50; ii the log Kow is greater than or 

equal to 3; or iii the Koc is greater than or equal to 1000. 

14 Data are required if the TGAI is organic and i Estimated Environmental Concentration (EEC) 

either from testing or modeling is greater than 0.1 of the acute LC50/EC50 values of any tested 

invertebrate; and ii the half-life of the active ingredient in the sediment is estimated to be greater 

than or equal to 10 days from aerobic soil metabolism study, aerobic aquatic soil metabolism study 

or other method of estimation and if any of the following conditions exist: 

a the soil partition coefficient (Kd) is greater than or equal to 50; b the log Kow is greater than or 

equal to 3; or c the Koc is greater than or equal to 1000. 

15 Sediment testing with estuarine/marine test species is required if the product is intended for 

direct application to the estuarine or marine environment or the product is expected to enter the 

environment in concentrations, which the Agency believes to be significant, either by runoff or 

erosion, because of its expected use or mobility patterns. 

16 Data are required when the product label permits construction of honeybee hives or use in the 

hives and the LD50 is less than 11 micrograms per bee for one or more active ingredients in the 

formulated end-use product. 

Response: see response 160.41 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27490 

Comment Code: 169200 

Comment: The Panel’s alternative proposal is intended to provide clearer instructions to registrants, 

taking into account the specific considerations and applicability of these types of requirements for 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 969 

antimicrobial pesticides and to incorporate appropriate tiering to avoid unnecessary testing. This 

alternative proposal incorporates the new Use Pattern categories proposed in Appendix B that are 

relevant, clear and applicable to antimicrobial pesticides. Where a use is excluded from the definition 

of an antimicrobial pesticide or from the definition of a pesticide chemical, it should be excluded 

from this section. For uses which are pesticidal but not within the scope of the definition of 

antimicrobial pesticides, a reference should be to the appropriate sections of the data requirements 

for conventional or biochemical pesticides. 

A. Proposed Alternative Section 158.2240 Data Requirements for Nontarget Organisms 

If antimicrobial use pattern categories are described elsewhere in the regulation besides Section 

158.100, specific reference to the identification and description must be incorporated into the 

following paragraph. LANXESS offers the following revisions to Section 158.2240(a). 

(a) General . Sections 158.100 through 158.130 describe how to use this table to determine the 

environmental chemistry data requirements for a particular pesticide product. Notes that apply to an 

individual test and include specific conditions, qualifications, or exceptions to the designated test are 

listed in paragraph (e) of this section 

The existing paragraphs (b) and (c) should be replaced with the following: 

(b) Use Patterns. (1) The general use patterns for antimicrobial nontarget organism data 

requirements are ‘Indoor Institutional, Residential, and Commercial,’ Aquatic, and Material 

Preservatives, where these are identified as follows 

(a) Indoor institutional, residential and commercial includes the use of sanitizers, disinfectants, 

virucides and similar products for the following: on hard surfaces; on soft surfaces; in the air; as 

laundry disinfectants and sanitizers; as swimming pool disinfectants or algaecides (public or private, 

including pool, hot tubs, and spas); on medical equipment; and the use in any of the types of 

facilities that fall within these definitions. This use pattern is included only when the product is not a 

hazardous waste and when the label does not restrict against disposal or rinsing down a sanitary 

sewer for a use that could result in such an exposure. 

(b) Aquatic areas involve uses that result in the potential for direct exposure of natural bodies of 

water to antimicrobials, although the exposure likely is limited and is not a direct application to 

aquatic sites. These include once- through cooling systems (where no pretreatment of the treated 

discharge occurs), antifoulant coatings, and ballast water treatments. 

(c) Material Preservatives include wood preservatives as well as any other type of preservative where 

the final article is used outdoors on a significant basis and there is reliable evidence that the article, 

under anticipated conditions of use, will release the antimicrobial preservative in sufficient quantities 

to produce environmental exposures of concern 

(2) Data are not required if the end- use product is a gas, a highly volatile liquid, a highly reactive 

solid, or a highly corrosive material 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 970 

(c) Use of products as aquatic herbicides or agricultural fungicides is outside of the scope of these 

data requirements. Registrants of such uses should refer to Subpart G or to Section 158.2060 of this 

Part. 

The table of data requirements at paragraph (e) should be replaced by the following, and the 

definition of ROC as residue of concern should be added to paragraph (d). 

[See table on pages 9-10 of appendix F in PDF docket ID EPA-HQ-OPP-2008-0110-0064] 

Footnotes: 

1 Data are required only when environmental exposure is likely to result under normal usage 

conditions as determined by appropriate assessment methods. 

2 Data are required only when potential for exposure to avian species has been determined by 

appropriate assessment methods. Data are preferred on one waterfowl or one upland game bird 

species. 

3 Testing should be conducted either on a marine or a freshwater species based on the potential 

conditions of exposure. 

 4 Data are required when the degree of environmental exposure and the environmental fate 

characteristics indicate the expected environmental concentration of the ROC in the aquatic 

environment is greater than or equal to 0.01 the EC50 or LC50 determined in any acute aquatic 

nontarget organism testing. 

5 Data are required when one of the following conditions is met: i. The product or its degradates 

will be introduced directly into an aquatic environment (such as a ballast water treatment). ii Data on 

the TEP are required only when scientifically valid models indicate the maximum expected 

environmental concentration (MEEC) or the estimated environmental concentration (EEC) is 

greater than or equal to the LC50 or EC50 of the LC50 or EC50 of the ROC when the end-product 

is used as directed. 

 6 Data are required for marine species if the potential exists for exposure to marine biota and either 

of the following criteria is met: i the octanol/water partition coefficient of the active ingredient 

and/or its major degradates is > 1000, or ii the hydrolytic half life is greater than 5 days at pH 5, 7, 

or 9. 

 7 Data are required for one waterfowl species if the avian acute oral toxicity for the active 

ingredient is less than or equal to 100 mg a.i./kg and there is potential for exposure in avian feed 

items from the active ingredient or its degradates. Data on one upland game bird species are 

required if the avian dietary LC50 in the first species tested is less than or equal to 500 ppm a.i. in 

the diet. 

8 For aquatic use patterns, data are required on one waterfowl and one upland game bird species but 

only when results from the tier I acute avian oral toxicity study indicate an LD50 value that would be 

equivalent to a dietary concentration of greater than 0.20 ppm. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 971 

 9 Data are required if any of the following criteria is met: i. Birds may be subjected to repeated or 

continued exposure to the active ingredient or any of its transformation products especially 

preceding or during the breeding season. ii. The active ingredient or any of its metabolites or 

degradation products is stable in the environment to the extent that potentially toxic amounts may 

persist in the avian feed. iii. The active ingredient or any of its major metabolites or degradation 

products are stored or accumulated in plant or animal tissues as indicated by the octanol/water 

partition coefficient (Kow is greater than or equal to), accumulation studies, metabolic release and 

retention studies, or as indicated by structural similarity to known bioaccumulative chemicals. iv. 

Any other information such as that derived from mammalian reproduction studies that indicate 

reproduction in terrestrial vertebrates may be adversely affected by the anticipated use of the 

pesticide product. 

 10 Data are required when the product label permits construction of honeybee hives or use in the 

hives. 

 11 Data are required when results from the Tier 2 testing indicate a NOAEC of less than 0.5 ppm 

and environmental exposure is anticipated at levels of concern. 

 12 Data are required based on results of lower tier studies, intended use pattern and environmental 

fate characteristics, and adverse effects that indicate potential exposure. 

 13 Data are required if TGAI is organic and the half-life of the active ingredient in the sediment is 

estimated to be greater than or equal to 10 days from aerobic soil metabolism study, aerobic aquatic 

soil metabolism study or other method of estimation and if any of the following conditions exist: i 

the soil partition coefficient (Kd) is greater than or equal to 50; ii the log Kow is greater than or 

equal to 3; or iii the Koc is greater than orequal to 1000. 

14 Data are required if the TGAI is organic and i Estimated Environmental Concentration (EEC) 

either from testing or modeling is greater than 0.1 of the acute LC50/EC50 values of any tested 

invertebrate; and ii the half-life of the active ingredient in the sediment is estimated to be greater 

than or equal to 10 days from aerobic soil metabolism study, aerobic aquatic soil metabolism study 

or other method of estimation and if any of the following conditions exist: . a the soil partition 

coefficient (Kd) is greater than or equal to 50; b the log Kow is greater than or equal to 3; or c the 

Koc is greater than or equal to 1000. 

15 Sediment testing with estuarine/marine test species is required if the product is intended for 

direct application to the estuarine or marine environment or the product is expected to enter the 

environment in concentrations, which the Agency believes to be significant, either by runoff or 

erosion, because of its expected use or mobility patterns. 

 16 Data are required when the product label permits construction of honeybee hives or use in the 

hives and the LD50 is less than 11 micrograms per bee for one or more active ingredients in the 

formulated end-use product. 

Response: see response 160.41 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Non-Target Organism Exposure Section (160) Page 972 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 28997 

Comment Code: 169200 

Comment: III. ALTERNATIVE PROPOSAL FOR ECOLOGICAL EFFECTS DATA 

REQUIREMENTS 

The assessment of potential risks to nontarget species resulting from environmental exposure to 

antimicrobial pesticides is only relevant under limited circumstances. Any uses that occur indoors 

should not be subject to environmental exposure or nontarget species risk assessments to be 

consistent with the requirements for conventional or biochemical pesticides. 

Response: see responses 1 and 160.41 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 28999 

Comment Code: 169200 

Comment: III. ALTERNATIVE PROPOSAL FOR ECOLOGICAL EFFECTS DATA 

REQUIREMENTS 

The assessment of potential risks to nontarget species resulting from environmental exposure to 

antimicrobial pesticides is only relevant under limited circumstances. Any uses that occur indoors 

should not be subject to environmental exposure or nontarget species risk assessments to be 

consistent with the requirements for conventional or biochemical pesticides. 

Response: see responses 1 and 160.41 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 973 

White Paper on the Use of SAR and QSAR (170) 

Verbatim Comments and Response References for the White Paper on Use of 

SAR and QSAR Section 

Comment Code: 170000 White Paper on the use of SAR and QSAR (structure-activityrelationship/SAR, and quantitative structure-activity-relationship/QSAR) 

Commenter Name: Ray S. McAlister 

Commenter Organization: CropLife America 

Letter ID: 0079 

Comment ID: 25467 

Comment Code: 170000 

Comment: CLA supports and encourages the Agency’s intent, as discussed in the preamble to the 

proposed rule, to employ integrated testing strategies, including computational tools such as QSAR , 

to streamline testing requirements (thus making them "more intelligent," as per the Agency’s vision). 

The Agency is making progress in using these tools and other innovative risk assessment practices 

and policies to improve regulation of conventional pesticides and should apply them also to 

antimicrobial pesticides. 

Response: see response 170.2 

Commenter Name: Patrick H. Quinn 

Commenter Organization: Innovation and Reform Group (IRG) 

Letter ID: 0080 

Comment ID: 25490 

Comment Code: 170000 

Comment: Comments 

The IRG appreciates the opportunity to comment on the Proposed Rule Regarding Data 

Requirements for Antimicrobial Pesticides, 73 Fed. Reg. 59382 (October 8, 2008) ("the Proposed 

Rule"). IRG members recognize the enormous scope and complexity of EPA’s Proposed Subpart 

158W Rule and the years of effort dedicated to its development. Some aspects of the Proposed Rule, 

including its stated intent to increase the use of SAR/QSAR and alternative toxicology while 

reducing use of animals in its assessments, are to be commended, but these approaches have not 

been clearly integrated into the rule itself. 

Response: see responses 4 and 170.2 

Commenter Name: Rodger Curren 

Commenter Organization: Alternative Testing Working Group (ATWG) 

Letter ID: 0092 

Comment ID: 25510 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 974 

Comment Code: 170000 

Comment: Comments on Proposed Rule The ATWG appreciates the opportunity to comment on 

the Proposed Rule Regarding Data Requirements for Antimicrobial Pesticides, 73 Fed. Reg. 59382 

(October 8, 2008) ("the Proposed Rule"). ATWG members recognize the enormous scope and 

complexity of EPA’s Proposed Subpart 158W rule and the years of effort dedicated to its 

development. Some aspects of the Proposed Rule, including its stated intent to increase the use of 

SAR/QSAR as well as alternative toxicology (non- animal) in its assessments, are to be commended, 

but these approaches have not been clearly integrated into the rule itself. 

Response: see response 170.2 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25572 

Comment Code: 170000 

Comment: *In CFR 158W, there is a proposal to move towards an integrated testing strategy (ITS) 

that would incorporate the use of techniques such as ‘omics,’ Structure Activity Relationship (SAR) 

and Quantitative Structure Activity Relationship (QSAR) data, biomonitoring, and epidemiology 

studies, rather than relying solely on traditional animal bioassays. Although the PMRA is in the 

process of scoping out the possibility of incorporating alternative test methods such as QSAR/SAR 

into its testing paradigm, policy development on this subject is still in preliminary stages, and the 

PMRA recognizes the ongoing work regarding validation with respect to ITS. The PMRA 

recommends that the EPA continue to require the submission of traditional animal tests (i.e. 

according to the current testing paradigm) during the ITS validation phase to ensure maximum 

harmonization between the agencies. 

Response: see response 4 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25591 

Comment Code: 170000 

Comment: Section Number XVIII. 

Title Alternate Testing Paradigms 

Paragraph A. Structure Activity Relationship (SAR) Paragraph 4, p. 59421 

Excerpt from Federal Register An integrated approach would focus on using all relevant, credible 

information on the chemical of interest. Applicants are cautioned that such an approach will require 

a different type of thought process which will incorporate significantly more planning and ‘‘data 

mining’’ types of activities than making arrangements to conduct the required studies. However, it 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 975 

could also offer a flexibility that is not always present under the currently-used, guideline-driven 

(study-by- study) approach. 

HC Comment The PMRA would like to know whether there is guidance on how a risk assessment 

will be conducted if an applicant were to choose an integrated approach instead of a study-by-study 

approach to register a new antimicrobial product? Also, the PMRA would like to gain further 

understanding of the criteria that will be utilized to determine data quality for the "data mining" 

activities. 

 Section Number XVIII. 

Title Alternate Testing Paradigms 

Paragraph A. Structure Activity Relationship (SAR) Paragraph 7, p. 59422 

Excerpt from Federal Register The submitter of such information would be expected to supply a 

rationale describing the utility of the information and provide documentation on the scientific 

validity of the information. The determination that the predicted data fulfills the data requirement 

would be at the sole discretion of the Agency. 

HC Comment The PMRA seeks clarification regarding the type of documentation that will be 

required to demonstrate scientific validity of the information. 

 Section Number XVIII. 

Title Alternate Testing Paradigms 

Paragraph B. International Life Sciences Institute and Health and Environmental Sciences Institute 

Approaches Paragraph 4, p. 59423 

Excerpt from Federal Register All available information would be considered: Not only toxicity and 

dose response data from other guideline or non-guideline studies, but also structure- activity 

relationships, data on the mechanism or mode of action of the chemical, pharmacokinetic data, 

studies that examine agerelated sensitivity or susceptibility to chemical exposure, and information on 

potential or actual exposure to humans. These data could be used to inform a more targeted testing 

approach in the design of studies, or to support a position that the requirement for specific 

toxicology tests should be waived (i.e., the studies are not needed) or fulfilled via a means other than 

data generation, such as SAR. 

HC Comment There is a lack of emphasis on mechanism and mode of action, especially in the 

supporting white paper. Data from mechanistic studies may be crucial for more targeted testing. 

Furthermore, it should be noted that the metabolism study is not required for low exposure. 

The PMRA is interested in hearing the EPA’s opinion regarding the above points, and suggests that 

if an applicant chooses to use an integrated approach for the registration of a low-exposure 

antimicrobial, then the conduct of a metabolism study should be recommended (Note: Further 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 976 

discussion regarding the requirement of metabolism data appears below under comments for Test 

note #35). 

Response: see responses 170.1, 170.3, 80.57 and testnote 80.35 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25635 

Comment Code: 170000 

Comment: Section Number XVIII. 

Title Alternative Testing Paradigms 

Paragraph p. 59421 

Excerpt from Federal Register General comment 

HC Comment The PMRA is exploring use of QSAR tools, but they are presently not used to replace 

empirical data/information in the environmental assessment of pesticide active ingredients. These 

tools, currently restricted to components of EPI Suite, have been used occasionally on a case-bycase basis to estimate values for physical chemical properties of transformation products (e.g. Kow) 

in association with supporting empirical data and similarly derived estimates for the parent chemical 

to gain a measure of confidence in the estimations. Correlation between empirical data and predicted 

values for the parent compound has not always been sufficient to warrant the use of predicted 

values for the transformation products. In our opinion, prediction of more complex fate values for 

transformation products or parent compound has not yet been sufficiently validated to provide 

sufficient confidence in the calculation of expected concentration of pesticides in various 

compartments of the environment and associated exposure to wildlife and humans. The 

environmental directorate, in collaboration with the health directorate, has developed a proposal for 

an assessment by the Canadian Council of Academies on the scientific status of integrated testing 

strategies in the human health and environmental risk assessment of pesticides. Staff members in the 

Environmental Assessment Directorate are actively working to further understand and explore the 

utility and application of QSAR tools in environmental evaluation of pesticides. 

Response: EPA looks forward to receiving the results of the assessment by the Canadian Council 

of Academies. 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25637 

Comment Code: 170000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 977 

Comment: Comments on the White Paper - Use of Structure-Activity Relationship (SAR) 

Information and Quantitative SAR (QSAR) Modeling For Fulfilling Data Requirements for 

Antimicrobial Pesticide Chemicals and Informing EPA’s Risk Management Process 

General Considerations: 

* Data quality, endpoint of interest and datasets will vary depending on which model is used. 

Therefore, utilizing multiple SAR/QSAR models to confirm a prediction will strengthen the result. 

* Mode/mechanism of action may be a better approach in categorizing chemical groups rather than 

using chemical structure similarity 

* SAR/QSAR model should not imply that empirical data is no longer required to fulfil a data 

requirement. It is important to generate empirical data especially for novel chemicals because this 

information would contribute to the enhancement of the dataset and improve SAR/QSAR models. 

The validity of SAR/QSAR predictions would be diminished if datasets were based solely on 

modelled results. 

* Validation of SAR/QSAR models, development of guidance documents and standardization of 

the integrated approach would strengthen the acceptability of predictions for regulatory purposes. 

Furthermore, collaborations with the EPA will aid in this effort. 

* QSAR tools are presently not used to replace empirical data/information in the environmental 

assessment of pesticide active ingredients at the PMRA. These tools, currently restricted to 

components of EPI Suite, have been used occasionally, however, on a case-by-case basis to estimate 

values for physical chemical properties of transformation products (e.g. Kow) in association with 

supporting empirical data and similarly derived estimates for the parent chemical to gain a measure 

of confidence in the estimations. Correlation between empirical data and predicted values for the 

parent compound has not always been sufficient to warrant the use of predicted values for the 

transformation products. In our opinion, prediction of more complex fate values for transformation 

products or parent compound has not been sufficiently validated to provide sufficient confidence in 

the calculation of expected concentration of pesticides in various compartments of the environment 

and associated exposure to wildlife and humans. 

* The environmental directorate, in collaboration with the health directorate, has developed a 

proposal for an assessment by the Canadian Council of Academies on the scientific status of 

integrated testing strategies in the human health and environmental risk assessment of pesticides. 

* Staff members in the environmental directorate have been participating in the QSAR courses 

organized by Environment Canada to further understand and explore the utility and application of 

QSAR tools in environmental evaluation of pesticides. 

* Integrated testing strategies must be comprehensive such that they address all requirements of 

traditional testing paradigms. 

Detailed Considerations: 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 978 

Section Number 1. 

Title Introduction 

Paragraph 1, p. 2 

Excerpt from White Paper The use of the results of such testing (measured data) is a logical, 

scientifically-rigorous process that identifies the physical, chemical, and environmental fate 

properties of the pesticide chemical as well as the doses and endpoints at which an adverse effect 

occurs in various species. 

HC Comment Measured data also identifies the biological activity and may also elucidate the mode 

of action of a pesticide chemical. 

 Section Number 1. 

Title Introduction 

Paragraph 2, p. 3 

Excerpt from White Paper It would be a poor use of societal resources to routinely require the 

submission and governmental review of a multi-million dollar database for every active ingredient if 

there were alternate methods of determining which chemicals could be evaluated in a scientifically 

rigorous manner using mostly predicted data. 

HC Comment Although it is financially taxing to generate measured data for each active ingredient, 

there needs to be an appropriate balance between measured and predicted data. Furthermore, the 

general public should be informed on the alternate methods used for regulatory purposes and the 

uncertainties associated with measured data compared to predicted data. 

 Section Number 1. 

Title Introduction 

Paragraph 4, p. 3 

Excerpt from White Paper SAR and Quantitative SAR (QSAR) modeling results can sometimes be 

used instead of measured data, but modeled data cannot be preferentially substituted for wellconducted studies (measured data). 

HC Comment This is an important qualification on the use of (Q)SAR data. However, if an 

applicant is building a weight of evidence rationale for an antimicrobial that includes readily available 

published studies, in vitro test results, predictive modeling, etc., there may be some cases where 

predictions from multiple robust predictive methods (eg. category approaches, (Q)SAR, etc.) should 

be given more weight than published studies of lower quality for the same endpoint. The PMRA 

suggests the addition of text to reflect this point. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 979 

 Section Number 1. 

Title Introduction 

Paragraph 2, p. 4 

Excerpt from White Paper Just as measured data have uncertainties, predicted data also have 

uncertainties. Use of different models (developed using different methods and sets of data) would 

necessarily have different degrees and types of uncertainties. Therefore, QSAR models must be used 

by informed practitioners and within appropriate assessment scenarios. Expert judgment is required 

to determine the appropriate model to use, the limitations of a particular model approach, and the 

degree of confidence that can be placed in any given model prediction. For example, a model should 

strike an appropriate balance between sensitivity (few negatives) and precision (few false positives). 

HC Comment The PMRA suggests the addition of text to this section to emphasize that the 

limitations, confidence and uncertainties in model predictions need to be clearly documented when 

building weight of evidence arguments that include predictive data. 

It should be noted that in some cases, it may be preferable to rely on models that are more heavily 

weighted towards sensitivity rather than precision. QSAR models providing a greater number of 

false positives may give greater assurance that pesticides of potential concern are identified since 

protection of human health and environment is a key element in a pesticide assessment. The PMRA 

suggests the addition of text to address this point. 

 Section Number 4 

Title SAR and QSAR 

Paragraph 2, p. 7 

Excerpt from White Paper * Group or category: Instead of having a unique dataset for each 

member of the group, the data from a defined group of structurallyrelated chemicals is "pooled." 

This is based on the premise that structurally-similar chemicals often have similar physical/chemical 

properties, and sometimes behave in a similar manner in biological systems. Such an approach is 

predictive in nature, and can provide a means of extrapolating the available data from one member 

to another with a certain level of confidence. Such extrapolations can estimate expected adverse 

effects but cannot exactly predict the magnitude of the response. *Analog: The unknown chemical is 

compared to a different, but very similar, structurally-related chemical for which there is a good 

toxicity database. *Combination: A combination of the analog and category approaches in which the 

unknown chemical is compared to a class of chemicals for which there is a sufficient "pool" of 

toxicity data 

HC Comment The three approaches incorporate dataset(s) from another or multiple structurallyrelated chemicals. It is important to determine if there are any data ownership or data compensation 

issues with the dataset(s) used in the pooling of structurally-related chemicals. Suggest revising the 

last sentence under Group or category to: "Such extrapolations may predict the likelihood of adverse 

effects but cannot exactly predict the magnitude of the response." 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 980 

 Section Number 4 

Title SAR and QSAR 

Paragraph 3, p. 8 

Excerpt from White Paper Numerous articles from open literature and internet sources clearly state 

a consensus position within the scientific community that (Q)SAR results are not considered to be 

superior to measured data. 

HC Comment There is consensus that (Q)SAR results are not superior to measured data and should 

not be used in a stand-alone manner, instead these types of data should be considered in an 

integrative weight of evidence approach. 

 Section Number 5 

Title Use of SAR or QSAR in Assessing Antimicrobial Data Needs 

Paragraph 5, p. 9 

Excerpt from White Paper For certain chemicals under the appropriate circumstances (e.g., very low 

exposure estimates) and especially for those chemicals of lower toxicity (based on category/group or 

analogue approaches, and expert judgment), it is likely that the use of SAR and QSAR could provide 

relevant and appropriate scientifically-rigorous information for consideration during the weight-ofthe evidence evaluation that occurs as part of the hazard identification and risk assessment process. 

HC Comment It should be noted that many commercial and public (Q)SAR models developed for 

the prediction of endpoints relevant to human health do not contain significant numbers or diversity 

of lower toxicity chemicals in their databases. In addition, (Q)SAR models are not designed to 

predict chemical inactivity but rather the presence or absence of structural features related to 

activity. The PMRA suggests these points be taken into consideration, and the text amended 

accordingly. 

 Section Number 6 

Title Office of Pollution, Prevention and Toxics (OPPT) Experience with Using SAR 

Paragraph 3, p. 11 

Excerpt from White Paper OPPT’s qualitative SAR assessment is based on a "nearest analog" 

approach and is an expert judgment system in which various parts of the chemical’s molecular 

structure "alerts" those performing the assessment to the potential for adverse effects. 

HC Comment Are there established criteria in determining the "nearest analog" to the chemical of 

interest? If so, the PMRA recommends that this be described in the text. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 981 

 Section Number 12 

Title The Types of Information that Would be Useful to OPP 

Paragraph 1, p.27 

Excerpt from White Paper For use of surrogate data (measured data on a chemical that is 

structurally- related to the chemical substance under review) all of the above considerations also 

apply. In fact, well-conducted guideline studies or peer-reviewed literature on a surrogate chemical 

could receive greater weight than summary or anecdotal information on the chemical substance that 

is being evaluated. 

HC Comment While data from surrogate chemicals may be useful, such data must be bridged with 

data from the chemical substance under review to ensure compatibility between the surrogate data 

to that of the chemical substance under review. In the absence of bridging data, it would not be 

possible to ensure that data from the surrogate chemical provides accurate information on the 

behaviour of the chemical under review. In addition, the surrogate data should provide an 

appropriate amount of information on how the study was conducted and what data were obtained 

rather than providing only values for end-points measured. The PMRA suggests adding text to 

address the necessity of bridging rationales when the use of surrogate data is proposed. 

 Section Number 12 

Title The Types of Information that Would be Useful to OPP 

Paragraph 3, p. 29 

Excerpt from White Paper At this time, the use of SAR is not yet a standardized approach in the 

Office of Pesticide Programs, and is being handled on a case-by-case basis. Therefore, OPP has not 

yet developed a standardized format for submission of such information. 

HC Comment One standardized format that could be considered by OPP is the European 

Chemicals Bureau (ECB) QSAR Model Reporting Format (QMRF) and the QSAR Prediction 

Reporting Format (QPRF). The templates may be useful for summarizing and reporting key 

information on QSAR models and substance-specific predictions. 

 Section Number 14 

Title Acceptance of QSAR models by OPP 

Paragraph 1 p.32 

Excerpt from White Paper Consistent with the earlier Report from the Expert Group, (OECDf), 

the Validation Guidance re-emphasizes that the acceptance of (Q)SARs must be considered within a 

specific regulatory context. Furthermore, it is explicitly stated that: 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 982 

"the validation of (Q)SAR models for regulatory purposes are best carried out by the regulatory 

authorities of the member countries. In the foreseeable future, the acceptance of (Q)SARs as a 

nontesting alternative source of data in making decisions will be based on the reliability and 

transparency of a specific (Q)SAR model within a specific regulatory context. Consequently, the 

validation principles for (Q)SAR models are intended to guide regulatory agencies in the evaluation 

of performance of (Q)SAR for specific decision processes at a higher level than the criteria used to 

judge statistical validity." 

Therefore, it is up to each regulatory authority to determine if there is a sufficient understanding of 

the information generated by the (Q)SAR assessment, if the use of the model was appropriate given 

the circumstances of intended use, and if the predicted data is of the quality and reliability needed 

for their regulatory purposes. 

HC Comment The recommendation of validating QSAR models by regulatory bodies would be an 

opportunity for PMRA and EPA collaboration. 

 Section Number 14 

Title Acceptance of QSAR models by OPP 

Paragraph 3 p.32 

Excerpt from White Paper Pesticide applicants are urged to first consider using the QSAR modeling 

and expert system tools that have been developed and used for some time by EPA, such as 

ECOSAR, EPI Suite, and OncoLogicTM , which are publicly available via the Agency website. 

HC Comment The QSAR tools developed by EPA are a good starting point. However, it should be 

noted that the selection of an appropriate model will depend on the endpoint of interest, type of 

prediction (quantitative or qualitative), the domain of applicability in the model and the dataset used 

to train the model. Therefore, other public/commercial models should not be ruled out. 

Response: see responses 170.1, 170.6 and 170.7 

Commenter Name: Jay Feldman 

Commenter Organization: Beyond Pesticides 

Letter ID: 0067 

Comment ID: 25714 

Comment Code: 170000 

Comment: SAR and QSAR 

EPA proposes to utilize structure activity relationships (SAR) and quantitative structure activity 

relationship (QSAR) modeling to assist in the fulfillment of data requirements for antimicrobials. 

These techniques involve the comparison of the molecular structure of chemicals to that of other 

structurally-related chemicals for which data are available. These structural similarities can be used to 

make predictions about the physical, chemical and/or biological activity of the chemical being 

assessed. The use of these practices could potentially conserve resources, increase efficacy and 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 983 

provide information for a chemical with otherwise limited data. The use of SARs and QSARs should 

be a supplement to data submitted and should by no means be a substitute for available, reliable, 

measured data (laboratory studies). 

The agency has a history of utilizing SARs, however, it has been usually on a case-by-case basis and 

generally sporadic. It has been our experience that the agency chooses to utilize SARs when it is 

convenient to do so, and ignores them in other cases if the weight against the use of the chemical 

were to increase. We hope that the agency would be consistent in its use of SARs, even when done 

on a case-by-case basis. We also recommend that the use of SARs be used to predict modes of 

action of chemicals, as they relate to common mechanisms of toxicity. The agency has a tendency to 

recognize structural similarities between chemicals while dismissing the potential of having similar 

modes of action, despite scientific evidence demonstrating similar adverse impacts/endpoints for 

pesticidal substances with structural similarities. (Please refer to Beyond Pesticides’ previous 

comments for the preliminary RED for triclosan and the petition to ban 2,4-D.) 

Response: see response 170.3 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25797 

Comment Code: 170000 

Comment: Use of SAR and QSAR 

U.S. EPA seeks comment on the use of predictive techniques to fulfill the Part 158 Subpart W data 

requirements, and specifically on when and if the use of Structure-Activity Relationship (SAR) and 

Quantitative SAR (QSAR) should be codified in Part 158, Subpart A (page 59422). Tri-TAC is wary 

of the use of SAR and QSAR techniques to fulfill physiochemical and biodegradation data 

requirements. Dr George O'Connor of the University of Florida has found triclocarban, in 

particular, to be an example of a chemical with predicted Kow, solubility, and half-life values that are 

different from measured values. If incorrect parameters are used in environmental fate models, the 

accuracy of transport, exposure, and risk estimates can be adversely affected. Since the proposed 

rule requires evidence supporting the use of SAR/QSAR values and that evidence usually is 

achieved through physical measurements, it would seem more reasonable and scientifically valid to 

simply require measurements in place of estimates in these cases. This is particularly true since in the 

case of solubility and partitioning, and in some cases biodegradation, physical measurements are 

quick, inexpensive, and guided by Office of Pesticide Programs' documents. Similar concerns exist 

for codification in Part 158, Subpart A, since it would mean that SAR/QSAR techniques would be 

applicable to conventional, biochemical and microbial, and antimicrobial pesticide chemicals. 

Response: see response 170.4 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25893 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 984 

Comment Code: 170000 

Comment: Use of SAR and QSAR 

U.S. EPA seeks comment on the use of predictive techniques to fulfill the Part 158 Subpart W data 

requirements, and specifically on when and if the use of Structure-Activity Relationship (SAR) and 

Quantitative SAR (QSAR) should be codified in Part 158, Subpart A (page 59422). CASA is wary of 

the use of SAR and QSAR techniques to fulfill physiochemical and biodegradation data 

requirements. Dr George O'Connor of the University of Florida has found triclocarban, in 

particular, to be an example of a chemical with predicted Kow, solubility, and half-life values that are 

different from measured values. If incorrect parameters are used in environmental fate models, the 

accuracy of transport, exposure, and risk estimates can be adversely affected. Since the proposed 

rule requires evidence supporting the use of SAR/QSAR values and that evidence usually is 

achieved through physical measurements, it would seem more reasonable and scientifically valid to 

simply require measurements in place of estimates in these cases. This is particularly true since in the 

case of solubility and partitioning, and in some cases biodegradation, physical measurements are 

quick, inexpensive, and guided by Office of Pesticide Programs' documents. Similar concerns exist 

for codification in Part 158, Subpart A, since it would mean that SAR/QSAR techniques would be 

applicable to conventional, biochemical and microbial, and antimicrobial pesticide chemicals. 

Response: see responses 170.4 and 170.2 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25964 

Comment Code: 170000 

Comment: The Agency also provides the SAR/QSAR supplement within this proposal and this is 

commendable; however, based on the current proposal, registrants would be discouraged from 

utilizing this approach. The need for an adequate "weight of evidence" is not clear or explicit within 

this document and again relies on the Agency's judgment in the determination of an acceptable 

weight of evidence argument. 

Response: see response 170.1 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26080 

Comment Code: 170000 

Comment: Structure-Activity Relationships (SARs). USEPA requested feedback on the potential 

use of SARs as the basis of developing estimated values for various data requirements. We do not 

believe that SARs are currently sufficiently robust to form the basis of reliable estimates of aquatic 

toxicity data or environmental fate data. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 985 

Response: see response 170.8 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26118 

Comment Code: 170000 

Comment: Use of SAR and QSAR 

U.S. EPA seeks comment on the use of predictive techniques to fulfill the Part 158 Subpart W data 

requirements, and specifically on when and if the use of Structure-Activity Relationship (SAR) and 

Quantitative SAR (QSAR) should be codified in Part 158, Subpart A (page 59422). The Districts is 

wary of the use of SAR and QSAR techniques to fulfill physiochemical and biodegradation data 

requirements. Dr. George O'Connor of the University of Florida has found triclocarban, in 

particular, to be an example of a chemical with predicted Kow, solubility, and half-life values that are 

different from measured values. If incorrect parameters are used in environmental fate models, the 

accuracy of transport, exposure, and risk estimates can be adversely affected. Since the proposed 

rule requires evidence supporting the use of SAR/QSAR values and that evidence usually is 

achieved through physical measurements, it would seem more reasonable and scientifically valid to 

simply require measurements in place of estimates in these cases. This is particularly true since in the 

case of solubility and partitioning, and in some cases biodegradation, physical measurements are 

quick, inexpensive, and guided by Office of Pesticide Programs' documents. Similar concerns exist 

for codification in Part 158, Subpart A, since it would mean that SAR/QSAR techniques would be 

applicable to conventional, biochemical and microbial, and antimicrobial pesticide chemicals. 

Response: see responses 170.4 and 170.2 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26164 

Comment Code: 170000 

Comment: The Proposed Subpart 158W Rule provides OPP with a unique opportunity to design a 

data requirements structure which anticipates the rapid changes in toxicology which are inevitable 

over the next 10-20 years. A full and specific integration of QSAR/SAR opportunities within the 

Rule is critical as is a Final Rule which encourages and is designed to accommodate the integration 

of new in vitro and computation toxicology alternatives without the need for lengthy and uncertain 

Federal rulemaking. 

Response: see responses 4 and 170.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26419 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 986 

Comment Code: 170000 

Comment: A. SAR/QSAR 

The Panel believes that the use of SAR and alternative techniques to addressing data requirements 

for all pesticides is permitted by existing regulations and policies. The Agency has long relied upon 

consideration of structural similarities to identify potential areas of concern or to identify where 

concerns are unlikely. For example, the OPPTS testing guideline for determining acute toxicity of 

chemicals including pesticides (OPPTS Guideline 870.1000) identifies that structural similarity is an 

important approach to minimizing animal testing: 

In order to minimize the need for animal testing for acute effects, the Agency encourages the review 

of existing acute toxicity information on chemical substances that are structurally related to the agent 

under investigation. 

In fact, EPA has a history of employing alternative approaches for hazard identification on 

antimicrobial pesticides. For example, in 1988 the Agency determined that an analog SAR approach 

was appropriate for the ADBAC and DDAC clusters of quaternary ammonium compounds (PR 88-

2). In those two cases, a single compound within each cluster was designated as the model 

compound and a full database to address the generic data requirements (toxicology, ecotoxicology, 

environmental fate) was developed on that compound. All other members of each cluster were 

allowed to rely upon the data generated for the model compound. Clusters were based largely on 

structural characteristics. 

Since then, other compounds have been allowed to rely upon (bridged to) the model compound 

data, again largely based upon a structural similarity. There are other examples where the Agency has 

followed a similar approach for at least some of the generic data requirements for antimicrobial 

pesticides as well as for other types of pesticide chemicals (both active and inert components). The 

Agency has long used structural similarity to require additional targeted testing (e.g., acute delayed 

neurotoxicity for organophosphates, specific studies to evaluate neurotoxicity of classes of chemicals 

known to be neurotoxic, special persistence studies for types of chemicals known to be persistent or 

bioaccumulative). 

The use of SAR/QSAR for antimicrobial pesticides is consistent with the approach already taken by 

EPA for other pesticide products and the Proposal should therefore be revised to explicitly permit 

consideration of alternate approaches such as SAR and QSAR. 

In the Proposal, EPA has prepared and requested comments on a white paper entitled "Use of 

Structure-Activity Relationship (SAR) Information and Quantitative SAR (QSAR) Modeling for 

Fulfilling Data Requirements for Antimicrobial Pesticide Chemicals and Informing EPA’s Risk 

Management Process" (hereafter "SAR White Paper"). The SAR White Paper does not provide 

adequate guidance as to how registrants of antimicrobial pesticides could use alternative techniques 

such as SAR to address the guideline-driven data requirements. For example, the White Paper does 

not explain when systemic toxicity requirements would be obviated because local effects are the 

primary toxic mode of action. Nor is there guidance as to how such compounds should be 

otherwise evaluated, including what information is needed for risk management. This is a critical 

obstacle to the furtherance of alternative approaches. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 987 

The White Paper’s descriptions of when SAR could be considered are often vague. For example, the 

White Paper states that SAR could be considered "for appropriate chemicals," or "under very low 

exposure estimates" or for "lower toxicity chemicals," without any clear guidance as to what those 

phrases mean. 

The White Paper identifies many limitations to the current state of the use of SAR/QSAR but fails 

to provide guidance as to how an applicant might be able to use what is currently available to 

address data requirements. The lack of a clear process within the Agency for the review of 

information submitted by an applicant, even following the type of hierarchy identified within the 

White Paper (page 26), has resulted in numerous rejections by the Agency of the alternative 

information and a requirement to conduct a guideline study. Unless and until the Agency has clear 

policies, procedures, and processes for evaluating the alternative types of information in a rational, 

transparent, and scientifically defensible manner, the regulatory process will continue to devolve to 

the guideline-driven, study dependent, standard approach. 

Response: see responses 170.2 and 170.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26421 

Comment Code: 170000 

Comment: The Panel is encouraged by the Agency’s steps toward improving the regulatory process 

by incorporating new science and new approaches, including the use of techniques such as SAR and 

QSAR. EPA’s SAR White Paper provides a general overview of the state of the science and 

indicates the Agency’s willingness to consider alternative approaches. However, better guidance, 

both internal and external, is needed to ensure that such willingness can be translated into reality. 

Response: see response 170.1 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26609 

Comment Code: 170000 

Comment: QSAR and SAR White Paper: 

P&G is in full agreement with the Agency’s use of QSAR, SAR and other weight of evidence type 

approaches to fulfill toxicology data requirements. The use of SAR/QSAR for antimicrobial 

pesticides is consistent with the approach already taken by EPA for other pesticide products and the 

Proposal should therefore be revised to explicitly permit consideration of alternate approaches such 

as SAR and QSAR. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 988 

Response: EPA acknowledges Proctor and Gamble's support for using SAR and QSAR, and other 

WOE approaches. see also response 170.2 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26611 

Comment Code: 170000 

Comment: The White Paper’s descriptions of when SAR could be considered are often vague. For 

example, the White Paper states that SAR could be considered "for appropriate chemicals," or 

"under very low exposure estimates" or for "lower toxicity chemicals," without any clear guidance as 

to what those phrases mean. The SAR White Paper does not provide adequate guidance as to how 

registrants of antimicrobial pesticides could use alternative techniques such as SAR to address the 

guidelinedriven data requirements. The White Paper identifies many limitations to the current state 

of the use of SAR/QSAR but fails to provide guidance as to how an applicant might be able to use 

what is currently available to address data requirements. In general, the White Paper would be more 

useful to registrants if it clearly identified areas where SAR/QSAR could be used. Also, the Agency 

should define the internal review process for such data. It has been P&G’s experience that nonroutine risk assessments must be conducted outside of the existing product review process and takes 

a second PRIA review period to complete. It would be helpful to standardize this type of risk 

assessment within the Agency such that only a standard review period is required. 

Response: see response 170.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27076 

Comment Code: 170000 

Comment: [FN73: While the data requirement regulation should explicitly permit consideration of 

alternate approaches, it is also essential that the Agency have clear guidance available outside of the 

regulation itself to allow registrants to effectively utilize current and future alternate approaches 

rather than traditional or out-dated testing methodologies. While LANXESSis strongly supportive of 

the use of all available science in making regulatory decisions, including the use of predictive 

techniques such as SAR and the appropriate use of a weight of evidence approach, we believe that 

specific direction regarding the use of such alternative techniques should be provided through 

Agency guidance, rather than as part of the data requirement regulations.] 

Response: see response 170.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27088 

Comment Code: 170000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 989 

Comment: A. SAR/QSAR 

LANXESS believes that the use of SAR and alternative techniques to addressing data requirements 

for all pesticides is permitted by existing regulations and policies. The Agency has long relied upon 

consideration of structural similarities to identify potential areas of concern or to identify where 

concerns are unlikely. For example, the OPPTS testing guideline for determining acute toxicity of 

chemicals including pesticides (OPPTS Guideline 870.1000) identifies that structural similarity is an 

important approach to minimizing animal testing: 

"In order to minimize the need for animal testing for acute effects, the Agency encourages the 

review of existing acute toxicity information on chemical substances that are structurally related to 

the agent under investigation." 

In fact, EPA has a history of employing alternative approaches for hazard identification on 

antimicrobial pesticides. For example, in 1988 the Agency determined that an analog SAR approach 

was appropriate for the ADBAC and DDAC clusters of quaternary ammonium compounds (PR 88-

2). In those two cases, a single compound within each cluster was designated as the model 

compound and a full database to address the generic data requirements (toxicology, ecotoxicology, 

environmental fate) was developed on that compound. All other members of each cluster were 

allowed to rely upon the data generated for the model compound. Clusters were based largely on 

structural characteristics. 

Since then, other compounds have been allowed to rely upon (bridged to) the model compound 

data, again largely based upon a structural similarity. There are other examples where the Agency has 

followed a similar approach for at least some of the generic data requirements for antimicrobial 

pesticides as well as for other types of pesticide chemicals (both active and inert components). The 

Agency has long used structural similarity to require additional targeted testing (e.g., acute delayed 

neurotoxicity for organophosphates, specific studies to evaluate neurotoxicity of classes of chemicals 

known to be neurotoxic, special persistence studies for types of chemicals known to be persistent or 

bioaccumulative). 

The use of SAR/QSAR for antimicrobial pesticides is consistent with the approach already taken by 

EPA for other pesticide products and the Proposal should therefore be revised to explicitly permit 

consideration of alternate approaches such as SAR and QSAR. 

In the Proposal, EPA has prepared and requested comments on a white paper entitled "Use of 

Structure-Activity Relationship (SAR) Information and Quantitative SAR (QSAR) Modeling for 

Fulfilling Data Requirements for Antimicrobial Pesticide Chemicals and Informing EPA’s Risk 

Management Process" (hereafter "SAR White Paper"). The SAR White Paper does not provide 

adequate guidance as to how registrants of antimicrobial pesticides could use alternative techniques 

such as SAR to address the guideline-driven data requirements. For example, the White Paper does 

not explain when systemic toxicity requirements would be obviated because local effects are the 

primary toxic mode of action. Nor is there guidance as to how such compounds should be 

otherwise evaluated, including what information is needed for risk management. This is a critical 

obstacle to the furtherance of alternative approaches. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

White Paper on Use of SAR and QSAR (170) Page 990 

The White Paper’s descriptions of when SAR could be considered are often vague. For example, the 

White Paper states that SAR could be considered "for appropriate chemicals," or "under very low 

exposure estimates" or for "lower toxicity chemicals," without any clear guidance as to what those 

phrases mean. 

The White Paper identifies many limitations to the current state of the use of SAR/QSAR but fails 

to provide guidance as to how an applicant might be able to use what is currently available to 

address data requirements. The lack of a clear process within the Agency for the review of 

information submitted by an applicant, even following the type of hierarchy identified within the 

White Paper (page 26), has resulted in numerous rejections by the Agency of the alternative 

information and a requirement to conduct a guideline study. Unless and until the Agency has clear 

policies, procedures, and processes for evaluating the alternative types of information in a rational, 

transparent, and scientifically defensible manner, the regulatory process will continue to devolve to 

the guideline-driven, study dependent, standard approach. 

Response: see responses 170.1 and 170.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27090 

Comment Code: 170000 

Comment: LANXESS is encouraged by the Agency’s steps toward improving the regulatory 

process by incorporating new science and new approaches, including the use of techniques such as 

SAR and QSAR. EPA’s SAR White Paper provides a general overview of the state of the science 

and indicates the Agency’s willingness to consider alternative approaches. However, better guidance, 

both internal and external, is needed to ensure that such willingness can be translated into reality. 

Response: see response 170.1 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Endangered Species Section (180) Page 991 

Endangered Species (180) 

Verbatim Comments and Response References for the Endangered Species 

Section 

Comment Code: 180000 Endangered species 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26397 

Comment Code: 180000 

Comment: The rigor and extensiveness of EPA’s environmental fate and ecotoxicity data 

requirements for conventional pesticides is predicated on the fact that conventional pesticides are 

broadcast directly to the environment and that runoff and other discharges are not subject to other 

statutory schemes. These concerns are not relevant to the control of point source discharges such as 

once-through antimicrobial uses. Nonetheless, the data requirements applied to once-through uses 

have been largely adopted from the conventional data requirement regulation, without explanation 

or any consideration of the differences. These should be reconsidered and the current proposed 

requirements withdrawn.[FN#58:EPA needs to recognize the manner in which antimicrobials may 

result in environmental exposure and the regulations under statutes other than FIFRA in order to 

promote effective and efficient regulation of these products. The same recognition is critical to any 

reasonable approach to regulating antimicrobial pesticides with regard to endangered and threatened 

species, as discussed in Appendix M.] 

Response: see responses 180.1 and 180.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26992 

Comment Code: 180000 

Comment: The rigor and extensiveness of EPA’s environmental fate and ecotoxicity data 

requirements for conventional pesticides is predicated on the fact that conventional pesticides are 

broadcast directly to the environment and that runoff and other discharges are not subject to other 

statutory schemes. These concerns are not relevant to the control of point source discharges such as 

once-through antimicrobial uses. Nonetheless, the data requirements applied to once-through uses 

have been largely adopted from the conventional data requirement regulation, without explanation 

or any consideration of the differences. These should be reconsidered and the current proposed 

requirements withdrawn.[FN58: EPA needs to recognize the manner in which antimicrobials may 

result in environmental exposure and the regulations under statutes other than FIFRA in order to 

promote effective and efficient regulation of these products. The same recognition is critical to any 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Endangered Species Section (180) Page 992 

reasonable approach to regulating antimicrobial pesticides with regard to endangered and threatened 

species, as discussed in Appendix M.] 

Response: see responses 2 and 180.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27125 

Comment Code: 180000 

Comment: Although not directly part of the FIFRA registration data requirements for 

antimicrobials, EPA also solicits comments on specific issues relating to possible future rulemakings 

that will help ensure compliance with the Endangered Species Act. 73 Fed. Reg. at 59425. According 

to EPA, there are several antimicrobial uses with the potential for environmental exposure that must 

be considered in EPA’s role to protect endangered and threatened species. These include "wood 

preservatives, antifoulant paints, industrial wastewater discharges, [and] ballast water discharges." 

Response: The commenter is correct that EPA specifically requested comments on ESA 

implications for antimicrobials. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27126 

Comment Code: 180000 

Comment: EPA is concerned that geographic areas of use of antimicrobials are less well- defined 

than those for agricultural pesticides, where "there is greater specificity relative to where a pesticide 

may be used." This conclusion is based on the approach adopted by EPA for agricultural pesticides, 

which involves delineation of use sites and overlapping them with locations of endangered or 

threatened species. According to EPA, it will be much more difficult to "delineate, and overlay" 

antimicrobial use sites with endangered or threatened species locations. Id. 

In general, the Panel does not believe that the program EPA has in place for assessing potential 

impacts on endangered and threatened species is relevant to antimicrobials and their uses. 

Antimicrobials are not broadcast into environmental media. To the extent that environmental 

exposures occur, they result from point-source discharges or slow release from pesticide-containing 

materials. Such releases are subject to control under multiple laws and regulations. Thus, there are 

numerous opportunities to address antimicrobial releases to the environment other than through 

FIFRA. EPA should adopt an approach for antimicrobials that is applicable to its uses and users, 

and that accounts for these other environmental statutes and regulations. 

In many ways, it is premature to try to determine how EPA should approach antimicrobials with 

regard to endangered species. This is because there is no mature program currently in place for 

antimicrobial environmental risk assessment generally. As discussed in Appendix H, the Panel does 

not believe that the Agency has defined appropriate or reliable sources of data for estimating 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Endangered Species Section (180) Page 993 

potential environmental releases. Moreover, there are few or no Agency-accepted methodologies or 

models currently available for antimicrobial uses that will produce scientifically sound environmental 

risk assessments. 

Response: see responses 180.1 and 180.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27720 

Comment Code: 180000 

Comment: APPENDIX K 

COMMENTS on POTENTIAL FUTURE RULEMAKINGS REGARDING ENDANGERED 

SPECIES ACT COMPLIANCE 

Although not directly part of the FIFRA registration data requirements for antimicrobials, EPA also 

solicits comments on specific issues relating to possible future rulemakings that will help ensure 

compliance with the Endangered Species Act. 73 Fed. Reg. at 59425. According to EPA, there are 

several antimicrobial uses with the potential for environmental exposure that must be considered in 

EPA’s role to protect endangered and threatened species. These include "wood preservatives, 

antifoulant paints, industrial wastewater discharges, [and] ballast water discharges." 

Response: The commenter is correct that EPA specifically requested comments on ESA 

implications for antimicrobials. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27721 

Comment Code: 180000 

Comment: EPA is concerned that geographic areas of use of antimicrobials are less well- defined 

than those for agricultural pesticides, where "there is greater specificity relative to where a pesticide 

may be used." This conclusion is based on the approach adopted by EPA for agricultural pesticides, 

which involves delineation of use sites and overlapping them with locations of endangered or 

threatened species. According to EPA, it will be much more difficult to "delineate, and overlay" 

antimicrobial use sites with endangered or threatened species locations. Id. 

In general, LANXESS does not believe that the program EPA has in place for assessing potential 

impacts on endangered and threatened species is relevant to antimicrobials and their uses. 

Antimicrobials are not broadcast into environmental media. To the extent that environmental 

exposures occur, they result from point-source discharges or slow release from pesticide-containing 

materials. Such releases are subject to control under multiple laws and regulations. Thus, there are 

numerous opportunities to address antimicrobial releases to the environment other than through 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Endangered Species Section (180) Page 994 

FIFRA. EPA should adopt an approach for antimicrobials that is applicable to its uses and users, 

and that accounts for these other environmental statutes and regulations. 

In many ways, it is premature to try to determine how EPA should approach antimicrobials with 

regard to endangered species. This is because there is no mature program currently in place for 

antimicrobial environmental risk assessment generally. As discussed in Appendix H , LANXESS 

does not believe that the Agency has defined appropriate or reliable sources of data for estimating 

potential environmental releases. Moreover, there are few or no Agency-accepted methodologies or 

models currently available for antimicrobial uses that will produce scientifically sound environmental 

risk assessments. 

Response: see responses 180.1 and 180.2 

Comment Code: 181000 Types of data that could be useful for conducting the assessment required 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27127 

Comment Code: 181000 

Comment: Below, the Panel provides some initial comments on the topics on which EPA 

requested specific comment. 

1. The types of data that could be useful for conducting the assessment required. 

The Panel assumes that EPA will consider endangered species impacts only in the event that 

environmental Levels of Concern (LOCs) are exceeded, based on environmental risk assessments. 

In conducting risk assessments, it is critical that EPA use the most reliable data for estimating both 

anticipated toxicity and exposures, and use only models that are appropriate to the specific 

antimicrobial uses. Based on the Proposed Rule, the Panel is concerned that the data EPA intends to 

use will grossly overestimate environmental exposures resulting from many antimicrobial uses. The 

Panel is equally concerned that EPA intends to apply models that were developed for agricultural 

uses that are irrelevant and scientifically inappropriate to apply to antimicrobial uses. Until EPA 

scientifically substantiates data requirements to use in estimating antimicrobial environmental 

exposures and modeling the potential for risks from such exposures, it will not be feasible to make 

any meaningful determinations on potential impacts to endangered species. 

Response: see response 180.5 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27128 

Comment Code: 181000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Endangered Species Section (180) Page 995 

Comment: The other critical issue in EPA’s current approach is determining how to "delineate" 

areas of antimicrobial use and locations of endangered and threatened species. As discussed below, 

the Panel does not believe that the overlapping of locations of pesticide use and endangered species 

populations is appropriate for antimicrobials. In any case, there may be no single answer with regard 

to different antimicrobial product types. They will have to be viewed in appropriate contexts. And 

the other regulatory requirements limiting use and exposure will have to be integral to each 

evaluation. 

Response: see response 180.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27142 

Comment Code: 181000 

Comment: Significantly, most of the uses that EPA believes offer the potential for environmental 

exposure are not regulated solely under FIFRA, in contrast to agricultural pesticide uses. They are 

subject to other federal, state and local laws and regulatory schemes. For example, there are 

numerous state and local ordinances that control the use of treated wood, particularly when an 

installation will result in contact with bodies of water. To develop an approach to evaluating impacts 

on endangered species, EPA should conduct a thorough evaluation of these permitting requirements 

and laws to evaluate the types of data they provide and to determine whether they mitigate 

exposures sufficiently to eliminate concerns about environmental impacts. 

Response: see response 180.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27144 

Comment Code: 181000 

Comment: Similar evaluations must also be made of the ways in which antimicrobial discharges are 

regulated under other EPA-administered programs. For example, industrial waste water discharges 

are regulated pursuant to the Clean Water Act (CWA) by the Office of Water. Direct discharges to 

surface water are subject to NPDES permits, and discharges to publicly owned waste water 

treatment facilities (POTWs) must meet pretreatment standards. To perform a meaningful ESA 

evaluation the impact of these regulatory programs should be considered. 

Response: see response 180.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27722 

Comment Code: 181000 
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Comments and Response References: 

Endangered Species Section (180) Page 996 

Comment: Below, LANXESS provides some initial comments on the topics on which EPA 

requested specific comment. 

1. The types of data that could be useful for conducting the assessment required. 

LANXESS assumes that EPA will consider endangered species impacts only in the event that 

environmental Levels of Concern (LOCs) are exceeded, based on environmental risk assessments. 

In conducting risk assessments, it is critical that EPA use the most reliable data for estimating both 

anticipated toxicity and exposures, and use only models that are appropriate to the specific 

antimicrobial uses. Based on the Proposed Rule, LANXESS is concerned that the data EPA intends 

to use will grossly overestimate environmental exposures resulting from many antimicrobial uses. 

LANXESS is equally concerned that EPA intends to apply models that were developed for 

agricultural uses that are irrelevant and scientifically inappropriate to apply to antimicrobial uses. 

Until EPA scientifically substantiates data requirements to use in estimating antimicrobial 

environmental exposures and modeling the potential for risks from such exposures, it will not be 

feasible to make any meaningful determinations on potential impacts to endangered species. 

Response: see response 180.5 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27723 

Comment Code: 181000 

Comment: The other critical issue in EPA’s current approach is determining how to "delineate" 

areas of antimicrobial use and locations of endangered and threatened species. As discussed below, 

LANXESS does not believe that the overlapping of locations of pesticide use and endangered 

species populations is appropriate for antimicrobials. In any case, there may be no single answer 

with regard to different antimicrobial product types. They will have to be viewed in appropriate 

contexts. And the other regulatory requirements limiting use and exposure will have to be integral to 

each evaluation. 

Response: see response 180.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27725 

Comment Code: 181000 

Comment: ignificantly, most of the uses that EPA believes offer the potential for environmental 

exposure are not regulated solely under FIFRA, in contrast to agricultural pesticide uses. They are 

subject to other federal, state and local laws and regulatory schemes. For example, there are 

numerous state and local ordinances that control the use of treated wood, particularly when an 

installation will result in contact with bodies of water. To develop an approach to evaluating impacts 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments and Response References: 

Endangered Species Section (180) Page 997 

on endangered species, EPA should conduct a thorough evaluation of these permitting requirements 

and laws to evaluate the types of data they provide and to determine whether they mitigate 

exposures sufficiently to eliminate concerns about environmental impacts. 

Response: see response 180.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27727 

Comment Code: 181000 

Comment: Similar evaluations must also be made of the ways in which antimicrobial discharges are 

regulated under other EPA-administered programs. For example, industrial waste water discharges 

are regulated pursuant to the Clean Water Act (CWA) by the Office of Water. Direct discharges to 

surface water are subject to NPDES permits, and discharges to publicly owned waste water 

treatment facilities (POTWs) must meet pretreatment standards. To perform a meaningful ESA 

evaluation the impact of these regulatory programs should be considered. 

Response: see response 180.1 

Comment Code: 182000 Projections of how long it would take to generate the needed data 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27146 

Comment Code: 182000 

Comment: 2. Projections of how long it would take to generate the needed data. 

The Panel believes that the regulatory programs that directly impact antimicrobial users with regard 

to environmental releases are a critical component of any evaluation of antimicrobials for purposes 

of endangered species impact. OPP should commit to creating and maintaining a database of the 

programs that impact all antimicrobial uses where the potential for environmental exposure exists. 

The Panel would be willing to work with EPA on such an effort, including identifying whether 

existing information sources and programs could be used, and the types of information that should 

be captured and the manner in which that information should be incorporated in environmental risk 

assessments. Obviously, these efforts would require several years, although an exact estimate is 

impossible because of numerous variables, including the amount of resources to be devoted to such 

an undertaking. 

Response: see response 180.5 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
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Comments and Response References: 

Endangered Species Section (180) Page 998 

Letter ID: 0064 

Comment ID: 27728 

Comment Code: 182000 

Comment: 2. Projections of how long it would take to generate the needed data. 

LANXESS believes that the regulatory programs that directly impact antimicrobial users with regard 

to environmental releases are a critical component of any evaluation of antimicrobials for purposes 

of endangered species impact. OPP should commit to creating and maintaining a database of the 

programs that impact all antimicrobial uses where the potential for environmental exposure exists. 

LANXESS, as a member company of the American Chemistry Council’s Biocide Panel, would be 

willing to work with EPA on such an effort, including identifying whether existing information 

sources and programs could be used, and the types of information that should be captured and the 

manner in which that information should be incorporated in environmental risk assessments. 

Obviously, these efforts would require several years, although an exact estimate is impossible 

because of numerous variables, including the amount of resources to be devoted to such an 

undertaking. 

Response: see response 180.5 

Comment Code: 183000 Whether antimicrobial use sites can be adequately correlated with 

endangered species locations, and suggested methods for doing so 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27160 

Comment Code: 183000 

Comment: 3. Whether antimicrobial use sites can be adequately correlated with endangered species 

locations, and suggested methods for doing so. 

The Panel does not believe that the approach EPA has adopted for agricultural pesticides would be 

helpful with regard to most antimicrobial uses. For example, to the extent that discharges resulting 

from use of antimicrobials are point- source discharges, it is far more appropriate to address 

endangered species considerations based on site-specific point-source discharge regulations than 

under FIFRA. 

Response: see response 180.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27161 

Comment Code: 183000 
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Comments and Response References: 

Endangered Species Section (180) Page 999 

Comment: Where an antimicrobial use involves permitting under another regulatory program, it is 

essential to determine whether such permitting is or can be used to address endangered species 

considerations. Even where geographic areas of use are less defined, it is essential that reasonable 

and scientifically valid methods are used to determine spatially where impacts can be significant and 

therefore limit the scope of any endangered species assessment. For example, with the case of 

antifoulant paints, the areas of concern are primarily limited to harbors and marinas. Structures or 

boats in open water are unlikely to present the potential for significant exposures. 

Response: see responses 180.1 and 180.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27163 

Comment Code: 183000 

Comment: In conclusion, the Panel does not believe that the approach EPA has adopted for 

agricultural pesticide uses for evaluating endangered species impacts is likely to be helpful in 

addressing analogous issues relevant to antimicrobials. Instead, EPA must recognize and incorporate 

into its environmental risk assessment process for antimicrobials (1) reliable and relevant 

information and data on potential exposures, including those obtained from other regulatory 

programs, and (2) the ability of other regulatory programs to limit or mitigate exposures. 

Response: see responses 180.1 and 180.2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27165 

Comment Code: 183000 

Comment: In addition, it also is important that EPA adopt sound, scientifically valid methods for 

conducting environmental risk assessments for antimicrobial uses. In the Panel’s view, this will 

require reproposal of this regulation. Until that is completed, it is difficult to anticipate the extent to 

which impacts on endangered species can be expected to result from such uses. 

Response: see responses 2 and 180.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27731 

Comment Code: 183000 

Comment: 3. Whether antimicrobial use sites can be adequately correlated with endangered species 

locations, and suggested methods for doing so. 
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Comments and Response References: 

Endangered Species Section (180) Page 1000 

LANXESS does not believe that the approach EPA has adopted for agricultural pesticides would be 

helpful with regard to most antimicrobial uses. For example, to the extent that discharges resulting 

from use of antimicrobials are point- source discharges, it is far more appropriate to address 

endangered species considerations based on site-specific point-source discharge regulations than 

under FIFRA. 

Response: see response 180.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27732 

Comment Code: 183000 

Comment: Where an antimicrobial use involves permitting under another regulatory program, it is 

essential to determine whether such permitting is or can be used to address endangered species 

considerations. Even where geographic areas of use are less defined, it is essential that reasonable 

and scientifically valid methods are used to determine spatially where impacts can be significant and 

therefore limit the scope of any endangered species assessment. For example, with the case of 

antifoulant paints, the areas of concern are primarily limited to harbors and marinas. Structures or 

boats in open water are unlikely to present the potential for significant exposures. 

Response: see responses 180.1 and 180.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27734 

Comment Code: 183000 

Comment: In conclusion, LANXESS does not believe that the approach EPA has adopted for 

agricultural pesticide uses for evaluating endangered species impacts is likely to be helpful in 

addressing analogous issues relevant to antimicrobials. Instead, EPA must recognize and incorporate 

into its environmental risk assessment process for antimicrobials (1) reliable and relevant 

information and data on potential exposures, including those obtained from other regulatory 

programs, and (2) the ability of other regulatory programs to limit or mitigate exposures. 

Response: see responses 180.1 and 180.2 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27736 

Comment Code: 183000 

Comment: In addition, it also is important that EPA adopt sound, scientifically valid methods for 

conducting environmental risk assessments for antimicrobial uses. In LANXESS’s view, this will 
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Comments and Response References: 

Endangered Species Section (180) Page 1001 

require reproposal of this regulation. Until that is completed, it is difficult to anticipate the extent to 

which impacts on endangered species can be expected to result from such uses. 

Response: see response 2 and 180.2 
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Comments and Response References: 

Guidelines Section (190) Page 1002 

Guidelines (190) 

Verbatim Comments and Response References for the Guidelines Section 

Comment Code: 190000 Guidelines 

Commenter Name: Patrick H. Quinn 

Commenter Organization: Innovation and Reform Group (IRG) 

Letter ID: 0080 

Comment ID: 25495 

Comment Code: 190000 

Comment: The Final Rule must clearly permit and encourage the incorporation of new approaches 

without the need for rulemaking. Changes in acute toxicology, for example, will come rapidly during 

the next 5 years with OPP needing to update its testing guidelines for eye irritation, skin irritation, 

and likely other endpoints far more rapidly than rulemaking would allow. 

Response: see response 80.99 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25788 

Comment Code: 190000 

Comment: Tri-TAC requests that toxicity test results measuring water quality impacts rely upon 

U.S. EPA standard water quality test species and methods listed in Methods for Measuring the 

Acute Toxicity of Effluents and Receiving Waters to Freshwater and Marine Organisms, 2002 (EPA 

821-R-02-012), Short Term Methods for Estimating the Chronic Toxicity of Effluents and 

Receiving Waters to West Coast Marine and Estuarine Organisms, 1995 (EPA/600/R-95/136), and 

Short Term Methods for Estimating the Chronic Toxicity of Effluents and Receiving Waters to 

Marine and Estuarine Organisms, 2002 (EPA-821-R-02-014). 

Antimicrobial pesticide data requirements for uses that discharge to POTWs should require both 

acute and chronic toxicity test results for at least one freshwater invertebrate, vertebrate, and plant 

species and at least one marine/estuarine invertebrate, vertebrate, and plant species utilizing the 

above-mentioned U.S. EPA standard water quality test species and procedures. The acute and 

chronic toxicity data is essential for screening-level environmental assessments since U.S. EPA will 

need to use adverse effect concentrations in the Exposure and Fate Assessment Screening Tool (EFAST) to evaluate potential impacts. 

Response: see response 190.1 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 
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Comments and Response References: 

Guidelines Section (190) Page 1003 

Letter ID: 0069 

Comment ID: 25883 

Comment Code: 190000 

Comment: CASA requests that toxicity test results measuring water quality impacts rely upon U.S. 

EPA standard water quality test species and methods listed in Methods for Measuring the Acute 

Toxicity of Effluents and Receiving Waters to Freshwater and Marine Organisms, 2002 (EPA 821-

R-02-012), Short Term Methods for Estimating the Chronic Toxicity of Effluents and Receiving 

Waters to West Coast Marine and Estuarine Organisms, 1995 (EPA/600/R-95/136), and Short 

Term Methods for Estimating the Chronic Toxicity of Effluents and Receiving Waters to Marine 

and Estuarine Organisms, 2002 (EPA-821-R-02-014). 

Antimicrobial pesticide data requirements for uses that discharge to POTWs should require both 

acute and chronic toxicity test results for at least one freshwater invertebrate, vertebrate, and plant 

species and at least one marine/estuarine invertebrate, vertebrate, and plant species utilizing the 

above-mentioned U.S. EPA standard water quality test species and procedures. The acute and 

chronic toxicity data is essential for screening-level environmental assessments since U.S. EPA will 

need to use adverse effect concentrations in the Exposure and Fate Assessment Screening Tool (EFAST) to evaluate potential impacts. 

Response: see response 190.1 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26110 

Comment Code: 190000 

Comment: The Districts request that toxicity test results measuring water quality impacts rely upon 

U.S. EPA standard water quality test species and methods listed in Methods for Measuring the 

Acute Toxicity of Effluents and Receiving Waters to Freshwater and Marine Organisms, 2002 (EPA 

821-R-02-012), Short Term Methods for Estimating the Chronic Toxicity of Effluents and 

Receiving Waters to West Coast Marine and Estuarine Organisms, 1995 (EPA/600/R-95/136), and 

Short Term Methods for Estimating the Chronic Toxicity of Effluents and Receiving Waters to 

Marine and Estuarine Organisms, 2002 (EPA-821-R-02-014). 

Antimicrobial pesticide data requirements for uses that discharge to POTWs should require both 

acute and chronic toxicity test results for at least one freshwater invertebrate, vertebrate, and plant 

species and at least one marine/estuarine invertebrate, vertebrate, and plant species utilizing the 

above-mentioned U.S. EPA standard water quality test species and procedures. The acute and 

chronic toxicity data are essential for screening-level environmental assessments since U.S. EPA will 

need to use adverse effect concentrations in the Exposure and Fate Assessment Screening Tool (EFAST) to evaluate potential impacts. 

Response: see response 190.1 
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Comments and Response References: 

Guidelines Section (190) Page 1004 

Comment Code: 191000 Unavailability of draft/lack of final guidelines 

Commenter Name: Eileen J. Moyer 

Commenter Organization: Reckitt Benckiser, Inc. 

Letter ID: 0076 

Comment ID: 25418 

Comment Code: 191000 

Comment: III. THE PROPOSED DATA REQUIREMENTS SHOULD NOT BE ADOPTED 

UNTIL REFERENCED DATA GUIDELINES ARE AVAILABLE OR FINALIZED 

The proposed Subpart 158W is intended to specify the data requirements for antimicrobial 

pesticides. The Agency has spent considerable time and resources in developing this proposal. 

However, we are concerned with the Agency's reliance on guidance documents that are not available 

to registrants or that have not been adopted through the public process of notice and comment. 

For example, the data requirements table in Section 158.2220, Product Performance, lists various 91 

series performance guidelines that have never been published. Reckitt has proactively worked with 

EPA in conjunction with CSPA to develop a series of product performance guidelines (810) that 

were intended to replace a portion of the 91 series. The Agency has yet to publish these draft 

guidelines for public comment. In addition, there are still a number of performance guidelines that 

are in the early phases of drafting or have not been drafted at all. 

Numerous other guidelines are also lacking. Various guidelines for non-target organisms and nontarget plants were made available in draft form in 1996, but have not been finalized or updated since 

that time. There are a number of exposure, environmental fate and residue chemistry guidelines that 

are not available at all. 

Our lack of knowledge of the contents of many of the data requirements makes it impossible to 

determine the full impact of the regulation on Reckitt's business. Further, we do not have the ability 

to determine the appropriateness of the data requirements for the products we register or know 

exactly what data must be generated to support product registrations. We cannot adequately 

comment on the appropriateness of these data requirements when we either do not know what the 

actual requirements are or whether the previously proposed data requirements will be applied as 

proposed. Additionally, it is possible that in the years since some of these guidelines have been 

proposed the science may have advanced so that reliance on the drafts may not provide results that 

would meet today's requirements. 

Response: see responses 70.1, 191.1, and 191.3 

Commenter Name: Kelly K. Naujock 

Commenter Organization: S.C. Johnson & Son, Inc. 

Letter ID: 0063 

Comment ID: 25424 

Comment Code: 191000 
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Comments and Response References: 

Guidelines Section (190) Page 1005 

Comment: An area of special concern to us is the efficacy guidelines appearing on page 59432 in 

the table entitled "Table - Antimicrobial Product Performance Data Requirements". This table 

references the 91 guidelines for generation of efficacy data. The 91 guidelines, published in draft in 

1982, were never deemed final. Further, they are not currently publicly available. The Agency has 

been working on the 810 guidelines for several years and we have been reassured several times that 

these guidelines are near completion. In fact, they should be published with a 60-day comment 

period during the first quarter of this year. Given these considerations, the referenced data 

requirements table should be amended to reference the appropriate 810 guidelines and this rule 

should be finalized after the 810 guidelines are published. 

Response: see responses 191.1 and 70.1 

Commenter Name: Sally Hayes 

Commenter Organization: Scientific & Regulatory Consultants, Inc. (SRC) 

Letter ID: 0066 

Comment ID: 25458 

Comment Code: 191000 

Comment: EPA purports that the proposed rule provides enhanced clarity and transparency to the 

regulated community allowing registrations to be managed more efficiently. However, this proposed 

rule references Guidelines for efficacy, non-target organisms and non-target plants that have only 

been provided in draft form over 10-20 years ago. The science, Agency policies, and product 

innovations in the intervening years have made these drafts (which are not available in any public 

venue) outdated. In addition, the proposed rule references exposure, environmental fate and residue 

chemistry guidelines that are not available at all. 

Response: see response 191.1 

Commenter Name: Sally Hayes 

Commenter Organization: Scientific & Regulatory Consultants, Inc. (SRC) 

Letter ID: 0066 

Comment ID: 25460 

Comment Code: 191000 

Comment: The lack of guidelines also makes it impossible to determine the true impact of this 

proposed rule on the regulated community. We are unable to determine whether the data outlined in 

the proposed rule will be relevant. It also makes it impossible to assess the true economic impact 

this rule will have. This rule can be neither clear nor transparent when there are major gaps in the 

guidance needed by registrants. 

Response: see response 191.3 

Commenter Name: Sally Hayes 

Commenter Organization: Scientific & Regulatory Consultants, Inc. (SRC) 

Letter ID: 0066 

Comment ID: 25462 

Comment Code: 191000 
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Comments and Response References: 

Guidelines Section (190) Page 1006 

Comment: It is not appropriate to move forward with this rule until all relevant guidelines have 

been published for public comment and finalized. Therefore, we strongly support CSPA in their 

recommendation to withdraw this proposed rule until the appropriate guidance documents have 

been developed, vetted for public comments and published in final form. 

Response: see responses 2 and 191.1 

Commenter Name: Ray S. McAlister 

Commenter Organization: CropLife America 

Letter ID: 0079 

Comment ID: 25466 

Comment Code: 191000 

Comment: EPA should not list data requirements in the proposed rule for which no Guideline 

exists. When the Agency revised the data requirements for conventional pesticides in 2007, there 

were some study Guideline numbers listed as "required," for which no Guideline or study protocol 

yet exists. This situation causes considerable confusion and should not occur in the data 

requirements for antimicrobials. 

Response: see 191.1 

Commenter Name: Abigail Trueblood 

Commenter Organization: Dow Chemical Company 

Letter ID: 0082 

Comment ID: 25481 

Comment Code: 191000 

Comment: The absence of clear guidance documents extends to the conduct of risk assessments 

for antimicrobials. As discussed in the ACC Biocides Panel comment letter, current examples of 

inconsistencies in recent REDS and Registration Reviews make clear the need for transparent 

guidance on risk assessment to support data requirements. 

Response: see response 191.5 

Commenter Name: Abigail Trueblood 

Commenter Organization: Dow Chemical Company 

Letter ID: 0082 

Comment ID: 25483 

Comment Code: 191000 

Comment: Dow has additional concerns regarding Human Exposure data requirements. Within the 

preamble of the Proposal it states that a primary intent of the document is to provide guidance on 

when various studies would be required so that a registrant could be properly prepared. This does 

not occur to any great measure in the exposure sections of this document, i.e. the applicator and 

post application sections. In point of fact there is little, if any practical guidance in this section; the 

advice contained within this section is to seek input from EPA.. Essentially all studies are "required" 
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Comments and Response References: 

Guidelines Section (190) Page 1007 

and the other guidances referenced in this section have not yet been written, or are out of date (they 

don't account for limitations imposed by the HSRB), or are not applicable (treating biocides in the 

same manner as conventional pesticides). EPA needs to provide clear guidance that would allow a 

registrant to understand the requirements. As it currently stands it appears to be up to the individual 

reviewers to interpret and can create uneven requirements from one company or product to another. 

EPA needs to have other guidelines in place before finalizing this guideline (something also noted by 

OMB), a clear statement of what is required when and why, guidelines that understand the pragmatic 

and practical realities imposed by other regulations (such as those that created the HSRB) and 

guidelines that recognize that antimicrobials are different from conventional biocides in a number of 

respects. 

Response: see responses 3, 191.1, and 191.6 

Commenter Name: Abigail Trueblood 

Commenter Organization: Dow Chemical Company 

Letter ID: 0082 

Comment ID: 25486 

Comment Code: 191000 

Comment: There are a number of tests referenced in the data tables contained within the Proposal 

for which there are no guidelines available on the Agency website. This is particularly true for nontarget organisms, non-target plants and environmental fate testing. Among those referenced tests are 

several which evidentially are based on the old Part 161 series of environmental fate series; however, 

in the absence of specific test guidelines available, it is impossible to run studies with confidence 

these will be acceptable to the Agency. There are a number of test guidelines available in the OECD 

300 series (environmental fate) which have been used in Europe for product registration under the 

Biocidal Products Directive (BPD). Dow would urge the Agency to ensure harmonization of its 

testing requirements with the BPD requirements and to incorporate these into a reproposal of this 

rule. 

Response: see responses 191.1 and 191.4 

Commenter Name: Elizabeth Tannehill 

Commenter Organization: Mason Chemical Company 

Letter ID: 0078 

Comment ID: 25504 

Comment Code: 191000 

Comment: The purpose of the proposed rule is to revise and update the existing data requirements 

for antimicrobial pesticides. Mason Chemical Company believes the proposed data requirements for 

antimicrobials (Part 158W) are not ready to implantation due to the lack of complete data 

requirements and are requesting the Agency withdraw this proposal until such time as the 

appropriate guidance documents can be developed with careful public comment, peer review and 

final adoption. 

Response: see response 2 
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Comments and Response References: 

Guidelines Section (190) Page 1008 

Commenter Name: Elizabeth Tannehill 

Commenter Organization: Mason Chemical Company 

Letter ID: 0078 

Comment ID: 25505 

Comment Code: 191000 

Comment: The Agency is showing reliance on guidance documents that are not available to 

registrants and have not been adopted through the public process of notice and comment as 

required by law. Because of this, Mason Chemical Company is unable to determine the full impact 

of the proposed regulation or the appropriateness of the data requirements on our products. For 

instance, we have been actively working through several groups to assist EPA in the development of 

a series of product performance guidelines (810s). These have yet to be published for public 

comment and have not been adopted though they are referred to in Part 158W. In addition, the 

science currently required and being relied on by the Agency to ensure the safety and efficacy of our 

products has advanced over the years so much so that reliance on this science might not provide the 

results necessary to meet today’s requirements. 

Response: see responses 70.1, 70.2, 70.3, 70.4, and 191.3 

Commenter Name: Susan E. Little 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0068 

Comment ID: 25519 

Comment Code: 191000 

Comment: While the guidelines in the proposal do not adequately address the unique exposures 

that antimicrobials have in comparison to conventional pesticides, it is essential that guidelines be 

written with antimicrobials in mind and proposed and finalized for Part 158W. 

Response: see response 191.6 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25541 

Comment Code: 191000 

Comment: b. Lack of Data Guidelines 

The proposed Subpart 158W is intended to specify the data requirements for antimicrobial 

pesticides. The Agency has spent considerable time and resources in developing this proposal. 

However, CSPA is concerned with the Agency's reliance on guidance documents that are not 

available to registrants or that have not been adopted through the public process of notice and 

comment. 

Response: see response 191.1 
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Comments and Response References: 

Guidelines Section (190) Page 1009 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25542 

Comment Code: 191000 

Comment: For example, the data requirements table in [Section]158.2220 Product Performance 

lists various 91 series performance; i.e. efficacy, guidelines that have never been published. CSPA 

has been working with EPA over the past several years to develop a series of product performance 

guidelines (810) that were intended to replace a portion of the 91 series. The Agency has yet to 

publish these draft guidelines for public comment. In addition, there are still numerous guidelines 

that are in the early phases of drafting or have not begun drafting at all. 

Response: see responses 191.1 and 70.1 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25543 

Comment Code: 191000 

Comment: Numerous other guidelines are also lacking. Various guidelines for non-target organisms 

and non-target plants were made available in draft form in 1996, but have not been finalized or 

updated since that time. There are a number of exposure, environmental fate and residue chemistry 

guidelines that are not available at all. 

Our lack of knowledge of the contents of many of the data requirements makes it impossible to 

determine the full impact of the regulation on the regulated community. Further, we do not have the 

ability to determine the appropriateness of the data requirements for the applicable products or 

know exactly what data must be generated to support product registrations. We cannot adequately 

comment on the appropriateness of these data requirements when we either do not know what the 

actual requirements are or whether the previously proposed data requirements will be applied as 

proposed. Additionally, it is possible that in the years since some of these guidelines have been 

proposed the science may have advanced so that reliance on the drafts may not provide results that 

would meet today's requirements. 

For these reasons, CSPA believes this proposal is not ready for public comment. We ask that EPA 

withdraw the proposal until such time that appropriate guidance documents have been developed, 

vetted for public comment and peer review and are subject to final adoption. EPA must provide a 

transparent process in the development of guidelines. Once final guidance documents have been 

published the Agency can then re-propose this regulation. 

Response: see responses 2, 191.1, and 191.3 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 
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Comments and Response References: 

Guidelines Section (190) Page 1010 

Comment ID: 25554 

Comment Code: 191000 

Comment: To that end, the members of CSPA strongly object to promulgation of 40 CFR Part 158 

subpart W in absentia of the finalized 810 guidelines. The antimicrobial product performance 

requirements table provided on page 59432 of the Proposed Rule refers to the guidelines which 

were proposed in 1991 and to date have not been published and have never been finalized. The 91 

guidelines do not "reflect current scientific knowledge and current Agency regulatory practices." 

CSPA worked jointly with the Agency to develop the following proposed guidelines: 

 * 810.2000 - General Considerations * 810.2100 - Sterilants * 810.2200 - Disinfectants * 810.2300 - 

Sanitizers 

The last drafts of the above guidelines available to CSPA for consideration are from early 2006. The 

Agency has stated that these referenced 810 guidelines will publish in draft 1st quarter of 2009 with a 

60-day comment period. 

In addition, there are several outstanding 810 guidelines which are either in draft form and/or have 

not yet been drafted. CSPA encourages the Agency to collaborate with Industry to develop these 

outstanding guidelines building upon the successful endeavor for the development of the 810.2000, 

2100, 2200 and 2300 guidelines. It is CSPA's position that this proposed 40 CFR Part 158 rule 

cannot be promulgated until all 810 guidelines are published and finalized. 

Response: see responses 191.1, 70.1, and 70.2 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25569 

Comment Code: 191000 

Comment: d. Comments on Data Requirements/References 

The Antimicrobial Product Performance Data Requirements Table on page 59432 referencing the 

91 guidelines which have never been finalized and are not publically available. As noted previously in 

our comments, we do not believe that it is appropriate to move forward with Part 158W until all 810 

Guidelines are final. When the 810 Guidelines are complete CSPA recommends the table below, 

which references the 810 guidelines, replace the table currently in the Proposed Part 158W Rule. 

[See Table listing suggested data requirement guidelines on p. 11 PDF Docket ID EPA- HQ-OPP2008-0110-0086.pdf] 

 At this time, none of the 810 guidelines above are finalized and only 810.2000, 810.2100, 810.2200 

and 810.2300 are being prepared for publication for comment this fiscal year. In the absence of 810 

guidelines for each of the use- site/desired claim sets provided in the table, a non-level playing field 

is created. A most recent example is the registration of copper alloys with public health claims, but 

no guidance has been provided to registrants for how such claims can be achieved on treated 
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Comments and Response References: 

Guidelines Section (190) Page 1011 

articles. CSPA cannot support a proposed rule until there are finalized data guidelines in place for 

reference. 

Response: see responses 191.1, 70.1, and 70.2 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25654 

Comment Code: 191000 

Comment: Conclusion 

CSPA appreciates the opportunity to comment on the proposed 158 W regulations. The proposed 

regulation refers to numerous guidance documents that are not in existence. Without those 

documents we are unable to provide complete and thorough comments. It is not appropriate to 

move forward with finalizing this proposed regulation until such time that appropriate guidance 

documents have been developed, vetted for public comments and published in final form. 

Response: see response 191.1 

Commenter Name: Lisa M. Amadio 

Commenter Organization: JohnsonDiversey, Inc. 

Letter ID: 0084 

Comment ID: 25691 

Comment Code: 191000 

Comment: Lack of Data Guidelines The proposed Subpart 158W is intended to specify the data 

requirements for antimicrobial pesticides. Many of the data requirements are based on guidance 

documents that have not been made available to registrants nor implemented through the public 

process of notice and comment. This is especially evident for efficacy guidelines, as well as those for 

non-target organisms and non-target plants. Because we do not know the contents of these 

requirements, we cannot comment on the impact they will have to our registrations, nor how they 

will influence the registration process. Consequently, we strongly suggest that the proposed Subpart 

158 W is not ready for further public comment, much less implementation. We urge the Agency to 

issue a revised draft with another opportunity for public comment. 

Response: see responses 191.1 and 2 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25735 

Comment Code: 191000 

Comment: EPA also states that the purpose of the new data requirements is to update and improve 

the scientific knowledge and current Agency practices. While this is appropriate with any data 
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Comments and Response References: 

Guidelines Section (190) Page 1012 

requirement rule, it is critical to ensure that all required guidance documents and protocols relative 

to those data requirements are finalized to help ensure registrants have appropriate information 

prior to data generation and to avoid registration delays. At this time, there are several relevant 

guidance documents which have not been finalized and published. For example, CSPA has worked 

extensively with EPA's Antimicrobial Division to develop 810 efficacy guidelines for 810.2000 

(General Considerations), 810.2100 (Sterilants), 810.2200 (Disinfectants) and 810.2300 (Sanitizers). 

The last Agency draft of these guidelines has been available since 2006. Previously, the Agency had 

projected that the 810 guidelines would be published in draft by 1 st quarter 2009 with a 60 day 

comment period. The Agency has recently reported that due to procedural changes there is not a 

projected date for the drafts to be published for public comment. In addition, there are several 810 

guidelines which are either in draft or have not yet been drafted. 

Response: see responses 191.1 and 70.1 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25737 

Comment Code: 191000 

Comment: Having the appropriate guidelines available for reference is critical to the regulated 

community being able to address the data requirements, as the Guidelines identify essential 

components and considerations for the conduct of studies to fulfill data requirements. Comments 

from the ACC Biocides Panel indicate there are approximately 30 of the OPPTS Guidelines cited 

within the Proposal that have not yet been issued by EPA. Registrants therefore do not have the 

necessary guidance for evaluating whether a particular data requirement is applicable or how best to 

address the data requirement. This is a significant concern and clearly indicates the proposed rule is 

not ready for finalization without considerable revision. 

Response: see response 191.1 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25739 

Comment Code: 191000 

Comment: Therefore, Ecolab joins the ACC Biocides Panel and CSPA in strongly objecting to the 

promulgation of the proposed 40 CFR 158 subpart W in the absence of necessary guidelines and 

protocols for data generation. Going forward without these guidelines, would result in a meaningless 

and ineffective rule, resulting in significant registration application delays. In addition, the Office of 

Management and Budget's comments to the proposed Part 158W rule, struck through "plans" and 

inserted "will" finalize guidelines before publishing a final rule establishing antimicrobial data 

requirements. 

Response: see response 191.1 
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Comments and Response References: 

Guidelines Section (190) Page 1013 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25754 

Comment Code: 191000 

Comment: Section 158.2220 - Product Performance Ecolab agrees with and supports the 

comments submitted by CSPA that 158W should not be finalized or implemented until all 810 

guidelines are finalized. The proposed rule refers to the 91 guidelines which were proposed in 1991 

and to date have not been published or finalized. The current 91 guidelines fall short of reflecting 

current scientific knowledge and current Agency practices. CSPA's Antimicrobial Efficacy Group 

(AEG) has worked closely with EPA's Antimicrobial Division to develop the 810.2000, 810.2100, 

810.2200, and 810.2300 efficacy guidelines which have yet to be published for comment. In addition 

there are several outstanding 810 guidelines which have not be published or even drafted. As stated 

previously, OMB comments to the 158W rule require EPA to finalize all guidelines prior to 

publication of 158W as a final rule. 

Response: see responses 191.1, 70.1, and 70.2 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25773 

Comment Code: 191000 

Comment: In conclusion, Ecolab requests that the Agency implement the proposed 158W rule only 

when all required guidelines critical to data generation are completed and finalized. In addition, the 

recommendations provided with these comments and the comments from ACC and CSPA should 

be addressed prior to promulgation of a final rule. 

Response: see response 191.1 

Commenter Name: William C. Balek 

Commenter Organization: ISSA 

Letter ID: 0074 

Comment ID: 25861 

Comment Code: 191000 

Comment: [In particular, ISSA supports the following aspects of the ACC Biocides Panel 

Comments:] * EPA's proposed subpart l58W does not provide adequate guidance to the regulated 

conununity; 

* Guidelines are not available for numerous data requirements; 

Response: see response 191.1 

Commenter Name: Victoria Jones 
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Comments and Response References: 

Guidelines Section (190) Page 1014 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25908 

Comment Code: 191000 

Comment: [In the Panel's comments, 12 major discussion points are presented as follows:] * Final 

guidelines are not available for numerous data requirements 

Response: see response 191.1 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25920 

Comment Code: 191000 

Comment: Based on these comments, Clorox believes the proposed rule should be withdrawn, 

rewritten and reissued for public comment. 

The significant lack of affirmative guidelines as presented in the proposal make it virtually 

impossible for a registrant to determine what exact data would be required for a registration. 

We urge the Agency to finalize the many guidelines that are referenced throughout the proposal. 

Response: see responses 2 and 191.1 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25930 

Comment Code: 191000 

Comment: Consumer Specialty Products Association Comments 

Efficacy Guidelines are not Finalized 

CSPA took the Industry lead on Product Performance-Efficacy Data Requirements. The comments 

provided by CSPA on Efficacy data represent the views of Clorox. In the absence of the 810 

guidelines, the proposed rule does not define the efficacy data requirements. A clear set of standards 

followed by both the Agency and registrants should be established to address antimicrobial data 

requirements. 

Additionally, the Agency has failed to incorporate a process to address public health emergencies or 

emerging pathogens. 

Response: see responses 70.1 and 70.5 
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Comments and Response References: 

Guidelines Section (190) Page 1015 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25931 

Comment Code: 191000 

Comment: The 810 guidelines should be published and finalized prior to issuing 158W, and an 

approach to address public health issues would address our concerns. 

Response: see responses 70.1 and 191.1 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25934 

Comment Code: 191000 

Comment: It is essential that guidelines be written with antimicrobials in mind and proposed and 

finalized for Part 158W. Without specific guidance, these requirements could be highly subjective. 

Guidance that establishes the scope of these requirements is critical to assuring that there is 

consistent and reasonable implementation of these requirements. In spite of the lack of direct 

guidance in the antimicrobial arena, the Antimicrobial Division of OPP has worked successfully with 

the AEJV to develop product use and usage data collected in an observational manner. These 

studies consisted of in- home observations of informed/consented consumers with respect to their 

use of products present in their household inventory and prospective diary survey instruments 

provided by informed/consented consumer participants. Additionally, some surveys were recall 

studies which did not involve product usage. Since these data have been generated by AEJV and 

submitted and used by the Agency, we encourage the Agency to incorporate similar survey tool 

recommendations in their product use guidelines, particularly in those areas where AEJV data would 

not suffice. 

Response: see responses 191.1 and 191.6 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26159 

Comment Code: 191000 

Comment: The Agency has been working on the development of guidelines to be included in the 

810 Series Pesticide Assessment Guidelines. The Chemical Specialties Product Association (CSPA) 

worked jointly with the Agency to develop the following proposed guidelines: 

810.2000 - General Considerations 810.2100 - Sterilants 810.2200 - Disinfectants 810.2300 - 

Sanitizers 
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Comments and Response References: 

Guidelines Section (190) Page 1016 

In addition, there are several outstanding 810 guidelines which are either in draft form and/or have 

not yet been drafted. P&G encourages the Agency to collaborate with Industry to develop these 

outstanding guidelines building upon the successful endeavor for the development of the 810.2000, 

2100, 2200 and 2300 guidelines. It is P&G’s position that this proposed 40 CFR Part 158 rule 

cannot be promulgated until all 810 guidelines are published and finalized. 

According to industry discussions with EPA, in contrast to the six categories proposed at 158.2220, 

EPA intends to publish guidance on the following categories. 

[See Table on page 3 in PDF docket ID EPA-HQ-OPP-2008-0110-0081.PDF] 

Response: see responses 191.1 and 70.2 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26162 

Comment Code: 191000 

Comment: Overall Efficacy Comments The critical need for science-based guidance on what EPA 

requires on efficacy of antimicrobial pesticides cannot be overemphasized. While EPA generally has 

committed to test method flexibility to meet its data requirements, applicants for antimicrobial uses, 

in fact, typically are required to use only test methods that have been explicitly approved by EPA or 

that meet with specificity methods that have been designated by EPA to support a particular claim. 

Despite EPA’s reliance on such specific test methods, some have not been validated, even after 

decades of use. Moreover, the essential role of the protocol review process with regard to efficacy 

data requirements is confirmed by the fact that two PRIA fee categories were added to the 

antimicrobial PRIA fees table with the 2008 PRIA reauthorization. These fee categories were added 

to the PRIA-covered actions because of an interest by registrants in obtaining some predictability 

with regard to review time frames. Even with the creation of these fee categories, the process for 

obtaining protocol approval or even Agency guidance is a slow and uncertain process. P&G submits 

the development of a guidance document outlining the overall protocol review process and 

registrant requirements are considered and added to the list of efficacy guidelines. 

EPA stated in the Preamble to this proposed regulation that it was intended to provide "revisions . . 

. needed to reflect current scientific knowledge and current Agency regulatory practices." 73 Fed. 

Reg. at 59382. Unfortunately, as noted, this portion of the proposal is not current. Moreover, it is 

not consistent with EPA’s statement that it "agrees with HHS that both current antimicrobial 

pesticide registrants and applicants seeking an antimicrobial registration should understand the 

applicability of the proposed data requirements, once promulgated." 73 Red. Reg. at .59426. Clearly, 

registrants and applicants will not be able to understand the applicability of the efficacy data 

requirements to important public health uses unless this Proposal is updated and the Agency 

guidance on antimicrobial efficacy requirements is finalized. 

Response: see responses 70.1 and 191.1 

Commenter Name: Janice L. Dhonau 
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Comments and Response References: 

Guidelines Section (190) Page 1017 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26212 

Comment Code: 191000 

Comment: C. Testing Guidelines Are Not Available to Provide Guidance 

It is unclear whether the testing guideline numbers referenced within the proposed rule refer to 

future documents based on the old Pesticide Assessment Guidelines or to some other type of 

guidance. Requiring data or information in accordance with unavailable criteria is inappropriate for a 

Proposed Rule. It is P&G’s position that this proposed 40 CFR Part 158 rule cannot be promulgated 

until all guidelines are published and finalized. . 

Response: see response 191.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26216 

Comment Code: 191000 

Comment: Similarly, the Proposal refers readers to guidance documents on many aspects of 

particular data requirements that are not available, are outdated, or were issued without following 

EPA’s own specified procedures including not providing an opportunity for public comment. 

Response: see response 191.1 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26219 

Comment Code: 191000 

Comment: 5) Environmental fate data are required to conduct an acceptable environmental risk 

assessment for the Use Pattern. However, the proposal provides no guidance or direction on how 

the Agency conducts an environmental risk assessment, or what criteria and uncertainty factors are 

used to determine if it is acceptable. Without this guidance, it is not possible to determine what 

testing is adequate to fulfill environmental fate data requirements. 

Response: see response 191.5 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26221 

Comment Code: 191000 
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Comments and Response References: 

Guidelines Section (190) Page 1018 

Comment: 6) Guidelines for many studies listed as environmental fate data requirements are not 

complete or available. These endpoints should not be required by the Agency until the study 

guidelines are issued as final, without restriction on the completeness of an acceptable 

environmental risk assessment. 

Response: see response 191.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26281 

Comment Code: 191000 

Comment: These examples demonstrate the inconsistency in EPA’s current practice and the need 

for stable, transparent guidance on risk assessment to support data requirements regulation. EPA 

should issue such guidance through the process it has established, which includes scientific review 

and public comment, and must be available prior to the publication of any draft data requirements 

regulation. 

Response: see response 191.5 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26282 

Comment Code: 191000 

Comment: In light of the absence of any guidelines on risk assessment (e.g., what risks will be 

assessed for what uses, how EPA will evaluate exposure and/or toxicity data, what safety factors will 

be applied and why), on the manner in which required data will be used in such assessments and on 

the regulatory decision criteria EPA will use once risk assessments are completed, the Panel does not 

have all the information it needs to submit meaningful comments on this particular aspect of the 

Proposal. Risk assessment guidance addressing these points must be developed and issued by EPA 

through the process set forth above, and the data requirements regulation reproposed with specific 

references to those guidelines included. 

Response: see responses 2 and 191.5 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26290 

Comment Code: 191000 

Comment: II. Final Guidelines Are Not Available for Many Data Requirements 
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Comments and Response References: 

Guidelines Section (190) Page 1019 

In many places, EPA’s Proposal on Subpart 158W refers to guidance documents that are either not 

available, are outdated, or that EPA has adopted without an opportunity for public comment. The 

absence of these guidelines makes it impossible to gauge the impact of the regulation or determine 

whether the requirements the Agency seeks to impose are rational. Unless the referenced guidelines 

are issued prior to any final regulation being issued, compliance with the final regulation will be 

impossible. 

In the Proposal, the Agency identifies an OPPTS Testing Guideline for almost all individual data 

requirements. The Proposal provides that "Guideline numbers are provided as 

information/guidance to applicants. These Guidelines set forth recommended instructions and test 

methods for performing a study to generate the required data. Since these are guidance documents, 

the applicant is not required to use these Guidelines, but may instead seek to fulfill the data 

requirement by other appropriate means . . ."[FN#28:Proposed Rule at 59387.] The Agency further 

states that "[the Guidelines] represent the recommended approach to developing high quality data 

that should satisfy EPA’s data needs for risk assessment." Id.[FN#29:These statements are 

consistent with existing regulations at 40 CFR [Section] 158.70(c), which provide that the guidelines 

"contain standards for conducting acceptable tests, guidance on the evaluation and reporting of data, 

definition of terms, and suggested study protocols."] Having the Guidelines available for reference is 

critical to the regulated community being able to address the data requirements, as the Guidelines 

identify essential components and considerations for the conduct of studies. 

Response: see responses 191.1 and 191.3 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26292 

Comment Code: 191000 

Comment: However, almost 30 of the OPPTS Guidelines EPA cites in the Proposal have not yet 

been issued. Registrants therefore do not have the necessary guidance for evaluating whether a 

particular data requirement is applicable or, if so, how best to address it. Nor is it possible to fully 

comment on the Proposal without the Guidelines, as the Guidelines identify the Agency’s 

expectations regarding the conduct of the required studies. 

The following is a listing of OPPTS Guidelines cited in the Proposal the Panel has been able to 

identify as not having been issued or finalized by the Agency. Several of these were released as 

"drafts" in early 1996, but have not been finalized. Moreover, given significant changes in science in 

the intervening thirteen years, it is questionable whether these drafts provide any degree of reliable 

guidance for current requirements. 

[See Table on page 17-19 "Availability of OPPTS Guidelines" in PDF docket ID EPA-HQ-OPP2008-0110-0088] 

It is vitally important that the Agency provide current, consistent, and reliable guidance and 

standards associated with each data requirement. EPA has established a transparent public process, 

including scientific review, for issuing these guidelines which, if followed, will accomplish this 
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Comments and Response References: 

Guidelines Section (190) Page 1020 

purpose.[FN#30:There is a specific process for the development of the OPPTS Guidelines, 

including draft publication in the Federal Register for public comment, peer review, and final 

publication. The required process is described at 61 Fed. Reg. 44308 (Aug. 18, 1996). The Agency 

should not propose reliance upon particular Guidelines until it has completed the notice and 

comment process and final Guidelines are publicly issued.] 

The Panel is concerned that the lack of publicly available guidance will result in inconsistent and 

inappropriate demands on registrants who have no way of determining what data the Agency 

expects and under what circumstances, which will create a greater burden on Agency resources and 

the regulated community than the current system. In addition, many of the guidelines currently 

available in draft form need to be updated by EPA to reflect current science and recent changes in 

Agency requirements and risk assessment approaches. Finally, many of the existing OPPTS 

Guidelines are inappropriate for certain antimicrobial chemistries, as they were developed with the 

traditional synthesized organic chemicals typical of conventional pesticides in mind. Specific 

comments on this issue are provided in the Section-by-Section Analysis of the Data Requirement 

Tables in Appendices B - I. 

Response: see responses 191.1 and 191.6 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26293 

Comment Code: 191000 

Comment: The Proposal’s citation of Guidelines that do not exist or are outdated makes it 

impossible for the Panel to meaningfully comment on the Proposal. The appropriateness of the tests 

EPA is seeking and the level of burden they will impose on both regulated parties and the Agency 

cannot be determined. For this reason, the Panel believes that EPA should withdraw this Proposal 

until it has developed appropriate final guidance for all data requirements and has articulated why 

and when each data requirement will be necessary and appropriate for particular antimicrobial 

products. 

Response: see response 2 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26378 

Comment Code: 191000 

Comment: Next, the Agency should reconsider its use of older testing guidelines, some of them 

issued more than a decade ago in 1996 and none yet finalized. These are no longer consistent with 

current science or policy and should be considered for revision prior to promulgation of a rule. 

Requiring data or information in accordance with hidden criteria is unreasonable in a data 

requirement regulation. The Agency must provide a clear rule from which an applicant can 

understand the requirements without consulting with the Agency. 
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Comments and Response References: 

Guidelines Section (190) Page 1021 

Response: see responses 3 and 191.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26715 

Comment Code: 191000 

Comment: Similarly, the Proposal refers readers to guidance documents on many aspects of 

particular data requirements that are not available, are outdated, or were issued without following 

EPA’s own specified procedures including not providing an opportunity for public comment. 

Response: see response 191.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26717 

Comment Code: 191000 

Comment: Next, the Agency should reconsider its use of older testing guidelines, some of them 

issued more than a decade ago in 1996 and none yet finalized. These are no longer consistent with 

current science or policy and should be considered for revision prior to promulgation of a rule. 

Requiring data or information in accordance with hidden criteria is unreasonable in a data 

requirement regulation. The Agency must provide a clear rule from which an applicant can 

understand the requirements without consulting with the Agency. (See Panel’s General Comments at 

Sections I and II.) 

Response: see responses 3 and 191.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26797 

Comment Code: 191000 

Comment: These examples demonstrate the inconsistency in EPA’s current practice and the need 

for stable, transparent guidance on risk assessment to support data requirements regulations. EPA 

should issue such guidance through the process it has established, which includes scientific review 

and public comment, and must be available prior to the publication of any draft data requirements 

regulation. 

Response: see response 191.5 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 
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Comments and Response References: 

Guidelines Section (190) Page 1022 

Letter ID: 0064 

Comment ID: 26805 

Comment Code: 191000 

Comment: In light of the absence of any guidelines on risk assessment (e.g., what risks will be 

assessed for what uses, how EPA will evaluate exposure and/or toxicity data, what safety factors will 

be applied and why), on the manner in which required data will be used in such assessments and on 

the regulatory decision criteria EPA will use once risk assessments are completed, LANXESS does 

not have all the information it needs to submit meaningful comments on this particular aspect of the 

current Proposal. Risk assessment guidance addressing these points must be developed and issued 

by EPA through the process set forth above, and the data requirements regulations re-proposed 

with specific references to those guidelines included. 

Response: see responses 2 and 191.5 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26806 

Comment Code: 191000 

Comment: II. Final Guidelines Are Not Available for Numerous Data Requirements 

In many places, EPA’s Proposal on Subpart 158W refers to guidance documents that are either not 

available, are outdated, or that EPA adopted without an opportunity for public comment. The 

absence of these guidelines makes it impossible to gauge the impact of the regulation or determine 

whether the requirements the Agency seeks to impose are rational. Unless the referenced guidelines 

are issued prior to any final regulation being issued, compliance with the final regulation will be 

impossible. 

In the Proposal, the Agency identifies an OPPTS Testing Guideline for each data requirement. The 

Proposal provides that "Guideline numbers are provided as information/guidance to applicants. 

These Guidelines set forth recommended instructions and test methods for performing a study to 

generate the required data. Since these are guidance documents, the applicant is not required to use 

these Guidelines, but may instead seek to fulfill the data requirement by other appropriate 

means..."[FN28: Proposed Rule at 59387.] The Agency further states that "[the Guidelines] represent 

the recommended approach to developing high quality data that should satisfy EPA’s data needs for 

risk assessment." Id.[FN29: These statements are consistent with existing regulations at 40 CFR 

[section 158.70(c), which provide that the guidelines "contain standards for conducting acceptable 

tests, guidance on the evaluation and reporting of data, definition of terms, and suggested study 

protocols."] Having the Guidelines available for reference is critical to the regulated community 

being able to address the data requirements, as the Guidelines identify essential components and 

considerations for the conduct of studies. 

Response: see responses 191.1 and 191.3 

Commenter Name: Stanley Oslosky 
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Comments and Response References: 

Guidelines Section (190) Page 1023 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26808 

Comment Code: 191000 

Comment: However, almost 30 of the OPPTS Guidelines EPA cites in the Proposal have not yet 

been issued. Registrants therefore do not have the necessary guidance for evaluating whether a 

particular data requirement is applicable or, if so, how best to address it. Nor is it possible to fully 

comment on the Proposal without the Guidelines, as the Guidelines identify the Agency’s 

expectations regarding the conduct of the required studies. 

The following is a listing of OPPTS Guidelines cited in the Proposal LANXESS has been able to 

identify as not having been issued or finalized by the Agency. Several of these were released as 

"drafts" in early 1996, but have not been finalized. Moreover, given significant changes in science in 

the intervening thirteen years, it is questionable whether these drafts provide any degree of reliable 

guidance for current requirements. 

 Availability of OPPTS Guidelines [SEE P. 22-23 OF EPA-HQ-OPP-2008-0110-0064.PDF (OR P. 

18-19 OF HARD COPY) FOR TABLE.] 

It is vitally important that the Agency provide current, consistent, and reliable guidance and 

standards associated with each data requirement. EPA has established a transparent public process, 

including scientific review, for issuing these guidelines which, if followed, will accomplish this 

purpose.[FN30: There is a specific process for the development of the OPPTS Guidelines, including 

draft publication in the Federal Register for public comment, peer review, and final publication. The 

required process is described at 61 Fed. Reg. 44308 (Aug. 18, 1996). The Agency should not propose 

reliance upon particular Guidelines until it has completed the notice and comment process and final 

Guidelines are publicly issued.] 

LANXESS is concerned that the lack of publicly available guidance will result in inconsistent and 

inappropriate demands on registrants who have no way of determining what data the Agency 

expects and under what circumstances, which will create a greater burden on Agency resources and 

the regulated community than the current system. In addition, many of the guidelines currently 

available in draft form need to be updated by EPA to reflect current science and recent changes in 

Agency requirements and risk assessment approaches. Finally, many of the existing OPPTS 

Guidelines are inappropriate for certain antimicrobial chemistries, as they were developed with the 

more traditional synthesized organic chemicals typical of conventional pesticides in mind. Specific 

comments on this issue are provided in the Section-by-Section Analysis of the Data Requirement 

Tables in Appendices B-I. 

Response: see responses 191.1 and 191.6 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26816 

Comment Code: 191000 
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Comments and Response References: 

Guidelines Section (190) Page 1024 

Comment: The Proposal’s citation of Guidelines that do not exist or are outdated makes it 

impossible for LANXESS to meaningfully comment on the Proposal. The appropriateness of the 

tests EPA is seeking and the level of burden they will impose on both regulated parties and the 

Agency cannot be determined. For this reason, LANXESS believes that EPA should withdraw this 

Proposal until it has developed appropriate final guidance for all data requirements and has 

articulated why and when each data requirement will be necessary and appropriate for particular 

antimicrobial products. 

Response: see response 2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26943 

Comment Code: 191000 

Comment: F. Comments on product use information and description of human activity data 

requirements 

It is essential that guidelines be proposed and finalized for these requirements and that the 

regulation be reproposed for comment once that is completed. Without guidance, it will be 

impossible for registrants and applicants to anticipate the manner in which EPA will interpret these 

requirements and the consequent burden they will impose. 

Response: see responses 191.1 and 2 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27004 

Comment Code: 191000 

Comment: C. Testing Guidelines Are Not Available to Provide Guidance 

It is unclear whether the testing guideline numbers referenced within the proposed rule refer to 

future documents based on the old Pesticide Assessment Guidelines or to some other type of 

guidance. Requiring data or information in accordance with unavailable criteria is a major drawback 

to this proposal. (See Panel’s General Comments at Section II.) 

Response: see response 191.1 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27015 

Comment Code: 191000 
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Comments and Response References: 

Guidelines Section (190) Page 1025 

Comment: [The following are some of the problems identified in the proposed rule:] 

5) Environmental fate data are required to conduct an acceptable environmental risk assessment for 

the Use Pattern. However, the proposal provides no guidance or direction on how the Agency 

conducts an environmental risk assessment, or what criteria and uncertainty factors are used to 

determine if it is acceptable. Without this guidance, it is not possible to determine what testing is 

adequate to fulfill environmental fate data requirements. 

Response: see response 191.5 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27017 

Comment Code: 191000 

Comment: [The following are some of the problems identified in the proposed rule:] 

6) Guidelines for many studies listed as environmental fate data requirements are not complete or 

available. These endpoints should not be required by the Agency until the study guidelines are issued 

as final, without restriction on the completeness of an acceptable environmental risk assessment. 

Response: see response 191.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27396 

Comment Code: 191000 

Comment: Next, the Agency should reconsider its use of older testing guidelines, some of them 

issued more than a decade ago in 1996 and none yet finalized. These are no longer consistent with 

current science or policy and should be considered for revision prior to promulgation of a rule. 

Requiring data or information in accordance with hidden criteria is unreasonable in a data 

requirement regulation. The Agency must provide a clear rule from which an applicant can 

understand the requirements without consulting with the Agency. (See LANXESS’s General 

Comments at Sections I and II.) 

Response: see responses 191.1 and 3 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27465 

Comment Code: 191000 
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Comments and Response References: 

Guidelines Section (190) Page 1026 

Comment: F. Comments on product use information and description of human activity data 

requirements 

It is essential that guidelines be proposed and finalized for these requirements. Without guidance, 

these requirements will be highly subjective. Guidance that establishes the scope of these 

requirements is critical to assuring that there is consistent and reasonable implementation of these 

requirements. 

Response: see response 191.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27513 

Comment Code: 191000 

Comment: C. Testing Guidelines Are Not Available to Provide Guidance 

It is unclear whether the testing guideline numbers referenced within the proposed rule refer to 

future documents based on the old Pesticide Assessment Guidelines or to some other type of 

guidance. Requiring data or information in accordance with unavailable criteria is a major drawback 

to this proposal. (See Panel’s General Comments at Section II.) 

Response: see response 191.1 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27518 

Comment Code: 191000 

Comment: 5) Environmental fate data are required to conduct an acceptable environmental risk 

assessment for the Use Pattern. However, the proposal provides no guidance or direction on how 

the Agency conducts an environmental risk assessment, or what criteria and uncertainty factors are 

used to determine if it is acceptable. Without this guidance, it is not possible to determine what 

testing is adequate to fulfill environmental fate data requirements. 

Response: see response 191.5 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27526 

Comment Code: 191000 

Comment: 6) Guidelines for many studies listed as environmental fate data requirements are not 

complete or available. These endpoints should not be required by the Agency until the study 
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Comments and Response References: 

Guidelines Section (190) Page 1027 

guidelines are issued as final, without restriction on the completeness of an acceptable 

environmental risk assessment. 

Response: see response 191.1 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1028 

Commenter Background; Introductions and Salutations (200) 

Verbatim Comments for the Commenter Background; Introductions and 

Salutations Section 

This section presents the portions of commenter submissions that contained salutations or simply provided background 

on the commenter organization. Verbatim text is provided below. No responses were necessary. 

Comment Code: 200000 Commenter Background; Introductions and Salutations 

Commenter Name: Eileen J. Moyer 

Commenter Organization: Reckitt Benckiser, Inc. 

Letter ID: 0076 

Comment ID: 25416 

Comment Code: 200000 

Comment: April 6, 2009 

Office of Pesticide Program (OPP) Regulatory Public Docket (7502) Environmental Protection 

Agency 1200 Pennsylvania Ave., NW Washington, DC 20460-0001 

RE: Proposed Rule on Data Requirements for Antimicrobial Pesticides, 73 Federal Register 59382. 

Docket Id number EPA-HQ-OPP-2008-0110. 

Dear Madam/Sir: 

Reckitt Benckiser Inc. ("Reckitt") respectfully submits the enclosed comments in response to the 

U.S. Environmental Protection Agency's ("EPA" or "Agency") proposal regarding Data 

Requirements for Antimicrobial Pesticides, 73 Fed. Reg. 59382 (October 8, 2008). Reckitt produces 

and distributes a wide range of consumer and institutional products. These include the Lysol(R) 

brand of disinfectants and disinfectant cleaners. 

Reckitt is a member of the Consumer Specialty Products Association and the American Chemistry 

Council Biocides Panel and supports the comments of both associations. Both of these 

organizations have submitted extensive comments on the proposed data requirements, therefore 

Reckitt is limiting its comments to address specific provisions within the proposed regulation and 

general concerns regarding the proposed data requirements. 

Commenter Name: Eileen J. Moyer 

Commenter Organization: Reckitt Benckiser, Inc. 

Letter ID: 0076 

Comment ID: 25420 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1029 

Comment Code: 200000 

Comment: Sincerely, 

Eileen J. Moyer Director of Regulatory Relations 

Commenter Name: Kelly K. Naujock 

Commenter Organization: S.C. Johnson & Son, Inc. 

Letter ID: 0063 

Comment ID: 25421 

Comment Code: 200000 

Comment: March 26,2009 

Office of Pesticide Program (OPP) Regulatory Public Docket (7502P) Environmental Protection 

Agency Rm. S-4400 One Potomac Yard (South Building) 2777 S. Crystal Drive Arlington, VA 22202 

 Subject: Proposed Rule on Data Requirements for Antimicrobial Pesticides, 73 Federal Register 

59382. Docket ID Number EPA-HQ-OPP-2008-0110. 

Dear Sir or Madam: 

These comments are submitted on behalf of S.C. Johnson & Son, Inc. regarding the Proposed Rule 

on Data Requirements for Antimicrobial Pesticides, 73 Federal Register 59382. The purpose of the 

proposed rule is to revise and update the existing data requirements for antimicrobial pesticides. S.C. 

Johnson & Son, Inc. supports the comments submitted by the Consumer Specialty Products 

Association (CSPA) and the American Chemistry Council Biocides Panel. S.C. Johnson & Son, Inc. 

encourages the Agency to carefully consider these comments and recommendations prior to 

finalizing the proposed rule. 

Commenter Name: Kelly K. Naujock 

Commenter Organization: S.C. Johnson & Son, Inc. 

Letter ID: 0063 

Comment ID: 25427 

Comment Code: 200000 

Comment: Thank you for the opportunity to comment on this important rule. Please do not 

hesitate to contact me if you need any additional information. 

Sincerely, Kelly K. Naujock Registration Specialist 262-260-2686 kknaujoc@scj.com 

Commenter Name: Jamie S. Heisig-Mitchell 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1030 

Comment ID: 25436 

Comment Code: 200000 

Comment: April 6, 2009 

RE: Docket ID no. EPA-HQ-OPP-2008-0110 Data Requirements for Antimicrobial Pesticides 

The Hampton Roads Sanitation District (HRSD), a wastewater treatment entity servicing 17 

counties and cities in southeastern Virginia, is pleased to provide comments on the referenced 

document. 

Commenter Name: Sally Hayes 

Commenter Organization: Scientific & Regulatory Consultants, Inc. (SRC) 

Letter ID: 0066 

Comment ID: 25455 

Comment Code: 200000 

Comment: April 6, 2009 

Office of Pesticide Program (OPP) Regulatory Public Docket (7502)) Environmental Protection 

Agency 1200 Pennsylvania Ave., NW Washington, DC 20460-0001 

 RE: Proposed Rule on Data Requirements for Antimicrobial Pesticides, 73 Federal Register 59382. 

Docket ID number EPA -HQ-OPP-2008-0110. 

Dear Sir/Madam: 

Commenter Name: Sally Hayes 

Commenter Organization: Scientific & Regulatory Consultants, Inc. (SRC) 

Letter ID: 0066 

Comment ID: 25463 

Comment Code: 200000 

Comment: SRC encourages the Agency carefully consider these and CSPA's comments and 

recommendations prior to finalizing the rule. 

We appreciate EPA's consideration of these comments. 

Sincerely, 

Sally Hayes Vice-President 

Commenter Name: Ray S. McAlister 

Commenter Organization: CropLife America 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1031 

Letter ID: 0079 

Comment ID: 25464 

Comment Code: 200000 

Comment: April 6, 20093 

Office of Pesticide Programs (OPP) Regulatory Public Docket (7502P) Environmental Protection 

Agency 1200 Pennsylvania Ave NW Washington, DC 20460-0001 

RE: Data Requirements for Antimicrobial Pesticides; Proposed Rule. 73 FR 59382. October 8, 2008. 

EPA Docket # EPA-HQ-OPP-2008-0110. 

Ladies and Gentlemen: 

CropLife America (CLA) is the national trade association representing the developers, 

manufacturers, formulators and distributors of plant science solutions for agriculture and pest 

management in the United States. CLA’s member companies produce, sell and distribute virtually all 

the crop protection and biotechnology products used by American farmers. We take this 

opportunity to present brief comments on the subject Proposed Rule. 

Commenter Name: Ray S. McAlister 

Commenter Organization: CropLife America 

Letter ID: 0079 

Comment ID: 25470 

Comment Code: 200000 

Comment: Sincerely, 

 Ray S. McAlister, Ph.D. Senior Director, Regulatory Policy 

Commenter Name: Abigail Trueblood 

Commenter Organization: Dow Chemical Company 

Letter ID: 0082 

Comment ID: 25471 

Comment Code: 200000 

Comment: April 3,2009 

OPP Regulatory Public Docket (7502P) Environmental Protection Agency Room S-4400 One 

Potomac Yard (South Building) 2777 South Crystal Drive Arlington, VA 22202 

RE: Docket ID Number EPA-HQ-Opp-2008- 1010 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1032 

The Dow Chemical Company (Dow) is pleased to have the opportunity to submit comments on the 

following proposed regulation: Data Requirements for Antimicrobial Pesticides.. 73 Fed. Reg. 

59382, October 8, 2008, ("Proposal" or "Proposed Rule"). Within this letter, the terms 

"antimicrobial" and "biocide" are used interchangeably. 

Commenter Name: Abigail Trueblood 

Commenter Organization: Dow Chemical Company 

Letter ID: 0082 

Comment ID: 25488 

Comment Code: 200000 

Comment: Dow appreciates the opportunity to make submit these comments, and will be happy to 

work with the Agency in further refinement of this rule. 

 Sincerely, 

 Abigail Trueblood Regulatory Specialist The Dow Chemical Company 

Commenter Name: Patrick H. Quinn 

Commenter Organization: Innovation and Reform Group (IRG) 

Letter ID: 0080 

Comment ID: 25489 

Comment Code: 200000 

Comment: COMMENTS OF INOVATION AND REFORM GROUP (IRG) ON EPA’S 

PROPOSED RULE REGARDING DATA REQUIREMENTS FOR ANTIMICROBIAL 

PESTICIDES 

73 FEDERAL REGISTER 59382 (October 8, 2008) 

EPA DOCKET NUMBER EPA-HQ-OPP-2008-0110 

 Patrick H. Quinn The Accord Group 1730 Rhode Island Ave., NW Suite 700 Washington, D.C. 

20036 202-289-9800 

IRG Member Companies Clorox Procter & Gamble Reckitt Benckiser 

 April 6, 2009 

COMMENTS OF INOVATION AND REFORM GROUP (IRG) ON EPA’S PROPOSED 

RULE REGARDING DATA REQUIREMENTS FOR ANTIMICROBIAL PESTICIDES 

73 FEDERAL REGISTER 59382 (October 8, 2008) 

EPA DOCKET NUMBER EPA-HQ-OPP-2008-0110 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1033 

 Background 

The Innovation Reform Group (IRG) is a coalition of antimicrobial registrants, founded in 2000, 

which works collaboratively with EPA’s Office of Pesticide Programs (OPP) to identify registration 

process improvements of mutual benefit to the Agency and the regulated community. Its members 

are: The Clorox Company, Procter & Gamble, and Reckitt Benckiser. IRG member companies 

manufacture a very substantial share of FIFRA registered antimicrobial products in the U.S. and 

have a critical interest in EPA’s proposed revisions to the Subpart 158W Rule. 

Commenter Name: Patrick H. Quinn 

Commenter Organization: Innovation and Reform Group (IRG) 

Letter ID: 0080 

Comment ID: 25492 

Comment Code: 200000 

Comment: The work of the IRG during the past eight years has focused on collaborative 

opportunities to work with the EPA professional staff on process reforms which offer OPP work 

process improvements while improving the certainty and predictability of OPP review mechanisms 

for registrants. Our work with the Antimicrobial Division and others in OPP have produced 

significant achievements including: Strategic Front-End Review; Disinfection Hierarchy and 

Emerging Pathogens Policy; OPP Label Review Committee; and Fragrance Data Base 

Modernization andNotification. 

Commenter Name: Elizabeth Tannehill 

Commenter Organization: Mason Chemical Company 

Letter ID: 0078 

Comment ID: 25502 

Comment Code: 200000 

Comment: April 3, 2009 

Office of Pesticide Program (OPP) Regulatory Public Docket (7502)) Environmental Protection 

Agency 1200 Pennsylvania Ave., NW Washington, DC 20460-0001 

RE: Proposed Rule on Data Requirements for Antimicrobial Pesticides, 73 Federal Register 59382. 

Docket id number EPA-HQ-OPP-2008-0110. 

Dear Sir/Madam: 

These comments are submitted on behalf of the Mason Chemical Company on the proposed rule on 

Data Requirements for Antimicrobial Pesticides, 73 Federal Register 59382. Mason Chemical 

Company is an active manufacturer of quaternary compounds, specializing in antimicrobial 

pesticides. We are an active member of Consumer Specialty Products Association (CSPA), the 

American Chemistry Council Biocides Panel, the Antimicrobial Exposure Joint Venture (AEJV) and 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1034 

the Antimicrobial Exposure Assessment Task Force II (AEATF II) as well as the ADBAC and 

DDAC joint ventures. 

Commenter Name: Elizabeth Tannehill 

Commenter Organization: Mason Chemical Company 

Letter ID: 0078 

Comment ID: 25507 

Comment Code: 200000 

Comment: Thank you for the opportunity to comment on this important rule. 

Sincerely, 

MASON CHEMICAL COMPANY 

 

Elizabeth Tannehill 

Commenter Name: Rodger Curren 

Commenter Organization: Alternative Testing Working Group (ATWG) 

Letter ID: 0092 

Comment ID: 25508 

Comment Code: 200000 

Comment: COMMENTS OF ALTERNATIVE TESTING WORKING GROUP (ATWG) ON 

EPA’S PROPOSED RULE REGARDING DATA REQUIREMENTS FOR ANTIMICROBIAL 

PESTICIDES 

73 FEDERAL REGISTER 59382 (October 8, 2008) 

EPA DOCKET NUMBER EPA-HQ-OPP-2008-0110 

Rodger Curren Institute for In Vitro Sciences, Inc. 30 West Watkins Mill Road Suite 100 

Gaithersburg, MD. 20878 301-947-6523 

Patrick H. Quinn The Accord Group 1730 Rhode Island Ave., NW Suite 700 Washington, D.C. 

20036 202-289-9800 

ATWG Companies Clorox Colgate Palmolive Dial Ecolab JohnsonDiversey, Inc. Procter & Gamble 

S.C. Johnson & Son, Inc. 

April 6, 2009 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1035 

COMMENTS OF ALTERNATIVE TESTING WORKING GROUP (ATWG) ON EPA’S 

PROPOSED RULE REGARDING DATA REQUIREMENTS FOR ANTIMICROBIAL 

PESTICIDES 

73 FEDERAL REGISTER 59382 (October 8, 2008) 

EPA DOCKET NUMBER EPA-HQ-OPP-2008-0110 

Background 

The Alternative Testing Working Group (ATWG) is an informal working group comprised of seven 

large consumer product companies: 

Clorox Colgate Palmolive Dial Ecolab JohnsonDiversey, Inc. Procter & Gamble S.C. Johnson & 

Son, Inc. 

Over the past five years, the ATWG has worked collaboratively with EPA senior toxicologists and 

managers, as well as with stakeholders from the animal welfare community and EPA’s Pesticide 

Program Dialogue Committee (PPDC) to develop a non-animal approach for evaluating eye 

irritation for antimicrobial cleaning product formulations. It is from that perspective that the ATWG 

offers its comments on EPA’s Proposed Subpart 158W Rule. 

Commenter Name: Susan E. Little 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0068 

Comment ID: 25513 

Comment Code: 200000 

Comment: Antimicrobial Exposure Joint Venture April 3, 2009 

COMMENTS ON EPA PROPOSED RULE ON DATA REQUIREMENTS FOR 

ANTIMICROBIAL PESTICIDES (40 CFR PART 158W) DOCKET IDENTIFICATION: EPAHQ-OPP-2008-0110 SUBMITTED BY: ANTIMICROBIAL EXPOSURE JOINT VENTURE, 

EPA COMPANY NO. 74887 

The Antimicrobial Exposure Joint Venture (AEJV), operating under the auspices of the Consumer 

Specialty Products Association (CSPA) Product Ingredient Review Program (PIR), is pleased to 

comment on the Proposed Rule on Data Requirements for Antimicrobial Pesticides which appeared 

in the Federal Register on October 8, 2008. 

The AEJV consists of 14 member companies (list attached) and was formed to address the 

Antimicrobial Division of the Office of Pesticide Programs need for use and usage data for 

residential use of antimicrobial products. 

Commenter Name: Susan E. Little 

Commenter Organization: Consumer Specialty Products Association (CSPA) 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1036 

Letter ID: 0068 

Comment ID: 25523 

Comment Code: 200000 

Comment: We appreciate the opportunity to comment on the Proposed Rule. If there are any 

questions or if there is anything at all I can do to assist, please do not hesitate to contact me at 

202/872-8110. Thank you very much. 

Sincerely yours, 

Susan E. Little, Executive Director CSPA/PIR Program On behalf of the Antimicrobial Exposure 

Joint Venture 

cc: William McCormick, Steering Committee Chair Antimicrobial Exposure Joint Venture Members 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25536 

Comment Code: 200000 

Comment: April 6, 2009 

OPP Regulatory Public Docket (7502P) Environmental Protection Agency Rm., S-4400 One 

Potomac Yard (South Building) 2777 S. Crystal Drive Arlington, VA 22202 

RE: Proposed Rule on Data Requirements for Antimicrobial Pesticides, 73 Federal Register 59382. 

Docket id number EPA -HQ-OPP-2008-0110. 

Dear Sir/Madam: 

These comments are submitted on behalf of the Consumer Specialty Products Association (CSPA) 

on the proposed rule on Data Requirements for Antimicrobial Pesticides, 73 Federal Register 59382. 

CSPA is the premier trade association representing the interests of approximately 240 companies 

engaged in the manufacture, formulation, distribution and sale of approximately $80 billion annually 

in the U.S. of hundreds of familiar consumer products that help household, institutional and 

industrial customers create cleaner and healthier environments. Our products include disinfectants 

and sanitizers that kill germs in homes, hospitals, industrial sites and restaurants; candles, fragrances 

and air fresheners that eliminate odors; pest management products for home and garden; cleaning 

products for use throughout the home; products used to protect and improve the performance and 

appearance of automobiles; and a host of other products used everyday. Through its product 

stewardship program Product Care®, scientific and business-to-business endeavors, CSPA provides 

its members a platform to effectively address issues regarding the health, safety, sustainability and 

environmental impacts of its products. For more information, please visit www.cspa.org. 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1037 

Commenter Name: Marion Law 

Commenter Organization: Health Canada: Pest Management Regulatory Agency 

Letter ID: 0085 

Comment ID: 25560 

Comment Code: 200000 

Comment: Apri1 6,2009 

 Debra Edwards Office of Pesticide Programs Regulatory Public Docket (7502P) Environmental 

Protection Agency 1200 Pennsylvania Ave., NW Washington DC, 20460 

Dear: Dr. Edwards, 

Re: EPA Docket Identification (lD) number: EPA-HQ-OPP-2008-0110 Data Requirements for 

Antimicrobial Pesticides, Federal Register Vol. 73, No. 196, Wednesday, October 8, 2008, Page 

59382 

As the Canadian regulatory authority for antimicrobial pesticides, the Pest Management Regulatory 

Agency (PMRA) of Health Canada is submitting detailed comments in response to the EPA 

proposal to revise and update the existing data requirements for antimicrobial pesticides. 

On behalf of the PMRA, I wish to thank the EPA for the opportunity to provide comments on this 

proposal. In addition, I would like to convey my appreciation of the extensive consultations that 

have taken place between the EPA and the PMRA over the past several years. These discussions 

have led to a higher degree of harmonization in the data requirements for antimicrobial pesticides 

than existed previously, and have served to strengthen communication between both agencies on 

issues relevant to regulatory science. Within the context of the NAFTA Technical Working Group 

on Pesticides, both agencies are committed to continuing the dialogue in an effort to better 

understand the basis for any remaining differences, as well as to working together to harmonize the 

conditions under which additional data elements are triggered. The PMRA looks forward to ongoing 

involvement in this regard. 

Sincerely, 

Marion Law Chief Registrar Pest Management Regulatory Agency 

Health Canada Comments on CFR158W (Federal Register dated October 8, 2008) 

Commenter Name: Brigid D. Klein 

Commenter Organization: Consumer Specialty Products Association (CSPA) 

Letter ID: 0086 

Comment ID: 25655 

Comment Code: 200000 

Comment: Sincerely, 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1038 

 Brigid D. Klein Vice President & General Counsel 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25657 

Comment Code: 200000 

Comment: April 6, 2009 

Office of Pesticide Programs (OPP) Regulatory Public Docket (7502P) Environmental Protection 

Agency (U.S. EPA) 1200 Pennsylvania Ave., NW. Washington, DC 20460-0001 

Kathryn Boyle Field and External Affairs Division (7506P) Office of Pesticide Programs 

Environmental Protection Agency 1200 Pennsylvania Avenue, NW. Washington, DC 20460-0001 

Subject: Data Requirements for Antimicrobial Pesticides (Docket No. OPP-2008-0110) 

Dear Ms. Boyle: 

San Francisco Department of the Environment’s (SFE’s) mission is to improve, enhance, and 

preserve the environment, and to promote San Francisco’s long-term well being. San Francisco 

adopted an Integrated Pest Management (IPM) ordinance in October 1996, which commits the City 

to a pest management approach on its own property that minimizes the use of toxic chemicals and 

controls pests by methods that pose a lower risk to public and environmental health.[FN1: San 

Francisco Integrated Pest Management Program - Chapter 3. http://tinyurl.com/csgzad.] Our city 

has chosen a proactive approach to pest management, chemical product selection, and green 

building based on the Precautionary Principle, using the best available science to identify costeffective measures that would minimize harm. We strongly believe that EPA should use its pesticide 

registration process to protect human health and prevent environmental problems with pesticides. 

Commenter Name: Lisa M. Amadio 

Commenter Organization: JohnsonDiversey, Inc. 

Letter ID: 0084 

Comment ID: 25688 

Comment Code: 200000 

Comment: April 3, 2009 

Office of Pesticide Programs (OPP) Regulatory Public Docket (7502)) Environmental Protection 

Agency 1200 Pennsylvania Ave., NW Washington, DC 20460-0001 

Subject: Proposed Rule on Data Requirements for Antimicrobial Pesticides, 73 Federal Register 

59382. Docket ID number EPA -HQ-OPP-2008-0110. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1039 

Dear Sir/Madam: 

These comments are submitted on behalf of JohnsonDiversey, Inc. (JDI) regarding the proposed 

rule on Data Requirements for Antimicrobial Pesticides, 73 FR 59382. JohnsonDiversey is a World 

Leader in Healthcare Disinfectant Products. 

Commenter Name: Lisa M. Amadio 

Commenter Organization: JohnsonDiversey, Inc. 

Letter ID: 0084 

Comment ID: 25690 

Comment Code: 200000 

Comment: Several of the comments submitted by CSPA and the Biocides panel are of particular 

importance to JohnsonDiversey, and we wish to emphasize our concurrence with these comments: 

Commenter Name: Lisa M. Amadio 

Commenter Organization: JohnsonDiversey, Inc. 

Letter ID: 0084 

Comment ID: 25694 

Comment Code: 200000 

Comment: Sincerely, 

Lisa M. Amadio NA Registered Products Manager 

Commenter Name: Jay Feldman 

Commenter Organization: Beyond Pesticides 

Letter ID: 0067 

Comment ID: 25701 

Comment Code: 200000 

Comment: April 6, 2009 Office of Pesticide Programs (OPP) Regulatory Public Docket (7502P), 

Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001 

Re: Data Requirements for Antimicrobial Pesticides. Docket Number: EPA-HQ-OPP-2008-0110 

Dear Sir/Madam: 

Commenter Name: Chris Geiger 

Commenter Organization: SF Environment 

Letter ID: 0071 

Comment ID: 25712 

Comment Code: 200000 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1040 

Comment: Thank you for this opportunity to offer our input regarding the proposed revised data 

requirements for antimicrobial pesticides. If you have any questions, please contact Chris Geiger at 

(415) 355-3759 or chris.geiger@sfgov.org. 

Sincerely, 

Chris Geiger, Ph.D. Green Purchasing Program Manager/IPM Program Manager 

Commenter Name: Jay Feldman 

Commenter Organization: Beyond Pesticides 

Letter ID: 0067 

Comment ID: 25724 

Comment Code: 200000 

Comment: Thank you for your attention to our comments. 

Respectfully, 

Jay Feldman Executive Director Beyond Pesticides 

Nichelle Harriott Research Associate Beyond Pesticides 

Commenter Name: Jamie S. Heisig-Mitchell 

Commenter Organization: Hampton Roads Sanitation District (HRSD) 

Letter ID: 0065 

Comment ID: 25726 

Comment Code: 200000 

Comment: HRSD welcomes these proposed changes and appreciates EPA's efforts to protect 

POTW's and our nation's waters. Thank you for your consideration of these comments. 

Respectfully, 

Jamie S. Heisig-Mitchell Environmental Scientist Hampton Roads Sanitation District 1436 Air Rail 

Avenue Virginia Beach, VA 23455 757-460-4220 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25727 

Comment Code: 200000 

Comment: April 3, 2008 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1041 

OPP Regulatory Public Docket (7502P) Environmental Protection Agency, Rm. S-4400 One 

Potomac Yard (South Bldg) 2777 S. Crystal Dr. Arlington, VA 22202 

RE: EPA-HQ-OPP-2008-0110 40 CFR Part 158 and 161 - Data Requirements for Antimicrobial 

Pesticides Proposed Rule - Federal Register, Vol. 73, No. 196 (October 8, 2008) 

Dear Sir or Madam: 

With sales of $6 billion and more than 26,000 associates, Ecolab is the global leader in cleaning, 

sanitizing, food safety and infection prevention products and services. Ecolab delivers 

comprehensive programs and services to the foodservice, food and beverage processing, healthcare, 

and hospitality markets in more than 160 countries. Therefore, Ecolab has a vital interest in ensuring 

that appropriate and cost effective data requirements are applicable to the registration of 

antimicrobial pesticides which provide public health and food safety benefits. 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 

Comment ID: 25729 

Comment Code: 200000 

Comment: Background The Environmental Protection Agency (EPA or the Agency) published a 

proposed rule in the October 8, 2008 Federal Register, entitled "Data Requirements for 

Antimicrobial Pesticides" for 40 CFR 158 and 161. In the notice, EPA proposed to revise and 

update the existing data requirements for antimicrobial pesticides. The Agency stated the proposed 

revisions are needed to reflect the following: 

1. current scientific knowledge 

2. current Agency regulatory practices; and 

3. to improve protection of the general population and as well as sensitive subpopulations. 

The proposed regulation summary goes on to state that these proposed data requirements are 

intended to further enhance the Agency's ability to make regulatory decisions about the human 

health and environmental fate and effects of antimicrobial pesticide products. 

In the October 8, 2008 Federal Register Notice, the Agency requested submission of comments 

from interested parties on or before January 6, 2009. At the request of industry, EPA extended the 

comment period to April 6, 2009. 

Commenter Name: James A. Westerhaus 

Commenter Organization: ECOLAB 

Letter ID: 0072 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1042 

Comment ID: 25774 

Comment Code: 200000 

Comment: Thank you for your attention to our concerns. 

Sincerely, 

James A. Westerhaus Vice President, Government Relations Ecolab 

John G. Wood Director, Product Registration and Compliance Ecolab 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25775 

Comment Code: 200000 

Comment: April 2, 2009 

Office of Pesticide Programs (OPP) Regulatory Public Docket (7502P) Environmental Protection 

Agency 1200 Pennsylvania Ave., NW. Washington, DC 20460-0001 

Attemton: Docket ID Number EPA-HQ-OPP-2008-0110 

Submitted via Electronic Email 

SUBJECT: Docket No. EPA-HQ-OPP-2008-0110 Data Requirements for Antimicrobial Pesticides 

Tri-TAC appreciates the opportunity to comment on the proposed changes to the data requirements 

for antimicrobial pesticides. Tri-TAC is a technical advisory group for Publicly Owned Treatment 

Works (POTWs) in California. The California Association of Sanitation Agencies, the California 

Water Environmental Association, and the League of California Cities jointly sponsor Tri-TAC. The 

constituency base for Tri-TAC collects, treats, and reclaims more than two billion gallons of 

wastewater each day and serves most of the sewered population of California. 

Commenter Name: James Colston 

Commenter Organization: Tri-TAC 

Letter ID: 0087 

Comment ID: 25805 

Comment Code: 200000 

Comment: Tri-TAC appreciates the opportunity to comment on the proposed rule. If you have any 

questions or require additional information, please contact Ms. Preeti Ghuman by phone at (562) 

699-7411, extension 2904, or by email at pghuman@lacsd.org. 

Sincerely, James Colston Chair Tri-TAC 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1043 

Cc: Debra F. Edwards, Director, U.S. EPA Office of Pesticide Programs Joan Harrigan-Farrelly, 

Director, U.S. EPA Office of Pesticide Programs, Antimicrobials Division Betty Shackleford, 

Associate Director, U.S. EPA Office of Pesticide Programs, Antimicrobials Division Norm Cook, 

Branch Chief, Antimicrobials Division William Diamond, Director, Field and External Affairs 

Division Donald Brady, Director, Environmental Fate and Effects Division Jack Housenger, 

Director, Biological and Economic Analysis Division Rick P. Keigwin, Jr., Director, Special Review 

and Reregistration Division Claire Gesalman, Branch Chief, Communications Services Branch, Field 

and External Affairs Division Jennifer McLain, Branch Chief, Policy and Regulatory Services Br, 

Field and External Affairs Division Ephraim King, Director, Office of Science and Technology 

Suzanne Schwartz, Acting Director, Office of Wetlands, Oceans, and Watersheds James A. Hanlon, 

Director, Office of Water, Office of Wastewater Management Alexis Strauss, Director, Water 

Division, USEPA Region IX Patti TenBrook, USEPA Region IX Debra Denton, USEPA Region 

IX Nan Singhasemanon, California Department of Pesticide Regulation Syed Ali, Division of Water 

Quality, State Water Resources Control Board Tom Mumley, Regional Water Quality Control 

Board, San Francisco Bay Diane Beaulaurier, Regional Water Quality Control Board, Central Valley 

Julie Chan, Regional Water Quality Control Board, San Diego Tracey Egoscoe, Regional Water 

Quality Control Board, Los Angeles Kelly D. Moran, Urban Pesticides Pollution Prevention Project 

Chris Hornback, Senior Director, Regulatory Affairs, National Association of Clean Water Agencies 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25806 

Comment Code: 200000 

Comment: April 6, 2009 

Regulatory Public Docket (7502P) Office of Pesticide Programs Environmental Protection Agency 

1200 Pennsylvania Ave. N.W. Washington, DC 20460-0001 

Re: Proposed revisions to U.S. pesticide data requirements for antimicrobial chemicals 73 Fed. Reg. 

59382 (October 8, 2008) Docket ID Number: EPA-HQ-OPP-2008-0110 

Via Regulations.gov 

To Whom It May Concern: 

The Humane Society of the United States and Humane Society Legislative Fund appreciate the 

opportunity to comment on the proposed rule to update the U.S. pesticide data requirements for 

antimicrobial chemicals (hereinafter "Proposed Rule"). 

By way of background, HSUS is the nation's largest animal protection organization- backed by more 

than 11 million Americans, or one of every 30. For more than a half-century, HSUS has been 

working for the protection of all animals through advocacy, education and hands-on programs. 

HSLF is a social welfare organization incorporated in 2004 under [section]501(c)(4) of the Internal 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1044 

Revenue Code as a separate lobbying affiliate of HSUS to pursue passage of animal protection laws 

at the state and federal level, to educate the public about animal protection issues, and to support 

humane candidates for office. 

We gratefully acknowledge the willingness of senior management and staff in EPA’s Office of 

Pesticide Programs to engage in an ongoing dialogue with animal protection stakeholders and to 

proactively explore opportunities for replacement, reduction and refinement of animal use in OPP 

regulatory programs. 

Thank you for your attention and responsiveness to these comments. Please direct any questions to 

the undersigned at tseidle@humanesociety.org. 

Sincerely, 

Troy Seidle Director of Science Policy 

 On behalf of: Humane Society Legislative Fund Humane Society of the United States People for 

the Ethical Treatment of Animals Physicians Committee for Responsible Medicine 

COMMENTS ON PROPOSED REVISIONS TO U.S. PESTICIDE DATA REQUIREMENTS 

FOR ANTIMICROBIAL CHEMICALS 

73 Fed. Reg. 59382 (October 8, 2008) 

Docket ID Number EPA-HQ-OPP-2008-0110 

April 6, 2009 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25807 

Comment Code: 200000 

Comment: OVERVIEW 

The revision of Part 158W offers a long awaited opportunity to streamline and modernize OPP’s 

pesticide data requirements for antimicrobials to minimize redundancies and open the door to 21st 

century technologies and testing paradigms that fulfill the common goals of effectiveness, efficiency, 

economy, and optimal protection of human health, the environment, and animal welfare. We 

welcome the increased level of attention by senior OPP management to the "3Rs" of replacement, 

reduction and refinement of animal use, including several proactive initiatives in this vein by certain 

OPP staff, and acknowledge the statement in the Proposed Rule at 59421 that "the Agency is 

committed to moving towards a more efficient and refined testing/risk assessment paradigm for 

antimicrobial pesticide chemicals." We nonetheless have a number of concerns regarding the 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1045 

proposed rule, which are briefly summarized below, and discussed in greater depth in the sections 

that follow. 

Commenter Name: Troy Seidle 

Commenter Organization: Humane Society 

Letter ID: 0090 

Comment ID: 25857 

Comment Code: 200000 

Comment: LITERATURE CITED 

Balls M. Are animal tests inherently valid? Alternatives to Laboratory Animals 2004; 32 (Suppl. 1): 

755-8. 

Barton HA, Pastoor TP, Baetcke K, Chambers JE, Diliberto J, et al. Acquisition and application of 

absorption, distribution, metabolism, and excretion (ADME) data in agricultural chemical safety 

assessments. Critical Reviews in Toxicology 2006; 36: 9-35. 

Basketter DA, York M, McFadden JP, Robinson MK. Determination of skin irritation potential in 

the human 4-h patch test. Contact Dermatitis 2004; 51: 1-4. 

Bremer S, Pellizzer C, Hoffmann S, Seidle T, Hartung T. The development of new concepts for 

assessing reproductive toxicity applicable to large-scale toxicological programmes. Current 

Pharmaceutical Design 2007; 13: 3047-58. 

Carmichael NG, Barton HA, Boobis AR, Cooper RL, Dellarco VL, et al. Agricultural chemical 

safety assessment: a multisector approach to the modernization of human safety requirements. 

Critical Reviews in Toxicology 2006; 36: 1-7. 

Cooper RL, Lamb-IV JC, Barlow SM, Bentley K, Brady AM, et al. A tiered approach to life stages 

testing for agricultural chemical safety assessment. Critical Reviews in Toxicology 2006; 36: 69-98. 

Curren R. Letter from IIVS to NICEATM/ICCVAM. 8 January 2008. 

 Dewhurst IC, Billington R, Lewis RW. Removing the second species mouse carcinogenicity study 

from the testing requirements for pesticide active substances (poster). 5 November 2007. 

2nd_species_no_mouse.pdf> 

Doe JE, Boobis AR, Blacker A, Dellarco V, Doerrer NG, et al. A tiered approach to systemic 

toxicity testing for agricultural chemical safety assessment. Critical Reviews in Toxicology 2006; 36: 

37-68. 

ECETOC-ECVAM. Workshop Report No. 12: Workshop on Triggering and Waiving Criteria for 

the Extended One-Generation Reproduction Toxicity Study. Brussels: August 2008. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1046 

ECHA. Guidance on Information Requirements and Chemical Safety Assessment. May 2008. 

en.htm ?time=1239064575> 

ECVAM. Statement on the Validity of In Vitro Tests for Skin Irritation. 27 April 2007. 

 ECVAM. Statement on the Scientific Validity of In Vitro Tests for Skin Irritation Testing. 5 

November 2008. 

 Ekwall B, Barile FA, Castano A, et al. MEIC evaluation of acute systemic toxicity. Part VI. The 

prediction of human toxicity by rodent LD50 values and results from 61 in vitro methods. 

Alternatives to Laboratory Animals 1998; 26 Suppl. 2): 617-58. 

Hamada S, Sutou S, Morita T, Wakata A, Asanami S, Hosoya S, et al. Evaluation of the rodent 

micronucleus assay by a 28-day treatment protocol: Summary of the 13th Collaborative Study by the 

Collaborative Study Group for the Micronucleus Test (CSGMT)/Environmental Mutagen Society 

of Japan (JEMS)-Mammalian Mutagenicity Study Group (MMS). Environmental Molecular 

Mutagenesis 2001; 37: 93-110. 

Hamada S, Nakajima K, Serikawa T, Hayashi M. The effect of aging on the results of the rat 

micronucleus assay. Mutagenesis 2003; 18: 273-5. 

Hayden PJ, Kandarova H, Armento A, Kubilus J, Klausner M. Development of an EpiDermTM In 

Vitro Skin Irritation Test (SIT) for the Globally Harmonized System (GHS) of Classification and 

Labeling of Chemicals. 18 March 2009. 

 Hurtt ME, Cappon GD, Browning A. Proposal for a tiered approach to developmental toxicity 

testing for veterinary pharmaceutical products for food-producing animals. Food and Chemical 

Toxicology 2003; 41: 611-9. 

ICCVAM. In Vitro Test Methods for Detecting Ocular Corrosives and Severe Irritants. 25 October 

2007. 

 ICCVAM. Draft ICCVAM Test Method Recommendations: LLNA Limit Dose Procedure. 7 

January 2008. pdf> 

Janer G, Hakkert B, Slob W, Vermeire T, Piersma A. A retrospective analysis of the twogeneration 

study: What is the added value of the second generation? Reproductive Toxicology 2007; 24: 97-102. 

Mangelsdorf M, Buschmann J, Orthen B. Some aspects relating to the evaluation of the effects of 

chemicals on male fertility. Regulatory Toxicology and Pharmacology 2003; 37: 356-69. 

NRC. Toxicity Testing in the Twenty-first Century: A Vision and a Strategy. Washington, DC: 

National Academy Press (2007). 

OECD. Mutual Acceptance of Data (MAD). 12 May 1981. 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1047 

 OPP. Guidance Document on Methodology for Determining the Data Needs and the Types of 

Assessments Necessary to Make FFDCA Section 408 Safety Determinations for Lower Toxicity 

Pesticide Chemicals. 7 June 2002. 

 Reaves ME, Kidwell J, Mendez E, Dellarco V, Dix D, et al. A Retrospective Analysis of 175 TwoGeneration Reproduction Toxicity Rat Studies to Support the Proposed Extended One-Generation 

Reproduction Study. Washington, DC: US EPA. 2008. 

Stoick K, Nitschke K, Sandusky C. Systemic testing by the dermal route can be precluded by new 

non-animal percutaneous absorption strategies. AATEX 2007; 14 (Special): 561-4. 

Commenter Name: William C. Balek 

Commenter Organization: ISSA 

Letter ID: 0074 

Comment ID: 25858 

Comment Code: 200000 

Comment: April 6, 2009 

U,S, Environmental Protection Agency Office of Pesticide Programs (OPP) Regulatory Public 

Docket (7502P) 1200 Pennsylvania Ave., NW Washington, DC 20460-0001 

RE: Docket Identification Number EPA-HQ-OPP-2008-0ll 0 

To Whom It May Concern: 

ISSA is providing comments in regard to EPA Docket No. EPA-HQ-OPP-2008-0110. 

Commenter Name: William C. Balek 

Commenter Organization: ISSA 

Letter ID: 0074 

Comment ID: 25869 

Comment Code: 200000 

Comment: Respectfully submitted, 

William C. Balek Director of Legislative Affairs ISSA 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25870 

Comment Code: 200000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1048 

Comment: April 2, 2009 

Office of Pesticide Programs (OPP) Regulatory Public Docket (7502P) Environmental Protection 

Agency 1200 Pennsylvania Ave., NW. Washington, DC 20460-0001 Attn: Docket ID Number EPAHQ-OPP-2008-0110 

Submitted Electronically 

Docket No. EPA-HQ-OPP-2008-0110 Data Requirements for Antimicrobial Pesticides 

The California Association of Sanitation Agencies (CASA) is pleased to provide comments on the 

proposed changes to data requirements of antimicrobial pesticides. CASA represents more than 

ninety percent of the sewered population of California and has long been a proactive leader on 

wastewater, recycled water, and biosolids issues. 

Commenter Name: Harry T. Price 

Commenter Organization: California Association of Sanitation Agencies (CASA) 

Letter ID: 0069 

Comment ID: 25903 

Comment Code: 200000 

Comment: CASA appreciates the opportunity to comment on the proposed rule. If you have any 

questions or require additional information, please contact Ms. Preeti Ghuman by phone at (562) 

699-7411, extension 2904, or by email at pghuman@lacsd.org. 

Sincerely, Harry T. Price CASA President 

Cc: Debra F. Edwards, Director, U.S. EPA Office of Pesticide Programs Joan Harrigan-Farrelly, 

Director, U.S. EPA Office of Pesticide Programs, Antimicrobials Division Betty Shackleford, 

Associate Director, U.S. EPA Office of Pesticide Programs, Antimicrobials Division Norm Cook, 

Branch Chief, Antimicrobials Division William Diamond, Director, Field and External Affairs 

Division Donald Brady, Director, Environmental Fate and Effects Division Jack Housenger, 

Director, Biological and Economic Analysis Division Rick P. Keigwin, Jr., Director, Special Review 

and Reregistration Division Claire Gesalman, Branch Chief, Communications Services Branch, Field 

and External Affairs Division Jennifer McLain, Branch Chief, Policy and Regulatory Services Br., 

Field and External Affairs Division Ephraim King, Director, Office of Science and Technology 

Suzanne Schwartz, Acting Director, Office of Wetlands, Oceans, and Watersheds James A. Hanlon, 

Director, Office of Water, Office of Wastewater Management Alexis Strauss, Director, Water 

Division, USEPA Region IX Patti TenBrook, USEPA Region IX Debra Denton, USEPA Region 

IX Nan Singhasemanon, California Department of Pesticide Regulation Syed Ali, Division of Water 

Quality, State Water Resources Control Board Tom Mumley, Regional Water Quality Control 

Board, San Francisco Bay Diane Beaulaurier, Regional Water Quality Control Board, Central Valley 

Julie Chan, Regional Water Quality Control Board, San Diego Tracey Egoscoe, Regional Water 

Quality Control Board, Los Angeles Kelly D. Moran, Urban Pesticides Pollution Prevention Project 

Chris Hornback, Senior Director, Regulatory Affairs, National Association of Clean Water Agencies 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1049 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25904 

Comment Code: 200000 

Comment: April 6, 2009 

(Sent via Federal eRulemaking Portal: http://www.regulations.gov) 

Office of Pesticide Programs 

Regulatory Public Docket (7502P) U.S. Environmental Protection Agency 1200 Pennsylvania Ave., 

NW Washington, DC 20460-0001 

Re: EPA-HQ-OPP-2008-0110 Data Requirements for Antimicrobial Pesticides (40 CFR Part 158W) 

To Whom It May Concern: 

The purpose of this letter is to submit written comments regarding the Environmental Protection 

Agency's (EPA) proposed rule for antimicrobial pesticides data requirements (Federal Register dated 

October 8, 2008). 

The Clorox Company, with world headquarters in Oakland, California, is a manufacturer and 

marketer of many well-known consumer products, including our namesake bleach and disinfectant 

cleaning products (Clorox Disinfecting Wipes, Formula 409 All-Purpose Cleaner, Pine-Sol, Clorox 

Germicidal Wipes, Clorox Toilet Wand), Green Works(R) natural cleaning products, Armor All(R) 

and STP(R) auto- care products, Fresh Step(R) and Scoop Away(R) cat litter, Kingsford(R) charcoal 

and barbecue products, Hidden Valley(R) and K C Masterpiece(R) dressings and sauces, Brita(R) 

water-filtration systems, Glad(R) bags, wraps and containers, and Burt's Bees(R) natural personal 

care products. Clorox is strongly committed to maintaining the safety of our products and 

minimizing the impacts of our products and manufacturing processes on the environment, as well as 

understanding the public health benefits that our products provide. 

Commenter Name: Victoria Jones 

Commenter Organization: Clorox 

Letter ID: 0075 

Comment ID: 25941 

Comment Code: 200000 

Comment: We appreciate the opportunity to submit comments on this important public policy 

issue and stand ready to provide additional information on request. Please contact Reza Rahaman at 

(925) 425-4336 if we can answer any questions. 

Sincerely, 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1050 

 Victoria Jones Vice President - Government Affairs and Community Relations 

 Reza S. Rahaman Vice President - Global Stewardship 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25942 

Comment Code: 200000 

Comment: April 1,2009 

U.S. Environmental Protection Agency Office of Pesticide Programs (OPP) Regulatory Public 

Docket (7502P) 1200 Pennsylvania Ave., NW Washngton, DC 20460-0001 

RE: Docket Identification Number EPA-HQ-OPP-2008-0110 

Dear Sir or Madam: 

Commenter Name: Adrian Krygsman 

Commenter Organization: Troy Corporation 

Letter ID: 0091 

Comment ID: 25967 

Comment Code: 200000 

Comment: Troy Corporation hopes that EPA will thoroughly review our and the Biocides Panel 

comments in order to develop a set of regulatory criteria that are practical and pertinent to the entire 

antimicrobial industry and its downstream users. 

Sincerely, 

Adrian Krygsman Director, Product Registration 

Cc: D.Shaw 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25968 

Comment Code: 200000 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1051 

Comment: April 3, 2009 Docket ID EPA-HQ-OPP-2008-0110 Office of Pesticide Programs 

Regulatory Public Docket (7502P) U.S. Environmental Protection Agency 1200 Pennsylvania 

Avenue, NW Washington, DC 204600-0001 Via: www.regulations.gov 

Dear Sir or Madam: 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25970 

Comment Code: 200000 

Comment: NACWA represents the interests of nearly 300 of the nation’s publicly owned 

wastewater treatment works (POTWs) or clean water agencies. NACWA’s members continue to 

face challenges as they strive to meet increasingly stringent Clean Water Act (CWA) requirements 

while having limited control over the toxic pollutants and other substances in the wastewater they 

treat. 

Commenter Name: Chris Hornback 

Commenter Organization: National Association of Clean Water Agencies (NACWA) 

Letter ID: 0070 

Comment ID: 25996 

Comment Code: 200000 

Comment: NACWA appreciates the opportunity to comment on the proposed data requirements 

of antimicrobial pesticides. Please contact me at 202/833-9106 if you have any questions. 

Sincerely, 

Chris Hornback Senior Director, Regulatory Affairs 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26016 

Comment Code: 200000 

Comment: April 3, 2009 

Office of Pesticide Programs (OPP) Regulatory Public Docket (7502P) Environmental Protection 

Agency (USEPA) 1200 Pennsylvania Ave., NW. Washington, DC 20460-0001 

Kathryn Boyle Field and External Affairs Division (7506P) Office of Pesticide Programs 

Environmental Protection Agency 1200 Pennsylvania Ave., NW. Washington, DC 20460-0001 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1052 

Subject: Data Requirements for Antimicrobial Pesticides (Docket No. OPP--2008-0110) 

Dear Ms. Boyle: 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26021 

Comment Code: 200000 

Comment: Background about CASQA 

CASQA is composed of stormwater quality management organizations and individuals, including 

cities, counties, special districts, industries, and consulting firms throughout California. CASQA was 

formed in 1989 to recommend approaches to the State Water Resources Control Board (State Water 

Board) for stormwater quality management in California. In this capacity, we have assisted and 

continue to assist the State Water Board with development and implementation of stormwater 

permitting processes. 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26037 

Comment Code: 200000 

Comment: Since 1999, CASQA has provided comments on selected USEPA pesticide registration 

and reregistration actions, including proposed changes in policies and regulations, and actions 

involving specific active ingredients that appear in urban runoff (e.g., polyhexamethylene 

biguanadine, copper, metam sodium, diazinon, chlorpyrifos, permethrin, cypermethrin). Our focus 

on pesticide registration issues is the result of numerous scientific studies conducted in California by 

stormwater programs, wastewater treatment plants, the University of California, California Regional 

Water Quality Control Boards, United States Geological Survey, and USEPA showing widespread 

toxicity in local creeks and rivers, urban runoff, and wastewater treatment plant effluent from 

pesticide residues. These studies have demonstrated that the use of some pesticides registered under 

the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) can and does adversely affect water 

bodies in California. Ironically, as a result of discharges of pesticides registered for use by USEPA 

under FIFRA, the State Water Board and USEPA have found many waters in urban areas of 

California to be impaired in accordance with Clean Water Act [Section] 303(d). 

Commenter Name: Chris Crompton 

Commenter Organization: California Stormwater Quality Association (CASQA) 

Letter ID: 0089 

Comment ID: 26060 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1053 

Comment Code: 200000 

Comment: Thank you for your consideration of our comments about USEPA’s proposed revised 

data requirements for antimicrobial pesticides. If you have any questions, please contact CASQA 

Executive Director Geoff Brosseau at (650) 365-8620. 

Sincerely, 

Chris Crompton, Chair 

Enclosures: 1. 40 CFR Part 136.3 (see Table 1A) [See PDF docket ID EPA-HQ-OPP-2008-110-

0089] 

2. Untitled compilation of swimming pool discharge requirements and educational material 

documenting discharges to both sewers and storm drains. [See PDF docket ID EPA-HQ-OPP2008-110-0089] 

3. Loretitsch, G., Puckorius & Associates (undated). Guidelines for Managing Water in Cooling 

Systems. Prepared for the City of San Jose, California. [See PDF docket ID EPA-HQ-OPP-2008-

110-0089] 

4. City of Palo Alto (1999). Cooling Water Systems Source Control Program. Fact Sheet. [See PDF 

docket ID EPA-HQ-OPP-2008-110-0089] 

5. City of Palo Alto (1997). Urban Pesticide Restrictions for Water Quality Protection. Fact Sheet. 

[See PDF docket ID EPA-HQ-OPP-2008-110-0089] 

6. Davidson, N. A., California Department of Pesticide Regulation (1995). Evaluation of Copperand Tributyltin-containing Compounds. Report Number EH-95-07. [See PDF docket ID EPA-HQOPP-2008-110-0089] 

7. Kaegi, R. et al. (2008). Synthetic TiO2 Nanoparticle Emission from Exterior Facades into the 

Aquatic Environment. Environmental Pollution v. 156, p. 233-239. [See PDF docket ID EPA-HQOPP-2008-110-0089] 

cc: Debra F. Edwards, Director, U.S. EPA Office of Pesticide Programs ( Joan Harrigan-Farrelly, 

Director, U.S. EPA Office of Pesticide Programs, Antimicrobials Division Betty Shackleford, 

Associate Director, U.S. EPA Office of Pesticide Programs, Antimicrobials Division Norm Cook, 

Branch Chief, Antimicrobials Division William Diamond, Director, Field and External Affairs Div. 

Donald Brady, Director, Environmental Fate and Effects Division Jack Housenger, Director, 

Biological and Economic Analysis Division Rick P. Keigwin, Jr., Director, Special Review and 

Reregistration Division Claire Gesalman, Branch Chief, Communication Services Branch, Field and 

External Affairs Div. Jennifer McLain, Branch Chief, Policy and Regulatory Services Br., Field and 

External Affairs Div. Ephraim King, Director, Office of Science and Technology Suzanne Schwartz, 

Acting Director, Office of Wetlands, Oceans, and Watersheds James A. Hanlon, Director, Office of 

Water, Office of Wastewater Management Alexis Strauss, Director, Water Division, USEPA Region 

IX Patti TenBrook, USEPA Region IX Debra Denton, USEPA Region IX Nan Singhasemanon, 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1054 

California Department of Pesticide Regulation Syed Ali, Division of Water Quality, State Water 

Resources Control Board Tom Mumley, Regional Water Quality Control Board, San Francisco Bay 

Diane Beaulaurier, Regional Water Quality Control Board, Central Valley Julie Chan, Regional Water 

Quality Control Board, San Diego Kelly D. Moran, Urban Pesticides Pollution Prevention Project 

Preeti Ghuman, Tri-TAC Jim Colston, Tri-TAC Chris Hornback, Senior Director, Regulatory 

Affairs, National Association of Clean Water Agencies 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 

Letter ID: 0073 

Comment ID: 26096 

Comment Code: 200000 

Comment: April 3, 2009 

Office of Pesticide Programs (OPP) Regulatory Public Docket (7502P) Environmental Protection 

Agency 1200 Pennsylvania Ave., N.W. Washington, DC 20460-0001 Attn: Docket ID Number 

EPA-HQ-OPP-2008-0110 

Submitted Electronically 

Docket No. EPA-HQ-OPP-2008-0110 Data Requirements for Antimicrobial Pesticides 

The Sanitation Districts of Los Angeles County (Districts) appreciate the opportunity to comment 

on the proposed changes to the data requirements for antimicrobial pesticides. As background, the 

Districts are a confederation of 24 independent special districts that serve the water pollution 

control and solid waste management needs of over five million people in Los Angeles County, 

California. Seventeen of the districts have collectively constructed an extensive regional sewerage 

system known as the Joint Outfall System (JOS), which conveys and treats approximately 450 

million gallons per day (MGD) of wastewater from 73 cities and unincorporated county areas. The 

JOS consists of seven treatment/water reclamation plants (WRPs) and 1,200 miles of large diameter 

trunk sewers that form a network connecting the treatment plants and ocean outfalls off Whites 

Point on the Palos Verdes Peninsula. The Districts also operate four WRPs in northern Los Angeles 

County serving the communities in and around the cities of Santa Clarita, Lancaster, and Palmdale. 

On an annual basis, over 50 MGD of reclaimed water is reused for applications including 

groundwater recharge, landscape irrigation, and industrial uses. The remainder is discharged to 

inland surface waters. The designated beneficial uses of the receiving waters to which the Districts' 

WRPs discharge are diverse and vary depending on location. These existing and potential use 

designations include groundwater recharge, water recreation, warm fresh water habitat, wildlife 

habitat, commercial and sport fishing, and rare, threatened or endangered species spawning, 

reproduction, and early development. Solid material removed during treatment is digested and 

dewatered. The resulting biosolids are either landfilled or beneficially reused. 

Commenter Name: Stephen Maguin 

Commenter Organization: Sanitation Districts of Los Angeles County 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1055 

Letter ID: 0073 

Comment ID: 26126 

Comment Code: 200000 

Comment: The Districts appreciates the opportunity to comment on the proposed rule. If you have 

any questions or require additional information, please contact Ms. Preeti Ghuman by phone at 

(562) 908-4288, extension 2904, or by email at pghuman@lacsd.org. 

 Very truly yours, 

Stephen R, Maguin Paul Martyn Head Industrial Waste 

 cc: Debra F. Edwards, Director, U.S. EPA Office of Pesticide Programs Joan Harrigan-Farrelly, 

Director, U.S. EPA Office of Pesticide Programs, Antimicrobials Division Betty Shackleford, 

Associate Director, U.S. EPA Office of Pesticide Programs, Antimicrobials Division Norm Cook, 

Branch Chief, Antimicrobials Division William Diamond, Director, Field and External Affairs 

Division Donald Brady, Director, Environmental Fate and Effects Division Jack Housenger, 

Director, Biological and Economic Analysis Division Rick P. Keigwin, Jr., Director, Special Review 

and Reregistration Division Claire Gesalman, Branch Chief, Communication Services Branch, Field 

and External Affairs Division Jennifer Mclain, Branch Chief, Policy and Regulatory Services Br., 

Field and External Affairs Division Ephraim King, Director, Office of Science and Technology 

Suzanne Schwartz, Acting Director, Office of Wetlands, Oceans, and Watersheds James A. Hanlon, 

Director, Office of Water, Office of Wastewater Management Alexis Strauss, Director, Water 

Division, USEPA Region IX Patti TenBrook, USEPA Region IX Debra Denton, USEPA Region 

IX Nan Singhasemanon, California Department of Pesticide Regulation Syed Ali, Division of Water 

Quality, State Water Resources Control Board Tom Mumley, Regional Water Quality Control 

Board, San Francisco Bay Diane Beaulaurier, Regional Water Quality Control Board, Central Valley 

Julie Chan, Regional Water Quality Control Board, San Diego Tracey Egoscoe, Regional Water 

Quality Control Board, Los Angeles Kelly D. Moran, Urban Pesticides Pollution Prevention Project 

Chris Hornback, Senior Director, Regulatory Affairs, National Association of Clean Water Agencies 

Commenter Name: Janice L. Dhonau 

Commenter Organization: Proctor & Gamble 

Letter ID: 0081 

Comment ID: 26156 

Comment Code: 200000 

Comment: COMMENTS OF PROCTER & GAMBLE ON EPA’S PROPOSED RULE 

REGARDING DATA REQUIREMENTS FOR ANTIMICROBIAL PESTICIDES 

73 FEDERAL REGISTER 59382 (October 8, 2008) 

EPA DOCKET NUMBER EPA-HQ-2008-0110 

Janice L. Dhonau Procter & Gamble 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1056 

5299 Spring Grove Ave. Cincinnati, OH 45217 513-627-7349 

April 6, 2009 

 COMMENTS OF PROCTER & GAMBLE ON EPA’S PROPOSED RULE REGARDING 

DATA REQUIREMENTS FOR ANTIMICROBIAL PESTICIDES 

73 FEDERAL REGISTER 59382 (October 8, 2008) EPA DOCKET NUMBER EPA-HQ-2008-

0110 

Background 

Procter & Gamble (P&G) appreciates the opportunity to comment on the Proposed Rule regarding 

Data Requirements for Antimicrobial Pesticides, 73 Federal Register 59382. P&G is the 

manufacturer and/or distributor of a number of antimicrobial pesticide products registered with 

EPA under FIFRA. In particular, we market both household and institutional disinfectants and 

sanitizers. 

Procter & Gamble is a member of both the American Chemistry Council’s Biocides Panel (the 

Panel) and the Consumer Specialty Product Association’s (CSPA) Antimicrobial Division. In 

addition to the attached comments, P&G is supportive of the comments submitted by both of these 

organizations. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26174 

Comment Code: 200000 

Comment: COMMENTS OF AMERICAN CHEMISTRY COUNCIL BIOCIDES PANEL ON 

EPA’S PROPOSED RULE REGARDING DATA REQUIREMENTS FOR ANTIMICROBIAL 

PESTICIDES 

73 FEDERAL REGISTER 59382 (October 8, 2008) 

EPA DOCKET NUMBER EPA-HQ-OPP-2008-0110 

Hasmukh C. Shah Ph.D. Manager Biocides Panel 703-741-5637 

Ted Waugh, Esq. Counsel, CPT Division 

 Of Counsel: Seth Goldberg, Esq. Steptoe & Johnson LLP 1330 Connecticut Avenue, NW 

Washington, D.C. 20036 

 April 6, 2009 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1057 

American Chemistry Council 1300 Wilson Boulevard Arlington, VA 22209 

TABLE OF CONTENTS 

LIST OF APPENDICES ..........................................................iii 

Executive Summary .............................................................1 

Introduction ..................................................................4 

I. EPA’s Proposed Subpart 158W does Not Provide Adequate Guidance to the Regulated 

Community ...........................................................8 

A. The Proposal Calls for Many Individual Consultations Rather than Establishing Applicable 

Regulatory Requirements .....8 

B. The Absence of Information on How EPA Plans to Conduct Risk Assessments and How it Plans 

to Use Data Generated by the Rule Is a Critical Shortcoming ..............................12 

II. Final Guidelines Are Not Available for Many Data Requirements ............16 

III. The Proposal Does Not Include Meaningful Tiering ........................20 

IV. Some Data Requirements for Antimicrobials Exceed those for Conventional Pesticides without 

Justification ................................25 

A. Environmental Fate Data Requirements ......................................27 

B. Non-Target Organism Data Requirements....................................................28 

C. Non-Target Plant Data Requirements ........................................28 

D. Toxicology Data Requirements ..............................................29 

V. The Proposal Does Not Recognize the Division of Jurisdiction between EPA and 

FDA..............................................31 

A. EPA’s Jurisdiction over Food Uses of Antimicrobials Is Limited by the Terms of the FFDCA 

.........................................31 

B. The Proposal Does Not Reflect the Statutory Division of Authority between FIFRA and 

FFDCA.............................................34 

C. The Proposal Should Clarify that Not All Food Uses Are Subject to Tolerance 

Requirements........................................................37 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1058 

D. EPA Has Not Identified a Clear Basis for Distinguishing Food Uses of Pesticides as Direct or 

Indirect ..........................................38 

VI. Potential Exposures to Antimicrobials Differ from Other Pesticides and Require Different 

Approaches..................................................39 

A. The Proposal Does Not Recognize that Environmental and Occupational Exposures to 

Antimicrobials Are Regulated under Other Statutes ...............42 

VII. Reliance upon Alternate Approaches Should Be Built into a Revised Proposal ...........................45 

A. SAR/QSAR ..................................................................47 

B. Recommendations ...........................................................49 

VIII. The Final Rule Should Apply Only to Applications Submitted After the Effective Date 

...........................................51 

A. Additional Data Would Be Required for Pending Applications ................52 

B. Additional PRIA Registration Fees Would Be Required for Pending 

Applications......................................................53 

IX. EPA’s Economic Analysis Underestimates the Cost of the Regulation and Its Impact on 

Registrants and Users................53 

A. EPA’s Economic Analysis Is Flawed because It Does Not Include Costs Incurred in Registration 

Review.........................................54 

B. The Costs of the Many Consultations Required by the Proposal Are Not Considered 

...................................................................56 

C. Agency Estimates of the Burdens on its Resources and its Planning to Meet Such Burdens Are 

Inadequate................57 

X. 158 W Should Include Procedures for Addressing Emerging Pathogens..........58 

XI. Current Part 158 Should Be Amended to Clarify Which Provisions Apply to 

Antimicrobials............................................59 

XII. EPA Must Submit the Antimicrobial Data Requirement Regulation for FIFRA Scientific 

Advisory Panel Review........................................60 

XIII. The Proposed Rule Does Not Comply with the Applicable Statutes and Executive Orders 

Governing Notice and Comment Rulemaking......................62 

A. Executive Order 12866......................................................62 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1059 

B. The Regulatory Flexibility Act (as amended by the Small Business Regulatory Enforcement 

Fairness Act)..........................................63 

C.Paperwork Reduction Act.....................................................65 

D. Executive Order 12988......................................................66 

Conclusion....................................................................66 

LIST OF APPENDICES 

Appendix Title 

A Scope of the Proposed Regulation B Proposed Use Categories and Patterns for Antimicrobial 

Pesticides C Proposed Data Requirements for Product Chemistry D Product Performance E 

Proposed Data Requirements for Toxicology F Proposed Data Requirements for Ecological Effects 

G Applicator and Post-Applicator Exposure H Proposed Data Requirements for Environmental 

Fate I Proposed Data Requirements for Residue Chemistry J Economic Analysis of Proposed U.S. 

EPA Biocide Data Requirements K The Proposed Rule 158W is Vague in These Sections L 

Background on the FDA Regulation of Food-Contact Sanitizing Solutions Under FFDCA and 

Estimation of Dietary Exposure M Potential Rulemakings of the Future for Endangered Species 

 Executive Summary 

The American Chemistry Council Biocides Panel ("the Panel") appreciates the opportunity to 

comment on the Proposal Regarding Data Requirements for Antimicrobial Pesticides, 73 Fed. Reg. 

59382 (October 8, 2008) ("the Proposal" or "the Proposed Rule'). The Panel is comprised of more 

than 50 companies that manufacture and formulate antimicrobial products. The Panel is among the 

principal associations of registrants in the antimicrobial industry. It represents active ingredient 

manufacturers and registrants of end use products that span a broad range of antimicrobial products 

and uses. Panel member companies are registrants of antimicrobials that are used in a broad array of 

applications, including: 

* preservatives for paints, coatings, fabrics, latex matrices, fuel, metalworking fluids and many other 

products; 

* water treatment chemicals; 

* antifoulants; 

* wood preservatives; and 

* disinfectants and sanitizers. 

The Panel is in a unique position to understand EPA’s Proposal and its potential impacts. The Panel 

also is well positioned to provide input on the Proposal from the perspective of the regulated 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1060 

community and has attempted to provide comprehensive comments on all of the issues raised by 

the Proposal. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26187 

Comment Code: 200000 

Comment: Introduction 

The American Chemistry Council Biocides Panel ("the Panel") appreciates the opportunity to 

comment on the Proposal Regarding Data Requirements for Antimicrobial Pesticides, 73 Fed. Reg. 

59382 (October 8, 2008) ("the Proposal" or "the Proposed Rule"). The Panel is comprised of more 

than 50 companies that manufacture and formulate antimicrobial products, and is among the 

principal associations of registrants in the antimicrobial industry. It represents active ingredient 

manufacturers and registrants of end use products that span a broad range of antimicrobial products 

and uses. These antimicrobials are essential to the control of pathogens in health care facilities, 

institutions, public spaces and homes, and the prevention and spread of infectious organisms. Panel 

member companies are registrants of antimicrobials that are used in a broad range of applications, 

including: 

* preservatives for paints, coatings, fabrics, latex matrices, fuel, metalworking fluids and many other 

products; * water treatment chemicals; * antifoulants; * wood preservatives; and * disinfectants and 

sanitizers. 

The Panel is in a unique position to understand EPA’s Proposal and its potential impacts. The Panel 

also is well positioned to provide input on the Proposal from the perspective of the entities that will 

be subject to the final regulation. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26674 

Comment Code: 200000 

Comment: Literature Cited 

Barton, H. A., T. P. Pastoor, K. Baetcke, J. E. Chambers, J. Diliberto, N. G. Dorrrer, J. H. Driver, 

C. E. Hastings, S. Iyengar, R. Krieger, B. Stahl, and C. Timchalk. 2006. The Acquisition and 

Application of Absorption, Distribution, Metabolism, and Excretion (ADME) Data in Agricultural 

Chemical Safety Assessments. Crit. Rev. Toxicol. 36: 9-35. 

Basketter, D. A., J. N. Bremmer, P. Buckley, M. E. Kammuller, T. Kawabata, I. Kimber, S. E. 

Loveless, S. Magda, D. A. Stringer, and H.-W. Vohr. 1995. Pathology Considerations for, and 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1061 

Subsequent Risk Assessment of, Chemicals Identified as Immuno-suppressive in Routine 

Toxicology. Food Chem. Toxicol. 33: 239-243. 

Batterhill, J. M. and R. J. Fielder. 1998. Mouse-specific Carcinogens: An Assessment of Hazard and 

Significance for Validation of Short-Term Carcinogenicity Bioassays in Transgenic Mice. Hum. Exp. 

Toxicol. 17: 193-205. 

Cohen, S. M. 2001. Alternative Models for Carcinogenicity Testing: Weight of Evidence Evaluations 

Across Models. Toxicol. Pathol. 29 (Suppl.): 80: 225-229. 

Cooper, R. L., J. C. Lamb, S. M. Barlow, K. Bentley, A. M. Brady, N. G. Doerrer, D. L. Eisenbrandt, 

P. A. Fenner-Crisp, R. N. Hines, L. F. H. Irvine, C. A. Kimmel, H. Koeter, A. A. Li, S. L. Makris, L. 

P. Sheets, G. J. A. Speijers, and K. E. Whitby. 2006. A Tiered Approach to Life Stages Testing for 

Agricultural Chemical Safety Assessment. Crit. Rev. Toxicol. 36: 69-98. 

Criswell, K. 2008. Unpublished Data from Presentation at Society of Toxicology Workshop on 

Contemporary Issues in Toxicology. Hemangiosarcoma in Rodents: Mode- of-Action Evaluation 

and Human Relevance. Arlington, VA. 

Doe, J. E., A. R. Boobis, A. Blacker, V. Dellarco, N. G. Doerrer, C. Franklin, J. I. Goodman, J. M. 

Kronenberg, R. Lewis, E. E. McConnell, T. Mercier, A. Moretto, C. Nolan, S. Padilla, W. Phang, R. 

Solecki. L. Tilbury, B. van Ravenzwaay, and D. C. Wolf. 2006. A Tiered Approach to Systemic 

Toxicity Testing for Agricultural Chemical Safety Assessment. Crit. Rev. Toxicol. 36: 37-68. 

Hermansky, S. J., D. A. Neptun, E. V. Weaver and B. Ballantyne. 1995. Clinical Pathology Changes 

Related to Cutaneous Irritaiton in the Fischer 344 Rat and New Zealand White Rabbit. J. Toxicol. 

Cut. & Ocular Toxicol. 14: 219-236. 

Hurtt, M. E., G. D. Cappon, and A. Browning. 2003. Proposal for a Tiered Approach to 

Developmental Toxicity Testing for Veterinary Pharmaceutical products for Food Producing 

Animals. Food Chem. Toxicol. 41: 611-619. 

Makris, S. L. 2004. Unpublished data. U. S. Environmental Protection Agency, Office of Pesticide 

Programs, Health Effects Division, Washington, DC. 

Monro, A. 1993. How Useful are Chronic (Life-Span) Toxicology Studies in Rodents in Identifying 

Pharmaceuticals that Pose a Carcinogenic Risk to Humans? Adverse Drug React. Toxicol. Rev. 12: 

5-34. 

Moser, V. C. and R. C. MacPhail. 1990. Comparative Sensitivity of Neurobehavioural Tests for 

Chemical Screening. Neurotoxicology 11: 335-344. 

Shelby, M. D. , K. T. Cain, C. V. Cornett, and W. M. Generoso. 1987. Acrylamide: Induction of 

Heritable Translocation in Male Mice. Environ. Mutagen. 9: 363-368. 

Tyl, R. W. and M. A. Friedman. 1997. Effects of Acrylamide on Rodent Reproductive Performance. 

Reprod. Toxicol. 17: 1-13. 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1062 

Usui, T., S. A. Griffiths, and C. E. Lumley. 1996. Industry Viewpoint: The Utility of the Mouse for 

the Assessment of the Carcinogenic Potential of Pharmaceuticals. In: Proceedings, Third 

International Conference on Harmonisation, Yokohama, 1995. F. D’Arcy and D. W. G. Harron, 

eds., pp. 279-284 Greystone Books, Antrim, N. Ireland. 

Van Oosterhout, J. P., J. W. Van der Laan, E. J. De Waal, K. Olejniczak, M. Hilgenfeld, V. Schmidt, 

and R. Bass. 1997. The Utility of Two rodent Species in Carcinogenic Risk Assessment of 

Pharmaceuticals in Europe. Regul. Toxicol. Pharmacol. 25: 6-17. 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26692 

Comment Code: 200000 

Comment: COMMENTS OF LANXESS CORPORATION ON EPA’S PROPOSED RULE 

REGARDING DATA REQUIREMENTS FOR ANTIMICROBIAL PESTICIDES 

73 FEDERAL REGISTER 59382 (October 8, 2008) 

EPA DOCKET NUMBER EPA-HQ-OPP-2008-0110 

April 6, 2009 

LANXESS CORPORATION 

111 RIDC PARK WEST DRIVE PITTSBURGH, PA 15275 

 TABLE OF CONTENTS 

LIST OF APPENDICES..........................................................iii Executive 

Summary.............................................................1 Introduction..................................................................4 I. 

EPA’s Proposed Subpart 158W does Not Provide Adequate Guidance to the Regulated 

Community...........................................................8 A. The Proposal Calls for Individual Consultation 

Rather than Establishing Applicable Regulatory Requirements............................................8 B. The 

Absence of Information on How EPA Plans to Conduct Risk Assessments and How it Plans to Use 

Data Generated by the Rule Is a Critical Shortcoming.....12 II. Final Guidelines Are Not Available 

for Numerous Data Requirements........16 III. The Proposal Does Not Include Meaningful 

Tiering........................20 IV. The Data Requirements for Antimicrobials Exceed those for 

Conventional Pesticides without Justification in Certain Specific Areas...................25 A. 

Environmental Fate Data Requirements......................................27 B. Non-Target Organism Data 

Requirements.....................................28 C. Non-Target Plants Data 

Requirements.......................................28 D. Toxicology Data 

Requirements..............................................29 V. The Proposal Does Not Recognize the Division of 

Jurisdiction between EPA and FDA..........................................................................31 A. EPA’s 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1063 

Jurisdiction over Food Uses of Antimicrobials Is Limited by the Terms of the 

FFDCA.................................................................31 B. The Proposal Does Not Reflect the Statutory 

Division of Authority between FIFRA and FFDCA..............................................................34 C. The 

Proposal Should Clarify that Not All Food Uses Are Subject to Tolerance 

Requirements.................................................................37 D. EPA Has Not Identified a Clear Basis for 

Distinguishing Food Uses of Pesticides as Direct or Indirect.............................................38 VI. 

Potential Exposures are Different for Antimicrobials and Require Different 

Approaches...................................................................39 A. The Proposal Does Not Recognize that 

Environmental and Occupational Exposures to Antimicrobials Is Significantly Reduced Due to the 

Manner in Which They are Regulated under Other Statutes...............................................43 B. 

Antimicrobials Perform Essential Functions that Must Be Considered in this 

Proposal.....................................................................45 VII. Reliance upon Alternate Approaches should 

be Built into this Proposal...48 A.SAR/QSAR...................................................................50 

B.Recommendations............................................................52 VIII. The Final Rule Should Apply Only 

to Applications Submitted After the Effective Date...............................................................54 A. 

Additional Data Would Be Required for Pending Applications................55 B. Additional PRIA 

Registration Fees Would Be Required for Pending 

Applications.................................................................56 IX. EPA’s Economic Analysis Underestimates 

the Cost of the Regulation and Its Impact on Registrants and Users..............................................57 A. 

The Costs of the Many Consultations Required by the Proposal Are Not 

Considered...................................................................59 B. Agency Estimates on its Burden and its 

Planning to Meet Such Burdens are Inadequate...................................................................60 X. 158 W 

Should Include Procedures for Addressing Emerging Pathogens.........61 XI. Current Part 158 should 

be Amended to Clarify Which Provisions Apply to 

Antimicrobials...............................................................62 XII. EPA Must Submit the Antimicrobial Data 

Requirement Regulation for FIFRA Scientific Advisory Panel Review.............................................63 

XIII. The Proposed Rule Does Not Comply with the Applicable Statutes and Executive Orders 

Governing Notice and Comment Rulemaking.....................65 A. Executive Order 

12866.....................................................65 B. The Regulatory Flexibility Act (as amended by the Small 

Business Regulatory Enforcement Fairness Act)....................................................66 C. Paperwork 

Reduction Act...................................................68 D. Executive Order 

12988.....................................................69 Conclusion...................................................................70 

LIST OF APPENDICES Appendix Title A Scope of the Proposed Regulation B Proposed Use 

Categories and Patterns for Antimicrobial Pesticides C Proposed Data Requirements for Product 

Chemistry D Product Performance E Proposed Data Requirements for Toxicology F Proposed 

Data Requirements for Ecological Effects G Applicator and Post-Applicator Exposure H Proposed 

Data Requirements for Environmental Fate I Proposed Data Requirements for Residue Chemistry J 

The Proposed Rule 158W is Vague in These Sections K Potential Rulemakings of the Future for 

Endangered Species 

 

Executive Summary 

LANXESS Corporation (LANXESS) appreciates the opportunity to comment on the Proposal 

Regarding Data Requirements for Antimicrobial Pesticides, 73 Fed. Reg. 59382 (October 8, 2008) 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1064 

("the Proposal" or "the Proposed Rule"). LANXESS is a chemical manufacture with over 60 

products registered with the EPA under FIFRA. LANXESS has both primary registration for active 

ingredients as well as formulations which span a broad range of antimicrobial products and uses. 

These antimicrobials are essential to the control of pathogens in health care facilities, institutions, 

public spaces and homes, and the prevention and spread of infectious organisms. LANXESS 

supplies products to companies in a broad range of applications, including: 

* preservatives for paints, coatings, fabrics, latex matrices, fuel, metalworking fluids and many other 

products; 

* water treatment chemicals; 

* antifoulants; 

* wood preservatives; and 

* disinfectants and sanitizers. 

LANXESS in a unique position to understand EPA’s Proposal and its potential impacts. LANXESS 

is well positioned to provide input on the Proposal from the perspective of the entities that will be 

subject to the final regulation. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26699 

Comment Code: 200000 

Comment: APPENDIX F COMMENTS ON PROPOSED DATA REQUIREMENTS FOR 

ECOLOGICAL EFFECTS 

I. Introduction.................................................1 

II. Comments on Proposed Rule (pages 59412-17; section 158.2240 and 158.2250), Data 

Requirements for Nontarget Organisms and Nontarget Plants ...........................................2 

III. Alternative Proposal for Ecological Effects Data Requirements...............................................7 

A. Proposed Alternative Section 158.2240 Data Requirements for Nontarget 

Organisms............................8 

B. Proposed Alternative Section 158.2250 Data Requirements for Nontarget Plant 

Protection....................12 

Commenter Name: Stanley Oslosky 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1065 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 26710 

Comment Code: 200000 

Comment: Introduction 

LANXESS Corporation ("LANXESS") appreciates the opportunity to comment on the Proposal 

Regarding Data Requirements for Antimicrobial Pesticides, 73 Fed. Reg. 59382 (October 8, 2008) 

("the Proposal" or "the Proposed Rule"). LANXESS is a chemical manufacture with over 60 

products registered with the EPA under FIFRA. LANXESS has both primary registration for active 

ingredients as well as formulations which span a broad range of antimicrobial products and uses. 

These antimicrobials are essential to the control of pathogens in health care facilities, institutions, 

public spaces and homes, and the prevention and spread of infectious organisms. LANXESS 

supplies products to companies in a broad range of applications, including: 

* preservatives for paints, coatings, fabrics, latex matrices, fuel, metalworking fluids and many other 

products; 

* water treatment chemicals; 

* antifoulants; 

* wood preservatives; and 

* disinfectants and sanitizers. 

LANXESS in a unique position to understand EPA’s Proposal and its potential impacts. LANXESS 

is also is well positioned to provide input on the Proposal from the perspective of the entities that 

will be subject to the final regulation. 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 26968 

Comment Code: 200000 

Comment: APPENDIX H 

COMMENTS ON PROPOSED DATA REQUIREMENTS FOR ENVIRONMENTAL FATE 

I.Introduction................................................................1 

II. Comments on Proposed Rule (pages 59406-12; section 158.2280), Data Requirements for 

Environmental Fate ........ .....................................................................2 
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Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1066 

A. Environmental Data Are Not Required for Indoor Uses for Other 

Pesticides....................................................................2 

B. Pesticide Disposal Is Not Regulated Under FIFRA ...........................3 

C. Testing Guidelines Are Not Available to Provide Guidance...................3 

D. Identification of Areas of Specific Concern ...............................3 

III. Alternative Approach for Environmental Fate Data Requirements............8 

A. Environmental Exposure Estimates Drive Data Needs by Tiered Testing .......8 

B. Specific Alternative Proposal for Environmental Fate Data Requirements ....9 

IV. Comments on the Use of the "Down the Drain" Screening Assessment and on the "Case Study" 

White Paper.....................13 

A. DtD Modeling is Site Specific.............................................14 

B. Is the Substance Suitable for DtD Modeling?...............................15 

C. Uncertainty in Application of DtD Model Results...........................15 

D. Summary Comments on the Use of DtD Modeling ..............................16 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27111 

Comment Code: 200000 

Comment: APPENDIX M 

COMMENTS on POTENTIAL FUTURE RULEMAKINGS REGARDING ENDANGERED 

SPECIES ACT COMPLIANCE 

Commenter Name: Hasmukh C. Shah 

Commenter Organization: American Chemistry Council Biocides Panel 

Letter ID: 0088 

Comment ID: 27174 

Comment Code: 200000 

Comment: APPENDIX I 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1067 

COMMENTS ON THE PROPOSED DATA REQUIREMENTS FOR RESIDUE CHEMISTRY 

I. Introduction...............................................................1 

II. Comments on the Proposed Rule.............................................2 

III. Alternative Proposal for Residue Chemistry Data Requirements.............4 

Commenter Name: Stanley Oslosky 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27281 

Comment Code: 200000 

Comment: APPENDIX E 

COMMENTS ON PROPOSED DATA REQUIREMENTS FOR TOXICOLOGY 

I. Introduction...............................................................1 II. Comments on Proposed Rule (page 59391-7, 

section 158.2230), Toxicology Data Requirements..................................................................3 A. 

Exposure Considerations:...................................................4 B. Comments on Acute Toxicity 

Requirements....................................4 C. Comments on Subchronic Toxicity 

Requirements...............................8 D. Comments on Chronic Toxicity and Carcinogenicity 

Requirements.............12 E. Comments on Developmental Toxicity and Reproduction 

Requirements..........15 F. Comments on the Mutagenicity Data Requirements............................18 G. 

Comments on Metabolism and Pharmacokinetics Data Requirements.............19 H. Comments on 

Companion Animal Safety Data Requirements.....................21 I. Comments on Dermal Penetration 

Data Requirements..........................21 J. Comments on Immunotoxicity Data 

Requirements..............................22 K. Overall Comments..........................................................23 III. 

Alternative Proposals for Toxicology Data Requirements..................23 A. Alternative Proposal 

1....................................................25 1. Tier I....................................................................25 2. Tier 

II...................................................................30 3. Tier III..................................................................31 B. 

Alternative Proposal 2....................................................33 1. Tiered Testing Options for Antimicrobial 

Pesticides.......................38 

I. Introduction 

This section of LANXESS Corporations’s comments addresses the toxicology data requirements. It 

should be read in conjunction with LANXESS’s main comment document, and points made there 

will not be repeated. Specifically, LANXESS provides comments on the conditions under which 

these data should be required, the assumptions that have been used to structure the requirements, 

and the standards applied to antimicrobials. In LANXESS’s view, the approach taken in the 

Proposal departs dramatically from EPA practice and commonly held toxicology concepts. 

Commenter Name: Stanley Oslosky 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1068 

Commenter Organization: Lanxess Corporation 

Letter ID: 0064 

Comment ID: 27366 

Comment Code: 200000 

Comment: Literature Cited 

Barton, H. A., T. P. Pastoor, K. Baetcke, J. E. Chambers, J. Diliberto, N. G. Dorrrer, J. H. Driver, 

C. E. Hastings, S. Iyengar, R. Krieger, B. Stahl, and C. Timchalk. 2006. The Acquisition and 

Application of Absorption, Distribution, Metabolism, and Excretion (ADME) Data in Agricultural 

Chemical Safety Assessments. Crit. Rev. Toxicol. 36: 9-35. 

Basketter, D. A., J. N. Bremmer, P. Buckley, M. E. Kammuller, T. Kawabata, I. Kimber, S. E. 

Loveless, S. Magda, D. A. Stringer, and H.-W. Vohr. 1995. Pathology Considerations for, and 

Subsequent Risk Assessment of, Chemicals Identified as Immuno-suppressive in Routine 

Toxicology. Food Chem. Toxicol. 33: 239-243. 

Batterhill, J. M. and R. J. Fielder. 1998. Mouse-specific Carcinogens: An Assessment of Hazard and 

Significance for Validation of Short-Term Carcinogenicity Bioassays in Transgenic Mice. Hum. Exp. 

Toxicol. 17: 193-205. 

Cohen, S. M. 2001. Alternative Models for Carcinogenicity Testing: Weight of Evidence Evaluations 

Across Models. Toxicol. Pathol. 29 (Suppl.): 80: 225-229. 

Cooper, R. L., J. C. Lamb, S. M. Barlow, K. Bentley, A. M. Brady, N. G. Doerrer, D. L. Eisenbrandt, 

P. A. Fenner-Crisp, R. N. Hines, L. F. H. Irvine, C. A. Kimmel, H. Koeter, A. A. Li, S. L. Makris, L. 

P. Sheets, G. J. A. Speijers, and K. E. Whitby. 2006. A Tiered Approach to Life Stages Testing for 

Agricultural Chemical Safety Assessment. Crit. Rev. Toxicol. 36: 69-98. 

Criswell, K. 2008. Unpublished Data from Presentation at Society of Toxicology Workshop on 

Contemporary Issues in Toxicology. Hemangiosarcoma in Rodents: Mode- of-Action Evaluation 

and Human Relevance. Arlington, VA. 

Doe, J. E., A. R. Boobis, A. Blacker, V. Dellarco, N. G. Doerrer, C. Franklin, J. I. Goodman, J. M. 

Kronenberg, R. Lewis, E. E. McConnell, T. Mercier, A. Moretto, C. Nolan, S. Padilla, W. Phang, R. 

Solecki. L. Tilbury, B. van Ravenzwaay, and D. C. Wolf. 2006. A Tiered Approach to Systemic 

Toxicity Testing for Agricultural Chemical Safety Assessment. Crit. Rev. Toxicol. 36: 37-68. 

Hermansky, S. J., D. A. Neptun, E. V. Weaver and B. Ballantyne. 1995. Clinical Pathology Changes 

Related to Cutaneous Irritaiton in the Fischer 344 Rat and New Zealand White Rabbit. J. Toxicol. 

Cut. & Ocular Toxicol. 14: 219-236. 

Hurtt, M. E., G. D. Cappon, and A. Browning. 2003. Proposal for a Tiered Approach to 

Developmental Toxicity Testing for Veterinary Pharmaceutical products for Food Producing 

Animals. Food Chem. Toxicol. 41: 611-619. 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Comments: 

Commenter Background; 

Introductions and Salutations (200) Page 1069 

Makris, S. L. 2004. Unpublished data. U. S. Environmental Protection Agency, Office of Pesticide 

Programs, Health Effects Division, Washington, DC. 

Monro, A. 1993. How Useful are Chronic (Life-Span) Toxicology Studies in Rodents in Identifying 

Pharmaceuticals that Pose a Carcinogenic Risk to Humans? Adverse Drug React. Toxicol. Rev. 12: 

5-34. 

Moser, V. C. and R. C. MacPhail. 1990. Comparative Sensitivity of Neurobehavioural Tests for 

Chemical Screening. Neurotoxicology 11: 335-344. 

Shelby, M. D. , K. T. Cain, C. V. Cornett, and W. M. Generoso. 1987. Acrylamide: Induction of 

Heritable Translocation in Male Mice. Environ. Mutagen. 9: 363-368. 

Tyl, R. W. and M. A. Friedman. 1997. Effects of Acrylamide on Rodent Reproductive Performance. 

Reprod. Toxicol. 17: 1-13. 

Usui, T., S. A. Griffiths, and C. E. Lumley. 1996. Industry Viewpoint: The Utility of the Mouse for 

the Assessment of the Carcinogenic Potential of Pharmaceuticals. In: Proceedings, Third 

International Conference on Harmonisation, Yokohama, 1995. F. D’Arcy and D. W. G. Harron, 

eds., pp. 279-284. Greystone Books, Antrim, N. Ireland. 

Van Oosterhout, J. P., J. W. Van der Laan, E. J. De Waal, K. Olejniczak, M. Hilgenfeld, V. Schmidt, 

and R. Bass. 1997. The Utility of Two rodent Species in Carcinogenic Risk Assessment of 

Pharmaceuticals in Europe. Regul. Toxicol. Pharmacol. 25: 6-17. 

.
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Appendix Page A-1 

Appendix 1 – List of Relevant EPA Comment Codes 

Comment 

Code Comment Topic Description Major Topic 

Area 

10000 General comments on the rule 

10 12000 Comments on other rules/issues (can include FIFRA, FFDCA, requirements, 

etc.) 

13000 Comments on clarity of the proposed data requirements for antimicrobial 

pesticides 

20000 Administrative comments on the rule 

20 

21000 Administrative process to develop this proposed rule (including outreach) 

22000 Relationship between proposed data requirements and EPA’s statutory 

determinations 

23000 Consistency of the proposed regulation with other regulations 

30000 Legal issues (such as implementation date, authority) 

30 

31000 Comments on EPA’s Authority 

32000 Harmonization with the Pesticide Management Regulatory Agency of Canada 

(PMRA) 

33000 Effective date for antimicrobials regarding future registrations of 

antimicrobials 

40000 Economic analysis 

40 

41000 General comments 

42100 Cost of Regulation 

42200 Cost of Registration/Re-registration 

42300 Agency Burden 

43000 Test costs analysis (including cost of consultations) 

50000 Pesticide use patterns 

50 

51000 General comments on the 12 use patterns 

52000 Specific use patterns 

52100 Agricultural 

52300 Commercial, institutional and industrial uses (such as metal working 

fluid/MWF) 

52400 Residential and public access 

52700 Materials preservative 

52800 Industrial processes and water systems 

52910 Wood preservatives 

52911 Swimming pools 

52912 Aquatic uses (such as ballast water) 

53000 Suggested additions, deletions or re-organization of use patterns 

60000 Product chemistry 60 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Appendix Page A-2 

Comment 

Code Comment Topic Description Major Topic 

Area 

70000 Product performance 70 

77000 Re-proposed definitions 

80000 Toxicology 

80 

81000 Acute toxicity studies 

82000 Subchronic studies 

83000 Chronic studies 

84000 Carcinogenicity 

85000 Prenatal development studies 

86000 Reproductive studies 

87000 Mutagenicity studies 

88000 Neurotoxicity studies (including comments on 90-day studies) 

89000 Immunotoxicity studies 

89100 Dermal Penetration studies 

89101 Metabolism and pharmacokinetics 

89110 Tiered approach for toxicology 

89111 

High exposure uses (including: food and drinking water; outdoor aquatic uses; 

indirect food uses with residues equal to or greater than 200 parts per billion 

(ppb); wood preservatives; metalworking fluids; swimming pools) 

89120 Toxicology data table (suggested additions, deletions, etc.) 

89130 Animal safety studies 

89140 Protocols on animal testing and animal testing alternatives 

89200 Commenter's Concept of Toxicology Data Requirements Table Revisions 

90000 Applicator/Handler (human exposure) 

90 

91000 Biological monitoring 

92000 Dermal exposure 

94000 Surrogate studies 

96000 Data and reporting requirements table for applicator/handler (suggested 

additions, deletions, etc.) 

97000 Ethical conduct of the research (Human Studies Review Board) 

98000 Commenter's Concept of Human Exposure Data Requirements Table 

Revisions 

100000 Post-application (human exposure) 

100 

101000 Soil residue dissipation studies 

102000 Indoor surface residue dissipation studies 

103000 Dermal exposure studies 

104000 Inhalation studies 

105000 Non-dietary exposure for residential uses 

107000 Commenter's Concept of Post-Application Exposure Data Requirements 

Table Revisions 
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Appendix Page A-3 

Comment 

Code Comment Topic Description Major Topic 

Area 

110000 Residue chemistry 

110 

111000 Direct food use 

112000 Indirect food use 

113000 Nature of the Residue in Plants 

115000 Residue Analytical Methods 

117000 Magnitude of Residue (MOR) Studies 

118000 Magnitude of Residue in Meat, Milk, Poultry, and Eggs 

119111 Food migration studies 

119115 Data and reporting requirements table for residue chemistry (suggested 

additions, deletions, etc.) 

119200 FDA regulation of FCSSS 

119300 Commenter's Concept of Residue Chemistry Data Requirements Table 

Revisions 

120000 Environmental risk assessment 

120 

121000 Factors considered in determining the high/low exposure groupings 

122000 High environmental exposure 

124000 Wood preservatives being regulated differently based on use patterns (land use 

vs. Aquatic use) 

125000 Letter from Environmental Working Group 125 

130000 Down-the-drain 

130 

132000 Biosolids 

134000 

Proposed approach for evaluating the potential impact of antimicrobial 

pesticide chemicals on waste water treatment plants and non-target organisms 

in receiving water bodies 

137000 Screening assessment on down-the-drain antimicrobial uses 

140000 Environmental fate 

140 

143000 Photodegradation in water study 

144000 Photodegradation in soil study 

145000 Activated sludge sorption isotherm study 

146000 Ready biodegradability study 

147000 Porous pot test 

148000 Modified activated sludge, respiration inhibition test 

149100 Aerobic soil metabolism study 

149110 Anaerobic soil metabolism study 

149120 Aerobic and anaerobic aquatic metabolism 

149130 Aquatic sediment studies 

149140 Monitoring of representative U.S. waters 

149150 Special leaching studies 

149160 Tiered approach to environmental fate studies 

149161 High exposure uses 
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Appendix Page A-4 

Comment 

Code Comment Topic Description Major Topic 

Area 

149170 Data and reporting requirements table for environmental fate (suggested 

additions, deletions, etc.) 

149180 Screening-level of fate assessments (three pronged-approach) 

149200 Commenter's Concept of Environmental Fate Data Requirements Table 

Revisions 

151000 Seedling emergence (Tier II – dose-response) 

150 

152000 Vegetative vigor (Tier II – dose-response) 

153000 Aquatic plant growth (Tier II – dose-response) 

154000 Terrestrial and aquatic field studies 

155000 Tiered approach to non-target plant protection studies 

157000 Commenter's Concept of Non-Target Plant Protection Data Requirements 

Table Revisions 

160000 Non-Target Organism Exposure 

160 

161000 Acute avian oral toxicity 

162000 Acute aquatic toxicity studies (LC50 fish and EC50 invertebrate) 

164000 Avian reproduction 

165000 Acute estuarine and marine study 

166000 Fish early life stage and aquatic invertebrate life-cycle study 

167000 Fish life cycle 

168000 Aquatic organisms, bioavailability, biomagnification toxicity tests 

169000 Simulated or actual field testing for aquatic organisms 

169100 Sediment testing 

169110 Honeybee protection 

169120 Tiered approach to non-target organism studies 

169122 Low exposure uses 

169130 Data and reporting requirements table for non-target organism (suggested 

additions, deletions, etc.) 

169200 Commenter’s Concept of Data Requirements Table for Non-Target 

Organisms 

170000 White Paper on the use of SAR and QSAR (structure-activityrelationship/SAR, and quantitative structure-activity-relationship/QSAR) 170 

180000 Endangered species 

180 

181000 Types of data that could be useful for conducting the assessment required 

182000 Projections of how long it would take to generate the needed data 

183000 Whether antimicrobial use sites can be adequately correlated with endangered 

species locations, and suggested methods for doing so 

190000 Guidelines 

190 

191000 Unavailability of draft/lack of final guidelines 

200000 Commenter Background; Introductions and Salutations 200 
EO 12866 Draft – Do Not Cite, Quote or Release during Review

Appendix Page A-5