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EO 12866_Antimicrobial Data Requirements_RIN 2070

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# Draft Comment Response

Document for the Data Requirements for

Antimicrobial Pesticides

(Categorized Public Comments)EO 12866 Draft – Do Not Cite, Quote or Release during ReviewEO 12866 Draft

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### Table of Contents

1. I NTRODUCTION AND O VERVIEW ........................................................................................... 1

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

EPA’s Categorization of Pu blic Comments and Document Organization ........................................ 1

2. M ASTER R ESPONSES BY T OPIC A REA ................................................................................... 5

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

General Comments on the Ru le (10) ............................................................................................. ........ 35

Administrative Comments on the Rule (20) ...................................................................................... ... 37

Legal Issues (30) ............................................................................................................. ........................... 41

Economic Analysis (40) ........................................................................................................ ................... 56

Antimicrobial Use Patterns (50) ............................................................................................... ............... 65

Product Chemistry (60) ........................................................................................................ .................... 73

Product Performance (70) ...................................................................................................... ................. 75

Toxicology (80) ............................................................................................................... ........................... 81
Applicator/Handler (Human Expo sure) (90) .................................................................................... 1 23

Post-application (Human Exposu re) (100) ....................................................................................... . 132

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

Environmental Risk Assessment (120) ........................................................................................... .... 167

Letter from Environmental Workin g Group (125)........................................................................... 172

Down-the-Drain (130)

.......................................................................................................... ................ 176

Environmental Fate (140) ...................................................................................................... ............... 197

Non-Target Plant Protection (150) ............................................................................................. ........ 218

Non-Target Organism Exposu re (160) ............................................................................................ ... 225

White Paper on the Use of SAR an d QSAR (170) ............................................................................ 250

Endangered Species (180) ...................................................................................................... ............... 254

Guidelines (190) .............................................................................................................. ....................... 257

3. V ERBATIM C OMMENTS AND R ESPONSE R EFERENCES BY T OPIC A REA .............................. 276

General Comments on the Ru le (10) ............................................................................................. ..... 276

Administrative Comments on the Rule (20) ...................................................................................... 322

Legal Issues (30) ............................................................................................................. ........................ 333

Economic Analysis (40) ........................................................................................................ ................ 370

Antimicrobial Use Patterns (50) ............................................................................................... ............ 433

Product Chemistry (60) ........................................................................................................ ................. 466

Product Performance (70) ...................................................................................................... .............. 472

Toxicology (80) ............................................................................................................... ........................ 504
Applicator/Handler (Human Expo sure) (90) .................................................................................... 6 84

Post-application (Human Exposu re) (100) ....................................................................................... . 708EO 12866 Draft

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Page ii Residue Chemistry (110) ....................................................................................................... ................ 730

Environmental Risk Assessment (120) ........................................................................................... .... 791

Letter from Environmental Workin g Group (125)........................................................................... 800

Down-the-Drain (130)

.......................................................................................................... ................ 810

Environmental Fate (140) ...................................................................................................... ............... 848

Non-Target Plant Protection (150) ............................................................................................. ........ 912

Non-Target Organism Exposu re (160) ............................................................................................ ... 920

White Paper on the Use of SAR an d QSAR (170) ............................................................................ 979

Endangered Species (180) ...................................................................................................... ............... 997

Guidelines (190) .............................................................................................................. ..................... 1008

Commenter Background; Introductions and Salutations (200) .................................................... 1034

A PPENDIX 1

– L IST OF R ELEVANT EPA C OMMENT C ODES ................................................... A-1



### List of Exhibits

Exhibit 1: Public Submissions Received in Resp onse to Data Requireme nts for Antimicrobial Pesticides; Proposed Rule ( 73 FR 59382) ....................................................................................... ......... 3EO 12866 Draft

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Introduction Page 1 

## 1. Introduction and Overview

Background

On October 8, 2008, EP A published in the Federal Register (73 FR 59382, docket number EPA– HQ–OPP–2008–0110) a proposed rule to revise and update the existing da ta requirem ents 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 submissi ons in the form of letters, e-mails, and/or postings to www.regulations.gov. All original public submissi ons can be found in the docket location, at www.regulations.gov, under Dock et 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, co rresponds to the Document ID EPA–HQ–OPP– 2008–0110–0067, that was submitted by the organi zation “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 testnote s test notes for each major topic area. Section 3 contains the correspon ding 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 signif icant commenter point or theme, which is then followed by EPA’s corresponding response. For ce rtain major topic areas, master responses are followed by testnotes test notes , including EPA’s proposed and final language for each of the

testnotes test notes (also numbered for the purposes of cross referencing with the verbatim comments).EO 12866 Draft

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Introduction Page 2 Section 3 provides verbatim public comments with corresponding response and t estnote test note cross referencing. These are first organized, as noted above, by major topic area, directly corresponding to 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 Test Note Cross Referencing For each verbatim comment, EPA has provided one or more cross references to relevant master response(s) or testnote test note (s). To find the cross refe renced master response or testnote test

note , readers can use the document Table of Contents to go to the referenced major topic area. For instance, all master responses and testnotes test notes for the major topic area of “Toxicology” are located in Section 2 and are numerically ordered wi th 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 processe d the comments and began to form ulate 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 C oncept of Toxicology Data Requirements Table Revisions”. Software search functions can also be used to find the referenced response or

testnote test note . Verbatim comments may have multiple cross references to responses and

testnotes test notes , 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; municipa lities and regulators; and non-governmental organizations and consumer groups. Exhibit 1, below, lists commenters by organization name and

Letter ID.EO 12866 Draft

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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 0090EO 12866 Draft

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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 Responsib le Medicine; Humane Society International; People for the Ethical Treatment of Animals 0104 (late comment)EO 12866 Draft

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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 repres ent four of the most common commen t themes that were submitted by stakeholders. EPA's responses are presented here, and cross referenced in the sections that follow.

Comment 1: Commenters stated th at 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 th e 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 de velopment 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 conven tional 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 thepreamble (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 en vironmental fateEO 12866 Draft

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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 discu ssed in the proposed rule (73 FR 59407), in recent ye ars 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 resu lt of being washed down the dr ain 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 instru mental in accomplis hing 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 three 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 test notes to the data requirements tables, and claimed that the proposed rule “leaves to o many standards and decisions to the sole discretion of EPA, creating uncertainty and, inevitab i l it y, inconsistency in regulatory decision making.” Too many determinations, the commenter asserted, are at “EPA’s discretion” because the proposal is vague without clear-cut cr iteria. 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 prov iding 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] orEO 12866 Draft

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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 asse ssment 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/risk assessment/guidance.htm). The Agen cy’s exposure and risk assessment procedures have been presented in numerous exposure and risk assessments for antimicrobial pesticides. EPA’s asse ssments reflect the best available data, and the state of the science of exposure
and risk assessment models, me thods, 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 extens ive description of the need for and use of submit ted studies (40 CFR 158.130). Additionally, as expl ained in the preamble to the an timicrobials 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 preser vatives.” (73 FR 59384)EO 12866 Draft

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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 inha lation 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 st andards. 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 rega rding 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 ‘foo d 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 expl ained in Unit XVI.A, misunderstands EPA’s authority under FIFRA and EPA’s practice as to antimicrobials since the passage of ARTCA. InEO 12866 Draft

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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 prov ided. 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 commen ter 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 test notes 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

testnotes test notes where consultation with the Agency is required or the phrase “as determined byEO 12866 Draft

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Master Responses: Most Common Comments Page 10 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. Te st 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 test notes cited by the commenter. EPA believes that the testnotes test notes contain adequate criteria for decision-making 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 test notes . 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 test notes 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 test notes meaningless as EPA would determine wh ether 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.

Consultation is a longstanding, commonly used and valuable process in EPA’s Pesticide Program. Applicants often meet with OPP staff on a pre-subm ission 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. EPAEO 12866 Draft

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Master Responses: Most Common Comments Page 11 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, suchmeetings 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 test notes 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 test note , “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 test notes for the final rule.

EPA has carefully reviewed each of the 37 testnotes test notes 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 test notes and resultant changes ar e 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” Consultation is voluntary, so this language has been

removed. 158.2220(a)(1) Product performance: Product performance requirement for all The Agency has not adequately stated the criteria for determining Under 40 CFR 158.75 EPA has the authority to require submission of dataEO 12866 Draft

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Master Responses: Most Common Comments Page 12 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.” whether product performance data for pesticide products registered or proposed for registrati on must be

submitted. Such information requires private consultation with the Agency. 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, t he 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 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 “IndirectEO 12866 Draft

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Master Responses: Most Common Comments Page 13 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

characterizati on (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 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 test

note . 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 nonrodent 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 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. Since the 1-year nonrodent (the dog) chronic study was not proposed (the study is no longer required), testnote test note
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,EO 12866 Draft

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Master Responses: Most Common Comments Page 14 study.” 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 test note 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 mayrequire a 1-year nonrodent study based on

consideration of

bioaccumulation and slow

elimination. The first

sentence of testnote test

note 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 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 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 test note
10 is attached to the 90- day non-rodent study as a

reminder that whereEO 12866 Draft

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Master Responses: Most Common Comments Page 15 determine if a longer duration dog toxicity study is needed.” 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 test note 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 second sentence

of testnote test note 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) T oxicology data: Test The Agency has not As a result of commentsEO 12866 Draft

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Master Responses: Most Common Comments Page 16 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 . . . ” 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. received, EPA removed proposed testnote test note

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 test note 12. The portion of testnote test

note 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.

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 Test note 17 to the requirement for a 90- day inhalation study in the

rat is meant as a costsaving 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 ofEO 12866 Draft

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Master Responses: Most Common Comments Page 17 study offers the applicantsan opportunity for costsaving. 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 test note : “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 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. The phrase “as determined by the Agency” has been

removed from the

testnote test note . 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 test note . The criteria speak for

themselves. 158.2230(e)(22) Toxicology data: Test

notes. “If the requirements for The Agency has not adequately stated the

criteria used to Under 40 CFR 158.75 EPA has the authority to require submission of dataEO 12866 Draft

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Master Responses: Most Common Comments Page 18 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 .” determine whether a subchronic 90-day oral study in the same species may be required. 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 study. 158.2230(e)(26) Toxicology data: Test

notes. “The developmental toxicity study in rodents may be

combined with the twogeneration reproduction study in rode nts 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 forthe 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 The Agency has not adequately stated the EPA believes that the concept of a protocol as aEO 12866 Draft

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Master Responses: Most Common Comments Page 19 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.” criteria for developing alternative proposed testing protocols. These required private negotiations are a procedure for the development of later

tests. basic description of a

standard of conduct forthe 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 consult with the Agency to determine other needed mutagenicity testing .” 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 test note 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 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 test note is intended to convey this message. EPA has revised

i t 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 reverseEO 12866 Draft

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Master Responses: Most Common Comments Page 20 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 test

note has been revised to

read as follows: Data are required when chronic or carcinogenicity studies are also required. 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

testno te test note 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, The Agency has not adequately stated how the Agency will

determine if the

transformation In response to comments,and as part of reevaluating these criteria, EPA determined to clarify

and revise the criteria forEO 12866 Draft

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Master Responses: Most Common Comments Page 21 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.” products of the parent compound are more toxic, persistent, bioaccumulative, or

have been shown to

cause adverse effects in mammalian or aquatic reproductive studies. 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

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 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).EO 12866 Draft

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Master Responses: Most Common Comments Page 22 with treated wood) or leachate residues (such as

from soil or water

contact with treated wood). 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

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. Proposed testnote test note 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 the

testnote test note have

been removed from

testnote test note 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 forthe 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. ConsultationEO 12866 Draft

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Master Responses: Most Common Comments Page 23 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 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 forthe 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. 158.2260(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.EO 12866 Draft

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Master Responses: Most Common Comments Page 24 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 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 useEO 12866 Draft

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Master Responses: Most Common Comments Page 25 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 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 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. This testnote test note was intended to indicate that these data may not be

needed for antimicrobials applied via a closed system. Based on comments requesting greater clarity in this

testnote, t estnote test note,

test note 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 exposureEO 12866 Draft

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Master Responses: Most Common Comments Page 26 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 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 adequateEO 12866 Draft

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Master Responses: Most Common Comments Page 27 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. 158.2270(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 test note

.

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 forthe 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 The Agency has not adequately stated the

criteria used to In response to comments,and as part of reevaluating these criteria,EO 12866 Draft

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Master Responses: Most Common Comments Page 28 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.” 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.” EPA determined to clarify

and revise the criteria for testing of transformation products by providing a single set 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 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)EO 12866 Draft

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Master Responses: Most Common Comments Page 29 contact with treated wood)or leachate residues (such as from

soil or water contact with treated wood). 158.2280(f)(12) Environmental fate:

Testnotes 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 forthe 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 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 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 test
note. Test note 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.EO 12866 Draft

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Master Responses: Most Common Comments Page 30 of studies conducted according to E11-97 is not 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

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 test
note. Test note 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 forthe 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 test note

.

158.2290(f)(23) Residue chemistry:

Test notes. “Migration

of residue data are required for antimicrobial The Agency has not adequately stated the

criteria used to

determine whether the EPA believes that the concept of a protocol as a basic description of a

standard of conduct forEO 12866 Draft

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Master Responses: Most Common Comments Page 31 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. ” protocol will be approved. These required private negotiations are a procedure for the development of later

tests. 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.

One commenter also asked that EPA “propose new 158W standards that enable registrants to determine default data requirements from readin g the regulation, without having to consult the Agency for many regist ration applications.” As st ated in the preamble [59386], testnote test note 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 da ta tables that are all “NR” and “R” and with no

testnotes test notes . 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 test notes describing the circumstances that information is needed provides significantly more information to the applicant.

However, EPA emphasizes that applicants ha ve 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 requir ements...are acceptable.” (§ 158.70(a )) Incomplete ap plications 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 test notes with such qualitative triggers. In such circumstances, the applicant using knowledge of the antimicrobial, an d 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 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 knowEO 12866 Draft

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Master Responses: Most Common Comments Page 32 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 21 st 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 Environmenta l Agents” (2006) and “Tox icity Testing in the 21 st 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 cell ular 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/pes ticides/science/test ing-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 combined with computer modeling to target animal testing to the specific data needed for human health and ecological risk assessments.EO 12866 Draft

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Master Responses: Most Common Comments Page 33 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 th e 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 te chnologies 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 propo sed rule in October 2008, OPP an nounced its stra tegic 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.

These advances will be incorporated within a risk assessment framework of problem formulation, hazard, dose response, exposure assessment, and risk characterization to support pesticideEO 12866 Draft

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Master Responses: Most Common Comments Page 34 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 real ize 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 21 st 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 public ly 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 k ey 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 is available at http://www.epa.gov/scipoly/sap/m eetings/2011/052411meeting.html#frn.EO 12866 Draft

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Master Responses: General Comments on the Rule (10) Page 35 

### 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 dist ributed 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 coatin gs, 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.EO 12866 Draft

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Master Responses: General Comments on the Rule (10) Page 36 Response 10.2: The Agency agrees with the commenter. It is important to have data of sufficient quality and completeness fo r risk assessment purposes. As discus sed 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 unde r the 875 series for Oc cupational and Residential Exposure Test Guidelines. There is also a Directions for Use gu ideline 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.EO 12866 Draft

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Master Responses: Administrative Comments on the Rule Section (20) Page 37 

### 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 commen ter 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 pro posed 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 comment er. On June 3, 1997, EPA presented an early version of the part 158W proposal in an open meeting to the Scient ific 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 pa rt 158 subpart W (also referred to as 158W), EPA requested that the SAP waive its review of the about

- to

- be

- draft proposed 158W because there were

no new scientific issues. The SAP waived its review of the draft proposed 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 EPA submitted the draft

final rule . FIFRA section 25 requires EPA to give to the SAP at least 60 days to review proposed regulations and 30 days to revi ew final regulations. However, on March 3, 2011, asking the SAP can determine to waive its review during statutory time periods. . The SAP waived its review on April 13, 2011, noting that the “final rule does not contain sc ientific issues that the Panel has not previously

considered.”

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.EO 12866 Draft

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Master Responses: Administrative Comments on the Rule Section (20) Page 38 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 to complete an assessment of an an timicrobial 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 test notes 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 stud ies 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 institutiona l 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.EO 12866 Draft

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Master Responses: Administrative Comments on the Rule Section (20) Page 39 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 considerations of the use of common data acceptab ility requirements, predicti ve 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 stan dards 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 m eeting 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 effe cts assessment methodologies. A scoping document from that meeting is available at: http://www.epa.gov/oppefed1/cwa_fi fra_effects_methodology/scope.html

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

In the Federal Register of November 1, 2010, EP A announced a national st akeholders meeting for December 1, 2010, concerning CWA and FIFRA Co mmon 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 assessment s, 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 acti ve ingredients from pesticide registrants. Under FIFRA, OPP can require studies on pesticide active ingredient(s) from pest icide registrants when the data are needed for an

OPP risk assessment and re gulatory 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 mindEO 12866 Draft

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Master Responses: Administrative Comments on the Rule Section (20) Page 40 when making this comment, but FIFRA does not include such a provision regarding mitigation

under the Clean Water Act.

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 duri ng 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 certif ied 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 co nducted an economic an alysis 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 comp liance 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 publ ished in October 2002. Th is is a policy and pr ocedural guidance for ensuring and maximizing the quality of the information disseminated by EPA. Proposed 158W was developed using these processes and procedures.EO 12866 Draft

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Master Responses: Lega l Issues Section (30) Page 41 

### 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 comp ares the current proc ess 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 forEO 12866 Draft

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Master Responses: Lega l Issues Section (30) Page 42 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 haza rdous 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 treatm ent works for the improvement of wastewater treatment, and maintaining the integrity of wetlands. EPA requires municipal wastewater treatmentplants 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 ap proval for a food additive.EO 12866 Draft

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Master Responses: Lega l Issues Section (30) Page 43 Response 30.6: If an antimicrobial is both a FIFRA “pesticide” and excluded from the definition of a “pesticide chemical” under FFD CA section 408, then both EPA and FDA would have regulatory authority over that substance – EPA under FIFR A, 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 theresponse 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 conclusion s about a pesticide. Afte r 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, an d that EPA also requires Publicly Owned Treatment Works (POTWs) to regula rly 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.”EO 12866 Draft

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Master Responses: Lega l Issues Section (30) Page 44 Through its pesticide registration process, EPA/OPP ev aluates 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 flushe s released down-the-drain, and th at 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 th e proposed screening level assessmen t 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 pe rformed differen tly than chemical-specific analyses used for required aquatic toxicity studie s 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) sample s of the permitted effluent in a minimum of five dilution (the effluent is diluted with the same water used as the control sample)EO 12866 Draft

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Master Responses: Lega l Issues Section (30) Page 45 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 comm enter 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, nati onal data requirements are tied to national use patterns and environmental and ecol ogical 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 re quiring 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 PeriodicEO 12866 Draft

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Master Responses: Lega l Issues Section (30) Page 46 Registration Review. Another commenter noted that EPA has provided reasonable notice to 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 determin ation 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 Agen cy’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 in 2008 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 t hree additional data requireme nts 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 slu dge units , and nature of the residue on surfaces.

Based on comments received, two other “new” data requirements are also being added that serve as alternatives to tests that were proposed (and are now being finalized): Simulation tests to assess the biodegradability of chemicals in discharged wastewater, and simulation test – aerobic sewage treatment: activated sludge units. Similarly, also based on comments, one ”new” data requirement, the nature of the residue on surfaces, is being added as a more definitive trigger or screen for determining whether one of the studies that was proposed – the migration study – must be

conducted.

EPA recognizes that during earl y 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 appl ication packages that ma y not have all of the newly required data in appropriate cases supported by adequate justification. This early implementation period could extend up to two 2 years post-promulgation for situations in which a more time-intensive new study is missing but co uld be less for other situ ations. 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 orEO 12866 Draft

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Master Responses: Lega l Issues Section (30) Page 47 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, th en 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 factors such as the required studies involved an d 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 re gistration fees. In that case, additiona l 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) woul d be required for antimicr obials 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 ballas t 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 withEO 12866 Draft

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Master Responses: Lega l Issues Section (30) Page 48 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. 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 sp ecified 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 PRIAcategories 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, an tifoulant paints/coatings, industrial processes and water circulating systems, aquatic areas, and others . Water circulating system s 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 intakeEO 12866 Draft

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Master Responses: Lega l Issues Section (30) Page 49 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 direct ly to surface water may require an NPDES permit. As discussed in the preamble to the proposed ru le (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 antimicr obial down-the-drain use. Before registering a new 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 FI FRA 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 “unreasonabl e adverse effects” standard for antimicrobial pesticides. This explanation specifically addressed EPA’s authority to require dietary risk information on antimicrobial pesticid es which are governed under the FFD CA under section 409 and not section 408. In this Response to Comments document, EPA has provided a further explan ation 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 Technica l Correction Act (ARTCA), Public Law 105-324, in 1998. ARTCA divided FFDCA jurisd iction 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 theEO 12866 Draft

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Master Responses: Lega l Issues Section (30) Page 50 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 FF DCA 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 additive s. 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 a “pesticide” in FIFRA by deleting the language restricting pesticide chemicals to those pesticides used in the production of raw agricultural co mmodities. [P.L 104-170 § 402, 110 Stat. 1489, 1513 (1996)]. Not only did Congress consol idate 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 pest icides resulting in residues in food. [7 U.S.C. § 136(bb)(2)].

In 1998 in the ARTCA, Congress mo dified slightly its FFDCA decisi on to consolidat e 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 subs tances from the coverage of the definition [ See 21 U.S.C. 321(q)]. More specifically , with certain qualif ications, 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 excepte d substances from the definition of pesticide chemical th at 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 subs tances 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 unchange d 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 rema ined FIFRA “pesticides”) while FDA re-acquired FFDCA jurisdiction over them under FFDCA sect ion 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 wi th the safety standard in FFDCA section 408. After all, FIFRAEO 12866 Draft

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Master Responses: Lega l Issues Section (30) Page 51 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 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 rema rks into the Congressional Record. [144 Cong. Rec. 27678-27679 (1998)]. Representative Bliley emph asized that the ARTC A 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 woul d not be changed.” (Id.). To remo ve 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 wh ether 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 FI FRA 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 followi ng the enactment of ARTCA of 1998.” [R2C Ref. 1]. For example, in an August, 2000, letter to EP A [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 unde r section 408 of the Federal Fo od, Drug, and Cosmetic Act (“FFDCA”), 21 U.S.C. § 321 et seq., [sic] before appr oving 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 sa me statute. . . . EPA has implem ented this policy of duplicativeEO 12866 Draft

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Master Responses: Lega l Issues Section (30) Page 52 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 Antimicr obial Regulation Technical Correctio ns Act (ARTCA) of 1998, Pub. L. 105-324 (1998). . . . [T]his interpreta tion is inconsistent with the pl ain 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 registration amendments to add us es covered by clearances issu ed 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 regula te antimicrobial food ad ditive 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

1 This is a longstanding interpretation of EPA in this se nse: 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 pe sticide 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 pestic ide 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.EO 12866 Draft

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Master Responses: Lega l Issues Section (30) Page 53 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 judg ments under the different regulatory

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 fa ct, Albright & Wilson America’s product became a rally ing point for the passage of AR TCA. [See 144 Cong. Rec. 24282 (1998) (statement of Rep. Bliley) (“one of the prod ucts 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 Amer icas’ under FFDCA section 408 but Al bright & 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). (Note this is the same as Ref. 3 to the final rule.)

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 November 3, 2000). (Note this is the same as Ref. 5 to the final rule.)EO 12866 Draft

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Master Responses: Lega l Issues Section (30) Page 54 R2C Ref. 3: McMahon, T; (D273502) (October 15, 2002); Sodium chlorite: ri sk assessment for use in swimming pools.

R2C Ref. 4: McMahon, T; (D272375 and D272376) (Jan uary 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 Thre shold of Regulation request for use of Chorine Dioxide on stored potatoes

R2C Ref. 6: Reregistration Eligibility Decision for Polyhexamethylene biguanidine (PHMD). September 30, 2004. Case 3122. See regulati ons.gov, Docket EPA-HQ-OPP-2004-0305. Also available at http://www.epa.go v/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 fo r Halohydantoins. Septembe r 2007. Case 3055. See regulations.gov, Docket EPA-HQ-O PP-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 regulati ons.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 regulati ons.gov, docket EPA-HQ-OPP-2006-0339. Also available at http://www.epa.go v/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) (Note this is the same as Ref. 6 to the final rule.)

R2C Ref. 12: Office of Pesticide Programs, U.S. EPA, Threshold of Regulation Po licy – Deciding Whether

A Pesticide With A Food Use Pattern Needs A Tolerance 12 (October 18, 1999) available at http://www.epa.gov/fedrgstr/EPA-P EST/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). (Note this is the same as Ref. 7 to the final rule.)

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). (Note this is the same as Ref. 11 to the final rule.)

R2C Ref. 15: Comments of Chemical Manufacturers Association’s Biocides Panel On EPA’s September 17, 1999 Proposed Rule on Registration Requirements for Antimicrobial PesticideEO 12866 Draft

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Master Responses: Lega l Issues Section (30) Page 55 Products and Other Pesticide Regulatory Ch anges for Codification (January 18, 2000) (Note this is the same as Ref. 4 to the final rule.)

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). (Note this is the same as Ref. 8 to the final rule.)

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). (Note this is the same as Ref. 9 to the final rule.)

R2C Ref. 18: American Chemistry Council, Biocides Panel, “EPA/FDA Jurisdiction for Food

Contact Antimicrobials” Vol. 2 Tab 7 (July 17, 2003) Biocides Pane l Comments on The Preliminary Risk Assessment for 1,4-Bis(bromoacetox y)-2-butene (BBAB) , (August 6, 2001). (Note this is the same as Ref. 10 to the final rule.)

R2C Ref. 19: McMahon, T; (D262970) (December 20, 2000); “Fit” Fruit and Vegetable Wash: Request for dietary risk assessment.EO 12866 Draft

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Master Responses: Economic Analysis Section (40) Page 56 

### 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 require ment 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:

C Dur = T D × P Dur

R

ur = ∑ C Dur Industry Cost of th e data requirements = ∑ (R

ur × N

ur )

whereEO 12866 Draft

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Master Responses: Economic Analysis Section (40) Page 57 C Dur = the expected cost of data requirement D on use pattern u for registration type r.

T D = the unit test cost of data requirement D.

P Dur = the test probability of data requirement D for use pattern u and registration type r.

R

ur = the expected cost of a registration action for use pattern u and registration type r. ∑ C Dur = the sum of the expected costs of all data requirements for use pattern u and registration

type r.

N

ur = the number of registrations for the industry on use pattern u for registration type r. ∑ (R

ur × N

ur ) = 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, supplement ed 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 cl aims to have based the test pr obabilities used to make their estimates on a sample of 29 regist ration review cases (not new re gistrations) 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 requirementsEO 12866 Draft

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Master Responses: Economic Analysis Section (40) Page 58 costs and incremental costs using the same unit test costs and test probabilit ies 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 Requiremen t 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 pr obabilities 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.EO 12866 Draft

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Master Responses: Economic Analysis Section (40) Page 59 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 baseli ne, 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 estima tes. EPA obtained new estimates fo r 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 becaus e 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.EO 12866 Draft

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Master Responses: Economic Analysis Section (40) Page 60 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 inve rtebrates (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 invertebrate s 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 $1,500,000EO 12866 Draft

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Master Responses: Economic Analysis Section (40) Page 61 Comment 40.2: A commenter noted that EPA’s economic analysis does not include the benefits that antimicrobials provide to individuals and indu stry, 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 th e docket at http://www.regulations.gov for this rule and titl ed “Economic Analysis of the Proposed Data Requirements for Antimicrobial Pesticides,” EP A discussed the benefits associated with antimicrobial pesticide use. EPA agrees that increasing the cost of new registrations may result in fewer new registrations. Regi strants 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, te sts 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 registrati ons and increased registra tion 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 pl aying field," and that a SBREFA analysis should

have been conducted.EO 12866 Draft

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Master Responses: Economic Analysis Section (40) Page 62 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 fo r the proposed 158W rule. An impact would not be considered significan t if fewer than 100 small businesses ar e 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) 128 66. 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 revi ew 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 change s 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.EO 12866 Draft

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Master Responses: Economic Analysis Section (40) Page 63 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 Agen cy’s economic analysis of the pr oposed 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 part 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 bu rden is estimated in Section 9 10 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 Registrati on Data ICR (OMB Control No. 2070-0 060), 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.EO 12866 Draft

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Master Responses: Economic Analysis Section (40) Page 64 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 prohibitio ns 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.EO 12866 Draft

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Master Responses: Antimicrobial Use Patterns Section (50) Page 65 

### 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 so me cases, that is best accomplis hed 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.EO 12866 Draft

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Master Responses: Antimicrobial Use Patterns Section (50) Page 66 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 final Environmental Fate Data Requirements Table and the non

- target organisms Nontarget Organism Data Requirements Table from “CR” to “R.” However, under the commenter’s six suggested use patterns, wood preser vatives 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 commente r thought that the 1997 document on us e 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 [593 90], 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.EO 12866 Draft

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Master Responses: Antimicrobial Use Patterns Section (50) Page 67 Comment 50.3: A commenter asked how does the Agency distinguish between a treated article and

the chemical used to treat the ar ticle for the pur poses 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 sp ecified. “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 coatin g, or wood products treated to protect the wood against insect or fungus infestation), if the pesticid e 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 ru le [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 ofEO 12866 Draft

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Master Responses: Antimicrobial Use Patterns Section (50) Page 68 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 both the land or and 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 final Environmental Fate Data Requirements Table and the Nontarget Organism Data Requirements Table were revised.

For the environmental fate final Environmental Fate Data Requirements 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 final Nontarget Organism Data Requirements 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.EO 12866 Draft

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Master Responses: Antimicrobial Use Patterns Section (50) Page 69 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 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 in direct 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 codifi ed in the final rule

include certain environmental fate and non

- target nontarget 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 definiti on 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.EO 12866 Draft

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Master Responses: Antimicrobial Use Patterns Section (50) Page 70 Comment 50.9: A commenter argued that EPA’s pr oposed 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 gutt ers, 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 warr anted, in a future update of th e 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 to gether exposure modelers, fate

scientists and risk assessors from state and Fede ral 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; theEO 12866 Draft

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Master Responses: Antimicrobial Use Patterns Section (50) Page 71 variability of urban scenarios that include not only sites exposed by runoff across hard surfaces such as pavement, but also sites exposed through runoff fr om large systems such as turfgrass; and the use 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 th at 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]. Inst ead 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 F ood Uses (<200 ppb); Swimmers, Aquatic Areas, Wood Preservatives, Metal Working Fluids; and All Other Nonfood Uses.EO 12866 Draft

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Master Responses: Antimicrobial Use Patterns Section (50) Page 72 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 40

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 regulati ons on false and misleading st atements, 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.EO 12866 Draft

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Master Responses: Product Chemistry Section (60) Page 73 

### 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 ch emicals 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 comm ent. 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 test note clearly refers th e reader to 40 CFR 158.345, entitled “Preli minary Analysis,” which contains more information on when testing is needed. This significant amount of information could not be

accommodated in a testnote test note

.

Comment 60.4: EPA should remo ve 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.EO 12866 Draft

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Master Responses: Product Chemistry Section (60) Page 74 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 effe cts risk assessments.

Comment 60.5: A commenter asserted that test note 23 to the tabl e 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 Test note 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 test note 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 test note 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 me thods for water solubility are provided in

Guidelines 830.7840 and 830.7860. The Agency has historically required da ta 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.EO 12866 Draft

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Master Responses: Product Performance Section (70) Page 75 

### 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 an d unavailable. What has happened to the new 810 guidelines? They were promised for publication in 2009.

Response 70.1: Four of the 810 series guidel ines (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 Notice of Availability of the final guidelines was published on March 16, 2012 (77 FR 15750). The guidelines for air, water an d textiles (810.2400, 810.2500, and 810.2600) will be published for public comment prior to the finalization of on September 15, 2011 (76 FR 57031). EPA announced the new antimicrobial s data requirements rule. [update] availability of these three final guidelines in the Federal Register of June 27, 2012 (77 FR 38280).

Comment 70.2: : Several commenters shared their belief that EPA was seeking 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’ at this time. Another commenter asked how the product performance sect ion of the proposed rule coul d 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 guidel ines (810.2000, 810.2100, 810.2200, and
810.2300 for sterilants, disi nfectants and sanitizers) were published in the Federal Register for public c omment on January 27, 2010 (75 FR 4308)

. These for public comment in the Federal Register of January 27, 2010 (75 FR 4308). The Notice of Availability of th e final guidelines was published on March 16, 2012 (77 FR 15750). Thr ee additional product pe rformance guidelines (810.2400, 810.2500, and 810.2600) published for pu blic comment on Sept ember 15, 2011 (76 FR 57031). EPA announced the avai lability of these three final guidelines in the Federal Register of June 27, 2012 (77 FR 38280).

The 810 guidelines represent the Agency’s current recommendations for conducting product performance studies to support antimicrobial pesticide label claims. That The 2010 Notice of Availability announced that the 810 guidelines series would be in corporated into the final data requirements regulation: As announce d, in this final rule EPA is replacing the 91 series designations proposed in the part 158, subpart W product pe rformance table with th e 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 Pe rformance Data Requirements Table. Three additional product performance guidelines ( 810.2400, 810.2500, and 810.2600) should be published forEO 12866 Draft

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Master Responses: Product Performance Section (70) Page 76 comment in a timeframe similar to that of publication of the final rule for Antimicrobial Data Requirements.

See response to comment 191.1 fo r a discussion on guidelines.

Comment 70.3: The 810 guidelin e development should be a high priority for EPA.

Response 70.3: The Agency agrees and is working to complete the guidelines.

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 in formation that was not previously av ailable 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.EO 12866 Draft

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Master Responses: Product Performance Section (70) Page 77 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 draf t 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 dr aft guideline 810.2000. (See re gulations.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 proposed for both part 158W and the 810 Guidelines. The definitions for sanitizer and disinfectant

wi ll be the same in both part 158W and in the 810 Guidelin es

.

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 su bstance, or mixture of

substances that reduces the bacteria l population in the inanimate environment by significant
numbers, (e.g., 3 log 10 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.”

EPA notes that a 3 log 10 reduction is the minimum log reduction needed to make a non-food contact surface sanitizing label claim, and is considered a significant reduction. This log reduction has been in place for over 40 years, is well accepted scientifically, and is listed as such in the guidance

document for non-food contact sanitizers.

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 de finitions 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 clai ms also make sterilant

claims.EO 12866 Draft

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Master Responses: Product Performance Section (70) Page 78 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 Agen cy 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 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 p ost has posted on the Antimicrobials Division website the parts of the 91 Guideline series that apply to testing of non-public health products. Althou gh, 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 referenc es in the 1982 guidelines are to the ol der 91 series, which is being replaced by the 810 series. To assist readers, EPA will has also post ed a cross-walk table so readers can locate the applicable secti on of the 810 Guidelines . For information, see http://www.epa.gov/oppad001/non-public-health.html

.

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 stan dard 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.EO 12866 Draft

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Master Responses: Product Performance Section (70) Page 79 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 ar e different from the definitions being fina lized 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.

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 appropriatenessof 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.EO 12866 Draft

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Master Responses: Product Performance Section (70) Page 80 (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.

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 th e Codex Alimentarius Co mmission. 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 Test note 1 from the conventional product performance data requirements table in 40 CFR 158.640] relevant to antimicrobial pesticides” be included as a testnot e test note to the antimicrobials product performance table.

Response 70.17: EPA has includ ed the relevant information in §158.2220(a) (1) and (2).EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 81 

### Toxicology (80)

Master Responses and Testnotes Test Notes for the Toxicology Section

Please note that EPA responses and testnotes test notes 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 “...ev ery disciplinary area and requirement has been reconsidered and many have been revised in prac tice.” 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 re gulatory 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

time frame of 2 to 3 years for development. Once a TTC

- based approach has been developed and piloted, then EPA would cons ider when/if the approach should be included in 158W Development and peer review of a TTC approach for antimicrobials is expected to occur over the next 1 to 2 years. Based on expert peer review and public comment, the Agency will make decisions regarding implementation

.

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 test note 3 to the toxicity table for conventional pesticides), and 40 CFR 161.340 ( testnote test note 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 test note 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 sens itization 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 concentrationEO 12866 Draft

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Master Responses: Toxicology Section (80) Page 82 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 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 test notes 3 and 5 to the Toxicology Table are contradictory.

Response 80.5: EPA does not believe that proposed testnotes test notes 3 and 5 are contradictory.

Testnote Test note 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 test note test note 3, then those four acute studies would be waived. Proposed testnote test note 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 test note 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 pesticid e label, thus mitigating against dermal contact.

Comment 80.6: A commenter thought that proposed testnote test note 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 Test note 6?

Response 80.6: Proposed testnote test note 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 test note 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 test note 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.EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 83 As a point of clarification, EPA is adding a new testnote test note to the final Toxicology Data Requirements Table in § 158.2230(g) to clarify that the neur otoxicity 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 neurotoxicity screen, then the acute neurotoxicity study in the rat would be required. The new

testnote test note 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 test note will become testnote test note 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 (FIF RA) and the Federal Food, Drug, and Cosmetic Act (FFDCA), and, similar to pesticide active ingred ients, 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 th e appropriate tolerances or tolerance exempti ons as established in 40 CFR part 180. Ne w inert ingredients ar e evaluated using a process that considers both hazard potential (i.e. toxicity) as well as exposure potential and are subjected to the same risk assessm ent 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 to xicological 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.EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 84 As required under FFDCA section 408(p), EPA has developed the Endocrin e 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. 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 test note 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 someproducts to be diluted before being used. The use-dilution testing is in addition to the asformulated-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 test note 2 to make this clearer.

Comment 80.12: Does Testnote Test note 2 to the Toxicity Table also apply to acute inhalation

studies?EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 85 Response 80.12: Yes, proposed testnote test note 2 specifically states “For the six acute toxicity studies...”, so the acute inhalation study is included in that grouping. EPA will add testnote test note
2 to the acute inhalati on study requirement.

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 test note 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 test note 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 non-irritating 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 test note 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 test note
and decided to remove testnote test note 11 from proposed 158W. Proposed testnote test note 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 test note 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/non-food approach, testnote test note (11ii) is no longer needed. In the final toxicity Toxicology Data Requirements Table, the data required for an indirect food-use is specified directly and a trigger is not needed.

Proposed testnote test note 12 specifies three triggers that would require the performance of a 21/28-day dermal study. EPA has also re-evaluated testnote test note 12 and agrees that the phrasesEO 12866 Draft

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Master Responses: Toxicology Section (80) Page 86 “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 all of the following criteria are met: 1) the intended use of the antimicrobial pesticide product is expected to result in dermal human exposure to the product , and ; (2) data from a subchronic 90-day dermal toxicity study are not available ; and (3) the 90-day dermal toxicity study has not been triggered (the third proposed trigger).

Comment 80.17: The antimicrobial data requirem ents 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 conven tional pesticide chemicals a 90-day oral study is required for non-food uses only if oral exposure could occur. (see testnote test note 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 test note 38 to clarify that an oral 90-day study is required if oral exposure could occur. EPA is also revising testnote test

note 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

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Master Responses: Toxicology Section (80) Page 87 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 ne urotoxicity study and/or the 90-day immunotoxicity study would be triggered based on the results of the enhanced 90-day oral study.

Response 80.19: As discussed in response to comm ents 80.18 and 80.6, the ne urotoxicity 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 lik ely 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 me asured in those designated groups. To clarify, EPA is revising testnote test note 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 derm al 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?EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 88 Response 80.21: In proposed testnote test note 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.

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 Area s, 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 antimicrob ial 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 test note 20 to read “considerable portion” instead of “limited portion” to read similarly to the comparable testnotes test notes 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 rout inely submitted to EPA, an d the data are used in EPA’s risk assessments. If the ap plicant 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 humanEO 12866 Draft

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Master Responses: Toxicology Section (80) Page 89 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 of the mouse bioassay for both cancer risk assessment and Reference Does (RfD) derivation for noncancer endpoints. When this analysis is comp leted, 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 alternat ive approaches, see response to comme nt 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 commen t. 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 (suc h 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 swi mmers in swimming pools, and via exposures to preserved wood products represent examples where significant exposure is expected to occur.EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 90 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 test

note 26 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 co ntended that EPA has misinter preted 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 th e information pr esented 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 test

note 28 as a trigger for reproductive toxicity study. Proposed testnote test note 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 recomme ndation 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-of-evidence 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 theEO 12866 Draft

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Master Responses: Toxicology Section (80) Page 91 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 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 det ecting more than 61 perc ent 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 reproducti ve 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.EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 92 Response 80.34: The Agency notes both in 40 CFR 158.500 ( testnote test note 25 to the toxicity table for conventional pesticides) and in the proposed antimicrobial pesticide data requirements rule (proposed testnote test note 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.

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 sh ould 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/T est_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 2 nd (F1) generation as specified in the reproductive toxicity testing guideline.

Comment 80.38: Several commenters felt that EPA should clarify proposed testnote test note 28, yet there were no specific suggestions as to how this testnote test note should be clarified. One commenter asked why is a waiver mentioned in proposed testnote test note 28? No other

testnotes test notes discuss waivers.

Response 80.38: Proposed Testnote test note 28 describes an information-based approach for conducting two studies (reproductive toxicity and DNT). These are complex studies that canEO 12866 Draft

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Master Responses: Toxicology Section (80) Page 93 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 test note 28, can be removed. An applicant can alwa ys submit a request for a waiver with a supporting rationale.

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 test note 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 as sociated 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/f rs/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 sh ould 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 a ssay 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 Test note 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.EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 94 Comment 80.43: A commenter noted that the mutage nicity 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/co mmittees/04_sccp/docs/sccp_s_08.pdf)

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 tothe 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 eval uation 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 ofEO 12866 Draft

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Master Responses: Toxicology Section (80) Page 95 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 effect s in the DNT will also on ly be observed at high doses, as the developing nervous system can be sensitive to chemic al 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.

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 st udies 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 test note 13 describes the limite d 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 exte nded 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 toEO 12866 Draft

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Master Responses: Toxicology Section (80) Page 96 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?

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 stud ies 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 t estnote test note 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.EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 97 Comment 80.55: A commenter thought that proposed testnotes test notes 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 test note 16 specifies the 90-day inhalation toxicity study is required if there is the likelihood of significant repeated inhalation exposure. Proposed testnote test

note 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 test note 14 specifies that a 90-day dermal toxicity study is re quired if the dermal route is the primar y route of exposure, or if the active ingredient is known to metabolize 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 test notes should be clearer, especially since they are inter-related, and

therefore will revise:

 Proposed testnote test note 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 test

note 7.

 Proposed testnote test note 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 test note 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 test note 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 t estnote test note 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 test note 37 specifies that the trigger for requ iring 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 ofEO 12866 Draft

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Master Responses: Toxicology Section (80) Page 98 exposure. If unacceptable risks are found, then either the subchronic dermal study or a dermal absorption study would be requ ired. 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 test note 37 to clarify this process. EPA also agrees that corrosive/irritant products should not be tested in dermal absorption studies. Therefore, testnote test note 3 which specifies that testing is not needed for corrosive materials is added as a trigger for not requiring the de rmal absorption study.

Comment 80.57: A commenter thought EPA had not clearly explained in testnote test note 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 test note 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 test note 35 will be split into two testnotes. Testnote test notes. Test note 35 will be revised to state “These data are required when chronic or carcinogenicity studies are required.” A

new testnote test note 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 conducti ng 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.EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 99 Comment 80.60: A commenter aske d 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 pp b level was previously establishe d 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 th e proposed rule, FDA

derived the 200 ppb is derived level by dividing FDA’s the cumulative exposure upper limit of 1000 ppb level by 5 to account for the fact that antimicrobial pesticides (e.g. biocides) are a class of pesticide that are generally to xic by design. The 200 ppb level is the co ncentration of the

antimicrobial residues in or on the food item. EPA is using 200 ppb as a 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 e qual to 200 ppb on or on the food item usually have fewer data requirements th an those that have residues that ar e greater than 200 ppb in or on the food item. For clarity, the following informati on concerning the 200 ppb le vel and its derivations

from FDA levels has be e n n added to §158.223 9 0 (d):

The 200 ppb level was originally used by the Food and Drug Administration with

re s pect 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 level 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 wi th 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.EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 100 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.

Comment 80.67: A commenter argu ed that EPA has not appropri ately considered the 1997 FIFRA Scientific Advisory Panel review in developing the toxicology data requirements for antimicrobials, and maintained that EPA is proposing to require mo re and higher tier studie s 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 commen t on five scientific di sciplines 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 publis hed on October 8, 2008 addr esses the SAP’s concerns.

Comment 80.68: A commenter prefer s the 3-category approach to to xicity test ing in the 1987 DCI.

Response 80.68: The 1987 DCI for antimicrobials specified three exposure categories (high, medium, and low) for addressing to xicology 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 me rged. Therefore the 3- category approach is no longer used.

Also, since the 1987 DCI, the use patt erns for antimicrobial pesticides have been clarified. These 12 use patterns were the ones presented to the SAP in 1997. Today, to speci fy 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 exposureEO 12866 Draft

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Master Responses: Toxicology Section (80) Page 101 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 require d for the same antimicrobial pesticide.

Proposed testnote test note 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.

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 comm ents 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 Toxicolo gy 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.EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 102 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 numb er. (note that C3 stands for column 3 of the data requirements table published in the final rule, similarly for C4, etc)

As previously discussed, the commenters provided two alternative approaches for data requirements for antimicrobials. As stated by the commenter, Alte rnative 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 test notes to define the triggers for moving from tier to tier. EPA does not believe that at this time, that this approach meets the needs Food? Swimm i ng 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

yesEO 12866 Draft

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Master Responses: Toxicology Section (80) Page 103 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 co mplex 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.

EPA has also evaluated Alternative Approach 2. While this alternative approach is in a table-type of
format, the testnotes test notes developed by the commenters are extremely detailed and contain information that EPA believes should be in guidance. However the commenters’ suggested

testnote test note 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 test note 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 test note is clearer and will modify the proposed testnote test note accordingly, to read: “There is a choice of assays, but the micronucleus rodent bone marrow assay is preferred; the rodent bone marrow assays using me taphase analysis (aberrati ons) are acceptable.”

EPA has already responded to the issues raised by the testnotes test notes 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 includ e within subpart W a new section 158.2235 which would be analogous to 40 CFR 158.510 for conven tional chemicals (Tiere d 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 chemistr y 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 informationEO 12866 Draft

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Master Responses: Toxicology Section (80) Page 104 from closely related chemicals to determine if the data can be bridged and from monitoring and incident data. On occasion Structure Activity Rela tionships (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.

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 se e response to co mments 140.5 and 160.3 for an explanation of transf ormation/degradation products fo r 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 test note 15)

Comment 80.76: A commenter stated that proposed testnote test note 3 should apply to all in vivo data requirements

Response 80.76: EPA disagrees with this comment. Proposed testnote test note 3 specifies two conditions (test material is corrosive to skin or pH is less than 2 or greate r 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 test note 3 assures that large amounts of a co rrosive 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 en dpoint 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.EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 105 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 requi red less data for a “clo sed” system than for an “open” system. EPA reduced the toxicology da ta requirements for a “clo sed” system provided that certain human exposure data were developed to address worker exposu res (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 re served 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 ch emical: 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 we ight-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 sh ould 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.EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 106 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

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 wit h 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 abso rption/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 absorp tion. 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 shou ld specifically state in its regulations that non-animal methods are acceptable for fulfilling a data requirement. The Draize study in rabbits

should be eliminated.EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 107 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 replac e 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.go v/oppad001/eye-irritation.pdf

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 ac ute 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 guide line (TG) 439, “In Vitro Skin I rritation: 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 OE CD 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 cons idered 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 “red uced” LLNA (r LLNA) 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 fo r dermal sensitizat ion (OCSPP 870.2600) on page 2 that the 

### “LLNA ...is a preferred alternative method, where ap plicable, to the traditional guinea pig test...”(see http://www.epa.gov/oppts/pubs/frs/publi cations/Test_Guidelines/series870.htm )EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 108 

### 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 Usin g Fewer Animals to Asse ss 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 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 eco toxicity 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 environmen t 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 nontarget 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 co mmenter 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) ofEO 12866 Draft

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Master Responses: Toxicology Section (80) Page 109 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 test note 36 to remove the phrase “through, but not limited to, direct application.”

Comment 80.98: A commenter asked for th e definition of domestic animals.

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 test note 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. Fede ral 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 animal s in order to advance animal welfar e 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 assert ed that EPA should require “ful l 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 assesse s 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.ep a.gov/oppfead1/trac/science/ . The Agency has also developed supplementary guidance for assessment of chemical mixtures, available at http://cfpub.epa.gov/ncea/cf m/recordisplay.cfm?deid=20533

Comment 80.101: A commenter stated that there is “limited value of acute system ic toxicity testing via the dermal route for the purpose of classification and labeling.”EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 110 Response 80.101: The Agency acknowledges the re ference citations (6 – 10) provided by the commenter. These citations provide information regarding the comparison of results of acute oral and acute dermal toxicity te sting 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.

With respect to in vitro dermal penetration assessments, OPP enco urages submission of such data to

evaluate the need for in vivo testing.

Comment 80.102: A commenter asked EPA to c onsider incorp orating the following OECD guidelines into the new part 158W to reduce the number of animals killed in LD 50 tests: OECD guidelines 436: Acute Inhalation To xicity - 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 us e of OECD 436 for acute inhalation toxicity. If a study conducted according to OECD 436 were submitted for th e 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 Th reshold 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 Test notes to the Antimicrobial Toxicology Data Requirements Table in the final rule will read as follows:

T80.1 Testnote Test note 1 to the final Toxicology Data Requirements 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 Test note 2 to the final Toxicology Data Requirements 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 labelingEO 12866 Draft

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Master Responses: Toxicology Section (80) Page 111 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 studie s 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 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 Test note 3 to the final Toxicology Data Requirements 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 Test note 4 to the final Toxicology Data Requirements 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 Test note 5 to the final Toxicology Data Requirements 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 Test note 6 to the final Toxicology Data Requirements 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:EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 112 For indirect food Uses < ≤ 200 ppb, and all other nonfood us es, data are required if the neurotoxicity screen in the 90-day oral rodent study or other data indicate neurotoxicity.

T80.7 Testnote Test note 7 to the final Toxicology Data Requirements Table

Proposed: 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 Test note 8 to the final Toxicology Data Requirements 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 Test note 9 to the final Toxicology Data Requirements 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 Test note 10 to the final Toxicology Data Requirements TableEO 12866 Draft

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Master Responses: Toxicology Section (80) Page 113 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 stea dy state to determine if a longer duration dog to xicity study is

needed.

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 slowly eliminated slowly. T his 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 also 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 Test note 11 to the final Toxicology Data Requirements 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 Test note 12 to the final Toxicology Data Requirements 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 all of the following criteria are met:EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 114 i. The intended use of the antimicrobial pesticide product is expected to result in repeated

, dermal human exposure to the product , and

. ii. Data from a subchronic 90-day dermal toxicity study are not available and

. iii. The 90-day dermal toxicity study has not been triggered

.

T80.13 Testnote Test note 13 to the final Toxicology Data Requirements Table

Proposed: 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 Test note 14 to the final Toxicology Data Requirements 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 Test note 15 to the final Toxicology Data Requirements 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 inhala tion route are required.EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 115 T80.16 Testnote Test note 16 to the final Toxicology Data Requirements 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: 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 Test note 17 to the final Toxicology Data Requirements 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 Test note 18 to the final Toxicology Data Requirements 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 neurotoxicityevaluations) may be required to provide information about potential neurotoxic effects from longterm exposures.

T80.19 Testnote Test note 19 to the final Toxicology Data Requirements 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:EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 116 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 Test note 20 to the final Toxicology Data Requirements Table

Proposed: 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, 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, da ta 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 , or food additive regulation or

clearance be established.

T80.21 Testnote Test note 21 to the final Toxicology Data Requirements 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 orga n (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 , or food additive regulation or

clearance 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

, ; orEO 12866 Draft

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Master Responses: Toxicology Section (80) Page 117 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 Test note 22 to the final Toxicology Data Requirements 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.

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 Test note 23 to the final Toxicology Data Requirements Table

Proposed: Testing in two species is required for all uses.

Final: Testing in two species is required for all uses.

T80.24 Testnote Test note 24 to the final Toxicology Data Requirements 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 Test note 25 to the final Toxicology Data Requirements Table

Proposed: Additional testing by other routes of exposure may be required if the pesticide is determined to be a prenatal developmental toxi cant after oral dosing.

Final: Additional testing by other routes of exposure may be required if the pesticide is determined to be a prenatal developmental toxi cant after oral dosing.

T80.26 Testnote Test note 26 to the final Toxicology Data Requirements TableEO 12866 Draft

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Master Responses: Toxicology Section (80) Page 118 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.

T80.27 Testnote Test note 27 to the final Toxicology Data Requirements Table

Proposed: A two-generation reproduction study is required.

Final: A two-generation reproduction study is required.

T80.28 Testnote Test note 28 to the final Toxicology Data Requirements 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 Test note 29 to the final Toxicology Data Requirements 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.EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 119 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 Test note 30 to the final Toxicology Data Requirements Table

Proposed: 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 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 Test note 31 to the final Toxicology Data Requirements Table

Proposed: To enhance the weight-of-evidence determination for the pesticide’s mutagenicity, the Agency requires submission of other mutagenicity test result s, 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:EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 120 To facilitate the weight-of-evidence determination for the pesticide’s mutagenicity, the Agency requires submission of other mutagenicity test result s, 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 Test note 32 to the final Toxicology Data Requirements 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.

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 strain s has already been conduc ted, 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 Test note 33 to the final Toxicology Data Requirements Table

Proposed:

For the in vitro mammalian gene mutation study, there is a choice of assays using either mouse lymphoma L5178Y cell thymidine kina se (tk) gene locus, maximizi ng assay conditions for small colony expression and detection; Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast (v79) cells, hypoxanthine- guanine phosphoribosyl tr ansferase (hgprt) gene lo cus, 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 kina se (tk) gene locus, maximizi ng assay conditions for small colony expression and detection; Chinese hamster ovary (CHO) or Chinese hamster lung fibroblast (v79) cells, hypoxanthine- guanine phosphoribosyl tr ansferase (hgprt) gene lo cus, accompanied by an appropriate in vitro test for clastogenicity; or CHO cells strains AS52, xanthine-guanine phosphoribosyl transferase (xprt) gene locus.

T80.34 Testnote Test note 34 to the final Toxicology Data Requirements 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:EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 121 There is a choice of assays, but the micronucleus ro dent bone marrow assay is preferred; the rodent bone marrow assays using metaphase analysis (aberra tions) are acceptable.

T80.35 Testnote Test note 35 to the final Toxicology Data Requirements 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.

T80.36 Testnote Test note 36 to the final Toxicology Data Requirements 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 Test note 37 to the final Toxicology Data Requirements Table Proposed: A risk assessment assuming that de rmal absorption is equal to oral absorption must be performed to determine if the dermal penetration study is requi red, and to identify th e 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 de termine if a dermal penetration study is required, and to identify the doses and du ration of exposure for which dermal absorption is to be quantified.

T80.38 Testnote Test note 38 to the final Toxicology Data Requirements Table

Proposed: N/A

Final: Required for antimicrobial nonfood uses, if oral exposure could occur.EO 12866 Draft

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Master Responses: Toxicology Section (80) Page 122 T80.39 Testnote Test note 39 to the final Toxicology Data Requirements 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 and pharmacokinetics studies.EO 12866 Draft

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Master Responses: Applicator/Handler (Human Exposure) Section (90) Page 123 

### Applicator/Handler (Human Exposure) (90)

Master Responses and Testnotes Test Notes for the Applicator/Handler (Human Exposure) Section

Please note that EPA responses and testnotes test notes 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 we re 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 fi nalized 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) andEO 12866 Draft

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Master Responses: 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 trea ted 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 test note test note 3 is sufficient to explain how one determines the venue for testing.

Response 90.3: EPA agrees with the commenter that proposed testnote test note 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 eval uations. The commenter also asked that when EPA stated that an

OSHA or American Conference of Governmental an d 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 cont rols and personal protective eq uipment (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 diffe rences. OPP’s data is su bmitted 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 epidemiologyEO 12866 Draft

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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 interpre tations of the same literature studie s. The TLV for formaldehyde is 300 ppb and the OPP “RfC” for occupati onal 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 prov ides 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 propos ed 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 indust rial 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) conc erning use of OSHA standard s. With modifications, the following language will appear in the final t oxicity Toxicology Data Requirements Table:

“ If EPA determines that indust rial 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 asse ssment 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.”EO 12866 Draft

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Master Responses: 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 effe cts in order to conduct the risk assessment. EPA risk assessments are, in part, conducted to dete rmine 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 clar ify that the poisoning

incident data must have a clear do se 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 informatio n 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 derm al or inhalation exposure data.EO 12866 Draft

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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 andinhalation (passive dosimetry) exposure data. The submission of biomonitoring data is a registrantbased decision. In some circumst ances 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 de rmal 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 su ch 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 da ta 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 test note 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 test note 10 is one of the triggers for the biomonitoring study. EPA agrees that proposed testnote test note 10 does not provide appropriate information and is removing the testnote test note . (EPA notes that due to renumbering, there is a new testnote test note 10.)

Comment 90.13: A commenter stated that Gu idelines 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.EO 12866 Draft

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Master Responses: Applicator/Handler (Human Exposure) Section (90) Page 128 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 changes have occurred in the last 10 years. The SAP meeting on worker exposure assessment methods in January 2007 (http://www.epa.gov/sc ipoly/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 co mpleted 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 (875.170 0 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

.

EPA agrees that for certain scientific disciplines or certain studies that antimicrobial-specific guidance may be needed. See resp onse to comment 191.6 for a discussi on 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) th is 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 test note 5 to the proposed Applicator Exposure Data Requirements Table and testnote test note 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 inhalationEO 12866 Draft

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Master Responses: Applicator/Handler (Human Exposure) Section (90) Page 129 studies for applicator exposure. Without this information, EPA cannot perform an exposure and

risk assessment.

The commenter’s descriptions in their suggested testno te test note 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 test note 4 indicated that EPA would provide guidance on the toxicity and exposure data needed for closed systems. EPA has revised testnote test

note 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 test note 1, to reflect the role of the HSRB, EPA is revising proposed testnote test note 1 to both the Applicator Exposure and the Post-Application Exposure Tables to acknowledge the role of HSRB review. Proposed testnote test note 1 will

become a new testnote test note 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 test note and “CR”classification. However, the incidental ingestion data requirement has been deleted from the postapplication table as discussed in response to comment 100.13.

Based on the comments received, the Testnotes Test Notes to the Antimicrobial Applicator Exposure Data Requirements Table in the final rule will read as follows:

T90.1: Testnote Test note 1 to the final Applicator Exposure Data Requirements 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 40EO 12866 Draft

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Master Responses: Applicator/Handler (Human Exposure) Section (90) Page 130 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).

T90.2: Testnote Test note 2 to the final Applicator Exposure Data Requirements 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 Test note 3 to the final Applicator Exposure Data Requirements 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 Test note 4 to the final Applicator Exposure Data Requirements 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:EO 12866 Draft

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Master Responses: Applicator/Handler (Human Exposure) Section (90) Page 131 EPA will consider waiving this data requirement for antimicrobials applied via closed loading systems if the antimicrobial has a low vapor pressure.

T90.5: Testnote Test note 5 to the final Applicator Exposure Data Requirements 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.EO 12866 Draft

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Master Responses: Post-application (Human Exposure) (100) Page 132 

### Post-application (Human Exposure) (100)

Master Responses and Testnotes Test Notes for the Post-application (Human Exposure) Section

Please note that EPA responses and testnotes test notes 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 commente r 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 th at there are existing exposure da ta 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.”EO 12866 Draft

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Master Responses: 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 test notes . 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 test notes 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 certaincircumstances, 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 s 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 specif ied the toxicity and exposure criter ia 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.EO 12866 Draft

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Master Responses: Post-application (Human Exposure) (100) Page 134 Response 100.6: EPA differs from OSHA in that we use pesticide label la nguage 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 conditionall y required the soil re sidue 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 require ment 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 surfa ce residue dissipation data for wo rkers 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”.EO 12866 Draft

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Master Responses: 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 test note 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 test note 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 test note 5 triggers the indoor resi due surface dissipation study for post-application occupational use sites “...if the human activity data indica te that workers are likely to have post-application dermal cont act 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 test note

.

Testnote Test note 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 test note 6 to provide greater clarity and has included some specific examples that routinely re quire surface residue data are provided in the

t estnote test note 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 inst ances the indoor surface residue dissipation study can be used to estimate post -application dermal exposu re. 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 test note 3 has been deleted. (It will be replaced by a different testnote test note .)

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 ofEO 12866 Draft

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Master Responses: Post-application (Human Exposure) (100) Page 136 requiring the inhalation exposure study is dependant upon several factors: vapor pressure and/or 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 test notes 7 and 9.

Comment 100.12: A commenter stated that the testnotes test notes for post-applicat ion dermal and inhalation data requirements should be written to be more specific about post-application exposures.

The commenter noted that the testnotes test notes should not be the same as those for applicator exposure. The commenter also maintained that proposed testnote test note 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 test notes to the proposed applicator and postapplication tables. The testnotes test notes describing the need for protocols and description of biomonitoring studies are similar. However, the testnotes test notes for dermal and inhalation studies are very different for post-application exposure versus applicator exposure. There are also more

testnotes test notes for post-application exposures when compared to applicator exposures. EPA

believes that the testnotes test notes strike the correct balance of specificity while offering some flexibility.

EPA disagrees with the commenter that parts of proposed testnote test note 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 Test

note 9 is revised to read: “Data are required for occu pational 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 stud y 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 usingEO 12866 Draft

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Master Responses: Post-application (Human Exposure) (100) Page 137 residue data from the treated surface combined with activity factors for children’s behaviors (e.g., 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 actualmonitoring 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 Data Requirements Table as well as the accompanying proposed testnote test note 12.

Based on the comments received, the Testnotes Test Notes to the Antimicrobial PostApplication Exposure Data Requirements Table in the final rule will read as follows:

T100.1: Testnote Test note 1 to the final Post-Application Exposure Data Requirements 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 (HSR B) (http://www.epa.gov/osa/hsrb/index.htm).

T100.2: Testnote Test note 2 to the final Post-Application Exposure Data Requirements 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 us es, data may be required if soil has the potential to be an important exposure pathway, and 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 p otential to be an important exposure pathway

.

T100.3: Testnote Test note 3 to the final Post-Application Exposure Data Requirements 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:EO 12866 Draft

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Master Responses: Post-application (Human Exposure) (100) Page 138 Protocols must be approved by the Agency prior to the initiation of the study.

T100.4: Testnote Test note 4 to the final Post-Application Exposure Data Requirements 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 Test note 5 to the final Post-Application Exposure Data Requirements 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 Test note 6 to the final Post-Application Exposure Data Requirements 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 use sites

. , schools, and daycare institutions. This includes but is not limited to the following: R esidential school s 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 Test note 7 to the final Post-Application Exposure Data Requirements 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.EO 12866 Draft

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Master Responses: Post-application (Human Exposure) (100) Page 139 Final: 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 Test note 8 to the final Post-Application Exposure Data Requirements 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 Test note 9 to the final Post-Application Exposure Data Requirements 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 Test note 10 to the final Post-Application Exposure Data Requirements Table

Proposed: Biological monitoring data are required when passive dosimetry techniques are not applicable for a particular exposure scenario (such as a swi mmer/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 Test note 11 to the final Post-Application Exposure Data Requirements TableEO 12866 Draft

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Master Responses: Post-application (Human Exposure) (100) Page 140 Proposed: Data reporting and calculations are required when any post-application exposure monitoring data are required.

Final: Proposed testnote test note 11 was renumbered and revised slightly; it is now testnote test note 10.

T100.12: Testnote Test note 12 to the final Post-Application Exposure Data Requirements 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 test note 12 was removed.EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 141 

### Residue Chemistry (110)

Master Responses and Testnotes Test Notes for the Residue Chemistry Section

Please note that EPA responses and testnotes test notes 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 Bi ocides Panel asse rted 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 fo r 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 appl y when a tolerance or toleranc e 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 re quirements 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 commentat ors noted the lack of clarity in th is 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 ge neral 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 ex emptions from toleranc es. 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 FREO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 142 59394). The proposed rule preamble’s discussion of residue chemistry da ta 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 re quire section 408 toleran ces as if they were covered by this provision. For example, both the pr eamble 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 th at 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) ma kes 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 re vised 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) th rough (iv) are renumbered as paragrap hs (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 cons istent 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-e valuated 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 an d indirect food uses are revised to “CR”EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 143 Proposed testnote test note 18 (now renumbered to testnote test note 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 re sponse to comment 110.35.

Comment 110.5: A commenter asse rted that EPA should reference IDREAM (Incidental Dietary Residential Exposure Assessm ent 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 re ason §158.2290(b)(1)(i) and (iii) were separate d was to make clear that §158.2290 applies to antimicr obials applied for the purpose of disinfecting animal or poultry drinking water as well as to antimicrobials appl ied to water for another purpose that have the “potential to result in residues” in animal or po ultry 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 s 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 re fer 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 §158.229 0(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 fo r Proposed Tolerances.

Comment 110.8: A commenter stat ed that additional clarification is needed concerning EPA’s statement: “in the absence of data [the Agency will] evaluate the need for a tolerance or toleranceEO 12866 Draft

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Master Responses: 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 woul d initially make regarding the migration of antimicrobial residues fr om 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 resi dues 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 forfood contact substances: chemistry recommendations (Ref. 11 to the proposed rule, in docket EPAHQ-OPP-2008-0110). Alternatively, or subsequently, the applic ant 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 test note 23 described anticipated in stances 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 test note 5, based partially on proposed testnote test

note 23, describes the circ umstances for triggering the migration study.

Comment 110.10: A commenter asked EPA to explain the term “post-harvest storage of

commodities.”EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 145 Response 110.10:“Postharve st storage of commoditi es” refers to storage of raw agricultural commodities (RACs) once they are harvested. The expression “Postharvest storage of commodities” was used in proposed testnote test note 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 Test notes 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 test note 3 is now part of new testnote test note 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 co uld 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 test note 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 test note 5 (now part of new testnote test note 8) was one of three triggers for the Nature of the Residue in Plant Study. The proposed testnote test note 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 test note (now renumbered to 8). The new testnote test note 8 combines proposed testnotes test notes 3, 4, and 5 and provides additional examples. Proposed testnote test

note 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 Studie s (plant metabolism stud ies) 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 test note

.

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.EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 146 Response 110.13: Appendix A to pa rt 161 is considered to be outd ated. 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 residu e in plants, and the an alytical 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 test

notes provide details of the triggers. “CR” is appropriate since the testnotes test notes provide adequate descriptions to trigger these studies. Proposed testnotes test notes 3, 4, and 5 were

combined to create new testnote test note 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 test

note 8.EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 147 EPA believes that proposed testnotes test notes 6, 7, and 8 are captured in new testnote test note 9. Even with the change in phrasing, EPA believes that the studies will be required at the same frequency as in the proposed rule.

See response to comment 110.32 for a discussion of the changes to th e 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 “resid ue 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 anti microbials could have an FFDCA sec. 408 toleranc e 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 co uld be applied to field, greenho use, 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 al so 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 antimicr obial in a food processing facility wo uld 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 n eed a section 408 toleran ce/tolerance exemption. However, even for

antimicrobials that fall under sect ion 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 test note 18. The commenter asked for clarification onEO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 148 “direct application to water” where there is “potential” that the use could be in human drinking

water is needed.

Response 110.17: EPA/OPP does not establish tolerances fo r 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 test note 18 (now renumbered to 12) triggers the potable water study. The new testnote test note 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 er maintained that t estnote test note 20 needs to be clarified.

Response 110.18: Proposed testnote test note 20 (now renumbered to testnote test note 14) triggers the Irrigated Crops study. The proposed testnote test note 20 (now 14) has been revised to contain the phrase “...applied directly to water used for irri gation 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 food-borne 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 th e proposed irrigated crop s 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 test note 14.

Comment 110.19: A commenter argued t estnote test note 21 needs to be revised to reflect the division of authority between EPA and FDA. Proposed residue chemistry testnote test note 21

addresses the conditions under which a food-handlin g 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 test note 21 (renumbered to testnote test note 3 in the final rule) described the trigger for the food-handling study. EPA disagrees with the commenter and does notEO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 149 believe that significant changes are needed to the first sentence of proposed testnote test note 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 antimicrobial in a food pr ocessing facility would fall un der 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 ma y 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 test note 21 (renumbered to testnote test note 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 ba sed 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 unde r 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, refe r 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 requirement s so that the food-hand ling study is now “CR” in the final Residue Chemistry Data Requirements 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.EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 150 Response 110.20: EPA agrees that intentional treatm ent 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)]. Intent ional or inadvertent exposure of livestock or their raw agricultural commodities to an antimicrobial, for example, to control spoilage 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 antimi crobials than for conventionals.

Response 110.21: EPA disagrees with this commen t. 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 commen t. 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 wa s not entirely clear regarding the their c ontention 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 test note

.

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 lowEO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 151 toxicity of the active ingredient or theoreti cal (modeled) estimates of exposure are adequate to assess dietary risk.”

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 specifica lly 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 commente rs 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 evalua tes the data and informatio n 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 th at the protocols/proced ures to be used to conduct individual studies or exposure assessments should no t be described in part 158W. Part

158W 158, subpart W 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 abou t 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.EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 152 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 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 test note 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 no te 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 th e safety standards for re gistration in FIFRA. If there is human exposure from a pesticide residue in food, FIFRA also requires that dietary risk from the pesticide be consiste nt 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 commente r 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) desc ribes 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 re sponses 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.EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 153 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. test note.

Response 110.28: Prior to the passage of the Food Quality Protection Act of 1996 (FQPA), EPA often relied upon a FDA clearan ce of a substance under FFDCA sec. 409 in assessing dietary risk under FIFRA. Now, FIFRA, as amended by FQPA , requires that EPA eval uate whether pesticide uses resulting in dietary exposure ar e 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” re sidential uses of pe sticides 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 se ction 408 but FFDCA section 408 do es require EPA to consider pesticide exposures from residential uses in evaluating whether to approve a pesticide tolerance.

FFDCA sec. 408 directs EPA to asse ss the safety of a pesticide tole rance 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, FFD CA sec. 408 requires EPA in assessi ng 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 relatedsubstances, 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 expressi ons were intended to be inte rchangeable. 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 agr ees with the commenter and ha s changed the “NR” to “CR.” Indirect Food Uses are treatments not directed at food for antimicrobial purposes but that , nevertheless, could inadvertently re sult in residues in food. Also see response to comment 110.14.EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 154 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 maintain ed 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 ti tle of the proposed data requirement “Proposed tolerance” is changed to “Proposed tolerance/tolera nce exemption.” This is a clarification of this data requirement as proposed. The testnote test note 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 covere d 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 toleranc e or exemption or clearance from FDA under

FFDCA section 409. To the extent a use under se ction 158.2290 is not subject to FFDCA section 408, a petitioner/applicant can fulf ill this requirement by referenc ing 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 on ly 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 test note 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 an alytical 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 met hods for tolerance/tolerance exemption enforcement:” “R”
becomes “CR”;EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 155 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 th at clarification is need ed. “R” is correct for storage stability studies. If a magnitude of the residue study is required, then the storage stability study is also required. EPA has revised proposed testnote test note 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 test note 15 has been

renumbered to 17 with very minor changes.

Comment 110.35: A commenter thought that proposed residue chemistry testnote test note 18 for the Potable Water data requirement conflicts with R for the Agricultural Premises use pattern.

Response 110.35: The Agency agrees with th e 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 Test note 18 (renumbered to 12) has been revised to include the conditions under which the Potable Water study is required.EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 156 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 ].

Response 110.36: All three of th e commenter-suggested tables ha d 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 same Supporting Information of the first section of the Residue Chemistry Table as proposed. However, EPA has adopted the commenters’ suggestion for a tiered format in the last two sections of the Residue Chemistry Table. After review, EPA believes the commenters’ suggested tiered approach is more suitable to antimicrobials than that proposed by EPA.

EPA has adopted the commenter’s suggested tier ed format. After revi ew, 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 c onduct 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 ex posure 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 residu e,” “Residue analytical method,” and “Storage stability.” These are each addressed individually below:

 Nature of residue on surface. The Agency agrees that this study is app licable 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 Guidel ine 850.1730) should substitu te 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 bioaccumul ation study is often not useful for residueEO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 157 chemistry purposes because characterization of fish residues is only required if the bioconcentration (of total residues) factor is >1000. Th e 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 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 residu e in livestock, Residue analytical methods for tolerance/tolerance exemption enforcement, Mu ltiresidue 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 th e 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 Data Requirements 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 hasEO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 158 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 test notes provide the conditions under which each study is required, li kely 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 exempt ion (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.

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 test note 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 es timates about 100 times those estima ted 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.EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 159 Response 110.37. The commenter did not address the subject proposed re gulation conc erning 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 test notes 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

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 Test

Notes to the Antimicrobial Residue Chemistry Data Requirements Table in the final rule

.

Since, as indicated in the table above, the testnotes test notes were rearranged and therefore renumbered from the proposed rule to the final rule, the proposed testnote test note is usually placed out of sequence and is numbered in parenthesis according to the proposal.EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 160 T110.1: Testnote Test note 1 to the final Residue Chemistry Data Requirements 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 us e is not covered by an existing to lerance 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 no t covered by an existing tolerance or tolerance exemption. If the use is subject to FFDCA sect ion 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 addi tive regulation or clearance for the food or feed use.

T110.2: Testnote Test note 2 to the final Residue Chemistry Data Requirements Table :

Proposed (2): An analytical reference st andard is required for any food or feed use requiring a tolerance. Material safety data sheets must accompany analytical st andards 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 Test note 3 to the final Residue Chemistry Data Requirements 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 Test note 4 to the final Residue Chemistry Data Requirements Table :

New testnote test note for new study (110.36)EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 161 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 Test note 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.

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 Test note 6 to the final Residue Chemistry Data Requirements 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 Test note 7 to the final Residue Chemistry Data Requirements 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 resi due study, as specified in § 158.2290(d) , is required, then storage stability data are also required, unless an alytical 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.EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 162 T110.8: Testnote Test note 8 to the final Residue Chemistry Data Requirements 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 antimi crobial, 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, 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 Test note 9 to the final Residue Chemistry Data Requirements 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 ma y 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 Test note 10 to the final Residue Chemistry Data Requirements Table :

Proposed (9):EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 163 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 tolerance or tolerance exemption 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 Test note 11 to the final Residue Chemistry Data Requirements 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:

If there is a numerical tolerance or tolerance exemption level to enforce, then testing is required to

determine whether the FDA/USDA Food and Drug Administration/United States Department of Agricultural 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 Test note 12 to the final Residue Chemistry Data Requirements 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 Test note 13 to the final Residue Chemistry Data Requirements 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 sitesEO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 164 or materials and make its way into bodies of water containing fish that may be used for human consumption.

T110.14: Testnote Test note 14 to the final Residue Chemistry Data Requirements 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 Test note 15 to the final Residue Chemistry Data Requirements Table :

Proposed: (16)Data are required when the pesticide use is a direct application to livestock. (17)Data are required if livestock premises are trea ted 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, metabolically-active livestock commodities (e.g., eggs), livestock feed or drinking water , 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 fat, 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 Test note 16 to the final Residue Chemistry Data Requirements 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.EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 165 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 Test note 17 to the final Residue Chemistry Data Requirements 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 ag ricultural 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 Test note 18 to the final Residue Chemistry Data Requirements Table :

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 degradat ion 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, wash ing, 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 test note 14: If the antimicrobial chemical may be applied to a field crop, then the residue chemistry data requirements of § 158.1410 apply, unless otherwise determin ed by the Agency on a case-by-case

basis.

Removed from testnotes test notes 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 determin ed by the Agency on a case-by-case

basis.EO 12866 Draft

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Master Responses: Residue Chemistry Section (110) Page 166EO 12866 Draft

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Master Responses: Environmental Risk Assessment Section (120) Page 167 

### 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 (America n 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, environmen tal 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 informationprovides 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 industrialEO 12866 Draft

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Master Responses: Environmental Risk Assessment Section (120) Page 168 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 ecologic al 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 co ncern 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 th e 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 an d 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 di scusses the EPA’s recent effort s 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 da ta 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 ec otoxicity 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, asEO 12866 Draft

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Master Responses: Environmental Risk Assessment Section (120) Page 169 well as changes in the proposed environmental fate data requirements for assessing down-the-drain releases, can be found in re sponse to comment 134.1.

Comment 120.4: A commenter argued that EPA has included an assumption of product misuse in determining the data requireme nts for an environmental risk assessment on p. 59405 of the proposed rule.

Response 120.4: In formulating th is 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 USEP A conduct risk assessment for wood preservatives differently. The commenter main tained 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 ack nowledges 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 pr actice 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 both

the land or and in the aquatic environment.EO 12866 Draft

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Master Responses: Environmental Risk Assessment Section (120) Page 170 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 Effe cts 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 appr oach could be consider ed 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/sa p/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 To xic 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 conc ern, 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 mamm als; 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 fo cuses on identifying diff erent risk assessment approaches for addressing the unique characteri stics 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.EO 12866 Draft

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Master Responses: Environmental Risk Assessment Section (120) Page 171 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 ri sk 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 Ec ological 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.EO 12866 Draft

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Master Responses: Letter from Environmental Working Group Section (125) Page 172 

### Letter from Environmental Working Group (125)

Master Responses for the Letter from Environmental Working Group Section

The following summary comments and EPA responses refer excl usively to comments receiv ed from the Environmental Working Group. Their verbatim complete comment letter follows in Sectio n 3 of this document.

Comment 125.1: A commenter stat ed 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 soundn ess 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 routinel y evaluates its risk as sessment 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 co mment 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 no n-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 huma n health risks that re sult 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 pesticidesEO 12866 Draft

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Master Responses: Letter from Environmental Working Group Section (125) Page 173 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 th e commenters’ co ncerns. When establis hing 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 assessm ent. 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 discus sed biological monitoring or biomonitoring studies for both appl icator and post-applica tion uses [59398]. Gene rally, 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 require surveys of blood-levels in the general population. EPA does, however, sometimes require environmental monitoring studies, such as the moni toring of representative U.S. waters. The AgencyEO 12866 Draft

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Master Responses: Letter from Environmental Working Group Section (125) Page 174 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 ar e 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 ex pects 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 standardiz ation 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.

Response 125.8: The intent of the proposed rule is to ensure that EPA has sufficient information to make regulatory decisions fo r antimicrobial pesticides.EO 12866 Draft

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Master Responses: Letter from Environmental Working Group Section (125) Page 175For 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, in cluding 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.EO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 176 

### 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 befo re 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 dishwa shing 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.EO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 177 Comment 130.3: A commente d r 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 re gistration 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 dete rminations, EPA requires more than 100 different scie ntific 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 nontarget organisms and plants. If so, EPA could then require additional studies to assure protection of non

target nontarget 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 degr adation/transformation pr oducts 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 thatEO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 178 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 theantimicrobial 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”, up dated 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 su bstance 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 conduc ting a down-the-drain analysis.

Comment 130.5: A commenter argu ed that EPA has developed a sc reening-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 disagr ees with this comment. To asse ss whether the pr oposed tiered approach for determining data requirements for anti microbial 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 descri bed 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 ri sk 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 sh ould 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 containingEO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 179 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 a ssessing the risk of la nd application of anti microbials 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 ba sed 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 ri sk assessment informat ion 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 comme nt, EPA did re-evaluate its orig inal 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, pon ds, 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 pl ant. Some of the types of wood preservative

facilities identified in the OECD ESD for wood preservatives include automated spraying plants,EO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 180 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 so me 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, wh ile referencing gu ideline 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 (C arbon 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/disp lay.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 Ac tivated Sludge Study, as described in “Simulation Tests to Assess the Primary and Ultimate Biodegradability of ChemicalsEO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 181 Discharged to Wastewater” (OCSPP 835.32 80) and the “Simulat ion 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 re quirement designation is “NR” and the data requirement designation for the “all other” use patterns category is “CR.”

As discussed on page 1 of Gu ideline OCSPP 835.3280, this gu ideline was developed based on

OECD Guideline 314 “Simulation Test s to Assess the Biodegradability of Chemicals Discharged in Wastewater”. Both guidelines contain five separate but related simulation st udies 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 Gu ideline 835.3280 contain a Figure entitled “Pathways for Chemicals Discharged to Wastewater” which illustrates the points in the wastewater treatment process that are simula ted by the guidelines. The OCSPP 835 guidelines are available at http://www.epa.gov/ocspp/pubs/frs/public ations/Test_Guidelines/series835.htm

A table to crosswalk the two guidelines is presented below:

Title OECD OCSPP Biodegradation in a sewer sy stem 314A Begins on page 12 Biodegradation in activated sl udge 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, 20, and 20 21 to the Environmental Fate Table come from the decision points in this flowchart

. , and considerations of the physical/chemical properties and
environmental fate characteristics which would determine if an antimicrobial and/or its transformation/ degradate produc ts (as described under § 158.2280( a)(2)) would be persistent enough to reach a WWTP. Also, proposed testnote test note 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 activa ted sludge study as desc ribed in the “Simulation Tests to Assess the Biodegradability of Chemicals Discharged in Wastewater,” the porous pot test, or the “Simulation Test – Aerobic Sewage Trea tment: A. Activated Sludge Units.”EO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 182 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 EC 50 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 Treatm ent: A. Activiated Sludge Units, or the Porous Pot Test (choice 1). ASRI test is performed

EC 50 ≤ 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 anal y sis Applicant conducts

Read y Bio

Pass Ready

Bio? Y es 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 StudyEO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 183  If the antimicrobial passes the ready biodegradability test, then no more testing is required and EPA will assume that 90 percent of the an timicrobial 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 cla sses of chemicals, the Ac tivated 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 Discharg ed in Wastewater” guideline.

Comment 134.3: A commenter noted that the DtD Down-the-Drain 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 variou s 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-D rain 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 st aff 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 an d 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-levelEO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 184 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.

Response 134.4: The E-FAST docu mentation 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 pl ants to surface water, EPA has recently demonstrated the feasibility of adapting OPPT’s methodology to estimate releases to surface water and exposures to aquatic organi sms from processing an d 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 an d water systems, swimmi ng pools, and others.

Comment 134.5: Some commenters questioned the justification for exceedance levels used by EPA to evaluate potential risks to a quatic 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 ma thematical models used to esti mate exposures and risks can be characterized as probabilistic or deterministic. Probabilistic modeling is a technique that utilizes theEO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 185 entire range of input data to develop a probability distribution of risk or exposure rather than a 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 da ys 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 informat ion 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. in EPA/OPPTS/OPPT's "Interpretive Assistance for Sustainable Futures Summary A ssessment", last updated August, 2011. (See http://www.epa.gov/oppt/sf/pubs /iad_discretes_092011.pdf ). 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 "The potential for chronic risk to aquatic organisms may exist ONLY if the PEC exceeds the chronic COC for 20 days or more per year. If exposure occurs for 20 days of more per year, the concentration of the chemical in

the surface water to may reach levels exceeding the hazardous level, the levels are not exceeded for a sufficient duration of time to induce any associated with chronic

effects

. (Lynch et al., 1994). 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 29 days in duration. Low conce nt r atio n 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”. ."

The justification for the potential for acute risks to aquatic organisms appears on page 12:

"The potential for acute risk to aquatic organisms exists if the predicted environmental concentration (PEC) is greater than the acute concentration of concern (COC).

If Acute COC > PEC Low concern for risk

If Acute COC < PEC Potential for risk"EO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 186 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 Test note 7 triggers the acute freshwater invertebrate toxicity study (TEP testing) and the acute freshwater fish toxicity study (TEP testing). Testnote Test note 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 concentrationson 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.

Response 134.7: EPA agrees that GIS-based to ols are useful for esti mating 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 wouldconsider 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 down-the-drain modeling would be applied in different geographic regions, like desert or water-restricted areas.

Response 134.9: The Down-the-Drain model is no t 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.EO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 187 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 comme nter stated that, itshould 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 th at if assuming 100 percent of th e 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 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 intere sted 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 suchmodels are applicable to domestic wastewater treatment plants in the United States, are welldocumented, are transparent, and meet EPA’s qua lity 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 co ncluding that the model and its an alytical 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) whic h 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 theEO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 188 WWTP (i.e., in sewer) are to be estimated and incorporated into the DtD Down-the-Down 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 down-the-drain , 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 exposu res, 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

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/I nterpretiveAssistance0107.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, Do cumentation 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 appropriat e 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.EO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 189 Comment 134.14: Some commenters contend that the DtD Down-the-Drain 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 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 dr ain 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 10 th and 50 th 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 a pplied 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 ofthe 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 10 th 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. LC
50 values for aquatic organisms serve as a basis for establishing end-points for determining potential for acute toxicity.EO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 190 (LC 50 , 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 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 degrad ates; 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 ex posures to a chemicalsubstance based on environmental fate and physical/chemical property inputs. Thus, the Down-theDrain 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 tran sported 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 conserva tive 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 conc entrations 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 toEO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 191 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 du ring the 158W Antimicrob ial 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 ru k l e and in the presentation

on the Down-the-Drain Model at the 158W An timicrobial Data Requ irements Wo rkshop 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 imme diately downstream of thos e plants as inputs and calculates the resultingprobability 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

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 estima te 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 down-the-drain 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 Down-the-Drain 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 toEO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 192 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 assess ment 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 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 comme nsurate 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.EO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 193 Comment 134.21: A commenter noted that, at the 158W Anti microbial 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 appr oach 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.

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 acut e 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 wastewat er treatment effluents, and need for endangered species risk assessment, the Agency required several non

- target nontarget 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 ap proach 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 ecolog ical risk assessment. Also see re sponse to comments 134.1 and 134.4.

Consequently, in the table, “ final Nontarget Organism Data Requirements ”, Table, 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 Test note 10 will be modified to remove the trigger since it is no longer needed.EO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 194 Comment 134.22: Several commenters believe that potential environmental impacts of cross-media

transfers need to be addressed in U.S. EPA’s en vironmental 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 pest icide 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 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 presen tation on the Down-the-Drain model that was given at the Pa rt 158W Antimicrobial Data Requirements Worksh op 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.

As a result of the review requi red under Executive Order 12866, addi tional changes were made to existing test note 18 and new test note 21 of the Environmental Fate Data Requirements Table. InEO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 195 making these changes EPA agrees that the potential exposure pathway (i.e., via the wastewater treatment plant (WWTP)) should be the first consideration in the applicability of these data requirements. The tiered structure of the Antimicrobial Environmental Fate Data Requirements table and accompanying test notes are intended to be used to determine which antimicrobials would be expected to reach a WWTP. For example, considerations that would determine whether or not the Agency would require biodegradation data for an antimicrobial include whether or not, based on physical/chemical properties and environmental fate characteristics, an antimicrobial would be persistent enough to reach a WWTP. However, in responding to this interagency comment EPA determined that additional conditions could be added that would further clarify the situations under which the data would be required. Thus, EPA is revising Test note 18 of the Environmental Fate Data Requirements Table, which disc usses specific criteria that would lead the Agency to not require any biodegradation data. The Agency plans to add two additional criteria to Test note 18 that reflect the Agency’s consideration of whether or not any of the uses on the product label would result in transport of the antimicrobial to a WWTP and wh ether or not an antimi crobial and degradates would be persistent enough to reach a WWTP. In addition, the Agency is also adding a Test note 21 to the Table of Antimicrobial Fate Data Requirements. This Test note pertains to the data requirement for the Activated Sludge Respiration Inhibition (ASRI) Test.

EPA’s is revising Test note 18 to the Antimicrobial Environmental Fate Data Requirements Table to include two additional triggers, as follows:

Current: 18. 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

Revised: 18. 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.

iv. Both the parent and all transformation/degradate products (as described under §

158.2280(a)(2)) have half-lives of less than 3 hours.

v. None of the registered or proposed product uses would result in transport of the
parent and its transforma tion/degradate products (as described under §
158.2280(a)(2)) to a wastewater treatment plant.

The Agency will add the following new test note 21:

21. The activated sludge respiration inhibition study is not required if none of the registered or proposed product uses would result in transport of the parent and its transformation/degradate products (as desc ribed under § 158.2280(a)(2)) to a wastewater treatment plant.EO 12866 Draft

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Master Responses: Down-the-Drain Section (130) Page 196EO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 197 

### Environmental Fate (140)

Master Responses and Testnotes Test Notes for the Environmental Fate

Section

Please note that EPA responses and testnotes test notes 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 pr oposed environmental fate data requirements for indoor uses of antimicrobials greatly ex ceed 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 appr oach 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 asse rted that there should not be any environmental fate data requirements for materi al 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.EO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 198 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.

Response 140.3: In response to comments, EP A 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 asse rted 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 so urces 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 va rious 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 degrad e. Similar determinations are ma de 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 re sponse to this comment an d 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

, ;

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Master Responses: Environmental Fate Section (140) Page 199 (iii) The moiety of concern (i.e., functional group in the parent chemical molecule that imparts adverse effects) remains intact.

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 determ ining 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 ab ove. Those criteria are discusse d 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 a ssessments. 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 th at 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

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Master Responses: Environmental Fate Section (140) Page 200 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 th e 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 activa ted 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.EO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 201 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 evaluate d the information provided and agrees that there should not be a distinction between industrial process and wa ter 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 addi tional clarification is

needed in the testnotes test notes . 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 test note 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 photodegra dation 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 chemical s in soil, first requires an understanding of the soils properties. Soil profiles are descriptions of soil properties, both physical and chemical. Examples of physical characteristic s 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 this final rule, EPA will retai n the has retained the requirement for a photodegradation in soil study for the wood preservatives use pattern. The photodegradation in soil study is required for allEO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 202 wood preservatives, except for two circumstances. First, if the antimicrobial is an inorganic substance or a metal salt, then a photodegradation study does not provide applicable information for inorganics and metal salts that do not degrade (chemically or biochemically). Second, if data from

the standardized soil profiles show that the chemical is likely to readily degrade microbially or undergo redox reactions (degrade chemically ) ), to such a degree that there is no formation of degradation/transformati on/leachate products of concern (as define d in § 158.2280(a)(2)), then the photodegradation study in soils may study would not be required needed . EPA will add a new

testnote is revising proposed test note 10 to the environmental fate table to replace p roposed

testnote 10

, which was removed

. in § 158.2280. New testnote 10 will explain this condition test note 10 explains these two conditions for not requiring the photodegradation in soil study

. , and reads as follows: Data are not required if the antimicrobial is an inorganic substance or a metal salt; or if the standardized soil profiles demonstrate that the antimicrobial is likely to readily degrade either microbially or via redox reactions (chemically) and no transformation/degradate/leachate products of concern (as described unde r § 158.2280(a)(2)) are produced.

Comment140.14: A commenter asserted that nutrient removal test should also be required.

Response 140.14: This proposed rule focuses speci fically on data require ments 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 io ns, 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 Biodegra dability of Chemicals Di scharged to Wastewater” (Guideline number OCSPP 835.3280). This guideline is based on the Organisation for Economic Co-operation and Development (OEC D) guideline 314. Both of th e OECD and OCSPP guidelines

were finalized in October 2008, at approximately the same time th at the proposed rule published. The second alternative test is entitled “Simulation Test – Aerobic Sewage Treatment: A. ActivatedEO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 203 Sludge Units” (OCSPP 835.3240) and is based on OECD guidelin e 303. This guideline was also

finalized in October 2008.

Both the OECD Guideline 303 and the OCSPP Gu ideline 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/f rs/publications/Test_G uidelines/series835.htm

A table to crosswalk the two guidelines is below:

Title OECD OCSPP Biodegradation in a sewer sy stem 314A Begins on page 12 Biodegradation in activated sl udge 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 test note 9?

Response 140.17: Proposed testnote test note 9 triggers the aerobic soil metabolism stud y. Based on the timing of and amounts of water released, soil surfaces can dry-out, thus alternating between wetand 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 test note 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 test note 10 was meant to trigger the anaerobic soil metabolism study and the aquatic metabolism studies. The proc ess for conducting these studies is to flood the soil system in the test environment (water-logging it) to mimic conditions in which the soil isEO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 204 continuously wet. However, based on comments received proposed testnote test note 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 test notes 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.

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 an timicrobial 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 main tained 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” woul d 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 down-the-drain modeling could affect the need for this study.

Response 140.21: Proposed testnotes test notes 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-of-evidence evaluation process, is confusing, and believes that one trigger ( testnote test note 13) would be sufficient for triggering the aquatic sediment study. EPA will remove testnote test note
5 from the t est n ote test note no. column for the aquatic sediment study. Based on this re-evaluation, EPA believes that the aquatic sedi ment study should also be requi red for the antifoulant coatings and paints use pattern since an antifoulant use would meet the criteria of the trigger: T estnote Test

note 13. “...data are required based on the potential for aquatic exposure and if the weight-ofevidence 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 isEO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 205 likely to result in adverse effects on non

- target nontarget 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 Down-the-Drain 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 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 m onitoring (studies) of representative US waters is a very rare occurrence. If EPA were to require such a monitori ng 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 inform ation as part of a new tes tnote test note 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 shou ld 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 en vironmental 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 commentersEO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 206 argued that both methods “overe stimate leach rates and are no t 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 test note 15 will be revised to re move the AWPA methods. Testnote Test note 12 is added to require protocol review.

Proposed testnote test note 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 test note 16 will be revised to remove the ASTM

methods. Testnote Test note 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 bi odegradation 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 as sessing 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, incl uding 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 th e “low” and “high” exposure descriptors. Instead EPA will use its 12 antimicrobial use patterns to define the required data.EO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 207 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 Eu ropean Union (EU) and OECD Countries including Canada to develop and harmonize test guidelines for wood preservative leaching test methodologies: OECD 313 (see ht tp://www.oecd.org/dat aoecd/33/45/ 43403332.pdf ) and OECD 107 (see http://www.oecd .org/dataoecd/33/45/43403332.pdf ).

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 pest icide 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 moderate ly persistent. If the half-life is greater th an 180 days, then the chemical is regarded as persistent.

Comment 140.31: A commenter mainta ined 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 asse rted that EPA should make its assessments and methodologies publicly available.

Response 140.32: The Agency’s exposu re and risk assessment proced ures have been presented in numerous exposure and risk assessments for antimi crobial 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 down-the-drain 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 result s 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?EO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 208 Response 140.33: The responses to th e 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 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 co mment 130.1 addresse s this qu estion. (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 minimu s 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 toxi c 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 EC 50 values of less than or equal to 20 mg/L are likely to pose serious problems for su bsequent testing. Based on these considerations, for antimicrobials with an EC 50 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 EC 50 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 orEO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 209 the Porous Pot Test, and the ASSI test (unless the conditions of new testnote test note 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.

Response 140.35: The Environmental Fate Data Requi rements 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 co mments 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 no ntarget 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 Gu ideline Numbers si nce 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 internationalEO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 210 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 deve loping high-quali ty data that should satisfy EPA’s data need s for risk assessment.” Applican ts may develop their own test protocols; but, are encouraged (and for certain st udies required) to submit them to EPA for review and acceptance prior to testing to assure that the study would provide EPA with the needed

information.

Based on the comments received, the Testnotes Test Notes to the Antimicrobial

Environmental Fate Data Requirements Table in the final rule will read as follows:

T140.1 Testnote Test note 1 to the final Environmental Fate Data Requirements 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 Test note 2 to the final Environmental Fate Data Requirements 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 ta iling 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 Test note 3 to the final Environmental Fate Data Requirements Table

Proposed:EO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 211 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 Te sts to Assess the Biodegra dability of Chemicals Discharged in Wastewater,” or simulation test – aerobic sewage treatment: A. activated sludge units.

i. If the ASRI test EC 50 is equal to or less than 20 mg/L, then the applicant must choose

either to:

A. Conduct 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

. ”;

i. If the ASRI EC 50 is equal to or less than 20 mg/L, then the applicant must choose either

to: (A). Conduct a Biodegradation i n Activated Sludge as described in the “Simulation Tests to Assess the Biodegradability of Chem icals Discharged in Wastewater”; ( B). Conduct the Porous Pot Test; or ( B. Conduct the porous pot test; or

C ).

. Conduct the simulation test – aerobic sewage treatment: A. activated sludge units.

ii. If the ASRI test EC 50 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 th e Biodegradability of Chemicals Discharged in Wastewater,” the porous pot test, or the simulation test – aerobic sewage treatment: A. activated sludge units.

T140.4 Testnote Test note 4 to the final Environmental Fate Data Requirements Table

Proposed: Required if the pass criteria for the ready biodeg radation 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 % percent removal of dissolved organic carbon (DOC) and 60 % percent removal of theoretical oxygen demand (ThOD) or theoretical carbon dioxide (ThCO
2 ) 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 re quired. 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: A. activated sludge units.EO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 212 T140.5 Testnote Test note 5 to the final Environmental Fate Data Requirements 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” all other use patterns category (a s 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, bi odegradability, and activated sludge, respiration

inhibition tests. .

T140.6 Testnote Test note 6 to the final Environmental Fate Data Requirements Table

Proposed: For industrial processes and wate r systems (once-through), data are required based on a weight-ofevidence evaluation of the results of the hydrolys is, 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 co lumn 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 Test note 7 to the final Environmental Fate Data Requirements Table

Proposed: Adsorption and desorption using a batch equilibrium method is preferred. In some cases, as when the antimicrobial pesticide degrades rapidly, soil co lumn 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 Test note 8 to the final Environmental Fate Data Requirements Table

Proposed:EO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 213 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 Test note 9 to the final Environmental Fate Data Requirements Table

Proposed: For industrial processes and wate r systems (once-through), and aquatic areas, data are required for

use sites that are in termittently dry.

Final: For industrial processes and water systems, and aquatic areas, data are required for use sites that are intermittently dry.

T140.10 Testnote Test note 10 to the final Environmental Fate Data Requirements 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, Data are not required if the antimicrobial is an inorganic substance
or a metal salt; or if the standardized soil profiles demonstrate that the antimicrobial is likely to readily degrade either microbially or via redox reactions (chemically ). ) and no transformation/degradate/leachate products of concern(as described in § 158.2250(a)(2)) are produced.

T140.11 Testnote Test note 11 to the final Environmental Fate Data Requirements 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 Test note 12 to the final Environmental Fate Data Requirements Table

Proposed:EO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 214 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 Test note 13 to the final Environmental Fate Data Requirements Table

Proposed: For industrial processes and wate r systems (once-throug h), antifoulant paints and coatings, andwood 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 sy stems, wood preservatives, and the “ all other ” use patterns category (as specified in § 158.2280(a)(3)), data are required based on th e 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.

T140.14 Testnote Test note 14 to the final Environmental Fate Data Requirements 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 nontarget freshwater, estuarine, or marine waters such that human or environmental expos ures 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 Test note 15 to the final Environmental Fate Data Requirements 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 WoodEO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 215 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 Test note 16 to the final Environmental Fate Data Requirements Table

Proposed: For antifoulant paints and coatings, a leaching study is required. The Agency accepts the following method or its equivalent: American Society fo r Testing and Materials (ASTM) Method D5108–90. Prior approval of studies conducted according to D5108–90 is not requir ed. 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 Test note 17 to the final Environmental Fate Data Requirements Table

Proposed: N/A

Final: Protocols, which include the residues of concern (such as parent, degradate/transformation product, and/or leachate residues) that wo uld be monitored, must be approved by the Agency prior to the initiation of the study.

T140.18 Testnote Test note 18 to the final Environmental Fate Data Requirements 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;EO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 216 ii. Relatively volatile, but not hydrophobic; iii. Highly reactive. iv. Both the parent and all transformation/degradate products (as described under §

158.2280(a)(2)) have half-liv es of less than 3 hours.
v. None of the registered or proposed product uses could result in transport of the parent and its transformation/degrada te products (as described under § 158.2280(a)(2)) to a wastewater treatment plant.

T140.1 Testnote Test note 19 to the final Environmental Fate Data Requirements 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 K

ow is less than 3.0.

T140.20 Testnote Test note 20 to the final Environmental Fate Data Requirements Table

Proposed: N/A

Final:

If the criteria of testnote ( test note 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 K

ow is greater than or equal to 3.0. iii. The antimicrobial is positively charged or polycationic.

iv. The EC 50 in the activated sludge, respiration inhibition test is less than or equal to 20 mg/L.

v. The EC 50 in the activated sludge, respiration inhibition test is greater than 20 mg/L, and the antimicrobial fails the ready biodegradability study.

T140.21 Test note 21 to th e final Environmental Fate Data Requirements Table

Proposed: N/A

Final: The activated sludge respiration inhibition study is not required if none of the registered or proposed product uses would result in transport of the parent and its transformation/degradate products (as described under § 158.2280(a)(2)) to a wastewater treatment plant.EO 12866 Draft

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Master Responses: Environmental Fate Section (140) Page 217EO 12866 Draft

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Master Responses: Non-Target Plant Protection Section (150) Page 218 

### Non-Target Plant Protection (150)

Master Responses and Testnotes Test Notes for the Non

- Target Nontarget

Plant Protection Section

Please note that EPA responses and testnotes test notes 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 resu lts of the algal studies.

Response 151.1: The criteria to trigger higher- tiered plant studies are sp ecified in proposed

testnotes test notes 2 and 5 to the proposed nontarget plant protection table. A toxicity level (EC 50 <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 test note 5 to the nontarget plant protection table.

In evaluating proposed testnote test note 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 determin ed by appropriate assessment method s.” 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 test note 2 to the final Nontarget Plant Protection Data Requirements 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 test note 2 also triggers the aquatic plant growth (aquatic vascular plant) study, and is still the appropriate trigger for that study. A new testnote test note 10 to the final Nontarget Plant Protection Data Requirements Table will be created to replace testnote test note 2

and which will read: “For the ‘All Other’ use patterns category (as sp ecified in § 158.2250(c)), data are required if the aquatic (algal) plant growth Tier II study demonstrat es detrimental effects at less than 1.0 ppm or mg/L.

Comment 152.1: A comm enter noted that in t estnote test note 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 test note 13 to the proposed nontargetEO 12866 Draft

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Master Responses: Non-Target Plant Protection Section (150) Page 219 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 test notes should be consistent.

Response 152.1: EPA re-evaluat ed and compar ed these two testnotes test notes . Both of these

testnotes test notes 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 test note 13 of the proposed nontarget organism table and proposed testnote test note 3 of the proposed nontarget plant protection table. The following changes are made to proposed testnote test note 3.

 EPA has reconsidered the octanol/water partition coefficent as a trigger (3i) for the final Nontarget Plant Protection Data Requirements 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 test note 13 of the proposed nontarget organism table, EPA noted that proposed testnote test note 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 test notes should be consistent in their approach to pH levels used as a trigger. EPA will revise proposed testn ote test note 3ii of the proposed nontarget plant protection table to read the same as proposed testnote test note 13iii of the proposed 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 final Environmental Fate Data Requirements

Table.

As part of the re-evaluation of proposed testnote test note 3, EPA also considered if, based on the

revised testnote test note , 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 test note 3 to the final Nontarget Organism Data Requirements Table and most particularly on the new trigger included in testnote test note 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, t estnote test note 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 te st species are specified in both proposed testnotes test notes 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 appl ied directly to the terrestrial environment: there are many indoor uses. However, there are uses such as wood preservatives, thatEO 12866 Draft

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Master Responses: Non-Target Plant Protection Section (150) Page 220 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 mo re realistic information than a laboratory study and would be required on a very infrequent basis. Proposed testnote test note 8 specifies the triggers for requiring a terrestri al field study, on a case by case basis.

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 oc currence, 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 explai ned herein, EPA believes that the pl ant 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 prea mble which discussed the expected ph ytotoxicity 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 di sposal, 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 plantsEO 12866 Draft

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Master Responses: Non-Target Plant Protection Section (150) Page 221 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 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 test notes 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. Thos e risks are assessed sepa rately for the various taxa including plants, categories (e.g., freshwater, saltwater), and sh ort-term (i.e., acute) and longerterm (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 an d 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 prop osed rule (73 FR 59387), “they represent the recommended approach to developing high-quality data that should satisfy

EPA’s data needs for risk assessm ent.” 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.EO 12866 Draft

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Master Responses: Non-Target Plant Protection Section (150) Page 222 Based on the comments received, the Testnotes Test Notes to the Non

- Target Antimicrobial Nontarget Plant Protection Table in the final rule will read as follows:

T152.1 Testnote Test note 1 to the final Nontarget Plant Protection Data Requirements Table

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 Test note 2 to the final Nontarget Plant Protection Data Requirements 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 Test note 3 to the final Nontarget Plant Protection Data Requirements Table

Proposed: For low environmental exposures, and industrial processes and water system s (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 [§ 158.228 0] indicate that the active ingredient or principal degradation products are no t 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 Test note 4 to the final Nontarget Plant Protection Data Requirements TableEO 12866 Draft

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Master Responses: Non-Target Plant Protection Section (150) Page 223 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: 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 Test note 5 to the final Nontarget Plant Protection Data Requirements 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 (EC 50 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 Test note 6 to the final Nontarget Plant Protection Data Requirements Table

Proposed: For industrial processes and wate r 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 Test note 7 to the final Nontarget Plant Protection Data Requirements 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 Environmental chemistry methods used to generate data must include the results of a successful confirmatory method trial by an independent laboratory.

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Master Responses: Non-Target Plant Protection Section (150) Page 224 T152.8 Testnote Test note 8 to the final Nontarget Plant Protection Data Requirements Table

Proposed: 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 Test note 9 to the final Nontarget Plant Protection Data Requirements 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 Test note 10 to the final Nontarget Plant Protection Data Requirements Table

Proposed: N/A

Final:

For the “All Other” all other use patterns category (a s 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.EO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 225 

### Non-Target Organism Exposure (160)

Master Responses and Testnotes Test Notes for the Non

- Target Nontarget Organism Exposure Section

Please note that EPA responses and testnotes test notes 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 as sessment under FIFRA. According to the commenter, it is unclear why exte nsive ecotoxicity data are required for indoor

uses of antimicrobials

Response 160.1: EPA believes that it is taking a flexible appr oach to the antimicrobial data requirements for non

- target nontarget organisms and has built a ti ered 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, anti foulant paints and coatin gs, 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 ru le (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 assessm ent. The results of the down-the-drain assessment would provide EPA with estimated environmental concentrations (EECs) which whenEO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 226 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 test note 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 transformati on 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 nontarget organisms. In response to this comment and response to comment 140. 5, as part of re-evaluating th ese criteria, EPA determined to clarify and revise the criter ia to read as follows:

Data on transformation/degradation products or leachate residues of the parent compound are also required to support registrati on, 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 nontarget organisms or no n

- target nontarget plants. These criteria wi ll also be added to the

non

- target nontarget plant table as new §158.225 0(b). EPA believes that non

- target nontarget 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 final Nontarget Organism s Data Requirements Table. Instead the appropriate test material(s) such as TGAI, degradate, or TEP isEO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 227 specified in the data requirements table in proposed 40 CFR 158.2240. This approach is also used

for the conventional nontar get organism table in part 158. Ge nerally, for ecologi cal 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 non

target 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 to gether, 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 pr oposed 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 Endocrin e 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.EO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 228 For further information on the EDSP including the status and test guidelines, please visit our website: http://www.epa.gov/endo/

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Comment 160.5: A commenter asked why the species selected for the acute avian toxicity data requirement (proposed testnote test note 1) are different from those selected for conventional pesticides ( testnote test note 3 in the 2007 final rule).

Response 160.5: Proposed testnote test note 1 to the antimicrobial data requirements table for nontarget 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 test note 3 in 40 CFR 158.630 (the non

- target nontarget 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 test note 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 test note 7, even though it is NR.

Response 160.7: Proposed testnote test note 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 test note 7, is confusing and that clarification is needed.

The data requirements for TEP testing and proposed testnote test note 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 both the land or and 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 down-the-drain assessment for all appropriate use patterns which would include wood preservatives and antifoulant pa ints and coatings (s ee response to comm ent 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 CREO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 229 Acute freshwater fish toxicity (TEP testing): change from NR to CR Acute estuarine and marine organisms toxicity (TEP testing): change from NR to CR

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 antifoulan t 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 test note 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 test note 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 test note 7 will be revised to include an additional trigger: Data are required when “the end-use antimicrobial product will be applied directly into an aquaticenvironment.” 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 solubl e 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 test

note , which is replacing proposed testnote test note 5 (which was removed). This new testnote test

note states that an applicant should request a waiver if the TEP cannot be tested.

EPA also notes that a testnote test note 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 test note is needed for clarity. Testnote Test note 3 is added to the line for acute freshwater fish toxicity.

EPA also notes that the toxicity trigger for proposed test note 3 was incorrect as proposed. Proposed test note 3 states: “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 ifEO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 230 the active ingredient or principal transformation products are stable in the environment and the LC 50 in the first species is greater than 1 ppm or 1 mg/L. For the “All Other” use patterns, data are required on two species of fish, one cold water species and one warm water species.”

Also for test note 3, instead of greater than 1 ppm or 1 mg/L, the toxicity trigger needs to read less than or equal to 1 ppm or 1 mg/L. If the LC
50 is greater than 1 ppm this means that chemical tested was moderately to practically non-tox ic on an acute basis. If the LC 50 is less than 1 ppm this means that chemical tested was highly to very highly toxic on an acute basis and would have a serious adverse affect(s) on the organism tested at low concentrations. EPA correctly stated the toxicity trigger as “less than” in two proposed test notes (2 and 5) to the Nontarget Plant Protection Table. For clarity, EPA has corrected test note 3 to the final Nontarget Organism Data Requirements Table, to ensure that we codify the appropriate trigger (less than or equal to) to indicate that testing is needed for chemicals that demonstrate high to very high toxicity on an acute basis.

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.

Response 160.8: EPA proposed to require ac ute 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 nontarget 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 extremel y 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 to terrestrial plants caused by pesticides has antimicrobialsEO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 231 have 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 aquatic testing guidelines. Algae is are used as the primary te st species for acute testing of evaluating effects to 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 these algal studies while only conducted over a few days 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 test

note 7(i).

Response 160.9: Proposed testnote test note 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

LC 50 or EC 50 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 test note 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 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 LD 50 of 100 mg ai/kg or less requires a precautionary label statement that the pesticide is toxic to bi rds. 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 LD 50 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 eval uated 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 test

notes and with the appropriate triggers EPA would be able to require th e 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 CREO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 232 Proposed testnote test note 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 test note 5 is no longer needed and will be removed. Proposed testnote test note 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 test note 6(iii).

Response 160.11: A Kow (oct anol-water partition coefficient) eq ual 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 test notes 1 and 6 (for the avian reproduction study) are contradictory as testnote test note 1 specifies the study is required for low exposures and testnote test note 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 test note 6.

Response 160.12: Proposed testnote test note 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 test note 1 to clarify.

Proposed testnote test note 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 test note 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 test note 6, and is required, then revised testnote test note 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 test notes 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 test note 9 triggers the acute estuarine/marine organism toxicity study. Proposed test note test note 10 triggers the fish early-life stage and the aquatic invertebrate lifecycle study. Both testnotes test notes use “if the parent compound and/or transformation products are likely to enter the ‘freshwater ( testnote test note 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 envi ronment. These factors can include including proximity of use sites to coastal areas or streams and rivers emptying in to coastal waters, potentialEO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 233 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 re sponse to comments, proposed

testnote test note 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 taki ng a flexible approach to its ecotoxicity data requirements by using a tiered system of data re quirements. The three required acute non

- target nontarget 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 us ing 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 nontarget 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 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 ch aracterize the hazard and the risk to non

- target nontarget 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 test note 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 test note 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 list ed for the estuarine/marine organism testing. Four of those guidelines are fo r invertebrate tests an d 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-EO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 234 larval test (850.1055) or for a sh ell-deposition test (850. 1025). The one required invertebrate test is typically conducted with a shri mp. Guideline 850.1035 is for th e mysid shrimp, the preferred invertebrate species, but a penaei d 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 test note 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 test note 12.

Response 160.19: Proposed testnote test note 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 test note 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 no-observed-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 triggere d. 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 test note 12.ii: 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 reques ted 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 reproducti on effects alone is not likely to trigger the

criteria in testnote12 test note12 .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 a ssessment process.EO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 235 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 qua lity 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. Cu rrently, 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 Apri l 18, 2011, there are 242 pe sticide 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 Administ rator Jackson’s priorities.

Comment 160.22: A commenter has concerns abou t the quality assurance built into the testing guidelines for aquatic toxicity.

Response 160.22: EPA agrees that qua lity 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 registra tion 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 160, (2) the study does not meet the requirement s 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.EO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 236 Comment 160.24: A commenter inqui red 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 ai r emissions from the PO TW. 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 environm ental exposure grouping” as a descriptor fo r identifying data requirements for non

- target nontarget 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 ade quately characterize risk. This decision would be made on a case-by-case basis an d 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.

Response 160.27: EPA disagrees with this comment. Proposed tes tnotes test notes 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 (K d ) is used as an expression of binding capability of the chemical to sediments. The Agency’s justification for using K d > 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 (K

ow

) and the soil organic carbon-water partition coefficient (K

oc ) also are used by EPA as part of its decision process. Both values are frequently more available

than either the K d or half-life values. Proposed testnote test note 17, the trigger for requiring an acute sediment study, considers all three of these values.

Next, as explained in proposed testnote test note 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 numb er of comments (43) on sediment testing submitted to the docket for the conventional chemicals. EPA responded to those comments onEO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 237 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 ac ute 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 us es, 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 test notes 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 cond itionally required for all use patterns: testing would be triggered based on the criteria in proposed testnotes test notes 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.

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 test note 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 guidel ines 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.EO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 238 Comment 160.31: A commenter asked why EPA is re quiring honey bee testing for antimicrobials.

Response 160.31: Insect pollinator te sting 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 both the land or and 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 Test

note 20 to the non

- t arget organism final Nontarget Organism Data Requirements Table will be revised to reflect this change.

Comment 160.32: A commenter main tained 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 re sponse 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 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 pestic ide. 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 valu e 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 test note 5, which is replacing proposed testnote test

note 5 to the proposed nontarget organism table (proposed testnote test note 5 was removed). New

testnote test note 5 to the nontarget organism Final Nontarget Organi sm Data Requirements Table states that an applicant should request a waiver if the TEP cannot be tested.EO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 239 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 an timicrobials, 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 ch aracterize the risk and, if necessary, to mitigate the risk.

Comment 160.37: A commenter disagrees with the triggers in testnote test note 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 ar e relevant. pH can vary widely among natural lakes, ranging from 4.5 in poorly buff ered bog lakes to greater than 9.0 in hard water lakes. An hydrolysis study (con ducted according to guideline 835. 2120) is conduc ted in buffered water. OPP does not require hydrolysis testing in marine water, neither for antimicrobial pesticides nor for conventional pesticides.

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 environmen t 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 nontarget 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 prov ided 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.”EO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 240 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 performe d 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]. Instea d 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 Final Nontarget Organism and the Nontarget Plant Protection Data Requirements Tables i n 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 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 re quirements 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.EO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 241 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, invertebrate s, 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 theenvironmental 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 de scribed 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

non

- target nontarget organisms. For example, if an applic ant 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 Guidelin e 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 na tions which maintain comprehensive testing requirements for pesticides and indu strial 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 re commended 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 final Nontarget Organism Data Requirements Table. These revisions are di scussed in response

to comments 160.7 and 160.28.EO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 242 Based on the comments received, the Testnotes Test Notes to the Non

- Target Nontarget Organism Data Requirements Table will read as follows:

T160.1: Testnote Test note 1 to the Non

- Target final Nontarget Organism Data Requirements 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 co atings, wood preservatives, and aquatic areas, data are required for two avian sp ecies: one waterfowl species and one upland game bird species. For the “ A ll O ther ” all other use patterns category (as sp ecified in § 158.2240(a)(5)), data are required for one avian species.

T160.2: Testnote Test note 2 to the Non

- Target final Nontarget Organism Data Requirements Table

Proposed: Data are required on one freshwater aquatic invertebrate species.

Final: Data are required on one freshwater aquatic invertebrate species.

T160.3: Testnote Test note 3 to the Non

- Target final Nontarget Organism Data Requirements Table

Proposed: For low environmental exposures, data are required on one species of fish, either one cold water species or a warm water species. Te sting on a second species is requir ed if the active ingredient or principal transformation products are stable in the environment and the LC 50 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 pattern s areas, data are required on two species of fish, one coldwater species and one warmwater species. For the “A ll 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 one warmwater species. Testing on a second species is required if the active ingredient or principal transformation products

are stable in the environment and the LC 50 in the first species is greater less than or equal to 1 ppm or 1 mg/L.EO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 243 T160.4: Testnote Test note 4 to the Non

- Target final Nontarget Organism Data Requirements 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 LD 50 ( TGAI testing) is less than or equa l 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 LC 50 in the first species test ed 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 LD 50 ( 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 LC 50 in the first species tested is less than or equal to 500 ppm a.i. in the diet.

T160.5: Testnote Test note 5 to the Non

- Target final Nontarget Organism Data Requirements Table

Proposed:

This is a new testnote test note ; proposed testnote test note 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.

T160.6: Testnote Test note 6 to the Non

- Target final Nontarget Organism Data Requirements 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 (K

ow

is greater than or equal to 1,000), ac cumulation studies, me tabolic release and rete ntion 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.EO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 244 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 (K

ow

is greater than or equal to 1,000), ac cumulation studies, me tabolic release and rete ntion 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 Test note 7 to the Non

- Target final Nontarget Organism Data Requirements 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 LC 50 /EC
50 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: 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 LC 50 /EC
50 of the TGAI. ii. When based on probabilistic modeling results: If the estimated 10 th percentile 7Q10 Surface Water Concentration exceeds the acute concentration of concern (i.e., one-half the

LC 50 /EC
50 ) 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 Test note 8 to the Non

- Target final Nontarget Organism Data Requirements 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.EO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 245 T160.9: Testnote Test note 9 to the Non

- Target final Nontarget Organism Data Requirements Table

Proposed: For low environmental exposures, industrial pr ocesses and water system s (once-through), wood preservatives, and aquatic areas, data are requir ed if the pesticide residues from the parent compound and/or transformation products are likely to enter the estuarine/marine environment.

Final:

For the “ A ll O ther ” all other use patterns category (as specifi ed 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 Test note 10 to the Non

- Target final Nontarget Organism Data Requirements

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 EC 50 freshwater invertebrates; acute LC 50 /EC
50 estuarine and marine organisms; acute freshwater fish LC 50 ).

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 EC 50 freshwater invertebrates; acute LC 50 /EC
50 estuarine and marine organisms; acute freshwater fish LC 50 ).

T160.11: Testnote Test note 11 to the Non

- Target final Nontarget Organism Data Requirements

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.EO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 246 T160.12: Testnote Test note 12 to the Non

- Target final Nontarget Organism Data Requirements

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 10 th 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.

T160.13: Testnote Test note 13 to the Non

- Target final Nontarget Organism Data Requirements

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.EO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 247 T160.14: Testnote Test note 14 to the Non

- Target final Nontarget Organism Data Requirements

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 Test note 15 to the Non

- Target final Nontarget Organism Data Requirements

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 Test note 16 to the Non

- Target final Nontarget Organism Data Requirements

Table

Proposed: Data are required if the intended use pattern, and the physical/chemical properties and

environmental fate characteristics of the antimicr obial 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.

Final: Data are required if the intended use pattern, and the physical/chemical properties and

environmental fate characteristics of the antimicr obial 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 Test note 17 to the Non

- Target final Nontarget Organism Data Requirements

Table

Proposed:EO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 248 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 (K d ) is equal to or greater than 50. ii. The log K

ow is equal to or greater than 3.

iii. The K

oc 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 (K d ) is equal to or greater than 50 L/kg.
ii. The log K

ow is equal to or greater than 3.

iii. The K

oc is equal to or greater than 1,000.

T160.18: Testnote Test note 18 to the Non

- Tar get final Nontarget Organism Data Requirements

Table

Proposed: Data are required if the EEC in sediment is > 0.1 of the acute LC 50/ EC 50 values and if one or more of the following conditions are met: i. The soil partition coefficient (K d ) is equal to or greater than 50 L/kg.
ii. The log K

ow is equal to or greater than 3.

iii. The K

oc 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 LC 50/ EC 50 values and if one or more of the following conditions are met: i. The soil partition coefficient (K d ) is equal to or greater than 50 L/kg.
ii. The log K

ow is equal to or greater than 3.

iii. The K

oc is equal to or greater than 1,000.

T160.19: Testnote Test note 19 to the Non

- Target final Nontarget Organism Data Requirements

Table

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 thisEO 12866 Draft

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Master Responses: Non-Target Organism Exposure Section (160) Page 249 environment in significant concentrations either by runoff or erosion, because of its expected use or mobility pattern.

T160.20: Testnote Test note 20 to the Non

- Target final Nontarget Organism Data Requirements

Table

Proposed: Data are required only for beehive applications when the beehive (empty or occupied) is treated.

Final:

For the “ All Other” all other use patterns category (a s 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 Test note 21 to the Non

- Target final Nontarget Organism Data Requirements

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.EO 12866 Draft

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Master Responses: White Paper on Use of SAR and QSAR (170) Page 250 

### 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 st ated 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 describe d 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 propose d 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,EO 12866 Draft

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Master Responses: White Paper on Use of SAR and QSAR (170) Page 251 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 In developing such a guidance document for pesticides and is seeking , EPA sought to harmonize its approach with that of Canada’s Pest Management Regulatory Authority. It is anticipated that The guidance document would be was issued as a North American Free Trade Agreement guidance document during 2011. [update] in

2012. This guidance document will adhere adheres to the five OECD princi ples that were discussed in the white paper

. Once finalized, this document will , and is now considered to be the definitive source of information for applicants seeking to use SAR and QSAR approaches for fulfilling data requirements for pest icide registration. For information, see http://www.epa.gov/oppfead1/internati onal/naftatwg/guidance/guidance.htm.

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, subpar t 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 co nsider 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 ev idence approach, all empirical da ta 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.EO 12866 Draft

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Master Responses: White Paper on Use of SAR and QSAR (170) Page 252 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 disagr ees with this comment. As disc ussed in response to comment 170.2, EPA encourages submitters to use SAR, QS AR, 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 po tential 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 ch emical 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/23/0,334 3,en_2649_34377_ 33957015_1_1_1_37465,00.html

In 2007, NAS [National Research Council (NRC) (2007) Toxicity Testing in the 21 st Century: A Vision and a Strategy. National Academy of Sciences, Washington, D.C.EO 12866 Draft

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Master Responses: White Paper on Use of SAR and QSAR (170) Page 253 http://www.nap.edu/catalo g.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 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 wi th this comment and believes that various SAR techniques and QSAR models are sufficiently robust for use in risk assessment, includ ing environmental risk

assessment. As discussed in re sponse to comment 170.1, EPA ha s 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 environm ental risk assessment documents. Also, OECD released its guidance document “Strategies for Grouping Chemicals for Data Gap Filling for Acute Aquatic Toxici ty Endpoints” duri ng April 2010. (see http://www.oecd.org/da taoecd/4/47/45133663.pdf ) See also response to comment 170.4.EO 12866 Draft

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Master Responses: Endangered Species Section (180) Page 254 

### 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 th reatened 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 antimicrob ial pesticides and agricultural pesticides. As disc ussed in the proposed rule (Oct ober 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 orEO 12866 Draft

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Master Responses: Endangered Species Section (180) Page 255 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 in 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 commen ter. EPA has a robust program for completing antimicrobial environmental risk assessments, as outlined in the preamble to the proposed rule [59405]. Environmental fate studies ev aluate the mobility, di stribution and dissip ation 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 th e toxicological hazards of pesticides to various nontarget organisms, such as bird s, 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 envir onmental 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. Append ix A to that document – Over view 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 assessme nt 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 fateEO 12866 Draft

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Master Responses: Endangered Species Section (180) Page 256 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 an d the down-the-drain asse ssment 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, source s, 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 sh ould evaluate other EPA-administered programs such as the Clean Water Act to evaluate the ty pes 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 wh at 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 specie s 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 sp ecific data needs.EO 12866 Draft

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Master Responses: Guidelines Section (190) Page 257 

### 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 requi rements from “conditionally required (CR)” or “not required (NR),” to “required (R).” Thus th e 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 requiremen t tables that will be codified in part 158W, OPP is specifying EPA/OPP’s Harmonized Test Guidelines. Studie s 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 pe rformed differen tly 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. Fo r 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 wi th a permit’s WET limit(s). WET test s use diluted and un diluted (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 concen tration 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 spec ific chemical substance.EO 12866 Draft

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Master Responses: Guidelines Section (190) Page 258 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. Howe ver, EPA/OPP disagrees that results from WET testing methods would provide the chemical-specifi c 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 need s. 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 es tablish 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 test ing is required, but also considers results of acute

and chronic tests for a quatic species that are included in EPA ORD’s Ecotoxicology database, ECOTOX. ECOTOX integrates three previo usly 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 speci es 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.EO 12866 Draft

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Master Responses: Guidelines Section (190) Page 259 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 ca se-by-case basis, that were not conducted inEO 12866 Draft

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Master Responses: Guidelines Section (190) Page 260 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 test notes 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 a ssure 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 re quirement. 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 stud ies with pesticides, stud y 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 Terre strial Field Dissipation Guidelin e (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 un der 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.”EO 12866 Draft

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Master Responses: Guidelines Section (190) Page 261 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 deve loping 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 th e quality or completeness of data needed for a licensing decision before study conduct or submission occurs.

In 2008, OMB, during its Execut ive Order 12866 review of the prop osed 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 resi due 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 59 399

– 59401). EPA intends to finalize these guidelines in the near future. Also http://www.epa.gov/scipoly/sap/m eetings/1998/march/cont ents.htm). Since the two product use information related guidelines (no. 875.1700 and No. 875.2700) are expected to provide similar guidance for the narrative descript ions that the related data requirements call for, EPA intends to update them together.

The indoor surface residue dissipa tion draft guideline (No. 875.2300) wi ll be updated before issued in final form to account for new advances in how exposure is measured and modeled, and to provide more information on additional methods. EPA intends to revise the draft guideline to expand the methods for antimicrobial uses, and has begun to work with EPA’s Office of Research and Development (ORD) to develop additional methods (e.g., one current project is to develop guidance for testing in small scale air chambers). EPA is also consulting with the Consumer Product Safety Commission (CPSC) to review their sampling methods for similar products (e.g., chemical leaching from fabrics).

As previously discussed, the data requirement referencing the non-dietary ingestion guideline was removed from the final Post-Applicator Exposure Data Requirements Table in § 158.2270 (see response to comment 100.13).

As the guidelines for exposure studies are upda ted, 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 (a s defined at 40 CFR 26.1102(i)), then the study must not be initiated before submission of protocols and supporting documentationEO 12866 Draft

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Master Responses: Guidelines Section (190) Page 262 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.

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 publishe d 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 pr oposed 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) for comment. These four guidelines 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 draf t guidelines have been in use by the Agency for several years. Three additional product perf ormance guidelines (810.2400, 810.2500, and 810.2600) should be published for comment in a timeframe similar to that of EPA announced the publication availability

of the final rule for Antimi crobial Data Requirements. Similarly, guidelines in the nontarget organism and plant protection guidelines should be finalized by the end of this year. Federal Register of March 16, 2012 (77 FR 15750).

As of May 4, 2011, Three additional produc t performance guidelines (810.2400, 81 0.2500, and 810.2600) published for public comment on September 15, 2011 (76 FR 57031). EPA announ ced the availability of these three final guidelines in the Federal Register of June 27, 2012 (77 FR 38280).EO 12866 Draft

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Master Responses: Guidelines Section (190) Page 263 Also in the Federal Register of June 27, 2012 (77 FR 38282), EP A announced the availability of 26 Ecological Effects Test Guidelines, Groups B, C, D and F. In finalizing the guidelines, EPA changed the numbering and/or titles of certain guidelines, and split or merged other guidelines. EPA continues to work to revise the remaining Ecological Effects Test Guidelines, Group A:

Fifteen of these aquatic nontarget animal guidelines are exp ected to final in 2013. Changes to other of these aquatic guidelines are more substantive and will require additional time.

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

As Proposed Data Requirement As Proposed Guideline Status According to ACC

Comments EPA’s Response on

Status

§158.2210 Product chemistry 830.1550 Product Identity and Co mposition No comment Final 830.1600 Description of Materials used to

Produce the Product No comment Final

830.1620 Description of Producti on Process No comment Final 830.1650 Description of Formulat ion 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 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 Stabilit y No comment Final 830.6319 Miscibility No comment Final

830.6320 Corrosion characteri stics No comment Final

830.6321 Dielectric Breakdown Voltage No comment Final 830.7000 pH No comment Final 830.7050 UV/Visible Light Abso rption No comment Final 830.7100 Viscosity No comment Final 830.7200 Melting Point/Meltin g Range No comment FinalEO 12866 Draft

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Master Responses: Guidelines Section (190) Page 264 Guideline

As Proposed Data Requirement As Proposed Guideline Status According to ACC

Comments EPA’s Response on

Status

830.7220 Boiling Point/Boilin g 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. Final

810.2300 Sanitizers for Use on Hard Surfaces – Efficacy Data Recommendations Guideline has not been

made available for public comment. Final

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 Final 810.2500 Air Sanitizers – Efficacy Data

Recommendations Guideline has not been

made available for public comment. Final

810.2600 Disinfectants for Use in Water -- Efficacy Data Recommendations. Guideline has not been

made available for public comment. Final

§158.2230 T oxicolog y 870.1100 Acute oral toxicity – rat No comment Final 870.1200 Acute dermal toxicity No comment Final

870.1300 Acute inhalation toxici ty - rat No comment Final 870.2400 Primary eye irritation - rabbit No comment Final Split CellsEO 12866 Draft

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Master Responses: Guidelines Section (190) Page 265 Guideline

As Proposed Data Requirement As Proposed Guideline Status According to ACC

Comments EPA’s Response on

Status

870.2500 Primary dermal irritation No comment Final

870.2600 Dermal sensitizat ion 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 toxici ty No comment Final

870.3250 90-Day dermal toxicity No comment Final 870.3465 90-Day inhalation - toxi city - 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 developm ental toxicity - rat and rabbit preferred No comment Final

870.3800 Reproduction and fertil ity 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 pharmaco kinetics No comment Final 870.7200 Companion animal sa fety No comment Final 870.7600 Dermal penetration No comment Final 870.7800 Immunotoxicity No comment Final § 158.2240 Nontarget organisms.

850.1010 Acute freshwat er invertebrates toxicity Not Final Draft ** *

850.1075 Acute freshwater fish toxicity Not Final Draft ** *

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 actu al field testing for aquatic organisms Not Final Draft ** *EO 12866 Draft

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Master Responses: Guidelines Section (190) Page 266 Guideline

As Proposed Data Requirement As Proposed Guideline Status According to ACC

Comments EPA’s Response on

Status

850.1735 Whole sediment ; acute freshwater

invertebrates Not Final Draft ** *

850.1740 Whole sedime nt; 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** Final

850.2200 Avian dietary toxicity Not Final Draft** Final 850.2300 Avian reproduction Not Final Draft** Final 850.3020 Honeybee acute contact Not Final Draft** Final 850.3030 Toxicity of residues to honeybees Not Final Draft** Final §158.2250 Nontarget plant protection

850. 4100, (previously

850. 4225 ) Seedling emergence and seedling growth (previously, Seedling emergence, Tier II – dose response ) Not Final Draft**

Final

850. 4150 (previously

850. 4250 ) Vegetative vigor (previously, Vegetative vigor , Tier II – dose response ) Not Final Draft** Final

850.4400 Aquatic plant toxicity test using Lemna spp. (previously, Aquatic plant growth (aquatic vascular plant) Tier II – dose response ) Not Final Draft** Final

850. 5 4 5 00 Algal toxicity (previously, Aquatic plant growth (algal) Tier II (dose response ) )) Not Final Draft** Final

850.4300 Terrestrial plants field study (previously Terrestrial field) Not Final Draft** Final

850.4450 Aquatic plants field study (previously, Aquatic field) Not Final Draft** Final

§158.2260 Applicator exposure

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 an d calculations Cited † FinalEO 12866 Draft

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Master Responses: Guidelines Section (190) Page 267 Guideline

As Proposed Data Requirement As Proposed Guideline Status According to ACC

Comments EPA’s Response on

Status

875.1700 Product use informatio n 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 diss ipation 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 informatio n 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 wa ter Not available, even in

draft Final

835.2410 Photodegradation in so il Not available, even in

draft Final

850. 6800 3

300

OECD

209 Activated Sludge, Respiration

Inhibition Test Cited † Draft (OECD guideline is

available on the OECD website) 835.1110 Activated Sludge So rption Isotherm Cited † Final 835.3110 Ready Biodegradability Cited † Final 835.3220 Porous Pot Study Cited † Final

835.3280 Simulation Te sts to Assess the Biodegradability of Chemicals Discharged in Wastewater NA Final

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 FinalEO 12866 Draft

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Master Responses: Guidelines Section (190) Page 268 Guideline

As Proposed Data Requirement As Proposed Guideline Status According to ACC

Comments EPA’s Response on

Status

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 Chemistr y 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). 860.1340 Residue analytic al 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 ## FinalEO 12866 Draft

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Master Responses: Guidelines Section (190) Page 269 Guideline

As Proposed Data Requirement As Proposed Guideline Status According to ACC

Comments EPA’s Response on

Status

860.1340 Residue analyt ical 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).

* T hese three draft guidelines were published, and have completed the public comment period

. EPA is working on the response

- to

- comments document and revi sions to the guidelines. Target for publication of final guidelines is 2011.

** * Revision activities are almost completed. Target for publication Fifteen of these aquatic nontarget animal guidelines are expected to final in 2013. Changes to other of final these aquatic guidelines is 2011 are more substantive and will require additional time.

*** The final guidelines for dermal (875.1100, .1200, .1300, .1400, .2400), inhalation (875.1300, .1400, .2500), and biological (875.1500, .2600) al ong with the draft guidel ine for indoor surface residue dissipation (875.2300) need to be revised based on the emer ging 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.

## 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 guidelineEO 12866 Draft

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Master Responses: Guidelines Section (190) Page 270 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 ar e 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.

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 co ntinuing to harmonize guidelines, to the extent practicable, as they are revised. As noted on its websiteEO 12866 Draft

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Master Responses: Guidelines Section (190) Page 271 http://www.epa.gov/pesticid es/science/guidelines.htm , EPA has several harm onization 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 durati on 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. Th e 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/risk ssessment/guidance.htm) The Agency’s exposure and risk assessment procedures have been presented in numerous exposure and risk assessments for antimicrobial pesticides. EPA’s asse ssment 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 an timicrobial 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 fo r 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. 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 explainedEO 12866 Draft

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Master Responses: Guidelines Section (190) Page 272 the need for each study and provided background information on the purpose for which each study would be required. Part 158, subpa rt B contains an extensive descri ption 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 establishi ng data requirements fo r 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 partic ular data requirements. With few exceptions, these rationales are also applicable to antimi crobial 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 i nhalation studies for a heating, ventilation, air conditioning, and refrigeration us es (73 FR 59395), the need for a food migration study (73 FR 59404), and the need for environmen tal 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 discip lines 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 “inapplicab le” 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 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 with nonpesticidal uses

.

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 delineat e the requirements for developing and submitting descriptions ofEO 12866 Draft

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Master Responses: Guidelines Section (190) Page 273 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 CO 2 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 th at study, the applicant has the choice of several biodegradation studies, including the Porous Pot, to perform. For 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 a pplications to crops and noncrop areas; they do not include appropriate guidance for antimicrobial pesticides at are, by 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 areEO 12866 Draft

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Master Responses: Guidelines Section (190) Page 274 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. 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, dome stic 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, part icularly 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 test note 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 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 Safe ty Testing, 870.7200 [The] application of antimicrobials to companion

animals removes those uses from the definition See response to comment 80.97EO 12866 Draft

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Master Responses: Guidelines Section (190) Page 275 of pesticide, as such uses would be considered as animal drugs. This testing guidance is not applicable to antimicrobial pesticides. 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, dir ect 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 e ggs 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 30.26EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 276 

## 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 Sanitati on District (HRSD)

Letter ID: 0065

Comment ID: 25437

Comment Code: 10000EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 277 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 presen t 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 Antimi crobial 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 oppo rtunity 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 as sessment and the acknowle dgement 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.EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 278 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 Ru le, 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.EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 279 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 regulati ons 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.59386EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 280 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 chemic al 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, weEO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 281 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: 10000EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 282 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 submission s 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 he alth. 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 chem icals 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.EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 283 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 fo r 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. BalekEO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 284 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 response s 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 No s. 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 co mments 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.EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 285 We are in support of the overall recommendation that, upon consideration of all comments, the Agency should redraft an d 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 Clarif y 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 theEO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 286 proposal but are particularly evident in the defi nitions 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 pestic ides (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. EPAEO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 287 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 prog ressive 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.EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 288 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 prov iding 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: 10000EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 289 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 an d 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: 10000EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 290 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 ri sk management approach.

* The Proposal states that any fi nal 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 thresh old-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: 10000EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 291 Comment: The Agency has identified the intended app licability 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: 10000EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 292 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-proposa l 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: 10000EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 293 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 an d 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.EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 294 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 append ices 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 opportunit y 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 app licability 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.EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 295 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/issu es (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 Antimi crobials 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 "antimic robial 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: 25778EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 296 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 Progra ms (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 Progra ms (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. ShahEO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 297 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 adequate ly address FIFRA’s requi rements 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 pr oposal based on the SAP’s 1997 review."[FN#82:73 Fed. Reg. at 59427.] The Panel be lieves, however, that SAP review is necessary. Many changes have occurred since the 1997 SAP me eting, including chan ges 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 da ta 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.EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 298 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 a bout the absence of an y information on the risk assessment process EPA inte nds 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 pu rposes. 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 shal l 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 Agen cy repropose the rule.

Response: See responses 2, 3, and 20.4EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 299 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 processe s 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 no t subject to, a toleranc e 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 "ens ure 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 wi th 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 antimicr obial 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..EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 300 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 cosm etics (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) re quires 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").] FI FRA provides that these regu lations should "accelerate and improve the review of antimicrob ial 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; andEO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 301 (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: 0064EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 302 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 pr oposal based on the SAP’s 1997 review."[FN84: 73 Fed. Reg. at 59427.] LANXESS beli eves that this request was improper, and that the SAP cannot waive its statutory review obligat ion. 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 da ta 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.EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 303 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 a bout the absence of an y information on the risk assessment process EPA inte nds 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 propos ed legislation and regulations shal l provide a clear legal standard for affected conduct rather than a general stan dard, 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 OsloskyEO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 304 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 no t subject to, a toleranc e 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;EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 305 (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 "ens ure 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 agreemen t 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 ap plicable 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 cosm etics (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: 0086EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 306 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 seriousomission 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: 0071EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 307 Comment ID: 25667

Comment Code: 13000

Comment: Product use information needed for all antimicrobials

SFE has reviewed many EPA risk assessments indi cating 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 assessme nt 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 expa nded 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 asse ss 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 Sanitati on District (HRSD)

Letter ID: 0065

Comment ID: 25725

Comment Code: 13000EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 308 Comment: *The data quality objectives for risk assessment of these compounds must be outlined in advance of study planning and data collection in or der 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 po ints 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 comment s 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 toEO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 309 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 HornbackEO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 310 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 anti microbials 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 No t 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:EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 311 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: 13000EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 312 Comment: For all of these reasons, the Panel strong ly 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 en able 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 addres s complexities, and unus ual 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 asse ssment 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 re gulatory 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 fo r 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 imposi ng requirements based on "limited" rather thanEO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 313 "considerable" exposure. However, there is no rati onale 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 approa ch 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: 13000EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 314 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 deci sions 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 En vironmental Agents. Inte rim 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 allowregistrants 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: 13000EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 315 Comment: The Panel recommends that 40 CFR [Sec tion] 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 Wh ich Provisions Apply to

Antimicrobials

EPA must revise relevant sections of the existing 40 CFR Sectio n 158 to clarify those provisions that are applicable to antimicrobia ls. In particular, Subparts A and B must be amende d to include the appropriate references to antimicrobial pesticides and to Su bpart 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 antimicrob ial 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 determin e 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:EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 316 * 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 Comment s 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 theEO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 317 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 en able 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, LANXE SS 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 assessme nts 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 assessment s for antimicrobial pesticides. Instead, decisions on necessary data, risk assessments to be performed and re gulatory 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 makeEO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 318 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 approa ch 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 alte rnate 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/t oxicitytesting/ as announced at 74 Fed Reg. 12847 (March 25, 2009)], and substantial resources are being devote d 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 su pport a risk management decision."[FN71: Section XVIII, page 59421.]

Response: see response 4

Commenter Name: Stanley Oslosky Commenter Organization: Lanxess Corporation

Letter ID: 0064EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 319 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 Rese arch Council (NRC) 2006, Toxici ty 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 requireme nt 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 haveEO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 320 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 Sectio n 158 to clarify those provisions that are applicable to antimicrobia ls. In particular, Subparts A and B must be amended to include the appropriate references to antimicrobial pesticides and to Su bpart 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 antimicrob ial 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 determin e what is and is not appl icable 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 Comme nts at Section I)

Response: See response 3

Commenter Name: Stanley Oslosky Commenter Organization: Lanxess Corporation

Letter ID: 0064EO 12866 Draft

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Comments and Response References: General Comments on the Rule (10) Page 321 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 191.6EO 12866 Draft

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Comments and Response References: Administrative Comments on the Rule Section (20) Page 322 

### Administrative Comments on the Rule (20)

Verbatim Comments and Response Re ferences 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 ou r 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 ru le (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 FIFRAEO 12866 Draft

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Comments and Response References: Administrative Comments on the Rule Section (20) Page 323 Scientific Advisory Pa nel (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 developmen tal 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 rele vant 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 SA P and presented an early version of the Part 158 W proposal. In the wake of th e Food Quality Protection Act (FQPA), EPA consulted with the SAP as to the newly mandated FFD CA 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 chan ged regarding risk asse ssment 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 execu tion of a separate FFDCA 408 clea rance for pesticid e 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 an d 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: 0088EO 12866 Draft

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Comments and Response References: Administrative Comments on the Rule Section (20) Page 324 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 an d 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) th e 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 be tween proposed data requir ements and EPA’s statutory

determinations

Commenter Name: Brigid D. Klein Commenter Organization: Consumer Specialty Products Association (CSPA)

Letter ID: 0086EO 12866 Draft

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Comments and Response References: Administrative Comments on the Rule Section (20) Page 325 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 pertai ning 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 th e Registrant Rather than establishing Applicable Regulatory RequirementsEO 12866 Draft

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Comments and Response References: Administrative Comments on the Rule Section (20) Page 326 A significant concern of the prop osed 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 in dicates 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 deta il 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.EO 12866 Draft

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Comments and Response References: Administrative Comments on the Rule Section (20) Page 327 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: 23000EO 12866 Draft

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Comments and Response References: Administrative Comments on the Rule Section (20) Page 328 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 treatm ent system and reach surface wate rs 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: 23000EO 12866 Draft

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Comments and Response References: Administrative Comments on the Rule Section (20) Page 329 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 sh ould 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 1EO 12866 Draft

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Comments and Response References: Administrative Comments on the Rule Section (20) Page 330 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 sh ould 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 OsloskyEO 12866 Draft

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Comments and Response References: Administrative Comments on the Rule Section (20) Page 331 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 Proposa l 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: 23000EO 12866 Draft

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Comments and Response References: Administrative Comments on the Rule Section (20) Page 332 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 1EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 333 

### 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 sa me time products contai ning 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: 30000EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 334 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) re quires EPA to issue regulations on the registration requirements for antimicrobial pesticides that recognize the unique uses of antimicrobials.[FN#1: Federal Insecticide, Fung icide, and Rodenticide Act (FIFRA), 7 U.S.C. [Sections] 136a (h) (3) ("FIFRA"). ] FIFRA provides that these regu lations 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];EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 335 (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 fo r process management.[FN 3: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 al so United States v. Picotto, 875 F.2d 345, 345- 48 (D.C. Cir. 1989) (holding that the agency could not "interpr et" 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 FD A 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.EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 336 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. Categorica l pretreatment standards for discharges to POTWs are found at 40 CFR sec. 40 3.6 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 system s. 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. Re g. 49060, 49087 ff. (Aug. 10, 2000).] Yet there is no recognition of this fundamental fact in the data requirement regulation.EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 337 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 regula tion 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 30.26EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 338 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 la w" 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 circ umvent 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 "interpr et" 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 FD A 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 (hol ding 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 formEO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 339 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 system s. 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 WaterEO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 340 Intake Structures at New Facilities, 65 Fed. Re g. 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 an d 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 regula tion 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: 30000EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 341 Comment: XIII. The Proposed Rule Does Not Comply with the Applicable Statutes and Executive Orders Governing Notice an d 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: 31000EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 342 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 im pose more stringent co nditions 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 addr ess 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. AEO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 343 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.ht m] 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 [S ection] 158.2240(f)(10). 11 Id. at [Section] 158.2270(b). 12 Id. at [Sec tion] 158.2290(f)(23). 10 al most all of these in stances 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 regula tion by FDA as food additives pursuant to FFDCA section 409, while others are regulated as pesticide chemicals by EPA pursuant to FFDCA sect ion 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.EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 344 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 es tablishes 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.], includin g all active and inert ingredie nts 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 contac t 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 re gulated 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, administer ed 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:EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 345 * 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 criter ia 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 fo od 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 find ing must be consistent with th e 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 110.1EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 346 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 So lid 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 thefood."[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 logica l 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 pr eamble 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 wo uld 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.]EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 347 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 authorit y 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 inco nsistent 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 proposeddata 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. ShahEO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 348 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 exem ption 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 ne w or continued registration. Given this linkage between registration and tolerances, it makes sense for EPA to define data requirements for both purposes: the data re quired 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 proposeddata 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 furthe r 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 FI FRA 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 pestic ides. 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 cl eared, 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 ex ist. This creates a host of prac tical problems, including waste of government resources, potential for inconsistent deci sions, 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. ShahEO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 349 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 re gulations.[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 pe sticide chemical residues in fo od under section 408 of the FFDCA (leaving the Food and Drug Admi nistration the sole au thority 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 regu lations. 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 consiste nt with that statutory provision. Where there are no antimicrobial uses su bject 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 regulati ons; see also 40 CFR 400-471 for industryspecific effluent guidelines and standards, which cover the vast majority of industrial and

institutional users of antimicrobi als, 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.EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 350 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. George town 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 a dded). 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 inva lid."[FN#75:Id. at 220 (cit ing General Telephone Co. of Southwest v. United States, 449 F.2d 846, 8 63 (5th Cir. 1971); Nat’l Assn. of Independent Television Producers and Distributors v. FCC, 50 2 F.2d 249, 255 (2d Cir. 1974). EPA’s actions in promulgating Subpart 158W may be set aside if found to be "arbitr ary, 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 Hazard ous 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 toEO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 351 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 regula tion by FDA as food additives pursuant to FFDCA section 409, while others are regulated as pesticide chemicals by EPA pursuant to FFDCA sect ion 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 es tablishes 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:EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 352 (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.], includin g all active and inert ingred ients 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 contac t 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 secti on 409, administered by FDA).

* Antimicrobials with food uses regulated as pesticide chemicals (subject to EPA jurisdiction under FFDCA section 408) incl ude the following:

** Antimicrobials applied to raw ag ricultural 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; andEO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 353 ** 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 a ssessment 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 responsi bility 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 in cludes 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 au thority under Section 409 to regulate food additives."[FN48: 73 Fed. Re g. 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 logica l 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 pr eamble 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 wo uld 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 forEO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 354 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 authorit y 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 inco nsistent 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 proposeddata 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 OsloskyEO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 355 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 exem ption 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 ne w 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 proposeddata 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, withou t 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 stan dard 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 pestic ides. 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 cl eared, 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 ex ist. This creates a host of prac tical problems, including waste of government resources, potential for inconsistent deci sions, 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 OsloskyEO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 356 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 regu lations.[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 pe sticide chemical residues in fo od under section 408 of the FFDCA (leaving the Food and Drug Admi nistration the sole au thority 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 regu lations. 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 consiste nt with that statutory provision. Where there are no antimicrobial uses su bject 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 addr ess 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.ht m] 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 CorporationEO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 357 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 an d Hazardous Wastes. Further, federal, state, and local laws address what may be discharged to PO TWs 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 addr ess 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.ht m] 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 30.2EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 358 Comment Code: 32000 Harmonization with th e 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 inthe 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 pr oposes 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 in tent. 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 subm ission of a scientifically vali d 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 applicabil ity of a data requirement (p. 59386).

Response: See response 30.13EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 359 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,EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 360 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. Se ction 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: 32000EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 361 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/co mments, please refer to the proposed CFR 158W rule for the EPA require ments, and to http: //www.hc-sc.gc.ca/cpsspc/pest/registran ttitulaire/ prod/_daco-codo/index- en g.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 indust rial process fluids and water systems use pattern) *** eith er an adsorption/desorption stud y 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 no t 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 requirementEO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 362 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 (t he 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: 33000EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 363 Comment: General Comments:

Implementation of Part 158W EPA states in the pr eamble "Impact of this Proposal on Future and Existing Registra tions" (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 strong ly 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 finali zation of 158W would un fairly 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 cost s 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, th e 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 Admini strative 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 effectiv e date. For registrations pending atEO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 364 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.EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 365 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 30.15EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 366 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 acco rdance with Section 3(c)(5) of FIFRA.[FN#77:7 U.S.C. [S ection] 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 isexperimental 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 30.15EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 367 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) (e mphasis 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 Ge neral Telephone Co. of Southwest v. United States, 449 F.2d 846, 863 (5th Cir. 1971); Nat’l Assn. of Independen t Television Producers and Distributors v. FCC, 502 F.2d 249, 255 (2d Ci r. 1974). EPA’s actions in promulgating Subpart 158W may be set aside if found to be "arbitrary, ca pricious, an abuse of disc retion, 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: 33000EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 368 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-g rant 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: 33000EO 12866 Draft

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Comments and Response References: Legal Issues Section (30) Page 369 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 acco rdance with Section 3(c)(5) of FIFRA.[FN79: 7 U.S.C. [section]136a(c)(5).]

Response: See response 30.15EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 370 

### 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." (Ec onomic 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 Consid er the Costs of Regi stration 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 coul d presently estimate the data gaps for existing antimicrobials arising out of Subpart W. (Economi c 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, thes e requirements will serve as the benchmark for identifying data gaps during EPA' s registration review, just as Part 158 served as the benchmark forEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 371 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 Requireme nts 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: 0089EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 372 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 Na tional 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 assessmen t 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: 40000EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 373 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 regula tory agencies, and municipalities. The additional costs of $35,000-70,000 per chemical incurred by registrants are sma ll 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 su ch 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 de signation of a water body as impa ired 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. Califo rnia estimates that its average cost for preparing a single TMDL is $600,000.[FN4:California State Wate r 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 Legi slature 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 pl ans 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 receivingEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 374 urban runoff. These special moni toring and site- specific res ponse 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 re quired in response to ongoing pesticide-related toxicity in its urbanized watersheds. This municipality anticipates ongoing costs of nearly $100,000 per year for moni toring 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 conclude s 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 40.6EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 375 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,EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 376 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 Bu siness Regulatory Enfo rcement 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 in dustry 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 pest icide 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 on e 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.EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 377 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 ProposalEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 378 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 dise ase 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 coo ling 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 hu lls 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 artifa ct 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 us es 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 andEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 379 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 se q.] The Biocide Panel (L ANXESS 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 import ant 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 CorporationEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 380 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: S ee 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; Sm all Business Regulatory Enforcement Fairness Act, Pub. L. No. 104-121, tit. II, 110 Stat. 857, 864-68 (1996).] These Acts dictat e 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 businessesEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 381 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 de fined 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 ineach 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 le ss 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 pest icide 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 re gistrants. Under this calculatio n, 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., Projec t Director James Johndrow Mark LeBel David Nagler

NERA Economic Consulting 200 Clarendon Street, 11th Floor Bo ston, Massachusetts 02116 Tel:

+1 617 927 4500 Fax: +1 617 927 4501 www.nera.com

AcknowledgementsEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 382 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 associat ions, and international agencies. The global te am 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, ou r more than 45 years of experience creating strategies, studies, reports, expe rt 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-1EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 383 A. Full Compliance Costs of Propose d 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 Potent ial 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 Co mplete the Cost Analysis ..................9

1.Unit Test Costs............................................................10

2. Tests Likely Required for Registration Review.............................11

a. Tests Relative to Various Base lines.......................................11

b. High and Low Values.......................................................12EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 384 3. Summary of Updated and Expanded Data......................................12

C. NERA Updated/Expanded Cost Estimates......................................12

1. NERA Estimates of Costs for New Registration s and Major New Uses/Amendments................................................13

2. NERA Estimates of Costs for Exis ting Registrants..........................13

a. Compliance Costs fo r Existing Registrants.................................14

b. Distribution of Costs for Existi ng Registrants............................14

3. NERA Expanded/Complet e 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 Co st per Firm.................................17

b. EPA’s Assessment of Small Busine ss Impacts................................17

c. Limitations of the EP A 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 An timicrobial Pesticides ar e Withdrawal.................24EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 385 IV. Conclusions and Implications.............................................26

A. Full Compliance Costs of Propose d 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 Bene fits of Antimicrobial Pe sticides ..................39

B. Estimating Social Welf are Effects of Antimicrobial Pesticide Withdrawal...40

1. Change in Cost, No Change in Quality......................................41

2. Change in Quality, No Chan ge 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 Tech nical 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 Ex pensive and Same Quality..... 42EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 386 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 Qual ity 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 an d 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 Ne w Registrations................................. 13

Table 3. Annual Costs for Existing Active Ingredients Related to Registration Review.

............................................ 14

Table 4. Total Compliance Cost s 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 Fi rm 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 vari ety of registration requirements, including requirements related to product and residue chemistry, toxicology, environmental fate, ecotoxicity, human exposure, and product performance.EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 387 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 up dated 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 grea ter 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 ManufacturersEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 388 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 ou t 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 li ttle 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 prof its 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.EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 389 Experience both in the U.S. and Europe suggests that testing and other registration requirements can affect the number of pesticide products avai lable 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 acti ve ingredients. By 1998, 62 percen t 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 heatEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 390 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 requi rements would include those re lated 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 Require ments for Antimicrobial Pesticid es"), 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.EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 391 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 th us 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 re sults. 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.EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 392 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-bu t using updated and expand ed 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 develope d 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 Indu strial Uses and Miscellaneous Low Exposure. The probabilities were estimated for three scenarios as follows:

a. Current practices. EPA used a sample of re gistrations 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,EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 393 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 requireme nts, 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 sta ff 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 catego ries 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 do llars. 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.EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 394 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 th e 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.EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 395 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 severa l 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 expe rience) and the baseline.

* Number of future requested regi stration 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 partic ular, 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;EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 396 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/studie s, 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 sc heduled for registration re view 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 th an seven years; 2. Common practi ce 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.EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 397 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 develo p 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 ma jor 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 registrati on 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 revi ew. As noted above, we develop three sets of cost estimate s, as well as "high" and "low" es timates for each of the three cases for registration revi ew- related costs.

1. NERA Estimates of Costs for New Regi strations 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 forEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 398 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 fo r 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, incl uding 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 re sults 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]EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 399 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 ingredie nts. Figure 3 shows the total cost s 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 suggest s 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 Registra tion Review and New Registrations or Major New Uses/Amendments, Ap pendix J, PDF docket ID EPA- HQ- OPP-2008-0110-0088]

Note: All costs in millions of dollars per year, assu med to be 2008 dollars. So urce: 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 mi llion 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.EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 400 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 po ssible 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 cost s during the 2000-2005 period, EPA es timated 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 nu mber 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 22EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 401 small firms, or only 4.4 percent of the 500 small pe sticide 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 requireme nts to be about $61,000. This figu re is based on EPA’s estimateEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 402 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 elev en 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: NE RA 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 otherEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 403 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 th e 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:EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 404 * 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 increa ses 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 re gulations 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 pr oposed regulation. Two cases seem particularly relevant: (1) the 1988 amendments to FIFRA; and (2) the Biocidal Pr oducts 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 sectio n 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 an d 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 betwee n $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 fe deral registrations. By Oc tober of 1989, nearly 19,300 registrations had been cancelled. Subse quently, an additional 8,000 registrations were cancelled. Of the 600 active ingr edients contained in registered products, 124 were withdrawn from the market by 1990 and a total of 212 were withdr awn 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-EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 405 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 Commi ssion (Commission of the Euro pean 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-appr oved 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 si milar 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 evalua tion 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 wi th evaluation at the time.

The EU published a progress repo rt on the Directive in October 2008. This report su ggests 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 theEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 406 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 antimi crobial 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 substitute s. 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.EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 407 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., Li chtenberg et al. 1998, Osteen and Kuchler 1987). Although thes e studies use the basic framework outl ined 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 co sts that should be incl uded in a full assessme nt 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 grea ter 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.EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 408 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 ou t 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 manufa cturers 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 substantialEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 409 reductions in the number of acti ve ingredients. By 1998, 62 percen t 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 risk s 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.eur opa.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 withEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 410 Article 18(5) of the Directive) and Progress Repo rt 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/en vironment/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&co ntext=vpc14. Accessed March
5, 2009.

Fagerstone, Kathleen A., and Edward W. Schafer Jr. 1998. "Status of APHIS Vertebrate Pesticides and Drugs." Proceedings of the Eight eenth Vertebrate Pest Conference. http://digitalcommons.unl.edu/cgi /viewcontent.cgi?article=1010&co ntext=vpc18. Accessed March
5, 2009.

Hydrotox GmbH, Okopol GmbH and Ri sk & Policy Analysts Ltd. 2007. "Study on Impact of the Implementation of Directive 98/8/EC Concerning th e 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/repo rt_101007pdf/_EN_1.0_&a=d. Accessed March 5, 2009.

Lichtenberg, Erik, Douglas Parker , and David Zilberman. 1988. "Margi nal 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 Prot otype Explicit Analyses for Pesticides. 1980. "Regulating Pesticides." National Academies Press, Washington D.C. http://www.nap.edu/open book.php?isbn=0309029465, Accessed March 5, 2009.

Osteen, Craig and Fred Kuchler. 1987. "Pesticide Regulatory Deci sions: Producti on Efficiency, Equity, and Interdependence." Ag ribusiness. Fall. 3(3): 307-22.

U.S. Environmental Protection Agency (EPA). 2008. "Data Re quirements for Antimicrobial Pesticides; Proposed Rule." Federa l Register 73, No. 196. October.

U.S. Environmental Protection Agen cy (EPA). 2008a. "Economic Anal ysis of the Pr oposed 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; andEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 411 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 provid e 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 regi stration review cases schedu led 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 th e 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 test s 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 ofEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 412 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 stabili ty testing. (h) Assumes five major cr ops. (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 antimicrobia l pesticide were withdrawn would be equal to the decrease in consumer and producer surplus for the final good relative to the substitute. (ConsumerEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 413 surplus refers to the value consumers place on the product relative to the price they pay; producer surplus refers to the revenue producers receive rela tive 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 somewher e 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 wi thdrawal 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 differentEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 414 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 di scussed 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: AntimicrobialSubstitutes 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 CostEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 415 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: AntimicrobialSubstitutes 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 theEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 416 decline in consumer willingness to pay for the prod uct, 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, Append ix 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 si tuation in which antimicrobials are replaced in a downstream product with materials th at are both inferior and more ex pensive. 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 Bo ston, 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 OsloskyEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 417 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 anti microbial pesticide registrations that occurred from 2000-2005. The ACC Biocides Panel sponsore d a more comprehensiv e 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.EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 418 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 info rmation 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 extens ive and resource intens ive 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 se rvices. Included in ou r 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: 41000EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 419 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, andEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 420 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 co st 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, wh ether 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 unan ticipated, 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, Se ction 13385(j) for further de tails.] 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 co st to POTWs to comply with TMDLs can be up to millions of dollars per water body per pollutant.EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 421 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, wh ether 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 unan ticipated, 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, Se ction 13385(j) for further de tails.] 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 co st 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, wh ether 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 byEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 422 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 Calif ornia 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 perm it 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.EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 423 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 registra tion 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 throug hout 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. atEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 424 59428. The Panel believes that this approach has resu lted in a serious undere stimate 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 Re view, 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 incr emental 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 th at registration review would bring in a larger
number of firms, the incremental cost is $450,000, still more th an 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 approa ch $22.5 million.[FN#90:Id. at 25.]EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 425 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 ag ency’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 informat ion 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 pro cess 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 OsloskyEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 426 Commenter Organization: Lanxess Corporation

Letter ID: 0064

Comment ID: 26732

Comment Code: 42200

Comment: I. EPA’s Proposed Subpart 158W does No t 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 existi ng 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 firstEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 427 antimicrobial cases undergoing Registration Re view, 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 estima tes 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 incremen tal costs-is approximately $750,000, near ly twelve times high er than the EPA’s estimate of $61,000.[FN90: See Appendix J, NE RA Economic Consulting, Economic Analysis of Proposed U.S. EPA Biocide Data Requirements: Prepared for the American Chemistry Council, at 18 (Mar. 2009).] After considering th at 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: 0064EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 428 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 ag ency’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 informat ion to calculate the provided burden estimates under the Paperwork Reduction Act (PRA).[FN1 00: 44 U.S.C. [section]3501 et seq.] The EPA should include the paperwork burden costs for existi ng registrants, who are required to undergo the registration review pro cess every fifteen years.[FN101: S ee EPA, Economic An alysis 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 co sts 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: 0088EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 429 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 ade quacy 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 whic h 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 fo r 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 CorporationEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 430 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 whic h 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 fo r 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 (inclu ding 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 andEO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 431 approval process for four applicator exposure studie s. Similar costs also will be incurred for other applicator and post- ap plication (40 CFR sectio n 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 co mply with Executi ve 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.EO 12866 Draft

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Comments and Response References: Economic Analysis Section (40) Page 432 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 studie s. Similar costs also will be incurred for other applicator and post- ap plication (40 CFR sectio n 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 co mply with Executi ve Order 12866.

Response: See responses 3 and 40.6EO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 433 

### Antimicrobial Use Patterns (50)

Verbatim Comments and Response Refe rences 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 Chem istry Specific Comments

(a) General. - This section refe rences the Antimicrobia l 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: 50000EO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 434 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: 50000EO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 435 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 de gree 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 requirement s (40 CFR 158.120).EO 12866 Draft

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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 th e use patterns of the product, toxici ty, 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 do cument [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 requ irements. The use patterns currently identified for conventional pesticides and biopes ticides in 40 CFR 158.100 are largel y 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 requireme nt 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 conven tional, biochemical and mi crobial 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 AreasEO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 437 The following definitions from 40 CFR 153.2 are applic able to the above reside ntial 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 th e 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 Re gistrants to Associat e Specific Use Sites with the Use Patterns Identified in the Regulations

The Agency has stated in the prea mble (73 Fed. Reg. at page 59 390) and identified at proposed section 158.2201(b) (Id. at 59431) that it proposes to post guidance on its we bsite to relate specific use sites to the general use patterns. The document proposed to be posted as guidance was developed in 1997 without public in put. The Panel believes that th e 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 AgencyEO 12866 Draft

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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.

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 re flecting 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 Da ta Requirements for Non- target Plant

Protection

If antimicrobial use pattern categories are described elsewhere in the regulations besides Section 158.100, specific referen ce to the identification and description must be incorporated into the following paragraph. P&G supports the Biocide Pane l’s revisions to Section158.2240(a) as follows:

(a) General . Sections 158.100 through 158.130 desc ribe 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 repl aced 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 toEO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 439 aquatic sites. These include once- through cooling systems (where no pretreatment of the treated discharge occurs), antifoulant coatin gs, 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 Sectio n 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 VAGU E 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.EO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 440 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 Requirem ents for Nontarget Plant

Protection

If antimicrobial use pattern categories are described elsewhere in the regulations besides Section 158.100, specific referen ce 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 desc ribe 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 coatin gs, 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

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 441 (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 Sectio n 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 requirement s (40 CFR 158.120).EO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 442 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 th e use patterns of the product, toxici ty, 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 docume nt[FN1: Appendix B to the Apri l 30, 1997 draft data requirements presented to the FIFRA SAP in June 1997, avai lable in the docket as EPA-HQ- OPP-0110-0043.] that EPA has been using as if it were final since it was issu ed in 1997. Consider ing these product types as use patterns has not been useful in defining data requirements. The use patterns currently identified for conventional pestic ides 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 requireme nt regulations, and appl icable 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 AreasEO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 443 The following definitions from 40 CFR 153.2 are applic able to the above reside ntial 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 th e 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 Re gistrants to Associat e Specific Use Sites with the Use Patterns Identified in the Regulations

The Agency has stated in the prea mble (73 Fed. Reg. at page 59 390) and identified at proposed section 158.2201(b) (Id. at 59431) that it proposes to post guidance on its we bsite to relate specific use sites to the general use patterns. The document proposed to be posted as guidance was developed in 1997 without public in put. LANXESS believes that th e 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 AgencyEO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 444 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 an d re-proposed reflec ting 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 Requirem ents for Nontarget Plant

Protection

If antimicrobial use pattern categories are described elsewhere in the regulations besides Section 158.100, specific referen ce to the identification and description must be incorporated into the following paragraph. LANXESS offers the followin g revisions to Section 158.2240(a).

(a) General . Sections 158.100 through 158.130 desc ribe 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 coatin gs, 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,EO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 445 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 Sectio n 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 3EO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 446 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 Su rfaces, 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 cont rol falls under USC 2 (Aquatic Non-Food Sites) for the PMRA,

but it is classified under Industrial Processe s and Water Systems by the EPA. The PMRA has defined antifouling co atings and their use on underwater stru ctures 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: 0081EO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 447 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 evalua te 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 atEO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 448 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 Proposa l 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 50.1EO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 449 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 Characteristic s 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 most ly 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 indu strial 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:EO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 450 * 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, inco rporation 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, inco rporation 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:EO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 451 (1) On humans or pets, (2) In, on, or around any struct ure, vehicle, article, surface, or area associatedwith 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.EO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 452 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 pres ervatives 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 CorporationEO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 453 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 pres ervatives 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 processe s 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. Certai n 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 di fferences 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 treatmen t 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 AgencyEO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 454 Letter ID: 0085

Comment ID: 25579

Comment Code: 52910

Comment: Section Number VIII.

Title Toxicology Data Requirements

Paragraph C. Groupings for Antimicrobial To xicology 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 whic h 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 cuttingEO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 455 materials, which generates waste material (fine piece s 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 encl osed [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 municipalwastewater treatment plant operations. The attachment [See attachments in PDF docket ID EPAHQ- OPP-2008-0110-0089] includes examples of a ttempts (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 ou tdoor discharges may flow directly to surfaceEO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 456 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 fa ce 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. ShahEO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 457 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. Whil e 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 source s of public drinking water are su bject to regulation pursuant to the Safe Drinking Water Act (42 USC secs. 300f to 300j-28) and to regulati on under the EPA Office

of Water’s Disinfection By- Product rules. 40 CFR Parts 141 an d 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 th at 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 Wa ter Act. The scope of the 158W regu lation 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: 52912EO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 458 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. Wh ile LANXESS agrees that algaecides used in manmade structures, facilities and processes are antimicrobial pesticide uses, these sites of application are not aquati c 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 source s of public drinking water are su bject to regulation pursuant to the Safe Drinking Water Act (42 USC secs. 300f to 300j-28) and to regulati on under the EPA Office of Water’s Disinfection By- Prod uct rules. 40 CFR Parts 141 and 142. Therefore, an y 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 sourcesEO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 459 pursuant to the Safe Drinking Wa ter Act. The scope of the 158W regu lation 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 qualityEO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 460 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. Di scharges 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 outdoo rs 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

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 461 * 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 da ta 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 re gulation at 40 CFR 158.100 or to replace proposed 158.2201. Within the data tables, general use patterns should be combined in to 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 re gulated community. The Pa nel 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: 26659EO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 462 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 suggest ed revisions that are applicable regardless of the alternative approach to the data requirement tables.

If antimicrobial use pattern catego ries are described in sections other than S ection 158.100, specific reference to the identification and description must be incorporated into the following paragraph. 158.2230(a) should be complete ly rewritten as follows:

(a) General . Sections 158.100 through 158.130 desc ribe 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 elim inated in its entirety and re placed with th e 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 trea ted 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 Sectio n 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

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 463 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 propose d 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. In door 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 re gulation at 40 CFR 158.100 or to replace proposed 158.2201. Within the data tables, general use patterns should be combined in to 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 recommendsEO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 464 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 suggest ed revisions that are applicable regardless of the alternative approach to the data requirement tables.

If antimicrobial use pattern catego ries are described in sections other than S ection 158.100, specific reference to the identification and description must be incorporated into the following paragraph. 158.2230(a) should be complete ly rewritten as follows

(a) General . Sections 158.100 through 158.130 desc ribe 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 elimin ated in its entirety and replac ed with the foll owing: (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 shou ld 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. LA NXESS 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 incorporateEO 12866 Draft

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Comments and Response References: Antimicrobial Use Patterns Section (50) Page 465 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 propo sed 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 80.72EO 12866 Draft

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Comments and Response References: Product Chemistry Section (60) Page 466 

### Product Chemistry (60)

Verbatim Comments and Response Refe rences 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 CEO 12866 Draft

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Comments and Response References: Product Chemistry Section (60) Page 467 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 convention al 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 foot notes 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 design ated as only applicable to thos e 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). Th e 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 PanelEO 12866 Draft

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Comments and Response References: Product Chemistry Section (60) Page 468 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 identi fied 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 mu st 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 ex plain that the Agency historically has been interested in data on solubility in other solven ts. 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 an d as indicated in the Agency’s St andard Operating Procedures for Product Properties, January 8, 2003), the data requireme nt itself should be re vised 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 applicab le 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.EO 12866 Draft

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Comments and Response References: Product Chemistry Section (60) Page 469 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 convention al 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 foot notes 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 design ated as only applicable to thos e pesticides (70 FR 12276, March 11, 2005). As such, antimicrobial registrants were not put on notice that they should have reviewedEO 12866 Draft

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Comments and Response References: Product Chemistry Section (60) Page 470 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). LANX ESS 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 identi fied 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 mu st 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 ex plain that the Agency historically has been interested in data on solubility in other solven ts. 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 anEO 12866 Draft

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Comments and Response References: Product Chemistry Section (60) Page 471 industry group in February 2004 an d as indicated in the Agency’s St andard Operating Procedures for Product Properties, January 8, 2003), the data requireme nt itself should be re vised 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 60.6EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 472 

### Product Performance (70)

Verbatim Comments and Response Refe rences 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 guidel ines 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 av ailable. The Agency has been working on the 810 guidelines for several years and we ha ve 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 referenc e the appropriate 810 guid elines 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 Emergi ng Pathogens an d Disinfection Hierarchy for Antimicrobial Products: Notice of Availability. Federal Register Vol. 72 No. 142 [EPA-HQ-OPP-2007-0086]. Attached here.EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 473This 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 simi lar 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 an d Disinfection Hierarch y 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, adap table to change and encourage OPP to seek out other such opportunities for toxicological innovation.

A Subpart 158W Final rule should include a di scussion 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 evalua te 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)EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 474 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 Oc t 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 pr omulgated." (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 ca se-by- case basis, submission of efficacy data for any pesticide product registered or propo sed 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 ResistanceEO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 475 and will monitor the issue, we feel that this is in adequate 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 Emer ging 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 infectio ns (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 fi rst 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.EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 476 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 pe rformance guidelines addr ess 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 require ments should addres s procedures for ad dressing 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: 0075EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 477 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 Cl orox. 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 av oid comment on the product performance data requirements in the Proposal by stating that the Agency "is not proposing to revise product performance data requi rements ([section] 158.2220) at this ti me." 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-publicEO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 478 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 fo r 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 viralpathogens 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:EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 479 * 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. EP A 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 ar e still used as internal guidance, but are not available to applicants andEO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 480 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 Gu idelines. The Consumer Specialt ies Product Association (CSPA) provided input to the Agency in the development of the following proposed guidelines:

810.2000 - General Considerations 810.2100 - St erilants 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 fr om early 2006. The Agency has stated that these referenced 810 guidelines will be published as draft for public co mments 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/ad workplan2009.pdf] Publication has not occurred as of the

date of these Comments.

According to discu ssions with EPA, in contrast to the six categories propo sed at 158.2220, EPA intends to publish guidance on the following categories.

Guideline Number* Data Requirement(Ba sed 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.EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 481 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, thes e definitions we re taken verbatim from the Agency’s proposal on antimicrobial registration proc edures 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 re vised 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 intend s to include the definitions pro posed at 40 CFR 158.2203 in its final 810 Series Guidance documents, the Panel que stions why such defini tions 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 pr oposal 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 no t 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.EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 482 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 afte r decades of use, and are recognized by EPA as highly variable.[FN#5:Numerous peer-reviewed sc ientific studies publis hed 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 cooperat ive agreement between EP A 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). Furthe rmore, 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 Congress ional Requesters, Disi nfectants, EPA Lacks Assurance They Work". GAO/RCED-90-139. Au gust.). 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 antimicr obial PRIA fees tabl e with the 2008 PRIA reauthorization.[FN#6:PRIA category A521 is for an internal AD revi ew 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 categori es 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: 26568EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 483 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 fo r 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, hoofEO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 484 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 viralpathogens 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. Th e 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: 70000EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 485 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. EP A 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 situatio n 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 Gu idelines. The Chemical Specialt ies 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 - SanitizersEO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 486 The Biocides Panel has participated with CSPA in this process. The last drafts of the above guidelines available to CSPA and the Panel are fr om early 2006. The Agency has stated that these referenced 810 guidelines will pu blish 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.go v/oppad001/pdf_files/a dworkplan2009.pdf]

Publication has not occurred as of the date of these Comments.

According to discu ssions with EPA, in contrast to the six categories propo sed 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- Sterila nts 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, thes e definitions we re taken verbatim from the Agency’s proposal on antimicrobial registration pr ocedures 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 toEO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 487 be rewritten before reproposal. LANXESS is not aware of any current plans for publication of an updated proposal.] However, as part of the pr ocess to develop the 810.200 0 series antimicrobial efficacy guidelines, these have been significantly re vised 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 defini tions 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 refl ect current scientific k nowledge and current Agency regulatory practices." 73 Fed. Reg. at 59382. Unfo rtunately, this portion of the proposal is not curren t. 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 afte r decades of use, and are recognized by EPA as highly variable.[FN5: Numerous p eer-reviewed scientific studies published in the 1980s (e.g., Rutala,EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 488 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; Ru tala, 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 Requester s, 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 adde d to the antimicrobial PRIA f ees 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 categori es 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: 0064EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 489 Comment ID: 27663

Comment Code: 70000

Comment: 2. Proposed Regulation # [Section] 158.2220(a)(1)

Text of the Proposed Regulation (emphasis a dded) 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 EP A's Antimicrobial Division to devel op 810 efficacy guidelines for 810.2000 (General Considerations), 810.2100 (Sterilants), 810.2200 (Disinfectants) an d 810.2300 (Sanitizers). The last Agency draft of these guidelines has b een available since 2006. Pr eviously, 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 fo r public comment. In addi tion, 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: 70000EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 490 Comment: Section 158.2220 - Product Perf ormance Ecolab agrees with and supports the comments submitted by CSPA th at 158W should not be finalized or implemented until all 810 guidelines are finalized. The proposed rule refers to the 91 guidelines wh ich 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 Antimicrobi al Division to develop the 810.2000, 810.2100, 810.2200, and 810.2300 efficacy guidelines which have yet to be published fo r comment. In addition there are several outstanding 810 guid elines which have not be published or even drafted. As stated previously, OMB comments to the 158W rule requ ire 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 Gu idelines. The Chemical Specialt ies Product Association (CSPA) worked jointly with the Agency to develop the following proposed guidelines:

810.2000 - General Considerations 810.2100 - St erilants 810.2200 - Disinfectants 810.2300 -

Sanitizers

In addition, there are se veral outstanding 810 guidelines which ar e 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 bu ilding 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 disc ussions with EPA, in contrast to the six cate gories 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 guid elines. The antimicrobial product performanceEO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 491 requirements table provided on page 59432 of the Proposed Rule re fers 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 - Di sinfectants * 810.2300 -

Sanitizers

The last drafts of the above guid elines available to CSPA for cons ideration are from early 2006. The Agency has stated that these referenced 810 guidelin es will publish in draft 1st quarter of 2009 with a 60-day comment period.

In addition, there are se veral outstanding 810 guidelines which ar e either in draft form and/or have not yet been drafted. CSPA encourages the Agency to collaborate with Industry to develop these outstanding guidelines bu ilding 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 Re quirements/References

The Antimicrobial Product Perfor mance Data Requirem ents 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 th at it is appropriate to move forward with Part 158W until all 810

Guidelines are final. When th e 810 Guidelines are complete CS PA 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 abov e are finalized and only 810.2000, 810.2100, 810.2200 and 810.2300 are being prepared for publication for comment this fisc al 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 70.1EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 492 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) LA NGUAGE DEFINING NON-SPECIFIC

PUBLIC HEALTH CLAIMS SUCH AS "SANIT ARY" AS FIFRA PUBLIC HEALTH CLAIMS

SHOULD BE ENACTED WITH MINOR MODIFICATIONS

Proposed Section 158.2203(b)(5) provides that a product will be consid ered 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 mi croorganism 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 "cle anliness" claim rather than as a pe sticidal 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 Advert ising Review Board (''N ARB''), 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 te rm 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, an d a false and misleadi ng 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 majori ty of respondent s are shown toEO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 493 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 conducte d 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 wa s "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 st ating that the proposal is consis tent with the September 17, 1999 proposed rule entitled "Registration Requirements for Antimicrobial Pesticide Products and Other Pesticide Regulatory Changes". Th e preamble indicates on page 59391 that comme nts 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 disinf ectants and sanitizers is not nece ssary in order for EPA to issue product performance data. Product performance da ta 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 alreadyEO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 494 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 de finition of a public health pesticide in cludes 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)EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 495 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 subs ection (§ 158.2203). The preamble st ates 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 Requireme nts for Antimicrobial Pe sticide Products and Other Pesticide Regulatory Chan ges". The preamble indicates on page 59391 that comments were received on the previously proposed rule and cons idered 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 performa nce 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 70.11EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 496 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 [Sec tion]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 in tent, 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 receive d in regards to the 1999 regulato ry proposal and why the Agency feels these policy decisions are necessary for inclusion in the current proposal.

CSPA feels EPA should not include fundamental po licy 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: 77000EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 497 Comment: a. Comments on Proposed Definitions:

The definitions provided on page 59431 sect ion 158.2203 are inconsistent with the FIFRA § 4(i)(4)(C)(i, ii, iii)) and with th e definitions that we re provided in comments on the draft 810.2000 guideline submitted by CSPA to the Agency in Fe bruary 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 provid ed 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 app lied on or in the living body of ma n or other animals. Antiseptic products are not identified as pe sticides and are regulated by the Food and Drug Administration.

Aseptic means free of microbia l contamination consistent wi th 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".EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 498 Biocide means any substance, or mixture of substances, intended to reduce the number of livingmicroorganisms (e.g., virucide-virus, mycobactericide- mycobacteria, algicide-algae; bactericidebacteria; fungicide-fungi; slimicide- slime-form ing 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, ch emically 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 livingmicroorganisms (e.g., virucide-virus, mycobactericide- mycobacteria, algicide-algae; bactericidebacteria; fungicide-fungi; slimicide- slime-fo rming microorganisms). (See also "biocide.")

Microbiological water purifier means any unit, water treatment product or system intended to
remove, kill or inactivate diseas e- 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".EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 499Slimicide 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 referenc ed in terms of efficacy level and not by target organism or inte nded 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 "Sanit izers" 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 pe sticides. (Page 59431 Proposed 158.2203).

With EPA proposing new definitions for the te rms "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 "antimicr obial," is inconsistent with the intent of 40 CFR 152.25(a) if it is not prop erly qualified as to its inte nded non-public health use.EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 500 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 registrant s 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)) Ther e 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 determ ining if a product must be regist ered 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 th at "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 propo sed 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 dr aft 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.EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 501 As was pointed out to the Agen cy in industry comments to th e 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 reclassifica tion of "sanitary" as a pesticide claim must be removed from the draft Part 158 W rule and addressed th rough the appropr iate 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 rega rding definitions on page 59431 section 158.2203 are inconsistent with FIFRA § 4(i)(4) (C)(i,ii, iii) an d 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 ha s 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 dataEO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 502 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 anti microbials. The proposed pa rt 158 advocates the viewthat 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 re quirement ru le. This should be removed from the proposed 158W

rule.

158W is a new rule for antimicrobials and must be thorough in providing de finitions 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: 77000EO 12866 Draft

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Comments and Response References: Product Performance Section (70) Page 503 Comment: Definitions One of the problems with this proposal is demonstrated by the set of definitions proposed for 158.2203. As EPA acknowledges, these de finitions were taken verbatim from the Agency’s proposal on anti microbial registration procedures and labeling, proposed in 1999, but never finalized. However, as part of the pr ocess to develop the 810.200 0 series antimicrobial efficacy guidelines, these have been significantly re vised 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 "disinfect ant" 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 registrant s becomes untenable; therefore we need EPA to establish clear definitions.

Response: see responses 70.6 and 70.11EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 504 

### 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 refo rm, 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: ConclusionEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 505 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 pain ts and coatings. Antifoul ants 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 th e 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 To xicology Requirements Paragraph 8 p. 59393EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 506 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. Cumu lative 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: 80000EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 507 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 li terature 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: 80000EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 508 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, ho wever, 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 regu lation 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 im posed 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 PanelEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 509 Letter ID: 0088

Comment ID: 26576

Comment Code: 80000

Comment: In 1997, the SAP recogn ized 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 juri sdiction over antimicrobia ls 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 do es 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 dete rmine 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 d ecisions. 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 thisEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 510 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" syst ems 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 th at 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 huma n 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,EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 511 Response: See responses 50.4, 80.79, 3, 80.60, 80.22, 2, 80.80, and testnotes test notes 80.11 and

80.20

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 neurotox icity." 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 test notes 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 im posed 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 pesticidesEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 512 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 an timicrobial pesticides,..c onform[ing] the degree and type of review to the risks and benefits presente d,...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 recogn ized 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 juri sdiction over antimicrobia ls 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 approa ch 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 determinationEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 513 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 dete rmine 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 d ecisions. 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" syst ems 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 th at 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 514 5. The Agency does not define "considerable" in the phrase "high human exposure is defined as that resulting over a considerable portion of huma n lifespan."[FN4: Page 59392.] This should be 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 test notes 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 neurotox icity." 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 test notes 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 515 Response: see response 2

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 a dditional 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 test note 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: 81000EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 516 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, 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 cl ear 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 re sult in a near doubling of acute study costs for registrants. The current price fo r six acute studies generally re quired is approximately $35,000- $70,000 and requires 70-100 test animals. The addition al cost for the use-diluti on studies is estimated at $20,000-30,000 and could require additional 30- 40 test animals to comple te. 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: 0088EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 517 Comment ID: 26590

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 addi tional 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 distribu tion Test note #2 specif ies 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 test note 80.2

Commenter Name: Hasmukh C. ShahEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 518 Commenter Organization: American Chemistry Council Biocides Panel

Letter ID: 0088

Comment ID: 26593

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 no te #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 test note 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 519 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

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 require d 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; on e "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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 520 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 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 ch emistry 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) demonstr ates 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 dama ge. 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 521 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

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 re sult in a near doubling of acute study costs for registrants. The current price fo r six acute studies generally re quired is approximately $35,000- $70,000 and requires 70-100 test animals. The addition al cost for the use-diluti on studies is estimated at $20,000-30,000 and could require additional 30- 40 test animals to comple te. 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 acuteEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 522 oral toxicity. The Agency will also need to work with some states, fo r example, California, to obtain their acceptance of this approach.

Response: see response 80.11

Commenter Name: Stanley Oslosky 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 test note 80.2

Commenter Name: Stanley Oslosky Commenter Organization: Lanxess Corporation

Letter ID: 0064

Comment ID: 27299

Comment Code: 81000EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 523 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 no te #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, 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 dist ribution except as required by study protocols or unless a variance is granted after consultation with the Agency".

Response: see response 80.4 and testnote test note 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 524 Response: see response 3

Commenter Name: Stanley Oslosky Commenter Organization: Lanxess Corporation

Letter ID: 0064

Comment ID: 27304

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. (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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 525 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 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 ch emistry 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) demonstr ates 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 dama ge. 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 526 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 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 di ssipation 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 stud y would be acute in nature.

Response: see response 80.75 and testnote test note 80.15EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 527 Commenter Name: Adrian Krygsman Commenter Organization: Troy Corporation

Letter ID: 0091

Comment ID: 25951

Comment Code: 82000

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 neurotoxicit y 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 in dicate 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 th e 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: 82000EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 528 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 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 [S ection] 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 RequirementsEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 529 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:

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 fo od 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 test note 80.12

Commenter Name: Hasmukh C. Shah Commenter Organization: American Chemistry Council Biocides Panel

Letter ID: 0088

Comment ID: 26614

Comment Code: 82000EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 530 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 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 syst ems. 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, an d 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 enhan ced endpoints for each area of testing are as

follows:EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 531 * 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, a ggression, biting, licking, and self- mutilation), and pharmacological effects (e.g. sedation). In addition to the extensive functional assessment just described, this study should al so 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 532 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 fo r a registrant to understand the requirement. (See

Panel’s General Comment s at Section I)

Response: see response 80.16, and testnotes test notes 80.9, 80.10, 80.11, and 80.36

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 torecognize 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 observation s (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 shou ld 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 533 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 (Baskette r 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 toxi city yields an inadequate marg in 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 sensit ive 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 pesticid es (Doe et al., 2006) indi cated that when the dog wa s 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 534 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: 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: Propo sed Rule at [sectio n]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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 535 Response: see response 3

Commenter Name: Stanley Oslosky Commenter Organization: Lanxess Corporation

Letter ID: 0064

Comment ID: 26874

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 indir ect food use (less than 200 ppb).[FN45: Pr oposed 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 536 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 test note 80.12

Commenter Name: Hasmukh C. Shah Commenter Organization: American Chemistry Council Biocides Panel

Letter ID: 0088

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 pr oduct 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] 158.223 0(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)EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 537 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 su bchronic 90-day oral study in the same species may be required.

Response: see response 3

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 syst ems. 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."EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 538 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
doses in the acute studies, an d 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 enha nced 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, a ggression, biting, licking, and self-mutilation), and pharmacological effects (e.g. sedation). In addition to the extensive functional assessment just described, this study should al so 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 (Baskette r 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. Blac ker, 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 539 Solecki. L. Tilbury, B. van Ravenzwaay, and D. C. Wolf. 2006. A Tiered Approach to Systemic Toxicity Testing for Agricultural Chemical Safety Assessment. Cr it. 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

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 interpre tation for a registrant to understand the requirement. (See LANXESS’s Gene ral Comments at Section I)

Response: see response 80.16, and testnotes test notes 80.9, 80.10, 80.11, and 80.36

Commenter Name: Stanley OsloskyEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 540 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 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 torecognize 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 observation s (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 shou ld 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); andEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 541 * 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 (Baskette r 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.

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 toxi city yields an inadequate marg in 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 sensit ive 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 pesticid es (Doe et al., 2006) indi cated that when the dog wa s 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: 82000EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 542 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 stea dy state to determine if a longer duration dog to xicity 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.

7. Proposed Regulation # [S ection] 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 pr oduct 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] 158.223 0(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,EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 543 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

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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 544 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

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 specifica lly 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 residu es 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 thesesituations, 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 "s ignificant," "minimal," an d "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 cr iteria for factors such as "frequency, magnitude and dura tion," 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 AgencyEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 545 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

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 da ta, (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 isEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 546 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 th at 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 da ta 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 no ted below, CSPA recommends that EPA adopt a 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 (empha sis 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 870.41 00, 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 allEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 547 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 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 548 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 ar e 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.

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-mont h assay in the male and female ra t (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. Mous e-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. Blac ker, 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. Cr it. Rev. Toxicol. 36: 37-68.

* Monro, A. 1993. How Useful are Chronic (Life-Span) Toxicology St udies in Rodents in Iden tifying 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 80.24EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 549 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

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 test note 18 with "or", so that the testnote test note reads identical to that in 158.500. Also see testnote test

note 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 20EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 550 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 test notes 80.19 and 80.20

Commenter Name: Hasmukh C. Shah Commenter Organization: American Chemistry Council Biocides Panel

Letter ID: 0088

Comment ID: 26629

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 ba sed 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, Re formatted, 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 551 Response: see testnote test note 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 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 Febr uary 2008; ECHA, Guidance on information requirements and chemical safety assessment Chapter R.7a: Endpoint specific guidance, dated May 2008. should clarify whet her positive findings in in vitro assays alone woul d 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 ba sed 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 PanelEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 552 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 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: 26850EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 553 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 (empha sis 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 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,EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 554 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

Comment: In sum, EPA has significantly broadened the circumstances under which data will be required for many antimicrobial uses by imposi ng requirements based on "limited" rather than "considerable" exposure. However, there is no rati onale 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 ar e 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 555 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-mont h assay in the male and female ra t (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. Mous e-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. Blac ker, 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 St udies in Rodents in Iden tifying 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: 83000EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 556 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 test note 18 with "or", so that the testnote test note reads identical to that in 158.500. Also see testnote test

note 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."EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 557 Response: see response 80.16 and testnotes test notes 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 ba sed 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 justificat ions 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 Febr uary 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 558 Response: see testnote test note 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) 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 test notes 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 ba sed 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: 83000EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 559 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: 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 crit eria set out in this subsection.

Response: see response 3EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 560 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 th ree criteria for requiring a mouse oncogenicity study for nonfood use conventional pesticide):

"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 addi tional 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 anti microbial 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 studiesEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 561 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 (Batte rhill 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 dram atic. While the oxygen satura tion 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 runn ing in perpetual overdrive, a state that leaves the mouse vulnerable to perturbation of its normal cellular processes.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 562 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

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. SFEfeels 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 st udy 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; co st 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 [F N#8:Memorandum from D. Grant, PMRA to N. Cook, US EPA. December 1, 2007. Reproductive toxi city testing in proposed 40 CF R 158W. Available in the docket as EPA-HQ-OPP-2008-0110-0015]. PMRA analyzed 91 pesticides for whic h full toxicologyEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 563 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 wo rds, 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 co mplete discussion of the PMRA document and

how it formed the basis fo r 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- gene ration 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 propertiesEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 564 (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 toxicity observed in other studies, developmental effects are observed in the first species, or if exposure is limited by physical/chemical pr operties, 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, feta l development, and neonatal deve lopment (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-a dverse-effect level (NOAEL), then no further te sting would be required in Tier II for reproduction and developmental toxicity.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 565 The F1- extended one-generation reproduction study proposed in this testing scheme has been evaluated by the ACSA Li fe 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 limi tation of this one- genera tion 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 postnatall y. The example given at the 1987 EPA workshop on latent effects was acrylamide (She lby 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 an d Friedman, 2003).

Although there is a perception that some compounds might exert an adverse effect only in a second generation, preliminary results (unpub lished 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 a ssay 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 posi tive must be assumed.

Response: see response 80.41

Commenter Name: Hasmukh C. ShahEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 566 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 in the male and female rat (Batte rhill 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 dram atic. While the oxygen satura tion 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 # [S ection] 158.2230(e)(26)EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 567 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 # [S ection] 158.2230(e)(28)

Text of the Proposed Regulation (emphasis adde d) 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 toxi city testing in proposed 40 CF R 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 seeEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 568 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 wo rds, 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 co mplete discussion of the PMRA document and

how it formed the basis fo r 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 569 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. Eisenb randt, P. A. Fenner-Crisp, R. N. Hines, L. F. H.
Irvine, C. A. Kimmel, H. Koeter, A. A. Li, S. L. Ma kris, L. P. Sheets, G. J. A. Speijers, and K. E. Whitby. 2006. A Tiered Approach to Life Stages Test ing 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: 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, feta l development, and neonatal deve lopment (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 twoEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 570 species using the same route of administration, and if there is a sufficient margin of exposure (> 1000) for the lowest no-observed-ad verse-effect level (NOAEL), th en 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 Li fe 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 limi tation of this one- genera tion 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 postnatall y. The example given at the 1987 EPA workshop on latent effects was acrylamide (She lby 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 an d Friedman, 2003).

Although there is a perception that some compounds might exert an adverse effect only in a second generation, preliminary results (unp ublished 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 assayEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 571 The Ames/Salmonella bacterial point mutation a ssay 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 posi tive 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

This study, conducted using in vitro methodology, provides an assessment of the degree of dermal absorption, and allows determinat ion 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 validat ed, and have been demons trated 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 572 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.

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 # [S ection] 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 # [S ection] 158.2230(e)(28)EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 573 Text of the Proposed Regulation (emphasis adde d) 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

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 regard ing why the possibility of submitting waivers is mentioned for these two studies only. It seems to impl y that these studies would be more likely to be

waived than others. The PMRA seeks the EPA’s co mment 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...EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 574 HC Comment The triggers for requi rement 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 test notes 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

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 st udy 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; co st 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 [F N#8:Memorandum from D. Grant, PMRA to N. Cook, US EPA. December 1, 2007. Reproductive toxi city testing in proposed 40 CF R 158W. Available in the docket as EPA-HQ-OPP-2008-0110-0015]. PMRA analyzed 91 pesticides for whic h 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 ofEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 575 providing comments on the proposal. In other wo rds, 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 co mplete discussion of the PMRA document and

how it formed the basis fo r 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- gene ration 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 thereEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 576 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 test note 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

The studies in this section of Tier I testing are designed to ensure adequate coverage of all life stages, e.g. preconception, feta l development, and neonatal deve lopment (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-a dverse-effect level (NOAEL), then no further te sting 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 Li fe 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 limi tation of this one- genera tion 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 postnatall y. The example given at the 1987EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 577 EPA workshop on latent effects was acrylamide (She lby 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 an d Friedman, 2003).

Although there is a perception that some compounds might exert an adverse effect only in a second generation, preliminary results (unp ublished 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: 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 toxi city testing in proposed 40 CF R 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 wo rds, 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 didEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 578 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 co mplete discussion of the PMRA document and

how it formed the basis fo r 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 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 eff ects observed in a reproduc tive screening test or effects on reproductive organs are observed in acute or subchronic tests."EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 579 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

The studies in this section of Tier I testing are designed to ensure adequate coverage of all life stages, e.g. preconception, feta l development, and neonatal deve lopment (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-ad verse-effect level (NOAEL), th en 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 Li fe 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 limi tation of this one- genera tion 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 postnatall y. The example given at the 1987EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 580 EPA workshop on latent effects was acrylamide (She lby 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 an d Friedman, 2003).

Although there is a perception that some compounds might exert an adverse effect only in a second generation, preliminary results (unp ublished 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: 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 & GambleEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 581 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 inappropriat e. In fact, the draft data requir ements 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 wi th requiring an Ames as say with antimicrobials

is discussed in some de tail in the preamble (page 59397). P& G recommends other options including

the mammalian cell mutati on assay in either mous e 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 isEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 582 inappropriate. In fact, the draft da ta requirements proposed in 1997 sp ecifically state "for chemicals designed to kill bacteria, a re verse mutation assay may be pe rformed in mouse lymphoma L5178Y cells in culture." The problems with requiring an Ames assay with antimicrobials is discussed in some detail in the preamble (p age 59397). It is unclear from eith er 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 To xicology Data Requirements) fo und on page 59434 has an incorrect guideline number listed under in vivo cytogenetics. The EPA should remove 870.5380 - Mammalian Spermatogonial Chromosome Aberrati on 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 test notes 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 assayEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 583 The Ames/Salmonella bacterial point mutation a ssay 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 posi tive 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

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 RequirementsEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 584 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 da ta requirements proposed in 1997 sp ecifically state "for chemicals designed to kill bacteria, a re verse mutation assay may be pe rformed in mouse lymphoma L5178Y cells in culture." The problems with requiring an Ames assay with antimicrobials is discussed in some detail in the preamble (p age 59397). It is unclear from eith er 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 To xicology Data Requirements) fo und on page 59434 has an incorrect guideline number listed under in vivo cytogenetics. The EPA should remove 870.5380 - Mammalian Spermatogonial Chromoso me 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 dete rmine the next level of testin g 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 test notes 80.31 and 80.32EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 585 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

The Ames/Salmonella bacterial point mutation a ssay 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."EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 586 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 (includi ng 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

Comment: Section Number VIII.

Title Toxicology Data Requirements

Paragraph H. 90-day Dermal and 90- day Inhala tion 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 appl icators. 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 prop osal outlined in this section of CFR 158W.

Section Number VIII.

Title Toxicology Data Requirements

Paragraph M. Developmental Toxici ty (DNT) Paragraph 3, p. 59396EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 587 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 encourag ed 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 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 WEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 588 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 "HVA C" 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 test notes 80.6 and 80.15

Commenter Name: James A. Westerhaus 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 neurotoxic ity 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 testEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 589 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 test note test note 18 with "or", so that the testnote test note reads identical to that in 158.500. Also see testnote test

note 80.18

Commenter Name: Hasmukh C. Shah Commenter Organization: American Chemistry Council Biocides Panel

Letter ID: 0088

Comment ID: 26643

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 pa ge 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 th e 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 test notes 80.28 and 80.30

Commenter Name: Hasmukh C. Shah Commenter Organization: American Chemistry Council Biocides Panel

Letter ID: 0088EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 590 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 torecognize 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 observation s (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 shou ld 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)EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 591 * In addition, the lymphoid tissue that drains or contacts the site of chemical administration should be specifically examined (Baskette r 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

Comment: Systemic Toxicity

If the rodent 90-day subchronic toxi city yields an inadequate marg in 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 sensit ive 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 pesticid es (Doe et al., 2006) indi cated that when the dog wa s 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)EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 592 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

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".EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 593 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 test note 18 with "or", so that the testnote test note reads identical to that in 158.500. Also see testnote test

note 80.18

Commenter Name: Stanley Oslosky Commenter Organization: Lanxess Corporation

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 ex ample, 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 establ ished 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 st udy is currently listed in Section M on page 59396 of the Federal Register notice (F R 73, No. 196. October 8, 2008).]EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 594 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 test notes 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

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 torecognize 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 observation s (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 shou ld also include a satellite group of animals forEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 595 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 (Baskette r 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.

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 toxi city yields an inadequate marg in 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 sensit ive 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 pesticid es (Doe et al., 2006) indi cated that when the dog wa s 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 596 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

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 test note 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 597 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 Immunotoxi city 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 inconsistenc y. 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 immu nization. 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 su ggest that a longer exposu re 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 598 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 test note 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 Immunotoxi city 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 inconsistenc y. 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 immu nization. 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 performedEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 599 at a later time point if data from ADME studies su ggest 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 test note 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 consiste nt 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 theEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 600 best science in moving to ward 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

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 Re port 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:Na tional Research Counci l (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 stra tegic vision and an implementation plan to address the NRC 2007 vision for the Agency.[FN#37:National Research Council (NRC). 2007. Toxicity Te sting in the 21st Century. A Vi sion 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: 26616EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 601 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 (Baskette r 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. Blac ker, 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. Cr it. 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 associ ated 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 602 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 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 fo rmulating 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 cond uct a meaningful and acceptable study. 3) The systemic dose cannot be de fined. 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 in dicates 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 test notes 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 respondEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 603 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 Pene tration 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 vi vo studies; 2) would ha rmonize 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 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 to ward 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 test note 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 VitroEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 604 This study, conducted using in vitro methodology, provides an assessment of the degree of dermal absorption, and allows determinat ion 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 validat ed, and have been demons trated 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 associ ated 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 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 605 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 fo rmulating 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 cond uct a meaningful and acceptable study. 3) The systemic dose cannot be de fined. 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 in dicates 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 test notes 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 Pene tration 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 vi vo studies; 2) would ha rmonize EPA requirements with those in the EU and elsewhere; and 3) reduces the unnecessary use of live animals.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 606 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 consiste nt 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 de rmal 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 active s 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 test note 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 determinat ion 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 validat ed, and have been demons trated 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: 89100EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 607 Other EPA Comment Codes and Descriptions: 89110 Tiered approach to toxicology studies; 89111 High exposure uses (including: food and drinki ng water; outdoor aquati c uses; indirect food uses with residues equal to or greater than 200 parts per bil lion (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 characterize d. 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

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 test note 80.35

Commenter Name: Hasmukh C. Shah Commenter Organization: American Chemistry Council Biocides PanelEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 608 Letter ID: 0088

Comment ID: 26648

Comment Code: 89101

Comment: G. Comments on Metabolis m 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 (P K) studies (870.7485) are require d (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 ex posures 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, an d 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 do cket 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 1EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 609 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 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 info rmed decisions when designing heal th 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. Dilib erto, N. G. Dorrrer, J. H. Driver, C. E. Hastings, S. Iyengar, R. Krieger, B. Stahl, and C. Ti mchalk. 2006. The Acquisit ion 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 te sts 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 610 Response: see responses 80.4 and 80.57, and testnote test note 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 satura tes 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 st udy 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: 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 stea dy state to determine if a longer duration dog to xicity 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. ShahEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 611 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

Comment ID: 27339

Comment Code: 89101

Comment: G. Comments on Metabolism and Pharma cokinetics 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 (P K) studies (870.7485) are require d (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 ex posures 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, an d 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) ifEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 612 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 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 613 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 re sults 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 te sts 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 1, 80.4, and 80.57, and testnote test note 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 st udy 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 614 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.

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: 89110EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 615 Comment: As important, the Proposed Rule insists upon specifically mandating the animal assay required for each toxicological endpoint, produc ing 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 Ru le insists upon specifically mandating the animal assay required for each toxicological endpoint, produc ing 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: Marion Law Commenter Organization: Health Canada: Pest Management Regulatory Agency

Letter ID: 0085

Comment ID: 25565

Comment Code: 89110

Comment: *There is some uncertainty re garding the tiered data syst em 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 an d 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: 25620EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 616 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 intr oduction 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 Fede ral 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 with exposure data, form the basis for the human risk assessment ...The duration of the toxicity study approximates the estimate d duration of human exposure...If a pest icide is used on food and requiresa tolerance, the dietary exposure may be over a lifetime, and thus chronic/cancer and multigeneration reproductive studie s 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 ti er what studies are reason able and appropriate in light of the toxicity of antimicrobials and likely and realistic human exposure to antimicrobials?

a. CSPA Urges EPA To Differentia te 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: 89110EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 617 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 ex posure 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.

c. EPA’s Note 17 accompanying [S ection]158.500 (first of two criter ia 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 de termined 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 us e dilution may result in "significant ex posure." [FN#4: Fede ral Register, 73(196),EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 618 10/8/2008, p. 59394- "EPA proposes to add a test no te 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. TheAgency 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

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 PP E 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 conducte d with the product formul ated for sale and dist ribution." 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 irri tation 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 619 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:

"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 distri bution 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 framew ork 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 3EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 620 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, 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 reco gnizes that continua l 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 Neon atal 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 Noti ce,[FN4: U.S. EPA. 2008. Data Requirements for Antimicrobial Pesticides; Proposed Rule. Federal Re gistrar, 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 80.62EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 621 Commenter Name: James A. Westerhaus Commenter Organization: ECOLAB

Letter ID: 0072

Comment ID: 25746

Comment Code: 89110

Comment: Draft 158 W Definition of "Hig h" and "Low" Exposure The us e 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" ca tegories. 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 use as "high exposure" when there is neither scient ific 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 sc ientific 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 be ing 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)EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 622 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.

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 previo usly 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: 89110EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 623 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

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 antimicr obials and demand di fferent 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 CorporationEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 624 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

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); Fina l 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 in to 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 80.59EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 625 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

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 TieringEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 626 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 requi rements, 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 compound s with greater potential hazard or with greater potential exposure generally require more information than compounds with lower potential hazard

or exposure.

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 dividi ng 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 va lue 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: To xicology Recommendations, Apri l 2002; and FDA, Guidance forEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 627 Industry: Preparation of Food Contact Notifications and Food Additive Petitions for Food Contact Substances: Chemistry Recommendations - Final Gu idance, April 2002. See also FDA, Estimating Dietary Intake of Substances in Food, August 2006; and FDA, Gu idance for Indust ry; 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 ad opt 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 concentrat ion of 200 ppb as equivalent to an estimated dietar y 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 directly to food and other indirect additives) than are used for food contact substances. Further,

even for biocides as fo od contact substances, the 200 ppb dietar y concentration is not an absolute level with absolute data requirements or an ab solute decision re garding 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 th e 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 requirement s 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 expos ure.[FN#33:Report of the June 1997 Meeting of the FIFRA Scie nce 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 rej ected 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 628 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 si gnificantl y 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.

Further, the Panel believes that the Proposal does not implement many of the recommendations made by the 1997 SAP and fails to provide any ra tionale 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 inco rporate meaningful tier ing for antimicrobial pesticides. The Panel’s suggested approach for doing so is set forth below.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 629 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

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 us es; indirect food uses with resi dues 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) minimizeEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 630 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 us es; indirect food uses with resi dues 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: 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).]EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 631 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."

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 TieringEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 632 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); Fina l 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 compound s with greater potential hazard or with greater potential exposure generally require more information than compounds with lower potential hazard

or exposure.

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 issu es 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: 89110EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 633 Comment: The Agency proposes setting a level of 200 ppb as a dividi ng 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 va lue 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

Food Contact Substances: Toxi cology Recommendations, Apr il 2002; and FDA, Guidance for Industry: Preparation of Food Contact Notifications and Food Additive Petitions for Food Contact Substances: Chemistry Recommendations - Final Gu idance, April 2002. See also FDA, Estimating Dietary Intake of Substances in Food, August 2006; and FDA, Gu idance for Indust ry; 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 EP A 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 concentrat ion of 200 ppb as equivalent to an estimated dietar y 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 fo od contact substances, the 200 ppb dietar y concentration is not an absolute level with absolute data requirements or an abso lute 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 Scie nce Advisory Panel, atEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 634 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 lette r of December 14, 2000, available at EPA-HQ-OPP-2007-0151.] EPA reject ed 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.

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 Re port 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: Na tional Research Counci l (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 Te sting in the 21st Century. A Vi sion 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: 89110EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 635 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 # [S ection] 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 crit eria 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 si gnificantly 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 ra tionale 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 636 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 conv entional pesticides,[FN1: 40 CFR 158.510.] and biochemical pesticides.[FN2: 40 CFR 158.2050.] The Proposal s hould be revised to in corporate meaningful tiering for antimicrobial pesticides. LANXESS’s suggest ed 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 us es; indirect food uses with resi dues equal to or greater than 200 parts per billion (ppb); wood preservatives; metalworking fluids; swimming pools)

Comment: A. Alternative Proposal 1EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 637 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 la rge, 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

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 preser vatives; 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 OsloskyEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 638 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

Comment Code: 89111 High exposure uses (i ncluding: food and drinking water; outdoor aquatic
uses; indirect food uses with re sidues 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 639 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

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 la rge, e.g. greater than 1000, Tier II and Tier IIIEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 640 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

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 (suggest ed 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. 59433EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 641 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

Comment: In 2007, the Panel proposed to the Agency a framework for capturin g 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 framewor k 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: 89120EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 642 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

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 RequirementsEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 643 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)

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: 89130EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 644 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 te sting alternatives

Commenter Name: Patrick H. Quinn Commenter Organization: Innovation and Reform Group (IRG)

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 encourag ing 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: 0092EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 645 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.

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 fi nal 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 Stra tegic Plan for Evaluating th e 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 notEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 646 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 encourag ing 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 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 emer ging science, and to improve Su bpart 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 comp rehensive 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 testingEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 647The 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 comb ine 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 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 b ecomes 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: 89140EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 648 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 Anti microbial 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

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 requireme nts 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 ma terial 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 649 Response: see response 80.76 and testnote test note 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

Letter ID: 0090

Comment ID: 25816

Comment Code: 89140

Comment: CROSSCUTTING ISSUES

* Setting data requirements based on realis tic estimates of hazard and exposure

The Proposed Rule states at 59387: "Today’s propos al 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 promulga ted in October 2007." Whil e 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: 89140EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 650 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 yearsalone, 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 evaluationof 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-incre asing number ofvalidated 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.

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 ma de for the endpoints of acute oral and inhalation toxicity, 90-day oral and inhalation toxicity, acute and 90- day neurotoxicity, chronic oral toxicity, carcinogenic ity, 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 ofnon-binding guidance or science-policy documents, as needed, to provide registrants with up-todate information concerning Agency-accepted alte rnative methods, testin g 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 chem icals legislation (ECHA, 2008).

Response: see response 80.83

Commenter Name: Troy Seidle Commenter Organization: Humane SocietyEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 651 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). Howeve r, 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 requirem ents." Proposed Rule at 59422.

Response: see response 80.68

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 previo us 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-specie s developmental studies as an un conditional 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 supp lied). 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 SocietyEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 652 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 pr oduct 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 lowestdiluted 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 rodent s 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 ra bbits. 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 produc ts. 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 test ing/risk assessment paradigm for antimicrobial pesticide chemicals." Proposed Rule at 59421. More over, 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 80.24EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 653 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 an d related methodologies have been among the most widely condemned regulatory tests on ethi cal 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 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 ca ses, 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: 89140EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 654 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

Comment: With respect to the proposed requirement of a 90-day oral toxicity study in both rodentand 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 specifi c recommendation by HESI-ACSA?We find this clear redundancy to be especially questionable in the case of recognized low-humanexposure use patterns. Pr oposed 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 "concl uded that in no instance...was the mouse carcinogenicity study critical to determining wh ether 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: 89140EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 655 Comment: With respect to prenatal developmental toxicity, we appreciate OPP’s attention to its requirements under FFDCA to consider the special su sceptibility/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 thespecificity 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 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 onlywhen 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 cert ain chemicals SAR assessments and QSAR modeling could potentially form a scientifically-sound ba sis for hazard and risk assessments used for regulatory decisions ." Proposed Rule at 59422. However, we are also mindful that OPP currentlydoes 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 acti ons 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: 25837EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 656 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

Comment ID: 25838

Comment Code: 89140

Comment: ENDPOINT-SPECIFIC ISSUE

* Acute systemic toxicity

As previously noted, two retrospective data anal yses -comprising nearly 1,900 substances, including 227 pesticides, tested for acute syst emic 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, werecommend 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 irritationEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 657 In 2007/8, European validation authorities endorsed the EpiD erm, 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 DS D scheme will be replaced in 2015 by the new Regulation (EC) No 1272/2008 on cl assification, labeling and packag ing (CLP), which is illustrated above for comparison.] In February 2009, these tests achieved regula tory 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

[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 stud ies 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 Dr aize score of 2.3 as bein g 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 endors ed 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 publishe d before the end of 2009. Acco rdingly, the specification in [section]158W data tables that rabbit s be used to evaluate eye irritation sh ould 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 sensitizationEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 658 Classical tests for skin sensitizat ion (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): "Bas ed 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 recomme nding the use of a limit dose LLNA in cases where a full risk assessment is deemed not to be necessary.

* Dermal penetration

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 Accep tance 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 ex posure in relation to antimicrobial use patterns (Propos ed Rule at 59395), we recomme nd making in vitro dermal absorption a Tier 1 data require ment, as alluded to by HESI-ACS A (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 vitroEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 659 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

Comment: * Reproductive toxicity

In the past several years, a number of publications have called into question the value of routine production of a second generati on for the evaluation of reproducti ve toxicity (Janer et al., 2007; Reaves et al., 2008; PMRA, in pr eparation). 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 ha s been subject to extensiv e 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 preferen tial 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 se nsitive 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 toxicityEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 660 For the reasons previously discussed, we urge OPP to move away from requi ring 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 re production study in rodents" (Pro posed 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 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 standalonestudy, 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 parame ters earlier -as part of a combin ation 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 test note 80.29

Commenter Name: Troy Seidle Commenter Organization: Humane Society

Letter ID: 0090

Comment ID: 25849

Comment Code: 89140

Comment: * ImmunotoxicityEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 661 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

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 test notes 80.19, 80.20, and 80.21

Commenter Name: Troy Seidle Commenter Organization: Humane SocietyEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 662 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

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 ToxC ast program as a means to support regulatory requirements. Not only does this provide a relatively inexpensive way to provide data but it alsoEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 663 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 Chemic als" 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.

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 onl y 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 664 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 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 regi strations. Unnecessary toxi city 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 80.4EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 665 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 consiste nt 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 to ward 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 scien ce, 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 an imal 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 st ructure activity relationship analyses, in vitro approaches, or computational toxicology. The regulations should explicitly allow the use of these and other new methods and approaches.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 666 As highlighted earlier, P&G further recommends that the Agency expand its efforts to adopt alternative approaches to addressing data requireme nts 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

Comment: 10) The use of validated alternative testing methods, SAR/QSAR, open literature
citations, and other means to sati sfy 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 un less their use to assess the su bstance 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)EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 667 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

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 re quired 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 sati sfy 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 80.81EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 668 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 Dock et (7502P) Office of Pesticide Programs Environmental Protection Agen cy 1200 Pennsylvania Ave. N.W. Washington, DC 20460-0001

RE: Proposed revisions to U.S. pe sticide data requirements for antimi crobial 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 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: Reconstruc ted 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 stan dards, to assess skin ir ritation potential.[FN1:

OECD Test Guideline 439: In Vitro Skin Irrita tion: Reconstructed Human Epidermis (RhE) Test Method. Available at http:/ /puck.sourceoecd.org/vl=38 75911/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 me thods, to classify substances fo r severe eye irritation, in 2008. These methods were also recommended for use by the European Committee for the Validation ofEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 669 Alternative Methods (ECVAM) Sc ience Advisory Coun cil (ESAC), in 2007, and an OECD test guideline was publ ished in 2009.

Furthermore, in July 2009 the ESAC endorsed th e use of a combined "bot tom 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. Av ailable 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 pr oducts announced by the EPA in June of 2009.[FN3: http://www.epa.gov/oppfead1/c b/csb_page/updates/2009/eye-st udy.html] We encourage the Agency to take steps to expand this program to other antimicrobial product classes in an expeditious

manner.

We again ask the Agency to remove recommendations to conduct the Draize eye test from the Part

158W data tables and communicate in stead 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 Societ y 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 th e 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 in to 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 th e UK Pesticide Safety Directorate [F N6: 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 exam ined unpublished acute oral an d dermal toxicity data for 195 pesticide active ingredients and 3,111 formulated products, conclu ding 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 slightlyEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 670 expanded data set of 240 pesticide ac tive ingredients tested subject to acute toxi city 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 rout e.[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. Examinin g 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 mult i- route mammalian acute systemic toxicity studies. Regulat Toxicol Pharmacol (submitted for publication).] [FN9: Indans et al 1998. Classification and labelling of new industrial chemicals fo r 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 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 regulati ons 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 regu lation 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 protectio n pesticide? Toxico logy 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 Toxi c Class Method [FN11: http://lysander.sourceoe cd.org/vl=1969840/cl=12/nw= 1/rpsv/ij/oecdjournals/1607310x/v1n4/s53/p1] an d 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 Threshol d approach for Acute Fi sh Toxicity [FN13: http://www.oecd.org/docume nt/30/0,3343,en_2 649_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 MedicineEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 671 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 test notes . 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

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 toxi city 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 - R R 7, 8EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 672 Data Requirements Use Pattern Test Note No.

Food Nonfood

rodent
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

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 dist ribution except as required by study protocols or unless a variance is granted after consultation with the Agency. .

3. Data are not required if test ma terial is corrosive to skin or ha s pH less than 2 or greater than

11.5.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 673 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 unde r 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 stud y 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 requ ired 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 acti ve 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 do se causing system ic toxicity.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 674 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 expos ures, 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.

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. Th e 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 fetaldevelopment, 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 675 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 st udy, 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 pr oposed testing protocols an d 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.

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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 676 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 th e 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 appr opriate 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 ther e is the potential for dermal absorption during product use.

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 inco rporates tiered testing in the toxicology data requirements.[FN#15:40 CFR [Section] 158.2050.] Beca use the uses of antimicrobial pesticides addressed by Subpart W result largely in low leve l and indirect contact with food, rather than deliberate addition, given the SAP 1997 recommendation to incorp orate 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 Option s for Antimicrobial PesticidesEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 677 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, applic ants should take into account the provisio ns of [Section]158.70. Ap plicants 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 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 recogniz es that this proposal is a dramatic changeEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 678 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.

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 dist ribution except as required by study protocols or unless a variance is granted after consultation with the Agency.

3. Data are not required if test ma terial is corrosive to skin or ha s 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 unde r 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 stud y is not required for food use chemicals if theEO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 679 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 requ ired 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.

12. The 90-day dermal study is not required if the acti ve 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 do se causing system ic 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 expos ures, 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]EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 680 (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.

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. Th e 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 fetaldevelopment, 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.EO 12866 Draft

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Comments and Response References: Toxicology Section (80) Page 68126. 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 st udy, 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 pr oposed 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.

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 neurologicaleffects 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 offsprin g. 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 (t k), 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.EO 12866 Draft

– Do Not Cite, Quote or Release during Review

Comments and Response References: Toxicology Section (80) Page 682 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 th ere 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]

(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 inco rporates tiered testing in the toxicology data requirements.[FN#15:40 CFR [Section] 158.2050.] Beca use the uses of antimicrobial pesticides addressed by Subpart W result largely in low leve l and indirect contact with food, rather than deliberate addition, given the SAP 1997 recommendation to incorp orate 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 presum es that LANXESS’s reco mmended revision to that section has been incorporated to explicitly direct applicants to consider alternative approaches.

Section 158.2235. Tiered Testing Option s for Antimicrobial PesticidesEO 12866 Draft

– Do Not Cite, Quote or Release during Review

Comments and Response References: Toxicology Section (80) Page 683 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, applic ants should take into account the provisions of [S ection]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 ar e 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 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 incl ude: (i) Chronic feeding studies in the rodent. (ii) Carcinogenicity. (iii) Metabolism study. (iv) Additional mutagenicity testing.

Response: see response 80.72EO 12866 Draft

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 684 

### Applicator/Handler (Human Exposure) (90)

Verbatim Comments and Response Refe rences 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) fo r 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 theseEO 12866 Draft

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 685 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

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 686It 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. Additi onally, 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.infoscient ific.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: 0075EO 12866 Draft

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 687 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., no titia(TM) - see www.infoscientific.c om). 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 "p otential for resident ial exposure." (Note: The RED, scheduled for September 2008, currently is not available on the EPA REDs webpage.) Su ch 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 variousEO 12866 Draft

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 688 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 reas onable worst case assu mptions 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 Antimi crobial 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 "p otential for resident ial exposure." (Note: The RED, scheduled for September 2008, currently is not available on the EPA REDs webpage.) Su ch 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

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 689 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 158.77 20(a)(2) acknowledge the existence of industrial worker health and safety standards. These st andards 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 appr oaches 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 co ncludes 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 90.4EO 12866 Draft

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 690 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 a pplicable toxicity stud ies." 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 a ssessment 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 dat a" 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

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 691 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 it s 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 test notes 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: 90000EO 12866 Draft

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 692 Comment: 24. Proposed Regulation # [Section] 158.2260(a)(1)

Text of the Proposed Regulation (emphasis a dded) Applicator exposure: General. "If EPA

determines that industrial standard s, 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

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 693 Response: EPA acknowledges Lanxess' support for the generation of applicator exposure monitoring data such as that of the Antimi crobial 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 Ar lington, VA on December 5. 2008. See 73 Fed. Reg. 63112 *October 23, 2008).] when it was stressed that either indo or 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." ThisEO 12866 Draft

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 694 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 test notes 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 shou ld 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 diffe rent than those for most agri cultural workers and the sameEO 12866 Draft

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 695 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 partic ularly true if Agency assu mptions 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: 90000EO 12866 Draft

– Do Not Cite, Quote or Release during Review

Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 696 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 "evi dence of potentially significant adverse effects...observed in any a pplicable toxicity stud ies." 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 standard s, 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 CorporationEO 12866 Draft

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 697 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: 0085EO 12866 Draft

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 698 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 ma y 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: 94000EO 12866 Draft

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 699 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 th an focusing on indi vidual 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 Agen cy 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: 94000EO 12866 Draft

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 700 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 Agen cy 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

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 701 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 generati on 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 tabl e for applicator/han dler (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. Postapplic ation Exposure p. 59399EO 12866 Draft

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 702 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 Pr otection 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 test note 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 test note 90.10EO 12866 Draft

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 703 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 Pr eamble (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 test notes 90.1 and 100.1

Commenter Name: Hasmukh C. ShahEO 12866 Draft

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 704 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 throug h 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 a ssess 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 pe sticide exposure monitoring st udies 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 HS RB review has placed on both the Agency and entities conducting these studies (73 Red. Reg. at 59398.) It is of the utmost impo rtance 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 test notes 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 throug h 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 pr ocedures that distinguish observational studies asEO 12866 Draft

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 705 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 test notes . 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

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 706 1. Consultation with the Agency is encouraged in the event the test guideline does not provide adequate information on all important aspects of th e 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 woul d 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

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Comments and Response References: Applicator/Handler (Human Exposure) Section (90) Page 707 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.EO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 708 

### Post-application (Human Exposure) (100)

Verbatim Comments and Response Re ferences 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 3EO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 709 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 by standers. 73 Fed. Reg. at 59399. Ho wever, there is nothing in the

administrative record to show EPA reviewed th e 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 pr ovision 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

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Comments and Response References: Post-application (Human Exposure) (100) Page 710 The data table for the most part lists all post a pplication studies as "required." However, the Panel submits that post-application data requirements sh ould 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 su bjective 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 wh ether 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: 26926EO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 711 Comment Code: 100000

Comment: The Proposal would require two new studies, so il 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 conventionalpesticides, 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. ShahEO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 712 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 standard s, 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 # [S ection] 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

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Comments and Response References: Post-application (Human Exposure) (100) Page 713 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 thatcan 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

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Comments and Response References: Post-application (Human Exposure) (100) Page 714 (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 aswell 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 hygienedata. 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

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Comments and Response References: Post-application (Human Exposure) (100) Page 715 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)EO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 716 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 # [S ection] 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: 100000EO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 717 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 dissipati on 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, th e 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 exposu re 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.EO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 718 Response: See response 100.1 and testnote test note 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 dissipati on 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, th e 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 exposu re 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 th e 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 test note 100.2.

Comment Code: 102000 Indoor surface residu e dissipation studiesEO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 719 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 in formation 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 necessa rily 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.EO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 720 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. Nonethel ess, 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 woul d lead to the availability of re sidue 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 test note 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 woul d lead to an expectatio n 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 test note 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 RequirementEO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 721 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 necessa rily 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 coatin gs, 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 test note 100.6

Commenter Name: Stanley Oslosky Commenter Organization: Lanxess Corporation

Letter ID: 0064EO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 722 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 woul d 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 test note 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 Expo sure 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 wo uld 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 Expo sure 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 discussionEO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 723 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 belie ves 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 test note 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 forapplicator 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 findingsEO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 724 from applicator exposure test ing and applicable ambient meas urements. 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 test note 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, obj ect-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 ExposureEO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 725 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 info rmation 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 antimi crobial pesticide." 73 Fed. Reg. at 5940 0. 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 "obser vational" 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 co mplexities 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 an d 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 followingEO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 726 application of the an timicrobial pesticide." 73 Red. Reg. at 5940 0. However, this st atement is entirely inconsistent with the examples provided in the Preamble. These examples do not represent reasonable criteria for when non- dietary oral in gestion 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 requi rement. 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 Expos ure Data Requirements

Table Revisions

Comment Summary: As part of their comments, the commenter provided an alternate Antimicrobial Post-Application Data Requirements Table with testnotes test notes . 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-Applicat ion Exposure Data Requirements

Use Sites

Guideline

Number Data Requirements Occupational Residential Test

Substance Test Note

No.
???? Indoor Surface Residue CR CR TEP 1, 2, 4EO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 727 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 th e 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 appl ication 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 reason able expectation that toxicologically sign ificant 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)EO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 728 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 aeroso ls 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). Ot her 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 indi cate 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.EO 12866 Draft

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Comments and Response References: Post-application (Human Exposure) (100) Page 729 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 a pplication 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 th e 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 90.15EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 730 

### Residue Chemistry (110)

Verbatim Comments and Response Refe rences 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 wi th 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 propos al 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 110.1EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 731 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. KleinEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 732 Commenter Organization: Consumer Specialty Products Association (CSPA)

Letter ID: 0086

Comment ID: 25617

Comment Code: 110000

Comment: Section 408 of FFDCA requires the establis hment 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 fr om 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 re quiring 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 Pa ull, D.H. 2005. Co-occu rrence of triclocarban

and triclosan in US water resources. Environm ental Science & Technology 39, 1420-1426. FN2: Kolpin, D.W., E.T. Furlong, M.T. Meyer, E.M. Th urman, et al. 2002. Pharmaceuticals, Hormones, and other organic wastewater cont aminants in U. S. streams, 1999- 2000: A national reconnaissance. Environ. Sci. Technol. 36, 1202-1211.] This means th at 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 allEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 733 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 patte rns that entail the releas e 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 sh ould 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 Certai n Antimicrobial Substan ces - October 9, 1998))

between EPA and FDA which was rescinded du e 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), whic h in turn drives the FFDCA section 408 data requirements for a food use antimicrobial pesticide registration. Some 10 year s 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 sharedEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 734 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 writte n table outlining the ju risdiction between EPA

and FDA and when residue cleara nces were required under Sect ions 408 and 409 of FFDCA. The current preamble and §158.2290 Residue Chemistry se ction of the proposed 158W rule falls disappointingly short of providing clarity as to when EPA requires the setting of a tolerance or tolerance exemption unde r section 408 of FFDCA. This section needs significant improvement in order for prospective registrants to clearly understand chemistry residue requirements for food use antimicrobials subj ect 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 F ood 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 dept h 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 toda y'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 statutor y authority to require an FFDC A 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)EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 735 * 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 contac t uses regulated as food additive s (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 fo od 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 pro posed 158W raise many questions th at 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 wh en residue chemistry data is required. In order for these data requirements to be meaningful, they Agency needs to clearly identify what antimicrobial pestic ide uses are subject to FFDCA 408 re gulation. 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. WesterhausEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 736 Commenter Organization: ECOLAB

Letter ID: 0072

Comment ID: 25766

Comment Code: 110000

Comment: In the preamble to Section 158.2290, the Agen cy needs to include sp ecific 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 explai ned in the 1999 Antimicrobial Food Additive Guid ance 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 proc ess water is under EPA jurisdiction and requires a FFDCA 408 clearance. Conversely, an timicrobials 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 anti microbials 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.EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 737 * 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 establis hment 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 fr om a dietary/safety st andpoint. 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 re quiring a dietary risk assessment for antimicrobials applied in the home setting.

Commenter Name: Victoria Jones Commenter Organization: Clorox

Letter ID: 0075

Comment ID: 25928EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 738 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 su bject 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 as sessment 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 diet ary 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 Docu ment at 8 (emphasis added).EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 739 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 sealan ts, 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 additi ve 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 se eking to assess dietary ri sks 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 Registrati on 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. Ot her 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 approv al under FFDCA section 408 or 409 is needed) but nonetheless EPA asserts that a "Tier 1 dietary sc reening 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 Regi stration 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: 110000EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 740 Comment: * The recent HHT RED provides another exam ple of EPA’s case-by-case approach to risk assessment. There, although HHT has no uses re quiring clearance unde r section 408 or 409 of FFDCA, EPA conducted "an indirect food use asse ssment."[FN#26:Grotan RE D 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 co ncluded that that both the aP AD 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 requ ired 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 110.1EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 741 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 tole rance" 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 fo r antimicrobial food uses. Su ch a move would usurp FDA’s statutory grant of jurisdiction un der 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 "f ood 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 substanc e 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 an d 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

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Comments and Response References: Residue Chemistry Section (110) Page 742 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 antimicrobia l is applied directly to food or water." 73 Fed. Reg. at 59401. However, these statem ents 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 curre ntly registered antimi crobials 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: 110000EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 743 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 su bject 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 wh ere 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 establishmen ts, 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 as sessment 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 Registrati on Review Summary [FN19: See Docket No. EPAHQ-OPP-2008-0879 at http://www.regula tions.gov for the Regist ration Review case file.] state that:

"Dietary (food) exposure could potentially occur because HHT/HMAE is used as a process preservative and an in-can preserva tive 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 diet ary 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

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Comments and Response References: Residue Chemistry Section (110) Page 744 Note that FDA does not currently regulate HHT/HMAE as a direct or indirect food additive.

Human Health Effects Scoping Docu ment 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 Regist ration 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 Ca se 3053, Nuosept 145 Regi stration Review Final Work Plan, September 10, 2008.]

The foregoing example is not an isolated case. Ot her 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 approv al under FFDCA section 408 or 409 is needed) but nonetheless EPA asserts that a "Tier 1 dietary sc reening level assessment" is trig gered [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 CorporationEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 745 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 re quiring clearance unde r 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 foll owing assertion of authority:

"Currently in part 161, a proposed tolerance is re quired for all food-use pa tterns. 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

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Comments and Response References: Residue Chemistry Section (110) Page 746 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 un der 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 "f ood 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 substanc e 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 "s econdary direct food addi tives," 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 an d 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 thisEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 747 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 definiti on 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 chem istry, 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 re sidue requirements only fo r these uses. Uses of

antimicrobials that fall under FFDCA 409 or othe r 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 110.1EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 748 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 establishmen ts, 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 RuleEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 749 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 fr om regulating uses for which EPA does not have jurisdiction under FFDCA 408, and clarify the vague re gulations. Because the proposed rule appears to be largely a reiteration of existing data requireme nts at 40 CFR Part 161 or

those for conventional pesticides at 40 CFR 158.1410, the proposed rule contains numerous inapplicable requirements and in appropriate 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 pr eamble 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 ju stification 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: 110000EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 750 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 inconsiste nt with EPA’s statutor y 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 prot ocols, 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/TSS18 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 policie s, 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 se ction 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 desc ribe 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 sectionEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 751 If antimicrobial use pattern cate gories are described elsewhere th an in Section 158.100, specific reference to the correct identification and description must be incorporated into the above paragraph.

In addition, section 158.22 90(b) should be rewritten clearly to identify the condit ions 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 refere nce to the identification and de scription 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 us e 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 pesticid e 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 RegulationEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 752 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 antimicrobia l is applied directly to food or water." 73 Fed. Reg. at 59401. However, these stat ements lead to a number of issu es 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 anim al drug or as a preservati ve 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 cu rrently registered antimi crobials 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 subj ect 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 wh ere plants or animals are deliberately produced in an aquatic (marine or fresh water) environment for human consumption. Indoor food uses include use ofEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 753 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 definiti on 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 Residu e Chemistry Data Requirements..........5EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 754 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 chem istry, 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 re sidue requirements only fo r these uses. Uses of

antimicrobials that fall under FFDCA 409 or othe r 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 delibe rately 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 establishmen ts, 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;EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 755 * 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 fr om regulating uses for which EPA does not have jurisdiction under FFDCA 408, and clarify the vague re gulations. Because the proposed rule appears to be largely a reiteration of existing data requireme nts at 40 CFR Part 161 or

those for conventional pesticides at 40 CFR 158.1410, the proposed rule contains numerous inapplicable requirements and in appropriate 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 pr eamble 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 ju stification 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 CorporationEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 756 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 wi th EPA’s statutory authority un der 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 in clude study protocols, methodolog y, 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 requir ements. Similarly,

Response: see response 110.25

Commenter Name: Stanley Oslosky Commenter Organization: Lanxess Corporation

Letter ID: 0064

Comment ID: 27648

Comment Code: 110000EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 757 Comment: LANXESS also believes that existing guidan ce, 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 iden tification and descript ion of antimicrobial use pattern categories described:

(a) General . Sections 158.100 through 158.130 desc ribe 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 cate gories are described elsewhere th an in Section 158.100, specific reference to the correct identification and description must be incorporated into the above paragraph.

In addition, section 158.22 90(b) should be rewritten clearly to identify the condit ions 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 refere nce to the identification and de scription 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 us e 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.EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 758 (3) Data may be required for nonfood uses if pesticid e 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 pestic ides. 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 pestic ides. As discussed elsewhere in these comments, the Agency should eliminate the us e 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 useEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 759 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 appl ications for antimicrobial prod ucts. 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 cleara nce is sufficient for a 408 clearan ce 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.EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 760 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/toleran ce 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 ex clusive 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 activi ty 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/toleran ce 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 ex clusive 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 110.8EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 761 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 guid eline 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 an timicrobial 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 test notes 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 gu ideline 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 a pplications 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 reas onable 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

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Comments and Response References: Residue Chemistry Section (110) Page 762 Response: see responses 110.10, 110.11, 110.12, 110.13, and 110.14, and testnotes test notes 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 adde d) 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 3EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 763 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 adde d) 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 antimicrob ials, especially given that many an timicrobials 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 us e in food processing facilities.

Response: see response 110.16 and testnote test note 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 re sidue 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 th e use could be in human drinking water.EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 764 Response: see response 110.17 and testnote test note 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 test note 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 ad ditive. EPA must conform this regulation to its statutory mand ate pursuant to FFDCA 408.

Response: see response 110.19 and testnote test note 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 antimicrob ials, especially given that many an timicrobials 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 us e in food processing facilities.

Response: see response 110.16 and testnote test note 110.15

Commenter Name: Stanley Oslosky Commenter Organization: Lanxess CorporationEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 765 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 re sidue 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 th e use could be in human drinking water.

Response: see response 110.17 and test note test note 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 test note 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 ad ditive. EPA must conform this regulation to its statutory mand ate pursuant to FFDCA 408.

Response: see response 110.19 and testnote test note 110.21

Comment Code: 118000 Magnitude of Residue in Me at, Milk, Poultry, and Eggs

Commenter Name: Brigid D. Klein Commenter Organization: Consumer Specialty Products Association (CSPA)EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 766 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. Converse ly, 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 test notes 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.EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 767 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 test notes 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: 118000EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 768 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 prot ocol.[FN12: Id. at [sec tion] 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 residueEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 769 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) coul d 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 servic ing, food manufacturing, and food processing. Crack, crevice and space treatments are examples of application areas where pests hide or throughEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 770 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 reside ntial uses are nonfood us es 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 pest icide 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 underEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 771 FIFRA.[FN#5:72 FR 60934, October 26, 2007, at pa ge 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 servic ing, 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 reside ntial uses are nonfood us es 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.EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 772 Comment Code: 119115 Data and reporting requirements ta ble 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 RequirementsEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 773 Paragraph §158.2290 Residue chemistry, Table - Antimicrobial Residue Chemistry Data Requirements p. 59444

Excerpt from Federal Regist er Analytical Methods (Gui delines 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 propo sed tolerance (Guideline 860.1550) whic h 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 clarif ication 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 Stor age 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 magn itude 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 Processe d 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 posth arvest 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. 59444EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 774 Excerpt from Federal Register Po table 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 test notes 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 diet ary 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 settin gs is an inappropriate use of the assumptions in the underlying Pa nel 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 knowle dge gained through years of da ta 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.EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 775 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 expos ures. 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, authorit y for establishing tole rances for components of food contact sanitizing solutions transferre d 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 EP A 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 saniti zing solutions as food additives under Section 409 of FFDCA (27 FR 8759, September 1, 1962, whic h codified these food additives at 21 CFR 121.2547). FDA maintained the authority to regu late these solu tions under FFDCA through the 1977 reorganization and republication, resulting in r ecodification of the food additive tolerances for sanitizing solutions at 21 CFR 178.1010 (42 FR 1 4609, March 15, 1977). In August 1996, with the passage of the FQPA amendments to FFDCA, author ity for regulating sanitizing solutions under

FFDCA was transferred from FDA under Se ction 409 to EPA unde r 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.EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 776 Following the transfer of authority for regulation of sanitizing solutions under FFDCA from FDA to EPA, EPA eventually recodi fied the regulations at 21 CFR 178.1010 to 40 CFR 180.940 (69 FR 23136, April 28, 2004). However, EP A’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 mann er 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 FFD CA 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 silverwa re 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 fr om 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 an d 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 andEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 777 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 so lutions, the FDA regula tions 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 be low 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 an d that 100% of the saniti zing 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 setting s after washing and rinsing; the sa nitizing 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.EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 778 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 soluti ons 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 mo deled 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 stat es "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 Pa nel 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 diffe rent at-use concentratio ns being proposed for different use scenarios (Attachment 7B)[See attachment 7B on page 71 of American Chemistry Council, Biocides Pa nel 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 eatingEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 779 facilities, using the standard model for that purp ose. 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 2 8051, 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 di d 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 attachment s 5A-5D on pages 36-54 of American Chemistry Council, Biocides Pane l 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 revi ew 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 attachment7A on page 43 of American Chemistry Council, Biocides Panel comments, PDF docket ID EPAHQ- OPP-2008-0110-0088]) simply discusses the at use concen trations and the important relationship to efficacy. The third memorandum (A ttachment 5C [See attach ment 5C on page 46 of American Chemistry Council, Biocides Panel comments, PDF docket ID EPA-HQ- OPP-2008- 0110-0088]) discusses the different a pproaches 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 dietar y exposure assuming the "worst case" for public eating facilities. Finally, the fourth memorandum (A ttachment 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 ex posure 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 us ed 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 IDEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 780 EPA-HQ- OPP-2008-0110-0088] ); this model cove rs 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 eval uating 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 attachment3 on page 19 of American Chemistry Council, Biocides Panel comments, PDF docket ID EPA-HQOPP-2008-0110-0088] discusses that FDA developed a mode l to estimate expo sure to sanitizer components from use of sa nitizers for Clean-in-P lace (CIP) appl ications. 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 illu strate 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/NH ANES 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 thei r professional judgment, were "foods pr ocessed 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 Attach ements 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/b everages it is 968, for egg/mayonnaise products it is 413, and for milkEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 781 (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 onpage 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 appropr iately (e.g., 1 mg of sani tizer in 1 kg of food is 1 ppm).

Thus, in its review of FAP 2B4301, FDA (Attach ment 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 formulatio n for use on food processing surfaces and utensils including dairy, assuming a residue of 1 mg saniti zer 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 Form ulation/1 mg san. sol) x (32.9 ug CA/35 ug Formulation) x (in2/ 968 g Beve rage/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 a pproaches 100%, the eaters-o nly and total sample cu mulative 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-200 8-0110-0088] calculated the 90th percentile EDIs, based on its assessment that these are appr oximately twice the mean levels. The following areEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 782 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 concentratio n 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 ca lculated in our 12-17-02 memorandum, reflecting the elimination of sani tizer 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 esti mate exposure for dairy uses, a separate calculation is not conducted for modeling exposure for this category.

In its review of FAP 1B 4245 (Attachment 8 [See attachment 8 on page 74 of American Chemistry Council, Biocides Panel co mments, 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 dete rmination of dietary exposures for these uses,

similar to what is discussed above in referen ce 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, exclud ing 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 expo sures 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

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Comments and Response References: Residue Chemistry Section (110) Page 783 0110-0088]; 7A [See attachment 7A on page 59 of American Chem istry Council, Biocides Panel comments, PDF docket ID EPA-HQ- OPP-2008-0110-008 8], 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 so me 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 (E DI) would be considerably less if m ilk 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 ou t 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, th is 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]) estima ted 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 Chemistr y Council, Biocides Panel comments, PDF docket ID EPA-HQ- OPP-200 8-0110-0088]) to includ e use on additional food processing equipment, specifically for the brewery, beverage, egg and mayonnaise industries. InEO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 784 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 Substa nces 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 Da ta Requirements Table

Revisions

Comment Summary: As part of their comments, the commenter provided an alternate Antimicrobial Residue Chemistry Data Requirements Table with testnotes test notes . EPA’s response is for the entire alternate testing scheme and not the individual parts.EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 785 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 & residue

of 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 2EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 786 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 T GAI, 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 T EP or

residue of

concern 1, 3, 4

* A 408 Tolerance Assessment is NOT required for residential food use patte rns. The applicability of a dietary assessment for residentia l 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 measur ed 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: 119300EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 787 Comment: Proposed 158.2290(c) should be eliminated in its entirety and propos ed 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, 4EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 788 860.1380 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 1EO 12866 Draft

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Comments and Response References: Residue Chemistry Section (110) Page 789 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 transpor ation, 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 propos ed 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.EO 12866 Draft

– Do Not Cite, Quote or Release during Review

Comments and Response References: Residue Chemistry Section (110) Page 790 [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 Trea tment 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 791 

### 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 Oct ober 2008, before a whol esale list of new da ta 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 134.10EO 12866 Draft

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Comments and Response References: Environmental Risk Assessment Section (120) Page 792 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 mi suse with environmen tal 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 preservati ves 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:Americ an 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 di scussions 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 itEO 12866 Draft

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Comments and Response References: Environmental Risk Assessment Section (120) Page 793 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:] * EP A assumes product misuse with environmental exposure.[FN#4:Page 59405.] Th is is not a valid justification to re quire 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 preservati ves 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: Americ an 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: 120000EO 12866 Draft

– Do Not Cite, Quote or Release during Review

Comments and Response References: Environmental Risk Assessment Section (120) Page 794 Comment: Equally significant, the 1997 di scussions 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 no t 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:] * EP A assumes product misuse with environmental exposure.[FN#4:Page 59405.] Th is is not a valid justification to re quire data to support a registration

decision.

Response: see response 120.4

Comment Code: 121000 Factors considered in determinin g 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: 121000EO 12866 Draft

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Comments and Response References: Environmental Risk Assessment Section (120) Page 795 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/informati on 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:EO 12866 Draft

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Comments and Response References: Environmental Risk Assessment Section (120) Page 796 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, sectio ns 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 ofEO 12866 Draft

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Comments and Response References: Environmental Risk Assessment Section (120) Page 797 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 sourcedischarges.] 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 regulate d 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 assessm ent 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 preservati ves at the site of treatment of the wood and considers potential exposure of neighbouring aquatic systems. The PMRA recognizesEO 12866 Draft

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Comments and Response References: Environmental Risk Assessment Section (120) Page 798 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 pot ential 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 antisa pstain and heavy-duty treatment facilities is the primary concern. Many wood preservative treatmen t 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 expo sure 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 preservative s, 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 120.5EO 12866 Draft

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Comments and Response References: Environmental Risk Assessment Section (120) Page 799 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 3EO 12866 Draft

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Comments and Response References:

Letter from Environmental Working Group Section (125) Page 800 

### 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 toxici ty 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 an timicrobial 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 stud ies. 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 forEO 12866 Draft

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Comments and Response References:

Letter from Environmental Working Group Section (125) Page 801 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; King sbury 2008; Kolpin 2002). For exampl e, the bodies of nearly 75% of Americans are polluted with triclosan (Calafat 2008). The reas on for this extens ive 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 wate r with these pesticides (Halden 2005; Young 2008). Once released into the environment, they pose grave risks to aquatic li fe (Coogan 2008; Lawrence 2009; Oliveira 2009; Orvos 2002; Tatarazako 2004; Yang 2008). Additionally, th ese antimicrobials have been associated

with adverse effects on thyroid, estrogen, and testostero ne hormone functi on (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, comple tely evade EPA oversight since they officially fallunder 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 registrati on has been later cancelled (NPI RS 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 ar e likely to be higher (Perencevich 2001).EO 12866 Draft

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Comments and Response References:

Letter from Environmental Working Group Section (125) Page 802 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 us e 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 appl ications (Aiello 2007). As summarized in a recent review, "of major concern is the possibility that triclosan resistance maycontribute to reduced susceptibility to clinically important antimicrobials, due to either crossresistance or co-resistance mechan isms...thus, widespread use of tr iclosan may repres ent 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 ma nufacturers’ 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 draftEO 12866 Draft

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Comments and Response References:

Letter from Environmental Working Group Section (125) Page 803 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 antimicr obial pesticides are developed and introdu ced 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 an d 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 system s that flush high volumes of pesticides down the drain or included asEO 12866 Draft

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Comments and Response References:

Letter from Environmental Working Group Section (125) Page 804 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 syst em 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 pestic ides, 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 re ported (Balmer 2004). Triclo carban is even more persistent than triclosan and th us may pose greater chronic toxi city 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 herbiv orous 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 antimicrob ial pesticides that have been associated with embryotoxicity, teratogenic de velopmental changes, and hatc hing 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 wast ewater treatment plants (Cha 2009). EP A’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 plan ts (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. EP A 2009). These findings are of great concernEO 12866 Draft

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Comments and Response References:

Letter from Environmental Working Group Section (125) Page 805 because triclosan and triclocarban can inhibits soil respiration and nitrification processes that are essential for preserving soil fe rtility (Waller 2009). Th ey can also disrupt oxygen-producing algal communities in waterways and form toxic degrad ation 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 terrest rial ecosystems and pr oductivity 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 info rmation 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. Envi ron Health Perspect 116(9): 1203-10.

Aiello AE, Larson EL, Le vy SB. 2007. Consumer antibacterial soap s: effective or just risky? Clin Infect Dis 45 Suppl 2: S137-47.

Aranami K, Readman JW. 2007. Photolytic degradat ion of triclosan in freshwater and seawater. Chemosphere 66(6): 1052-6.

Balmer ME, Poiger T, Droz C, Romanin K, Berg qvist PA, Muller MD, et al. 2004. Occurrence of methyl triclosan, a transformation product of the ba ctericide triclosan, in fish from various lakes in

Switzerland. Environ Sc i Technol 38(2): 390-5.EO 12866 Draft

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Letter from Environmental Working Group Section (125) Page 806 Binelli A, Cogni D, Parolini M, Riva C, Provini A. 2009. Cytotoxic and genoto xic 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 concentrat ions of triclosan in the U.S. population: 2003-2004. Envi ron Health Perspect 116(3): 303-7.

Caldwell KL, Jones RL, Verdon CP, Jarrett JM, Ca udill SP, Osterloh JD. 2008. Levels of urinary total and speciated arsenic in the US population: National Health and Nutr ition 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 antimicrob ials 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 disrupto r? Endocrinology 149(3): 1173-9.

Chu S, Metcalfe CD. 2007. Simultaneous determination of triclocarban and triclosan in municipal biosolids by liquid chroma tography tandem mass spectrometry. J Chromatogr A 1164(1-2): 212- 8.

Coogan MA, Edziyie RE, La Poin t 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 bioaccum ulation of triclocarb an, 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, Maillar d JY. 2009. Triclosan-tolerant bacteria: changes in susceptibility to antibiotics. J Hosp Infect.

Dokianakis SN, Kornaros ME, Lyberatos G. 2004. On the effect of pharma ceuticals 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/hu mantoxome/chemicals/chemic al.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

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Comments and Response References:

Letter from Environmental Working Group Section (125) Page 807 EWG. 2008c. Teen Girls' Body Burden of Hormone-Altering Cosmetics Chemicals. Available: http://www.ewg.org/reports/teen s [accessed December 18 2008].

EWG. 2009. Environmental Working Group's Skin Deep cosmetic safety database. Ingredient report: triclocarban. Available: http://skindeep.ewg.org/ingredi ent.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. Partitio ning, 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. Anth ropogenic Organic Comp ounds in Source Water of Nine Community Water Systems that Withdraw from Streams, 2002-05. U.S. Geological Survey Scientific Investigat ions Report 2008-5208. Available: ht tp://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 othe r organic wastewater contaminants in U.S. streams, 1999- 2000:

a national reconnaissance. Envir on Sci Technol 36(6): 1202-11.

Kumar V, Balomajumder C, Roy P. 2008. Disruption of LH-induced testoste rone 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: ca use for concern. Emerg Infect Dis 7(3 Suppl):

512-5.EO 12866 Draft

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Comments and Response References:

Letter from Environmental Working Group Section (125) Page 808 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. En viron Toxicol 20(2): 160-4.

NPIRS. 2008. National Pesticide Inform ation Retrieval System Available: http://ppis.ceris.purdue.edu/ [accessed June 13 2008].

Oliveira R, Domingues I, Koppe Grisolia C, So ares 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. Envir on 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 Anal ysis Technical Report. Statistical Analysis Report. Available: http:// www.epa.gov/waterscience/biosolids/tnsssoverview. html#results [a ccessed 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-i nhibiting ef fects of 12 antibacterial agents and their mixtures on the freshwater microalga Pseudokirchneriella subcapitata. Environ Toxi col 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 ov erview. Microb Drug Resist 12(2): 83-90.

Young TA, Heidler J, Matos-Perez CR, Sapkota A, To ler T, Gibson KE, et al. 2008. Ab initio and in situ comparison of caffeine, triclosan, and tricloca rban as indicators of sewage-derived microbes in

surface waters. Environ Sc i Technol 42(9): 3335-40.

Zorrilla LM, Gibson EK, Jeffay SC, Crofton KM, Se tzer 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

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Comments and Response References:

Letter from Environmental Working Group Section (125) Page 809 Response: See responses 125.1, 125.3, 125.4, 125.5, 125.6, 125.7, and 125.8.EO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 810 

### Down-the-Drain (130)

Verbatim Comments and Response Re ferences for the Down-the-Drain

Section

Comment Code: 130000 Down-the-drain

Commenter Name: Jamie S. Heisig-Mitchell Commenter Organization: Hampton Roads Sanitati on 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 term s 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 Sanitati on 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 Sanitati on 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 protectionEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 811 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 cond ucting "down-the-drain as sessments." 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 require ments. 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 classificationsEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 812 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 syst ems; recirculating industrial processes and water systems; materials preservatives; and swimming p ools. SFE and the SFPUC al so concur with EPA’s

classification of antifoul ant 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 Dr ain Model

This model proposed by the agency to estimate concentrations of chemicals in surface waters, as a result of disposal of consumer products into wast ewaters, 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

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Comments and Response References: Down-the-Drain Section (130) Page 813 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 Balm er, M.E., T. Poiger, C. Droz, K. Romanin et al. 2004. Occurrence of methyl triclosa n, a transformation product of th e bactericide tric losan, in fish

from various lakes in Switzerland. Environmenta l 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 addresse s the issue of "down the drai n" by proposing 4 new data requirements for use in screenin g level assessment of the fate of antimicrobials that reach Wastewater treatment plants ry vwTP'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 pest icide registration proce ss 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 reachEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 814 POTWs. The Agency has also proposed a tiered methodology to conduct down-the-drain assessments. Tri-TAC supports these re visions 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 aqua tic 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 require ments to assess those risks. Tr i-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 publicEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 815 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 monthl y intervals with an average co st of $500 and $1,000 for eachacute 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, disc hargers are typically required to conduct accelerated tests weekly for a minimum of si x 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 comp lexity 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. TheEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 816 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 aqua tic 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 requirement s to assess those risks. CASA co ncurs 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 publicEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 817 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 monthl y intervals with an average co st of $500 and $1,000 for eachacute 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, disc hargers are typically required to conduct accelerated tests weekly for a minimum of si x 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 comp lexity 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 Progra ms’ 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 andEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 818 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 pestic ides are a major step toward achieving this goal.

Response: EPA acknowledges NACWA's su pport 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 Eliminatio n 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 resp ectively. 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 to xicity 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 TI E 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 st andards 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 PubliclyEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 819 Owned Treatment Works (POTWs). To consider the potential impacts of pesticides discharged to POTWs, U.S. EPA has proposed four new data re quirements 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 aqua tic 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 requireme nts to assess those risks. The Di stricts concur with U.S. EPA'sEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 820 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 approximat ely monthly intervals with an av erage cost of $500 and $1,000 foreach 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, disc hargers are typically required to conduct accelerated tests weekly for a minimum of si x 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 comp lexity 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 diazin on-associated accel erated toxicity monitori ng 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: 130000EO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 821 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 explai n ecological effects da ta 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 trig gers and criteria are.

Response: see responses 130.3 and 134.20EO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 822 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: 130000EO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 823 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 ch aracteristics.

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 screenin g-level assessment indicates that the pesticide would partition to biosolids or into the air.EO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 824 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 Tech nology 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 applic ation 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: 132000EO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 825 Comment: The potential environmental impacts of the cross- media transfers of pesticides needs to

be addressed in U.S. EPA's environmental ri sk assessments. CASA supports higher-tiered

environmental studies in cases where the screenin g-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 applic ation 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

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Comments and Response References: Down-the-Drain Section (130) Page 826 * 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 bi osolids 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 screenin g-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 Tech nology 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 assessm ent. 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 ofEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 827 antimicrobial pesticides to biosolids land applic ation 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 Sanitati on 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 Sanitati on 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-MitchellEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 828 Commenter Organization: Hampton Roads Sanitati on 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 No vember 6, 2008, EPA staff imp lied 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 ma y 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 thisEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 829 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- FA ST Version 2.0. In our comments, Tri-TAC has requested the technical basis for assuming the surface water concentrations obtained from the 10thand 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 fact ors 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 hi gh-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. TheseEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 830 simple modifications to the procedures for down -the-drain assessments would result in better assessments of the potential im pacts to aquatic organisms.

In the presentation enti tled "158W Antimicrobial Data Requ irements 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 communiti es, 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 pe sticide. In the presentation enti tled "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 Nove mber 6, 2008, U.S. EPA states on slide number 110 that "when evaluating potential risks from effects to aquatic invertebrates and fishEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 831 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 permit s 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. Th erefore, 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 im pacts to aquatic organisms.

In the presentation enti tled "158W Antimicrobial Data Requ irements 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 communiti es, POTWs receive wastewater from residentialEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 832 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 processe s 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 pe sticide. In the presentation enti tled "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 Nove mber 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, theEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 833 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 conditionsEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 834 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- dr ain 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 wi th 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 st ream 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 hi gh-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 im pacts to aquatic organisms.

In the presentation enti tled "158W Antimicrobial Data Requ irements 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 communiti es, 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 accessEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 835 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 "remov al 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 Nove mber 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 134.5EO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 836 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 clearl y 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 va lues 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 30Q 5 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

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Comments and Response References: Down-the-Drain Section (130) Page 837 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 sepa rates the exposure and th e effects phases of the assessments and subjects chemicals to similar testing requirements rega rdless 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 an imals, 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 informationEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 838 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 th e 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: 134000EO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 839 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 clearl y 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 va lues 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, an d 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 30Q 5 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: 27173EO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 840 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, li ke 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 th e Use of DtD ModelingEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 841 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 clearl y 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 va lues 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, an d 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 30Q 5 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.).EO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 842 * 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

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Comments and Response References: Down-the-Drain Section (130) Page 843 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 th e 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 th e 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-t he-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 antimicrobialEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 844 pesticide may appear in wastewater effluent. The rule does not specifically address the potential foran 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 as sessments. 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, co mpost, 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 ci rcumstances. 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 RequirementsEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 845 We support the following proposed data requirements, most of which reflect current USEPA practice for new registrations. Th ese 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 adve rse 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 antimi crobials 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 circumst ances. Also see response 134.22

Commenter Name: Janice L. Dhonau Commenter Organization: Proctor & Gamble

Letter ID: 0081

Comment ID: 26342

Comment Code: 137000EO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 846 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 re quirements, "EPA specifi cally 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 co st 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."(O IT 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 re quirements, "EPA specifi cally 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 co st 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 uncer tainties 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 CorporationEO 12866 Draft

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Comments and Response References: Down-the-Drain Section (130) Page 847 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 re quirements, "EPA specifi cally 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 co st 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 uncer tainties 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."(O IT E- Fate Appendix, in EPA E-Fate Assessment of Octhilinone, Mar 30, 2007).

Response: see responses 140.1, 140.4, and 134.16EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 848 

### 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 modifi ed 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 deficiencyEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 849 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 si milar 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 foran 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 as sessments. 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, co mpost, 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 drinkingEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 850 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. Furlon g, M.T. Meyer, E.M. Thurman, et al. 2002. Pharmaceuticals, Hormones, and other organic wast ewater contaminants in U. S. streams, 1999-

2000: A National Reconnaissance. Environ. Sci. T echnol. 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.[FN 7: 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. Envi ron. Sci. Technol. 42 (13): 4996 -5001.] The agency cannot rule out that antimicrobial mixtures occurring in the envi ronment 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 beEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 851 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 hi gher 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 ma terials 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: 140000EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 852 Comment: Since 1999, CASQA has provided comments on selected USEPA pest icide 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 Ge ological Survey, and US EPA 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 Rodenticid e 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 (n on-single-pass) cooling water syst ems. 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 dock et ID EPA-HQ- OPP-2008-0110- 0089] cooling water systemsEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 853 management guidelines that explain this phenomenon and provide additional background on cooling water syst ems 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 wa ter 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 toaddress 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 exposu re.[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. DhonauEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 854 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 pestic ides,...conform[ing] the degree and ty pe of review to the risks and benefits presented,...[and] consider ing the use patterns of the produc t, 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 an timicrobial 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 da ta 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 antimi crobials 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.EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 855 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 identifi ed, 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.EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 856 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 issu es 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 en vironmental 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 theEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 857 data requirements to conform the review to reas onable worst case assu mptions rega rding 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 in dustrial 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 pr oduct disposal is not covered unde r 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 theEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 858 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 environmen tal exposure.[FN40: Co mpare 40 CFR 158.1100 with Proposed §158.2280. See pages 59442-443 fo r 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 forEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 859 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 asse ssments 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 59406-1 2; 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: 140000EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 860 Comment: A. Environmental Data Are Not Required for Indoor Uses for Other Pesticides

Given that neither 158.1300 nor 158.2060 require environmental fate da ta 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 PanelEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 861 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 # [S ection] 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 CF R 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 CorporationEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 862 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 59406-1 2; 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 Regula ted Under FIFRA.........................3

C. Testing Guidelines Are Not Availa ble to Provide Guidance................3

D. Identification of Areas of Specific Concern.............................3

III. Alternative Approach for Environm ental Fate Data Requirements.........8

A. Environmental Exposure Estimates Driv e 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 fo r 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

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Comments and Response References: Environmental Fate Section (140) Page 863 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 asse ssments 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 59406-1 2; 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 da ta for indoor use conventional nor biochemical pesticides, it is unclear why the Agency asserts that extensive data areEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 864 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 identifi ed, 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 dataEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 865 requirement regulation (40 CF R 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 # [S ection] 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 Sanitati on District (HRSD)

Letter ID: 0065

Comment ID: 25449

Comment Code: 143000EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 866 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: 27029EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 867 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. ShahEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 868 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 Sanitati on 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

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Comments and Response References: Environmental Fate Section (140) Page 869 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 backgr ound 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 levelEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 870 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 backgr ound evolution, many biocides will be toxic to the microbial community.

Response: see responses 140.15 and 140.34EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 871 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 studie s 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 140.16EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 872 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 inhi bition test

Commenter Name: Jamie S. Heisig-Mitchell Commenter Organization: Hampton Roads Sanitati on 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 ofEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 873 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

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Comments and Response References: Environmental Fate Section (140) Page 874 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 140.30EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 875 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 re quiring 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

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Comments and Response References: Environmental Fate Section (140) Page 876 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 "almo st 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 thatEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 877 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: 149130EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 878 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 af fects 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, itEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 879 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 ex plain how DtD modeling affects the need for this

test.

Response: see response 140.21

Comment Code: 149140 Monitoring of repres entative 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 dr inking 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: 149140EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 880 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 gene rate such guidance.EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 881 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 gene rate 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 140.31EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 882 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 fo r Determination of Copper Released from Antifoulant Coatings in Substitute Ocean Wa ter, ASTM Method Designation D6442-06 (ASTM, 2006). (This method replaces the ASTM method currently designat ed in the proposed regulation, D5108-90, published in 1990.) At section 1.4., ASTM states The results of th is 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 as sessments, 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 test note 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 fo r Determination of Copper Released from Antifoulant Coatings in Substitute Ocean Wa ter, ASTM Method Designation D6442-06 (ASTM,EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 883 2006). (This method replaces the ASTM method currently designat ed 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 fo r 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 resu lt 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 test note 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 treate d 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

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Comments and Response References: Environmental Fate Section (140) Page 884 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 am ount 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.EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 885 Lastly, EPA for wood preservatives referen ces AWPA method E11-97 or E20-04 and for

antifoulants ASTM Method D5108-90 "or their equivalents" as pref erred methods. However, thesemethods 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 test notes 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 fo r Testing and Materials (ASTM) Method D5108-90. Prior approval of studies conducted according to D5108-90 is not required. All other protoc ols 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 andEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 886 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 am ount 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 referen ces AWPA method E11-97 or E20-04 and for

antifoulants ASTM Method D5108-90 "or their equivalents" as pref erred methods. However, thesemethods 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 test notes 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 treate d 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 # [S ection] 158.2280(f)(16)EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 887 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 fo r Testing and Materials (ASTM) Method D5108-90. Prior approval of studies conducted according to D5108-90 is not required. All other protoc ols 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 RequirementsEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 888 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 areEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 889 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 statut es (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 te sting would be required.

Response: see response 140.10EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 890 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 te sting 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 pr oduct 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 CorporationEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 891 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 anEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 892 acceptable environmental risk assessment. However, test results that trigge r 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. La stly, 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 te sting 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. La stly, 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 pain ts, 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-targetEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 893 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 clas sifying antifoulant co atings and paints, wood preservatives, and aquatic area application as high environmental exposure.

Comment Code: 149170 Data and reporting requirements ta ble for enviro nmental 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 deni es 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. Th ese requirements should be applied to pesticides in Registration Review as well as to new antimicrobial pesticide registrations.EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 894 * 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 adve rse 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 antimi crobials 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: 149170EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 895 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 asse ssments (three pron ged-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 commentEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 896HC 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 th e 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

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Comments and Response References: Environmental Fate Section (140) Page 897 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 andEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 898 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 Environmen tal 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 test notes . 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 forEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 899 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 assessmen t methods must be relevant, clea rly 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 cate gories 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 rewr itten 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. Note s that apply to an indi vidual 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 produc ts 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), antifoulantEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 900 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 expos ure to waterways. Screen ing level risk assessment using physical chemical properties of the active ingredient and appropriate exposure modeling is

advisable.

4 Information is required when unre gulated 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 hydrolyt ic products, if any, show no abso rption 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

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Comments and Response References: Environmental Fate Section (140) Page 901 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 (K d ) 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

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Comments and Response References: Environmental Fate Section (140) Page 902 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 wher e 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 processEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 903 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 disc ussed 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 mann er 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 cate gories 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 co mpletely rewritten as follows.

(a) General . Sections 158.100 through 158.130 desc ribe how to use this table to determine the environmental fate data requirements for a particul ar 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 Commerci al,’ ‘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 thatEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 904 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 coatin gs, 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 1,7EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 905 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 resu lt 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 le aching studies or modeling estimates suggest that residues are likely to result in exposure to wa terways 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

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Comments and Response References: Environmental Fate Section (140) Page 906 5 Data are not required when the electronic absorption spectra, measured at pHs 5, 7, and 9, of the active ingredient and its hydrolyt ic products, if any, show no abso rption 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, ph otodegradation 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 (K d ) is [>=] 50; - The log Kow is [> =] 3; - The Koc is [>=] 1000.EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 907 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 wher e 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 908 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 disc ussed 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 mann er 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 cate gories 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 co mpletely rewritten as follows.EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 909 (a) General . Sections 158.100 through 158.130 desc ribe how to use this table to determine the environmental fate data requirements for a particul ar 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 coatin gs, 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 resu lt in such an exposure.EO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 910 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 le aching studies or modeling estimates suggest that residues are likely to result in exposure to wa terways Screening level risk assessment using physical chemical properties of the active ingredient and appropriate exposure modeling is advisable.

4 Information is required when unre gulated 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 hydrolyt ic products, if any, show no abso rption 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 exposureEO 12866 Draft

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Comments and Response References: Environmental Fate Section (140) Page 911 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 (K d ) 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 140.35EO 12866 Draft

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Comments and Response References: Non-Target Plant Protection Section (150) Page 912 

### Non-Target Plant Protection (150)

Verbatim Comments and Response Refe rences for the Non-Target Plant

Protection Section

Comment Code: 151000 Seedling emergence (Tie r 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 stud ies, 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 high er-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 high er-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

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Comments and Response References: Non-Target Plant Protection Section (150) Page 913 Response: see response 151.1

Comment Code: 152000 Vegetative vigor (Tie r 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 requir ement whereby the active and/or metabolites are addressed if they persist greater than 5 days at pH’s 5,7, 9.[F N#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- lifeEO 12866 Draft

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Comments and Response References: Non-Target Plant Protection Section (150) Page 914 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 gr eater than 5 days at pH’s 5,7, 9. [FN#10:Page 59438, note 13.] The EPA should be consistent in th is respect.

Response: see response 152.1

Comment Code: 153000 Aquatic plant growth (T ier 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 differen t 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] refe rences 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] refe rences 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

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Comments and Response References: Non-Target Plant Protection Section (150) Page 915 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 releva nt 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 fordata 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 fordata 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 154.2EO 12866 Draft

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Comments and Response References: Non-Target Plant Protection Section (150) Page 916 Comment Code: 155000 Tiered approach to non-targ et 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 Propose d [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 155.2EO 12866 Draft

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Comments and Response References: Non-Target Plant Protection Section (150) Page 917 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 Propose d [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 test notes . 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: 157000EO 12866 Draft

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Comments and Response References: Non-Target Plant Protection Section (150) Page 918 Comment: The LANXESS’s recommendations for revision s 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 1EO 12866 Draft

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Comments and Response References: Non-Target Plant Protection Section (150) Page 919 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 155.3EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 920 

### Non-Target Organism Exposure (160)

Verbatim Comments and Response Refere nces for the Non-Target Organism Exposure Section

Comment Code: 160000 Non-Target Organism Exposure

Commenter Name: Jamie S. Heisig-Mitchell Commenter Organization: Hampton Roads Sanitati on 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: 160000EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 921 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 resultin g 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 ty pes of review undertaken for antimicrobial pesticides,...conform[i ng] the degree and type of review to the risks an d 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: 26355EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 922 Comment Code: 160000

Comment: IV. Comments on Proposed Rule (pag es 59412-17; section 158.2240 and 158.2250), Data Requirements for Nontarget Or ganisms 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 othe r 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. DhonauEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 923 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)] Howeve r, there is no equivalent re quirement 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 theEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 924 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

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 925 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.] Howeve r, there is no equivalent re quirement 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 reprod uctive studies.[FN#5: Section 1582240 NonTarget Organisms, Paragraph 3.] More transparency and th e 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 th e 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 2EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 926 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 adve rse 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 requirement s 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...................................................................1EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 927 II. Comments on Proposed Rule (pages 59412-17; section 158.2240 and 158.2250), Data Requirements for Nontarget Organism s and Nontarget Plants....................2

III. Alternative Proposal for Ecologic al Effects Data Re quirements................7

A. Proposed Alternativ e Section 158.2240 Data Requ irements 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 statutoryEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 928 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 environmentalEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 929 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.] Howeve r, there is no equivalent re quirement 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 th e very major differences between the uses of antimicrobial pesticides and other pesticides with regard toEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 930 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 adve rse 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: 26471EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 931 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 test note 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 test note 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 test note 160.1

Comment Code: 162000 Acute aquatic toxicity studies (LC50 fish an d EC50 invertebrate)

Commenter Name: James Colston Commenter Organization: Tri-TAC

Letter ID: 0087

Comment ID: 25787

Comment Code: 162000

Comment: Aquatic Toxicity TestingEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 932 Water quality agencies have refined aquatic toxicity test methods and updated the organisms selected for these test methods since U.S. EPA origina lly 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, Da phnia 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 fr eshwater 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 POTW s 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 origina lly 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, Da phnia 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

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 933 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 fr eshwater 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 an timicrobial 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 ToxicityEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 934 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 or ganisms and their uses. PB -85-227049.] The Office of

Water insists on a more robust data set because inte rspecies 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 To xicity 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 se lection 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 urba n 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. IfEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 935 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, update s 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 origina lly 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, Da phnia 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 fr eshwater 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 an timicrobial 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 POTW s and receiving waters. U.S. EPA requires POTWs regularly conduct acute and chronic aquatic toxicity tests as conditions in NPDES permits;EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 936 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 testin g and discuss its ration ale 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 test note 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 test note 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 preserva tives, 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 test note 160.7

Commenter Name: Hasmukh C. ShahEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 937 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 test note 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 test note 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 e ffects:] * 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 test note 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, theEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 938 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 test note 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 e ffects:] * 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 test note 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- roundEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 939 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 deci sion 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: 164000EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 940 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 test note 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 wh ether it regards industri al 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 unde r footnote 6(iv).

Response: see response 160.12, and testnotes test notes 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

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 941 [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 toEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 942 support its selection of a log Kow of 3.0 to tr igger avian reproductive studies. 4 Page 59405. 5 Section 1582240 NonTarget Orga nisms, Paragraph 3.

Response: see response 160.11 and testnote test note 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 th rough), 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 test notes 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 orEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 943 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 test notes 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: 164000EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 944 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 test note 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 wh ether it regards industri al 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 unde r footnote 6(iv).

Response: see response 160.12, and testnotes test notes 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 Te sting: Footnotes 9/10 (Page 59 438) 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 specificEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 945 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 additi onal data are needed.

Response: see responses 3, 160.13 and 160.14, and testnotes test notes 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, re spectively.] 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 test note 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 e ffects:] * Aquatic Organism Test ing: 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 whet her 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 test notes 160.9 and 160.10

Commenter Name: Hasmukh C. ShahEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 946 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 acut e toxicity [FN#7:850.1045.] and a bi valve 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 test note 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 e ffects:] * Aquatic Organism Test ing: 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 whet her 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 additi onal data are needed.

Response: see responses 3, 160.13 and 160.14, and testnotes test notes 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 acut e toxicity [FN#7:850.1045.] and a bi valve 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

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 947 Response: see response 160.15 and testnot e test note 160.8

Comment Code: 166000 Fish early life stage and aqua tic 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 [Sect ion] 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 toEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 948 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 test note 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 pe sticide 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 CorporationEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 949 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 pe sticide 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 toxicityEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 950 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 (O ncorhynchus 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 sup port 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 test note 160.12

Commenter Name: Janice L. Dhonau Commenter Organization: Proctor & Gamble

Letter ID: 0081

Comment ID: 26511

Comment Code: 167000EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 951 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 test note 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 test note 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 trigge red 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 test note 160.12

Commenter Name: Stanley Oslosky Commenter Organization: Lanxess Corporation

Letter ID: 0064

Comment ID: 27419

Comment Code: 167000EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 952 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 test note 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 test note 160.12

Comment Code: 168000 Aquatic organisms, bioavailability , biomagnification toxicity tests

Commenter Name: Jamie S. Heisig-Mitchell Commenter Organization: Hampton Roads Sanitati on 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 Sanitati on District (HRSD)

Letter ID: 0065

Comment ID: 25454

Comment Code: 168000

Comment: Quality AssuranceEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 953 *Many of the aquatic toxicity methods fail to recommend adequate quality assurance procedures

such as reference tests which a ssess the ability of the testing sy stem 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 ma rine 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 test note 160.13EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 954 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 test note 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 test note 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.[F N#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

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 955 Response: see response 160.3 and testnote test note 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 en vironmental 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 nu mber 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 OsloskyEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 956 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 nu mber 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

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 957 * 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 test notes 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 test notes 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 manyEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 958 criteria would need to be met, indicating that ma ny 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 test notes 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: 26999EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 959 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

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 960 Response: see response 3

Comment Code: 169120 Tiered approach to non- target organism studies

Commenter Name: Jamie S. Heisig-Mitchell Commenter Organization: Hampton Roads Sanitati on 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 RequirementsEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 961 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 Pr oposed [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 re quired for all "low environmental exposure" uses.[FN#42:Compare 40 CFR 158.400 wi th 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 PanelEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 962 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 pr oduct disposal is not covered unde r 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 High er 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 riskEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 963 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 pr oduct disposal is not covered unde r 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 Or ganisms (Ecotox) As desc ribed 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 tabl e for non-target organism (suggested additions, deletions, etc.)

Commenter Name: Chris Geiger Commenter Organization: SF EnvironmentEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 964 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 deni es 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: 169130EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 965 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. Al so, 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 160.34EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 966 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 test notes . 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, theEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 967 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 sp ecies 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-ta rget Organisms.

If antimicrobial use pattern categories are described elsewhere in the regulation besides Section 158.100, specific referen ce 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 desc ribe 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 repl aced 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; asEO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 968 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 resu lt 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), antifo ulant coatings, and ballas t 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 requireme nts, 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 gr eater 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 969 7 Data are required for one waterfowl species if the avian acute oral toxicity for the active ingredient is less than or equa l to 100 mg ai/kg and there is pote ntial 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 th an 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 (K d ) 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 concernEO 12866 Draft

– Do Not Cite, Quote or Release during Review

Comments and Response References: Non-Target Organism Exposure Section (160) Page 970 (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 (K d ) 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 S ection 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 th e identification and description must be incorporated into the following paragraph. The Panel offers the following revisions to Section 158.2240(a).EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 971 (a) General . Sections 158.100 through 158.130 desc ribe 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 resu lt 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 coatin gs, 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 Sectio n 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 1EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 972 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, 16EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 973 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 grea ter 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 ex posure 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 spec ies tested is less than or equa l 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

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 974 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 gr eater 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 forEO 12866 Draft

– Do Not Cite, Quote or Release during Review

Comments and Response References: Non-Target Organism Exposure Section (160) Page 975 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 S ection 158.2240 Data Requirements for Nontarget Organisms

If antimicrobial use pattern categories are described elsewhere in the regulation besides Section 158.100, specific referen ce to the identification and description must be incorporated into the following paragraph. LANXESS offers the followin g revisions to Section 158.2240(a).

(a) General . Sections 158.100 through 158.130 desc ribe 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 resu lt 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 coatin gs, 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 materialEO 12866 Draft

– Do Not Cite, Quote or Release during Review

Comments and Response References: Non-Target Organism Exposure Section (160) Page 976 (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 Sectio n 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 envir onment (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 hydrolyt ic 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 pote ntial 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 977 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 160.41EO 12866 Draft

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Comments and Response References: Non-Target Organism Exposure Section (160) Page 978 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 sp ecies 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 ri sk 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 sp ecies 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 ri sk assessments to be consistent with the requirements for conventional or biochemical pesticides.

Response: see responses 1 and 160.41EO 12866 Draft

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 979 

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

Verbatim Comments and Response Refere nces for the White Paper on Use of
SAR and QSAR Section

Comment Code: 170000 White Paper on the use of SA R 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 (O ctober 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 develo pment. 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: 25510EO 12866 Draft

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 980 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 Propos ed Rule"). ATWG members reco gnize 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 proposa l to move towards an integr ated 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, itEO 12866 Draft

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 981 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 disc retion 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 meta bolism 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: FurtherEO 12866 Draft

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 982 discussion regarding the requirement of metaboli sm data appears below under comments for Test note #35).

Response: see responses 170.1, 170.3, 80.57 and testnote test note 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 unde rstand 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: 170000EO 12866 Draft

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 983 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 Info rming 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 mode ls, development of guidance docu ments 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 in gredients 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 be tween 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 comprehe nsive such that they address all requirements of traditional testing paradigms.

Detailed Considerations:EO 12866 Draft

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 984 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 biol ogical 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 ge nerate 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 beused 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 method s (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

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 985 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 a ssurance 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

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 986 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 Asse ssing 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 providerelevant 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 judg ment 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

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 987 Section Number 12

Title The Types of Information th at 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 th at 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 fo r 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

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 988 "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 andEO 12866 Draft

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 989 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 fulf ill 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 convention al, 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: 25893EO 12866 Draft

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 990 Comment Code: 170000

Comment: Use of SAR and QSAR

U.S. EPA seeks comment on the use of predictive techniques to fulf ill 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 convention al, 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

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 991 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 fulf ill 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 convention al, 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: 26419EO 12866 Draft

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 992 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 (OPPT S Guideline 870.1000) identifies th at 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 determin ed 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

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 993 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

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 994 Response: EPA acknowledges Proctor an d Gamble's suppor t 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 ar eas where SAR/QSAR could be used. Also, the Agencyshould 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: 170000EO 12866 Draft

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 995 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 (OPPT S Guideline 870.1000) identifies th at 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 determin ed 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

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Comments and Response References: White Paper on Use of SAR and QSAR (170) Page 996 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 170.1EO 12866 Draft

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Comments and Response References: Endangered Species Section (180) Page 997 

### 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 reco gnize 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 anyEO 12866 Draft

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Comments and Response References: Endangered Species Section (180) Page 998 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 FI FRA registration da ta requirements for antimicrobials, EPA also solicits comments on specific issues relating to possible future rulemakings that will help ensure co mpliance with the En dangered 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 wastew ater 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 antimicrob ials that is applicable to its uses and users,

and that accounts for th ese 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 estimatingEO 12866 Draft

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Comments and Response References: Endangered Species Section (180) Page 999 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 Endang ered 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 threaten ed species. These include "wood preservatives, antifoulant paints, industrial wastewater di scharges, [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 throughEO 12866 Draft

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Comments and Response References: Endangered Species Section (180) Page 1000 FIFRA. EPA should adopt an approach for antimicrob ials that is applicable to its uses and users,

and that accounts for th ese 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 as sessment 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: 181000EO 12866 Draft

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Comments and Response References: Endangered Species Section (180) Page 1001 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 thor ough 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, an d 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: 181000EO 12866 Draft

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Comments and Response References: Endangered Species Section (180) Page 1002 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 expo sures, 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 impactsEO 12866 Draft

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Comments and Response References: Endangered Species Section (180) Page 1003 on endangered species, EPA should conduct a thor ough 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, an d 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 gene rate 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 CorporationEO 12866 Draft

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Comments and Response References: Endangered Species Section (180) Page 1004 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 ca n 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: 183000EO 12866 Draft

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Comments and Response References: Endangered Species Section (180) Page 1005 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 a ssessments 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.EO 12866 Draft

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Comments and Response References: Endangered Species Section (180) Page 1006 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 willEO 12866 Draft

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Comments and Response References: Endangered Species Section (180) Page 1007 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 180.2EO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1008 

### Guidelines (190)

Verbatim Comments and Response Refe rences 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 liste d in Methods fo r Measuring the Acute Toxicity of Efflue nts and Receiving Waters to Freshwater and Marine Organisms, 2002 (EPA 821-R-02-012), Short Term Methods for Estimati ng the Chronic Toxici ty 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 Organism s, 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 willneed 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)EO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1009 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 met hods listed in Methods for Measuring the Acute Toxicity of Effluents and Receiving Waters to Fr eshwater and Marine Organisms, 2002 (EPA 821- R-02-012), Short Term Methods fo r Estimating the Chronic Toxici ty 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 willneed 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 liste d in Methods fo r Measuring the Acute Toxicity of Efflue nts and Receiving Waters to Freshwater and Marine Organisms, 2002 (EPA 821-R-02-012), Short Term Methods for Estimati ng the Chronic Toxici ty 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 Organism s, 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 willneed to use adverse effect concentrations in the Exposure and Fate Assessment Screening Tool (EFAST) to evaluate potential impacts.

Response: see response 190.1EO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1010 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 requirement s table in Section 158.2220, Produc t 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: 191000EO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1011 Comment: An area of special concern to us is the efficacy guidel ines 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 av ailable. The Agency has been working on the 810 guidelines for several years and we ha ve 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 referenc e the appropriate 810 guid elines 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: 191000EO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1012 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 th e data requirements for conventi onal 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"EO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1013 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 Proposalfor 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 base d on the old Part 161 series of envi ronmental 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 impl antation 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 2EO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1014 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 191.1EO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1015 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 tabl e 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 dr aft 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: 0086EO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1016 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 guid elines. The antimicrobial product performance requirements table provided on page 59432 of the Proposed Rule re fers to the gu idelines 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 - Di sinfectants * 810.2300 -

Sanitizers

The last drafts of the above guid elines available to CSPA for cons ideration are from early 2006. The Agency has stated that these referenced 810 guidelin es will publish in draft 1st quarter of 2009 with a 60-day comment period.

In addition, there are se veral outstanding 810 guidelines which ar e either in draft form and/or have not yet been drafted. CSPA encourages the Agency to collaborate with Industry to develop these outstanding guidelines bu ilding 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 Re quirements/References

The Antimicrobial Product Perfor mance Data Requirem ents 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 th at it is appropriate to move forward with Part 158W until all 810

Guidelines are final. When th e 810 Guidelines are complete CS PA 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 abov e are finalized and only 810.2000, 810.2100, 810.2200 and 810.2300 are being prepared for publication for comment this fisc al 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 treatedEO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1017 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 opportun ity to comment on th e 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 Subp art 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 publ ic comment, much less implemen tation. 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 dataEO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1018 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 EP A's Antimicrobial Division to devel op 810 efficacy guidelines for 810.2000 (General Considerations), 810.2100 (Sterilants), 810.2200 (Disinfectants) an d 810.2300 (Sanitizers). The last Agency draft of these guidelines has b een available since 2006. Pr eviously, 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 fo r public comment. In addi tion, 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 191.1EO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1019 Commenter Name: James A. Westerhaus Commenter Organization: ECOLAB

Letter ID: 0072

Comment ID: 25754

Comment Code: 191000

Comment: Section 158.2220 - Product Perf ormance Ecolab agrees with and supports the comments submitted by CSPA th at 158W should not be finalized or implemented until all 810 guidelines are finalized. The proposed rule refers to the 91 guidelines wh ich 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 Antimicrobi al Division to develop the 810.2000, 810.2100, 810.2200, and 810.2300 efficacy guidelines which have yet to be published fo r comment. In addition there are several outstanding 810 guid elines which have not be published or even drafted. As stated previously, OMB comments to the 158W rule requ ire 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 JonesEO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1020 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 ex act 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 Cl orox. 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 70.5EO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1021 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 pr ior 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 sp ecific guidance, thes e 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 Gu idelines. The Chemical Specialt ies Product Association (CSPA) worked jointly with the Agency to develop the following proposed guidelines:

810.2000 - General Considerations 810.2100 - St erilants 810.2200 - Disinfectants 810.2300 -

SanitizersEO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1022 In addition, there are se veral outstanding 810 guidelines which ar e 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 bu ilding 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 disc ussions with EPA, in contrast to the six cate gories 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 re authorization. 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 regulati on 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 no ted, 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 prom ulgated." 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. DhonauEO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1023 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 Asse ssment 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 positio n 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: 191000EO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1024 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 assessmen t 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 exposu re 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 RequirementsEO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1025 In many places, EPA’s Proposal on Subpart 158W re fers to guidance docume nts 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 appropriat e means . . ."[FN#28:Proposed Ru le 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 regulati ons at 40 CFR [Section] 158.70(c), wh ich 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 no t been finalized. Moreover, given significant change s 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 "Avail ability 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 thisEO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1026 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 proce ss 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.EO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1027 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 assessmen t 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 CorporationEO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1028 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 exposu re 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 a ssessment guidance addressing these poin ts must be deve loped 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 re fers to guidance docume nts 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 "[th e Guidelines] represent the recommended approach to developing high qualit y data that should sati sfy 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 th at the guidelines "contain stan dards for conduc ting 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 OsloskyEO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1029 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 no t been finalized. Moreover, given significant change s 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 th e 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: 191000EO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1030 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 Asse ssment 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: 191000EO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1031 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: 191000EO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1032 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 Asse ssment 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 studyEO 12866 Draft

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Comments and Response References: Guidelines Section (190) Page 1033 guidelines are issued as final, without restriction on the completeness of an acceptable

environmental risk assessment.

Response: see response 191.1EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1034 

### 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. Ver batim text is provided below. No responses were necessary.

Comment Code: 200000 Commenter Background; Intr oductions 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) En vironmental Protection Agency 1200 Pennsylvania Ave., NW Washington, DC 20460-0001

RE: Proposed Rule on Data Requirements for Anti microbial Pesticides, 73 Federal Register 59382. Docket Id number EPA-HQ-OPP-2008-0110.

Dear Madam/Sir:

Reckitt Benckiser Inc. ("Reckitt") respectfully su bmits the enclosed comments in response to the U.S. Environmental Protection Agency's ("EPA" or "Agency") proposal regarding Data Requirements for Antimicrobial Pe sticides, 73 Fed. Reg. 59382 (Octob er 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: 25420EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1035 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 Pu blic Docket (7502P) En vironmental Protection Agency Rm. S-4400 One Potomac Yard (South Build ing) 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 Antimi crobial Pesticides, 73 Federal Re gister 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. Naujoc k Registration Specialist 262- 260-2686 kknaujoc@scj.com

Commenter Name: Jamie S. Heisig-Mitchell Commenter Organization: Hampton Roads Sanitati on District (HRSD)

Letter ID: 0065EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1036 Comment ID: 25436

Comment Code: 200000

Comment: April 6, 2009

RE: Docket ID no. EPA-HQ-OPP-2008-0110 Data Re quirements for Antimi crobial 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)) En vironmental Protection Agency 1200 Pennsylvania Ave., NW Washington, DC 20460-0001

RE: Proposed Rule on Data Requirements for Anti microbial 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 AmericaEO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1037 Letter ID: 0079

Comment ID: 25464

Comment Code: 200000

Comment: April 6, 20093

Office of Pesticide Programs (O PP) Regulatory Public Docket (7502P) Environmental Protection Agency 1200 Pennsylvania Ave NW Washington, DC 20460-0001

RE: Data Requirements for Antimi crobial Pesticides; Proposed Ru le. 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, se ll 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 Protect ion Agency Room S-4400 One Potomac Yard (South Building) 2777 So uth Crystal Drive Arlington, VA 22202

RE: Docket ID Number EPA-HQ-Opp-2008- 1010EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1038 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" ar e 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-2008-0110EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1039 Background

The Innovation Reform Group (IRG) is a coalition of an timicrobial 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 regi stered antimicrobial products in the U.S. and have a critical interest in EPA’s propos ed 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 ei ght 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)) En vironmental Protection Agency 1200 Pennsylvania Ave., NW Washington, DC 20460-0001

RE: Proposed Rule on Data Requirements for Anti microbial 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) andEO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1040 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 Is land 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, 2009EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1041 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 Join t Venture April 3, 2009

COMMENTS ON EPA PROPOSED RULE ON DATA REQUIREMENTS FORANTIMICROBIAL 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)EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1042 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 Dock et (7502P) Environmental Prot ection Agency Rm., S-4400 One Potomac Yard (South Building) 2777 S. Crystal Drive Arlington, VA 22202

RE: Proposed Rule on Data Requirements for Anti microbial 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 associ ation representing the interest s of approximat ely 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.EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1043 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 Re gulatory 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, Federa l Register Vol. 73, No. 196, We dnesday, 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 (Fed eral Register date d 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,EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1044 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 (O PP) 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 Agen cy 1200 Pennsylvania Avenue, NW. Washington, DC 20460-0001

Subject: Data Requirements fo r 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 Mana gement (IPM) ordinance in Octo ber 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 greenbuilding 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 (O PP) Regulatory Public Docket (7502)) Environmen tal 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

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1045 Dear Sir/Madam:

These comments are submitted on behalf of JohnsonDiversey, Inc. (JDI) regarding the proposed rule on Data Requirements for Antimicrobial Pest icides, 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 Agen cy, 1200 Pennsylvania Ave., NW ., Washington, DC 20460-0001

Re: Data Requirements for Antimicrobial Pest icides. 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: 200000EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1046 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 Sanitati on 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 Enviro nmental 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, 2008EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1047 OPP Regulatory Public Dock et (7502P) Environmental Prot ection 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 Requirement s for Antimicrobial Pesticides Proposed Rule - Federal Regi ster, Vol. 73, No. 196 (October 8, 2008)

Dear Sir or Madam:

With sales of $6 billion and more than 26,000 asso ciates, 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 pr oposed 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 requ ested 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: 0072EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1048 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 (O PP) 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 Antimi crobial 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 addi tional information, plea se contact Ms. Preeti Gh uman by phone at (562) 699-7411, extension 2904, or by email at pghuman@lacsd.org.

Sincerely, James Colston Chair Tri-TACEO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1049 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, Region al 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. pe sticide 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 organiza tion incorporated in 2004 under [s ection]501(c)(4) of the InternalEO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1050 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 st atement in the Proposed Rule at 59421 that "the Agency is committed to moving towards a more efficient an d refined testing/risk assessment paradigm for antimicrobial pesticide chemicals." We nonetheless have a number of concerns regarding theEO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1051 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? Alte rnatives 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 Toxicolo gy 2006; 36: 9-35.

Basketter DA, York M, McFadden JP, Robinson MK. Determination of skin irritation potential in the human 4-h patch test. Contac t Dermatitis 2004; 51: 1-4.

Bremer S, Pellizzer C, Hoffmann S, Seidle T, Hartung T. The developmen t 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 th e modernization of human safety requirements.

Critical Reviews in Toxi cology 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 Review s 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 agricu ltural chemical safety assessment. Cr itical Reviews in Toxicology 2006; 36:

37-68.

ECETOC-ECVAM. Workshop Report No. 12: Worksh op on Triggering and Waiving Criteria for

the Extended One-Generation Reproduction Toxicity Stud y. Brussels: August 2008.EO 12866 Draft

– Do Not Cite, Quote or Release during Review

Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1052 ECHA. Guidance on Informati on Requirements and Chemical Safety Assessment. May 2008.

en.htm ?time=1239064575>

ECVAM. Statement on the Validity of In Vitr o 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 ev aluation 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 Anim als 1998; 26 Suppl. 2): 617-58.

Hamada S, Sutou S, Morita T, Wakata A, Asanami S, Hosoya S, et al. Ev aluation 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 Ocul ar Corrosives and Severe Irritants. 25 October

2007.

ICCVAM. Draft ICCVAM Test Method Recomme ndations: 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 Toxi cology 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.EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1053 OPP. Guidance Document on Methodology for Determining the Data Needs and the Types of Assessments Necessary to Make FFDCA Section 408 Safety Determ inations for Lower Toxicity Pesticide Chemicals. 7 June 2002.

Reaves ME, Kidwell J, Mendez E, Dellarco V, Di x D, et al. A Retrospective Analysis of 175 TwoGeneration Reproduction Toxicity Rat Studies to Support the Proposed Extended One-Generation Reproduction Study. Washin gton, DC: US EPA. 2008.

Stoick K, Nitschke K, Sandusky C. Systemic testing by the dermal route can be precluded by new non-animal percutaneous ab sorption 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: 200000EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1054 Comment: April 2, 2009

Office of Pesticide Programs (O PP) 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 Requi rements for Antimicr obial 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 addi tional information, plea se contact Ms. Preeti Gh uman by phone at (562) 699-7411, extension 2904, or by em ail 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, Offi ce 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, Region al 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 AgenciesEO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1055 Commenter Name: Victoria Jones Commenter Organization: Clorox

Letter ID: 0075

Comment ID: 25904

Comment Code: 200000

Comment: April 6, 2009

(Sent via Federal eRulemaking Port al: http://www.regulations.gov)

Office of Pesticide Programs

Regulatory Public Docket (7502P) U.S. Enviro nmental 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 pestic ides 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 Wo rks(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 Va lley(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 inform ation on request. Please contact Reza Rahaman at (925) 425-4336 if we can answer any questions.

Sincerely,EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1056 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 Av e., 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: 200000EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1057 Comment: April 3, 2009 Docket ID EPA-HQ-OPP-2008- 0110 Office of Pesticide Programs Regulatory Public Docket (7502P) U.S. Envi ronmental 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 intere sts 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 pestic ides. 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 (O PP) Regulatory Public Docket (7502P) Environmental Protection Agency (USEPA) 1200 Penns ylvania Ave., NW. Washington, DC 20460-0001

Kathryn Boyle Field and External Affairs Division (7506P) Office of Pesticide Programs Environmental Protection Agen cy 1200 Pennsylvania Ave., NW. Washington, DC 20460-0001EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1058 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 manage ment organizations and individuals, including cities, counties, special districts, industries, and consulting firms throughout California. CASQA was formed in 1989 to recommend approa ches to the State Water Resour ces Control Boar d (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 pest icide 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 Ge ological Survey, and US EPA 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 Rodenticid e 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: 26060EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1059 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 Br osseau 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 (undat ed). 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 Co ntrol Program. Fact Sheet. [See PDF docket ID EPA-HQ-OPP-2008-110-0089]

5. City of Palo Alto ( 1997). Urban Pesticide Restri ctions for Water Quality Protection. Fact Sheet. [See PDF docket ID EPA-HQ-OPP-2008-110-0089]

6. Davidson, N. A., California Department of Pesticide Regulati on (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). Synthe tic 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 Di vision 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,EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1060 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 (O PP) Regulatory Public Docket (7502P) Environmental Protection Agency 1200 Pennsylvania Ave., N.W. Washingt on, DC 20460-0001 Attn: Docket ID Number EPA-HQ-OPP-2008-0110

Submitted Electronically

Docket No. EPA-HQ-OPP-2008-0110 Data Requi rements for Antimicr obial 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 Outf all System (JOS), which convey s 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 eith er landfilled or beneficially reused.

Commenter Name: Stephen Maguin Commenter Organization: Sanitation Districts of Los Angeles CountyEO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1061 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 Mart yn 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, Offi ce 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, Region al 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 & GambleEO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1062 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 Pesticid es, 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, 2009EO 12866 Draft

– Do Not Cite, Quote or Release during Review

Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1063 American Chemistry Council 1300 Wils on Boulevard Arlington, VA 22209

TABLE OF CONTENTS

LIST OF APPENDICES ..........................................................iii

Executive Summary .............................................................1

Introduction ..................................................................4

I. EPA’s Proposed Subpart 158W does Not Prov ide 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 Availabl e 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 Requi rements....................................................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........................................................37EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1064 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 un der 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 Burden s on its Resources and its Planni ng 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 Pr ovisions 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 Ru lemaking......................62

A. Executive Order 12866......................................................62EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1065 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 Prop osed Rule'). The Panel is comprised of more than 50 companies that manufactur e 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 an d 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 regulatedEO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1066 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 Prop osed Rule"). The Panel is comprised of more than 50 companies that manufacture and formul ate 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. Ch ambers, 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. Cr it. 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, andEO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1067 Subsequent Risk Assessment of, Chemicals Iden tified as Immuno-sup pressive in Routine Toxicology. Food Chem. Toxicol. 33: 239-243.

Batterhill, J. M. and R. J. Fielder. 1998. Mouse-sp ecific 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 Carcinog enicity Testing: Weight of Evidence Evaluations

Across Models. Toxicol. Pathol . 29 (Suppl.): 80: 225-229.

Cooper, R. L., J. C. Lamb, S. M. Ba rlow, 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. Ko eter, A. A. Li, S. L. Makris, L. P. Sheets, G. J. A. Speijers, an d K. E. Whitby. 2006. A Tiered Appr oach to Life Stages Testing for Agricultural Chemical Safety Assessmen t. Crit. Rev. Toxicol. 36: 69-98.

Criswell, K. 2008. Unpublished Data from Presentation at Societ y of Toxicology Workshop on Contemporary Issues in Toxicology. Hemangiosarc oma 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. Cr it. Rev. Toxicol. 36: 37-68.

Hermansky, S. J., D. A. Neptun, E. V. Weaver and B. Ballantyne. 1995. Cl inical Pathology Changes

Related to Cutaneous Irritaiton in the Fischer 344 Rat and New Zeal and White Rabbit. J. Toxicol.

Cut. & Ocular Toxicol. 14: 219-236.

Hurtt, M. E., G. D. Cappon, and A. Browni ng. 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. Envi ronmental Protection Agency, Office of Pesticide Programs, Health Effects Di vision, Washington, DC.

Monro, A. 1993. How Useful are Ch ronic (Life-Span) Toxi cology 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. Comparat ive Sensitivity of Neurobehavioural Tests for Chemical Screening. Neur otoxicology 11: 335-344.

Shelby, M. D. , K. T. Cain, C. V. Cornett, an d W. M. Generoso. 1987. Ac rylamide: 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.EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1068 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 Book s, 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 Prov ide Adequate Guidance to the Regulated Community...........................................................8 A. Th e Proposal Calls for In dividual Consultation Rather than Establishing App licable Regulatory Re quirements............................................8 B. The

Absence of Information on How EPA Plans to Cond uct Risk Assessments and How it Plans to Use Data Generated by the Rule Is a Critical Shortc oming.....12 II. Final Guidelines Are Not Available for Numerous Data Requiremen ts........16 III. The Proposal Does Not Include Meaningful Tiering........................20 IV. The Da ta Requirements for Antimi crobials Exceed those for

Conventional Pesticides with out Justification in Certain Specific Areas...................25 A. Environmental Fate Data Requi rements......................................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 R ecognize the Division of Jurisdiction between EPA and FDA..........................................................................31 A. EPA’sEO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1069 Jurisdiction over Food Uses of Antimicrobials Is Limited by the Terms of the

FFDCA.................................................................31 B. Th e Proposal Does Not Re flect 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 Identi fied a Clear Basis for Distinguishing Food Uses of Pesticides as Direct or Indi rect.............................................38 VI. Potential Exposures are Different for Antimicrobials and Require Different Approaches...................................................................3 9 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 Ot her Statutes...............................................43 B.

Antimicrobials Perform Essential Functions that Must Be Considered in this Proposal.....................................................................45 V II. Reliance upon Altern ate 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 Afte r the Effective Date...............................................................54 A. Additional Data Would Be Requ ired for Pending Appl ications................55 B. Additional PRIA Registration Fees Would Be Required for Pending Applications.................................................................56 IX. EPA’s Economic Anal ysis 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...................................................................5 9 B. Agency Estimates on its Burden and its Planning to Meet Such Burdens are Inadequate...................................................................60 X. 158 W

Should Include Procedures for A ddressing Emerging Path ogens.........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 fo r FIFRA Scientific Adviso ry 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 Fe d. Reg. 59382 (October 8, 2008)EO 12866 Draft

– Do Not Cite, Quote or Release during Review

Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1070 ("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 an d 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 Or ganisms and Nontarget Plants ...........................................2

III. Alternative Proposal for Ecological Effects Data Re quirements...............................................7

A. Proposed Alternativ e Section 158.2240 Data Requ irements for Nontarget Organisms............................8

B. Proposed Alternative Section 158.2250 Data Requirements for Nontarget Plant

Protection....................12

Commenter Name: Stanley OsloskyEO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1071 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 Fe d. 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 an d 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 59406-1 2; section 158.2280), Data Requirements for

Environmental Fate ........ .....................................................................2EO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1072 A. Environmental Data Are Not Required for Indoor Uses for Other

Pesticides....................................................................2

B. Pesticide Disposal Is Not Re gulated Under FIFRA ...........................3

C. Testing Guidelines Are Not Availa ble to Provide Guidance...................3

D. Identification of Areas of Sp ecific Concern ...............................3

III. Alternative Approach for Environm ental Fate Data Requirements............8

A. Environmental Exposure Estimates Driv e Data Needs by Tiered Testing .......8

B. Specific Alternative Pro posal 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 fo r 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 IEO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1073 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 Requiremen ts..................................................................3 A. Exposure Considerat ions:...................................................4 B. Comments on Acute Toxicity Requirements....................................4 C. Comments on Subchronic Toxicity Requirements...............................8 D. Commen ts on Chronic Toxicity and Carcinogenicity Requirements.............12 E. Comments on De velopmental Toxicity and Reproduction Requirements..........15 F. Comments on the Mutagenicity Data Requirements............................18 G.

Comments on Metabolism and Phar macokinetics Data Requirement s.............19 H. Comments on Companion Animal Safety Data Requirements.....................21 I. Co mments on Dermal Penetration Data Requirements..........................21 J. Comments on Immunotoxicity Data Requirements..............................22 K. Overall Comments..........................................................23 II I. Alternative Proposals for Toxico logy 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 Op tions 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 an timicrobials. In LANXESS’s view, the approach taken in the Proposal departs dramatically from EPA practice and commonly held toxicology concepts.

Commenter Name: Stanley OsloskyEO 12866 Draft

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Comments:

Commenter Ba ckground;

Introductions and Sa lutations (200) Page 1074 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. Ch ambers, 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. Cr it. 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 Iden tified as Immuno-sup pressive in Routine Toxicology. Food Chem. Toxicol. 33: 239-243.

Batterhill, J. M. and R. J. Fielder. 1998. Mouse-sp ecific 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 Carcinog enicity Testing: Weight of Evidence Evaluations

Across Models. Toxicol. Pathol . 29 (Suppl.): 80: 225-229.

Cooper, R. L., J. C. Lamb, S. M. Ba rlow, 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. Ko eter, A. A. Li, S. L. Makris, L. P. Sheets, G. J. A. Speijers, an d K. E. Whitby. 2006. A Tiered Appr oach to Life Stages Testing for Agricultural Chemical Safety Assessmen t. Crit. Rev. Toxicol. 36: 69-98.

Criswell, K. 2008. Unpublished Data from Presentation at Societ y 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. Cr it. Rev. Toxicol. 36: 37-68.

Hermansky, S. J., D. A. Neptun, E. V. Weaver and B. Ballantyne. 1995. Cl inical Pathology Changes

Related to Cutaneous Irritaiton in the Fischer 344 Rat and New Zeal and White Rabbit. J. Toxicol.

Cut. & Ocular Toxicol. 14: 219-236.

Hurtt, M. E., G. D. Cappon, and A. Browni ng. 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 Ba ckground;

Introductions and Sa lutations (200) Page 1075 Makris, S. L. 2004. Unpublished data. U. S. Envi ronmental Protection Agency, Office of Pesticide Programs, Health Effects Di vision, Washin gton, DC.

Monro, A. 1993. How Useful are Ch ronic (Life-Span) Toxi cology 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. Comparat ive Sensitivity of Neurobehavioural Tests for Chemical Screening. Neur otoxicology 11: 335-344.

Shelby, M. D. , K. T. Cain, C. V. Cornett, an d W. M. Generoso. 1987. Ac rylamide: 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

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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 anti microbials 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 60EO 12866 Draft

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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 (suggest ed 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 th e 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 RevisionsEO 12866 Draft

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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 Ch emistry 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 trea tment 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 usesEO 12866 Draft

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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 aquati c 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 ta ke to generate the needed data

183000 Whether antimicrobial use sites can be adequately correlate d 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 200EO 12866 Draft

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Appendix Page A-5