59382 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Parts 158 and 161 

RIN 2070–AD30 

Data Requirements for Antimicrobial 

Pesticides 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Proposed rule. 

SUMMARY: EPA proposes to revise and 

update the existing data requirements 

for antimicrobial pesticides. The 

proposed revisions are needed to reflect 

current scientific knowledge and 

current Agency regulatory practices, and 

to improve protection of the general 

population as well as sensitive 

subpopulations. The proposed 

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. 

DATES: Comments must be received on 

or before January 6, 2009. 

ADDRESSES: Submit your comments, 

identified by docket identification (ID) 

number EPA–HQ–OPP–2008–0110, by 

one of the following methods: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the on-line 

instructions for submitting comments. 

• Mail: Office of Pesticide Programs 

(OPP) Regulatory Public Docket (7502P), 

Environmental Protection Agency, 1200 

Pennsylvania Ave., NW., Washington, 

DC 20460–0001. 

• Delivery: OPP Regulatory Public 

Docket (7502P), Environmental 

Protection Agency, Rm. S–4400, One 

Potomac Yard (South Bldg.), 2777 S. 

Crystal Dr., Arlington, VA 22202. 

Deliveries are only accepted during the 

Docket’s normal hours of operation 

(8:30 a.m. to 4 p.m., Monday through 

Friday, excluding legal holidays). 

Special arrangements should be made 

for deliveries of boxed information. The 

Docket Facility telephone number is 

(703) 305–5805. 

Instructions: Direct your comments to 

docket ID number EPA–HQ–OPP–2008– 

0110. EPA’s policy is that all comments 

received will be included in the docket 

without change and may be made 

available on-line at http:// 

www.regulations.gov, including any 

personal information provided, unless 

the comment includes information 

claimed to be Confidential Business 

Information (CBI) or other information 

whose disclosure is restricted by statute. 

Do not submit information that you 

consider to be CBI or otherwise 

protected through regulations.gov or email. The regulations.gov website is an 

‘‘anonymous access’’ system, which 

means EPA will not know your identity 

or contact information unless you 

provide it in the body of your comment. 

If you send an e-mail comment directly 

to EPA without going through 

regulations.gov, your e-mail address 

will be automatically captured and 

included as part of the comment that is 

placed in the docket and made available 

on the Internet. If you submit an 

electronic comment, EPA recommends 

that you include your name and other 

contact information in the body of your 

comment and with any disk or CD-ROM 

you submit. If EPA cannot read your 

comment due to technical difficulties 

and cannot contact you for clarification, 

EPA may not be able to consider your 

comment. Electronic files should avoid 

the use of special characters, any form 

of encryption, and be free of any defects 

or viruses. 

Docket: All documents in the docket 

are listed in the docket index available 

in regulations.gov. To access the 

electronic docket, go to http:// 

www.regulations.gov, select ‘‘Advanced 

Search,’’ then ‘‘Docket Search.’’ Insert 

the docket ID number where indicated 

and select the ‘‘Submit’’ button. Follow 

the instructions on the regulations.gov 

website to view the docket index or 

access available documents. Although 

listed in the index, some information is 

not publicly available, e.g., CBI or other 

information whose disclosure is 

restricted by statute. Certain other 

material, such as copyrighted material, 

is not placed on the Internet and will be 

publicly available only in hard copy 

form. Publicly available docket 

materials are available either in the 

electronic docket at http:// 

www.regulations.gov, or, if only 

available in hard copy, at the OPP 

Regulatory Public Docket in Rm. S– 

4400, One Potomac Yard (South Bldg.), 

2777 S. Crystal Dr., Arlington, VA 

22202. The hours of operation of this 

Docket Facility are from 8:30 a.m. to 4 

p.m., Monday through Friday, excluding 

legal holidays. The Docket Facility 

telephone number is (703) 305–5805. 

FOR FURTHER INFORMATION CONTACT: 

Kathryn Boyle, Field and External 

Affairs Division, Office of Pesticide 

Programs, Environmental Protection 

Agency, 1200 Pennsylvania Ave., NW., 

Washington, DC 20460–0001; mail code 

7506P; telephone number: 703–305– 

6304; fax number: 703–305–5884; e-mail 

address: boyle.kathryn@epa.gov. 

SUPPLEMENTARY INFORMATION:

I. General Information 

A. Does this Action Apply to Me? 

You may be affected by this action if 

you are a producer of pesticide products 

(NAICS 32532), antifoulants (NAICS 

32551), antimicrobial pesticides (NAICS 

32561) or wood preservatives (NAICS 

32519), importers of such products, or 

any person or company who seeks to 

register an antimicrobial, antifoulant 

coating, ballast water treatment, or 

wood preservative pesticide or to obtain 

a tolerance for such a pesticide. This 

listing is not intended to be exhaustive, 

but rather provides a guide for readers 

regarding entities likely to be affected by 

this action. Other types of entities not 

listed above could also be affected. The 

North American Industrial 

Classification System (NAICS) codes 

have been provided to assist you and 

others in determining whether this 

action might apply to certain entities. If 

you have any questions regarding the 

applicability of this action to a 

particular entity, please contact Norm 

Cook, Chief of the Risk Assessment and 

Science Support Branch in the 

Antimicrobials Division of the Office of 

Pesticide Programs at 703–308–8253 or 

via email, cook.norm@epa.gov. 

B. What Should I Consider as I Prepare 

My Comments for EPA? 

1. Docket. EPA has established a 

docket for this action under docket 

identification (ID) number EPA–HQ– 

OPP–2008–0110. Publicly available 

docket materials are available either in 

the electronic docket at http:// 

www.regulations.gov, or, if only 

available in hard copy, at the Office of 

Pesticide Programs (OPP) Regulatory 

Public Docket in Rm. S–4400, One 

Potomac Yard (South Bldg.), 2777 S. 

Crystal Dr., Arlington, VA 22202. The 

hours of operation of this Docket 

Facility are from 8:30 a.m. to 4 p.m., 

Monday through Friday, excluding legal 

holidays. The Docket Facility telephone 

number is (703) 305–5805. 

2. Tips for preparing your comments. 

When submitting comments, remember 

to: 

i. Identify the document by docket ID 

number and other identifying 

information (subject heading, Federal 

Register date and page number). 

ii. Follow directions. The Agency may 

ask you to respond to specific questions 

or organize comments by referencing a 

Code of Federal Regulations (CFR) part 

or section number. 

iii. Explain why you agree or disagree; 

suggest alternatives and substitute 

language for your requested changes. 


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iv. Describe any assumptions and 

provide any technical information and/ 

or data that you used. 

v. If you estimate potential costs or 

burdens, explain how you arrived at 

your estimate in sufficient detail to 

allow for it to be reproduced. 

vi. Provide specific examples to 

illustrate your concerns and suggest 

alternatives. 

vii. Explain your views as clearly as 

possible, avoiding the use of profanity 

or personal threats. 

viii. Make sure to submit your 

comments by the comment period 

deadline identified. 

II. Background 

A. What Action is the Agency Taking? 

The Environmental Protection Agency 

(EPA or the Agency) is proposing to 

establish a separate listing of the data 

requirements for antimicrobial 

pesticides in Title 40 of the Code of 

Federal Regulations (CFR) in subpart W 

of part 158. This proposal sets out use 

patterns that are designed to make it 

easier to determine which requirements 

apply to antimicrobial products. In 

addition to retaining most current data 

requirements for antimicrobials, this 

proposal incorporates nine new data 

requirements and revises other existing 

data requirements. 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. 

The Agency has previously issued 

updated data requirements for 

conventional pesticides, and 

biochemical and microbial pesticides in 

part 158. This proposal is part of a larger 

effort to update and improve all of the 

data requirements for pesticide 

regulatory purposes. Data requirements 

for antimicrobial pesticides, currently 

contained in part 161, are proposed to 

be revised and included in part 158 

upon promulgation. 

Generally, antimicrobials are 

considered to be those chemicals that 

disinfect and sanitize. However, within 

this proposal EPA is using the term 

antimicrobials to collectively refer to 

antimicrobial pesticides, antifoulant 

coatings and paints, and wood 

preservatives. 

As discussed in Unit XVIII.A., EPA 

has prepared 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,’’ a 

copy of which is contained in the 

docket for this proposed rule (Ref. 43). 

The white paper discusses the current 

level of information and usage of 

structure-activity-relationship (SAR) 

assessments and Quantitative SAR 

(QSAR) modeling to fulfill data 

requirements in the Pesticide Program. 

The Agency specifically seeks comment 

on this support document. 

Since many antimicrobial pesticides 

are typically rinsed down the drain, 

EPA has considered the potential 

impacts of pesticides that are discharged 

into wastewater treatment plants 

(WWTPs). This proposed rule addresses 

the issue of down-the-drain 

antimicrobials by proposing four new 

data requirements for use in a screeninglevel assessment on the fate of 

antimicrobials that reach a WWTP. To 

assess the impacts of this screening 

assessment and utility of the new data 

requirements for decision-making, EPA 

prepared four case studies (Ref. 42). The 

case studies, copies of which are 

contained in the docket for this 

proposed rule, are discussed in more 

detail in Unit XII.D. The Agency 

specifically seeks comment on the 

proposed approach for evaluating the 

potential impact of antimicrobial 

pesticide chemicals on WWTPs and 

nontarget organisms in receiving water 

bodies, and on the case studies, 

including the assumptions used in those 

studies, that were used to develop the 

proposed approach. EPA will consider 

comments specific to the case studies 

along with comments on the proposed 

approach, as the Agency evaluates the 

use of the proposed approach for downthe-drain antimicrobials in the final rule 

for antimicrobial data requirements. 

On October 26, 2007, EPA 

promulgated final rules establishing 

data requirements for conventional 

pesticides (72 FR 60934), and 

biochemical pesticides and microbial 

pesticides (72 FR 60988). These final 

rules were effective on December 24, 

2007, and are therefore the current part 

158. As part of those actions, on October 

24, 2007, (72 FR 60251) EPA preserved 

the original part 158 data requirements 

to provide continued regulatory 

coverage for antimicrobial pesticides 

until the Agency could promulgate a 

final regulation. To accomplish this, 

EPA transferred intact the original 1984 

data requirements of part 158 into a new 

part 161, entitled ‘‘Data Requirements 

for Antimicrobial Pesticides.’’ Part 161, 

which applies only to antimicrobial 

pesticides, contains the current data 

requirements for antimicrobial pesticide 

chemicals. 

As explained in the preamble to the 

conventional pesticide final rule, EPA 

intended to preserve the existing data 

requirements for antimicrobial 

pesticides until a new rule tailored 

specifically to antimicrobial pesticides 

could be promulgated. Part 161 is 

intended to be transitional. Once 

subpart W of part 158 is promulgated, 

there will be no need for part 161. 

Accordingly, EPA proposes to revoke 

part 161 upon the effective date of a 

final rule arising from today’s proposal. 

B. Reasons for Today’s Action 

Since the promulgation of part 158 in 

1984, the Agency has recognized that 

the tables and test notes promulgated in 

1984 failed to adequately address the 

unique applications, use patterns, and 

other factors germane to antimicrobial 

pesticides. Part 158 specifies the types 

of data and information generally 

required for making sound regulatory 

judgments under the Federal 

Insecticide, Fungicide, and Rodenticide 

Act (FIFRA). The types of actions for 

which these data are needed include 

experimental use, registration, amended 

registration, reregistration, or 

registration review (collectively referred 

to in this proposal as ‘‘registration’’). 

The information required under FIFRA 

for registration of food-use pesticides is 

also information the Agency needs in 

order to grant tolerances or exemptions 

from the requirement of tolerances 

under section 408 of the Federal Food, 

Drug, and Cosmetic Act (FFDCA). 

Required data are intended to provide 

information about the potential adverse 

effects of uses of pesticides, and to 

define what is generally expected from 

applicants for registration in support of 

their products. However, it must be 

emphasized that each applicant has the 

continuing obligation under FIFRA to 

demonstrate that an individual product 

meets the standard for registration 

under section 3 of FIFRA or section 408 

of FFDCA. Accordingly, as indicated in 

current § 158.75 and § 161.75, 

additional data may be needed to reflect 

the characteristics and use of specific 

pesticide products under review. 

Since the data requirements now set 

out in part 161 (formerly part 158) were 

first published in 1984, every 

disciplinary area and requirement has 

been reconsidered and many have been 

revised in practice. These changes have 

been needed because the state of the 

science underlying the data 

requirements has advanced, and 

because the Agency has learned in 

specific registration actions that 

additional or different data are 

necessary to make sound regulatory 

decisions. These case-by-case decisions 

have been made in accordance with 

§ 158.75, which allows the Agency to 

impose additional data requirements 


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beyond those specified in part 158 and 

now part 161. 

Use patterns specific to antimicrobial 

pesticides are not specified in part 161, 

as they were not set out separately when 

originally promulgated in 1984. As a 

result, applicants have needed to 

interpret the data requirements often via 

extensive consultation with and 

interpretation from the Agency to 

determine the antimicrobial data 

requirements for a particular product. 

Today, EPA is proposing that the 

antimicrobial pesticide requirements be 

codified in a separate subpart W to part 

158 with use patterns (see Unit IV.I. of 

this preamble) and groups of use 

patterns specific to antimicrobials. 

Today’s proposed rule is part of a 

series of rules to update all of the data 

requirements for pesticide products. On 

October 26, 2007, EPA published in the 

Federal Register two final rules to 

promulgate the data requirements for 

conventional (72 FR 60934), and 

biochemical and microbial (72 FR 

60988) pesticide chemicals. These rules 

and their proposals (conventional 

(March 11, 2005) (70 FR 12276) and 

biochemical and microbial (March 8, 

2006) (71 FR12072)) state the rationales 

for requiring and/or revising particular 

data requirements. With few exceptions, 

these rationales are also applicable to 

antimicrobial pesticide chemicals, and 

as such have not been repeated in 

today’s proposed rule. Today’s proposal 

discusses in detail only those revisions 

that are singularly applicable to 

antimicrobial pesticides, including 

antifoulants and wood preservatives. 

C. Benefits of this Proposal 

Greater detail on the benefits of this 

proposal is provided in the document 

entitled ‘‘Economic Analysis of the 

Proposed Change in Data Requirements 

for Antimicrobial Pesticides’’ which is 

available in the docket for this 

rulemaking (Ref. 44). The following 

briefly highlights the anticipated 

benefits: 

1. More refined assessments mean less 

uncertainty and clearer understanding 

of actual risks. EPA’s current applicator/ 

user exposure data base is not 

comprehensive, especially regarding 

exposures to antimicrobials in industrial 

and residential settings. The new data 

that would be collected once this 

proposal becomes final would allow the 

Agency to conduct improved pre- and 

post-application exposure assessments 

for applicators/users, and the general 

public. This will benefit not only 

workers (including applicators) and 

consumers by helping EPA to make 

better informed regulatory decisions 

that are neither too stringent nor too 

lenient, but also benefit the regulated 

industry by reducing the uncertainty in 

Agency risk assessments. Thus, today’s 

proposal will reduce, but not eliminate, 

uncertainty related to the risks posed by 

antimicrobial pesticides. 

2. Clarity and transparency to 

regulated community means savings. 

The enhanced clarity and transparency 

of the information presented in part 158, 

subpart W should enhance the ability of 

industry to efficiently manage their 

antimicrobial registration submissions. 

Applicants may save time and money by 

understanding when studies are needed. 

Having all required studies available to 

EPA at the time of application should 

halt potential delays in the registration 

process, thereby enabling registration of 

antimicrobial pesticides sooner. 

Products would enter the market faster. 

3. EPA information assists other 

communities in assessing pesticide 

risks. Scientific, environmental, and 

health communities find antimicrobial 

pesticide toxicity information useful to 

respond to a variety of needs. For 

example, medical professionals are 

concerned about the health of patients 

exposed to antimicrobials; poison 

control centers use and distribute 

information on toxicity and treatment 

associated with poisoning; and 

scientists use toxicity information to 

characterize the effects of antimicrobial 

pesticides and to assess risks of 

pesticide exposure. Similarly, those 

responsible for protection of nontarget 

wildlife need reliable information about 

antimicrobial pesticides and assurance 

that pesticides do not pose an 

unreasonable threat. The proposed 

changes will help the scientific, 

environmental, and health communities 

by increasing the breadth, quality, and 

reliability of Agency regulatory 

decisions by improving their scientific 

underpinnings. 

4. Better informed users mean 

informed risk-reduction choices. Better 

regulatory decisions resulting from the 

proposed changes should also mean that 

the label will provide better information 

on the use of the antimicrobial 

pesticide. A pesticide label is the user’s 

direction for using pesticides safely and 

effectively. It contains important 

information about where to use (or not 

use) the product, health and safety 

information to be read and understood 

before using a pesticide product, and 

how to dispose of that product. This 

benefits users by enhancing their ability 

to obtain antimicrobial pesticide 

products appropriate to their needs, and 

to use and dispose of products in a 

manner that is safe and environmentally 

sound. Applicators/users may benefit 

from label information based on the data 

submitted to the extent it helps inform 

their decisions about whether or how to 

use particular pesticides to avoid 

potential exposure. 

D. What is the Agency’s Authority for 

Taking this Action? 

This action is issued under the 

authority of sections 3, 4, 5, 10, 12, and 

25 of FIFRA as amended and section 

408 of FFDCA. The data required for a 

registration, reregistration, experimental 

use permit, or tolerance are listed in 40 

CFR part 158. 

III. Statutory and Historical 

Framework 

A. FIFRA 

Under FIFRA section 3, every 

pesticide product must be registered 

with EPA or specifically exempted 

under FIFRA section 25(b) before being 

sold or distributed in the United States. 

Under FIFRA, an applicant for a new 

registration or an existing registrant 

(collectively referred to as applicant in 

this proposal) must demonstrate to the 

Agency’s satisfaction that, among other 

things, the pesticide product, when 

used in accordance with widespread 

and commonly recognized practice, 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. EPA 

must determine that the standard for 

registration contained in FIFRA is met 

before granting a registration. 

1. Registration. Section 3 of FIFRA 

contains the requirements for 

registration. Specifically, FIFRA section 

3(c)(2) provides EPA broad authority, 

before and after registration, to require 

scientific testing and submission of the 

resulting data to the Agency by 

applicants for registration of pesticide 

products. An applicant must furnish 

EPA with substantial amounts of data 

on the pesticide, its composition, 

toxicity, potential human exposure, 

environmental properties, and 

ecological effects, as well as information 

on its product performance (efficacy) in 

certain cases. Although the data 

requirements are imposed primarily as a 

part of initial registration, EPA is 

authorized under FIFRA section 

3(c)(2)(B) to require a registrant to 

develop and submit additional data to 

maintain a registration. 

2. Reregistration. FIFRA section 4 

requires that EPA reregister each 

pesticide product first registered before 

November 1984. This date was chosen 

because pesticides registered after 1984 

were subject to the part 158 

requirements of the 1984 regulation. 


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EPA has completed the reregistration/ 

tolerance reassessment process for fooduse pesticides and expects to complete 

all reregistration activities by the 

statutory deadline of August 2008. 

3. Registration review. FIFRA section 

3(g) mandates that the registrations of 

all pesticides are to be periodically 

reviewed. Changes in science, public 

policy, and pesticide use practices occur 

over time. Through the new registration 

review program implemented via a 

regulation promulgated on August 9, 

2006 (71 FR 45719) (40 CFR part 155, 

subpart C), the Agency is periodically 

reevaluating all registered pesticides to 

assure that they continue to meet the 

statutory standard of no unreasonable 

adverse effects. Starting in 2006, 

registration review began to replace 

EPA’s reregistration program as the 

mechanism for systematic review of 

existing pesticides. The registration 

review process begins by reviewing the 

available information in the possession 

of the Agency and then determining the 

specific data needed for assessing a 

particular pesticide. Thus, the data 

needed, and the scope and depth of the 

Agency’s review will be tailored to the 

specific circumstances of a particular 

pesticide. This means that reviews will 

be commensurate with the complexity 

of the issues associated with each 

pesticide. 

4. Experimental Use Permits (EUPs). 

Subject to some exceptions, FIFRA 

section 5 requires persons seeking 

permission for experimental use of a 

pesticide under controlled condition to 

obtain an experimental use permit. A 

EUP allows limited use of a pesticide for 

specified experimental and data 

collection purposes intended to support 

future registration of the pesticide. 

Because a EUP is for limited use under 

controlled conditions, the data needed 

to support issuance of the permit are 

correspondingly less than those 

required for full registration. The 

regulations governing the issuance of 

EUPs are found in 40 CFR part 172. In 

its final rule ‘‘Data Requirements for 

Conventional Pesticides’’ EPA 

promulgated subpart C of part 158 to 

contain the data requirements for EUPs, 

which will be applied on a case-by-case 

basis to any EUP applications for an 

antimicrobial pesticide. 

5. Registration requirements for 

antimicrobials. FIFRA section 3(h) 

requires that EPA evaluate its 

registration process to identify 

improvements and reforms that will 

reduce historical review times for 

antimicrobial applications. This 

includes defining the classes of 

antimicrobial use patterns and the types 

of application review, conforming 

reviews to risks and benefits, ensuring 

efficacy, and meeting review time goals. 

EPA believes that this rule assists in 

meeting the section 3(h) mandate. By 

defining the 12 use patterns for 

antimicrobials in relation to the data 

required for a registration under FIFRA, 

EPA is providing clearer and more 

transparent information to applicants. 

This should result in submissions to 

EPA that contain the required data and 

therefore can be reviewed and evaluated 

more expeditiously. 

B. FFDCA 

FFDCA requires EPA to determine 

that the level of pesticide chemical 

residues in food and feed will be safe for 

human consumption. The safety 

standard set under FFDCA section 

408(b) and (c) defines safe as ‘‘a 

reasonable certainty that no harm’’ will 

result from exposures to pesticide 

chemical residues. The combination of 

aggregate and cumulative exposure 

assessments required by FFDCA section 

408 increases the nature and scope of 

EPA’s risk assessment, and potentially 

increases the types and amounts of data 

needed to determine that the FFDCA 

safety standard is met. 

Under FFDCA section 408, EPA is 

authorized to establish tolerances for 

pesticide residues in food and feed, or 

to exempt a pesticide from the 

requirement of a tolerance, if warranted. 

In this preamble, references to 

tolerances include exemptions from 

tolerance since the standards and 

procedures for both are the same. The 

safety standard applies to tolerances in 

a number of regulatory situations, 

including: 

•Tolerances that support registration 

under FIFRA; 

•Tolerances for imported products 

which are established to allow 

importation of pesticide-treated 

commodities, but for which no U.S. 

registration is sought; 

•Time-limited tolerances which are 

established for FIFRA section 18 

emergency exemptions; and 

•Temporary tolerances established for 

experimental use permits under FIFRA 

section 5. 

C. Linking FIFRA and FFDCA Safety 

Standards 

Under FIFRA section 2(bb), a 

pesticide that is inconsistent with, or 

does not meet, the FFDCA section 408 

safety standard poses an unreasonable 

adverse effect that precludes new or 

continued registration. Given this 

linkage between registration and 

tolerances, it makes sense for EPA to 

define data requirements for both 

purposes: The data required to support 

a determination of ‘‘reasonable certainty 

of no harm’’ under FFDCA are an 

integral part of the data needed for an 

‘‘unreasonable adverse effects’’ 

determination under FIFRA. 

Consequently, when promulgated, these 

proposed data requirements would 

encompass the basic data requirements 

for both registration and tolerancesetting determinations. EPA has 

authority to require additional data on 

a case-by-case basis. 

D. Scope of Proposed Subpart W 

FIFRA contains a number of 

provisions specific to ‘‘antimicrobial 

pesticides’’ as defined in FIFRA section 

2(mm). The statutory definition contains 

a complex construction of functionality, 

types of organisms, and intended use to 

describe what is encompassed by the 

term ‘‘antimicrobial pesticide.’’ EPA 

believes that the definition was 

primarily intended to be used in 

conjunction with the provisions of 

section 3(h), which contains 

requirements for process improvements, 

timeframes for review purposes, and 

other regulatory matters, but, 

significantly, does not include 

provisions pertaining to data 

requirements. The definition in section 

2(mm) as it relates to section 3(h) was 

discussed fully in a proposed rule 

issued in the Federal Register of 

September 17, 1999 (64 FR 50672). 

The statutory definition, however, 

does not mesh with the Agency’s needs 

in developing this proposed rule 

concerning data requirements. Data 

requirements depend upon the use 

pattern, taking into account the 

pesticide’s hazard and exposure 

profiles. How well the pesticide kills or 

repels particular pests are relevant 

factors in the determination of product 

performance data requirements. 

Neither FIFRA section 3(c)(2) nor 

section 3(h) requires the Agency to 

develop data requirements for an 

‘‘antimicrobial pesticide’’ as defined 

specifically in section 2(mm). Therefore, 

the scope of this proposal has been 

expanded beyond ‘‘antimicrobial 

pesticide’’ as defined by FIFRA section 

2(mm) to include related pesticides that 

are excluded from the 2(mm) definition. 

The broader applicability of this 40 CFR 

part 158, subpart W is intended to 

ensure that all pesticides currently 

considered as antimicrobial products for 

purposes of FIFRA section 33 fees and 

review periods are covered. 

Accordingly, this proposal applies to: 

• Antimicrobial pesticides, as defined 

in FIFRA section 2(mm). 

• Pesticide products for antimicrobial 

uses in/on food or feed. 

• Antifoulant paints and coatings. 


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• Wood preservatives. 

• Pesticide products intended to be 

manufactured into any of the above. 

IV. Introduction to Subpart W 

A. Data Requirements for Registration 

First promulgated in 1984, EPA’s 

pesticide data requirements outline the 

kinds of data and related information 

typically needed to register a pesticide. 

In this proposal, the data requirements 

are organized by scientific discipline 

(e.g., toxicology), just as the existing 

data requirements in part 158 for 

conventional, and biochemical and 

microbial pesticides and those in part 

161 for antimicrobials. A significant 

change in this proposal from the 

existing data requirements in part 161 is 

the introduction of 12 use patterns 

specific to antimicrobials. Since there is 

much variety in pesticide chemistry, 

exposure, and hazard, the requirements 

are designed to be flexible. Test notes to 

the data requirements tables explain the 

conditions under which data are 

typically needed. Essentially, the data 

requirements identify the questions that 

the applicant will need to answer 

regarding a pesticide product before the 

Agency can register it. Data 

requirements address both components 

of a risk assessment, i.e., the hazards 

that the pesticide presents, and the 

estimated level of exposure to humans 

or nontarget species. Having the 

appropriate information enables the 

Agency to understand when those 

hazards pose risks. The answer to one 

question may inform the kind of 

information needed to answer other 

questions. For example, a pesticide that 

is persistent and toxicologically potent 

may require more extensive exposure 

data to help establish a safe level of 

exposure. In addition, because a number 

of antimicrobials are used for public 

health purposes (for example, 

disinfectants, sterilants, or sanitizers), 

there are product performance data 

requirements to assure that the 

antimicrobial product works as 

intended. 

B. Structure of Part 158 

At this time data requirements for 

conventional, biochemical, and 

microbial pesticides are established in 

40 CFR part 158. Data requirements for 

antimicrobial pesticides are established 

in 40 CFR part 161. 

Part 158 contains general provisions 

concerning all pesticide data (subpart 

A), instructions on how to use the data 

tables that follow (subpart B), and a 

series of disciplinary data tables that are 

focused on conventional pesticides 

(subparts C – O). Individual subparts are 

devoted to biochemical (subpart U) and 

microbial (subpart V) pesticides. The 

revised data requirements for 

antimicrobial pesticides would be 

incorporated into part 158 as subpart W. 

C. Subpart W of Part 158 

Subpart W is proposed to be a 

freestanding series of tables and 

regulatory text establishing specific data 

requirements for each scientific 

discipline for antimicrobial pesticides. 

EPA recognizes that antimicrobial uses 

are generally different from the uses 

more typically associated with 

conventional pesticides (e.g., 

agricultural outdoor uses) and therefore 

can have different combinations of 

exposure considerations. The use 

patterns and expected exposures 

typically determine the data 

requirements for any pesticide. 

Antimicrobial pesticides are no different 

in this regard from conventional, 

biochemical, and microbial pesticides. 

The order of proposed subpart W 

mirrors that of the larger part 158: from 

product chemistry, to efficacy, to 

hazard/toxicity requirements (both 

human health and ecological toxicity), 

to exposure data requirements 

(application and post-application 

human exposures, and exposure to 

residues in food), and environmental 

fate requirements, which overlap human 

exposure through drinking water. Units 

V–XIV of this preamble describe the 

revisions to the current requirements. 

The proposed data requirement tables 

are comprehensive. Generally, the data 

requirements for each discipline are 

discussed separately, but the applicator 

and post-application exposure 

disciplines are discussed together in a 

single unit. 

D. Clarifying How to Use the Data 

Tables 

Part 158 subpart B contains a stepwise process to assist the applicant in 

determining the data needed to support 

its particular product. At this time 

subpart B is specific to the needs of 

conventional, and biochemical and 

microbial pesticides. The process 

needed for antimicrobials is no 

different. EPA is proposing certain 

clarifying changes to subpart B to 

specify the needs of antimicrobial 

pesticides. Specifically, EPA proposes 

to include antimicrobial use patterns in 

§ 158.100 and a reference to the 

antimicrobial use site index that will be 

available on the EPA website. 

While EPA is attempting to assist the 

applicant in subpart B, it is important to 

emphasize that it is the applicant’s 

obligation under FIFRA to demonstrate 

that an individual product meets the 

standard under FIFRA and that of 

FFDCA. Accordingly, applicants are 

encouraged to consult with the Agency 

on the appropriate data requirements, as 

proposed here, as related to their 

specific product prior to and during the 

registration process. 

EPA is continuing its current system 

of identifying the applicability of data 

requirements in the data tables. In 

essence, the data requirements illustrate 

the questions the registrant will need to 

answer about the safety of the pesticide 

product before the Agency can register 

it. Because of the variety of chemicals 

and use patterns, and because EPA must 

retain flexibility to tailor data 

requirements as appropriate, only 

qualitative descriptors are in the tables. 

Test notes provide more specific 

information on the applicability of 

specific data requirements. 

The table descriptors NR (not 

required), R (required), and CR 

(conditionally required) should be 

viewed as a general presentation, 

indicating the likelihood that the data 

requirement applies. The use of R does 

not necessarily indicate that a study is 

always required, but that it is more 

likely to be required than not. For 

example, if the applicant wanted to 

apply his pesticide to apples, then crop 

field trials would be required almost 

always on apples. However, if the 

physical/chemical properties of the 

chemical did not lend themselves to the 

test, such as performing an inhalation 

test with a chemical that is a solid and 

has an extremely low vapor pressure, 

then a waiver might be granted. 

Generally test notes for R studies 

discuss any particular circumstances 

when the testing might not be required. 

The use of CR means a study is less 

likely to be required. Triggers in the test 

notes indicate the circumstances under 

which the Agency has learned through 

experience that the information is 

needed. Although only an 

approximation, if percentages were to be 

assigned to indicate the need for a 

particular study, then R could be 

viewed as representing the submission 

of a study 50% to 100% of the time and 

CR would be up to 50%. 

Thus, NR, R, and CR are used for 

convenience to make the table format 

feasible, but serve only as a general 

indication of the applicability of a data 

requirement. In all cases, the test notes 

referred to in the table must be 

consulted to determine the actual need 

for the data. Applicants are also 

encouraged to visit the Agency’s 

website, entitled ‘‘Data Requirements for 

Pesticide Registration’’ (see http:// 

www.epa.gov/pesticides/regulating/ 

data_requirements.htm). Since it is not 


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possible to sufficiently delineate all 

circumstances in test notes, consultation 

with EPA is encouraged. 

The table format includes a column 

heading entitled ‘‘Guideline,’’ which 

refers to the OPPTS (Office of Pollution 

Prevention and Toxic Substances) 

Harmonized Test Guidelines. 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 such as 

alternative test methods, submission of 

an article from open literature, or use of 

modeling. The applicant may submit a 

protocol of his own devising for the 

Agency to review. However, the OPPTS 

Harmonized Guidelines have been 

developed through a rigorous scientific 

process, including extensive peer 

review by the FIFRA Scientific Advisory 

Panel. Additionally, many of the 

Guidelines have been harmonized 

internationally. As such, they represent 

the recommended approach to 

developing high-quality data that 

should satisfy EPA’s data needs for risk 

assessment. 

E. The Nature of Changes to 

Requirements 

Proposed subpart W does not differ 

greatly from the data requirements for 

conventional pesticides promulgated in 

October 2007. Where this proposal 

differs is in the explicit adaptation of 

those data requirements to 

antimicrobials. As previously discussed, 

antimicrobial uses were covered in the 

original (1984) part 158. However part 

158 (now transitioned for antimicrobials 

as part 161) was developed primarily for 

agricultural pesticides. Since the use 

patterns which now appear in tables in 

part 161 are not specific to 

antimicrobials, often it has been 

difficult to discern directly from such 

tables the data requirements for certain 

antimicrobials. Without extensive 

consultation with and interpretation 

from the Agency, frequently it has been 

difficult for applicants to effectively use 

the tables to determine which data 

requirements apply to antimicrobials. 

Today’s proposal reflects the Agency’s 

current needs for risk assessment of 

antimicrobials. Describing the 

antimicrobial data requirements in 

terms of use patterns specific to 

antimicrobial uses provides a clarity 

that should reduce the need for 

extensive consultations. 

There are nine new data requirements 

for antimicrobials set out in this 

proposal. Two (developmental 

neurotoxicity and immunotoxicity) are 

the same new data requirements as 

promulgated in the final rule for 

conventional chemicals (72 FR 60934) 

(see Unit VIII). While photodegradation 

in soil studies have been routinely 

required for conventional chemicals, 

this study would be a new data 

requirement for wood preservatives (see 

Unit XII). Similarly, two new exposure 

data requirements (soil residue 

dissipation and non-dietary ingestion 

exposure) are today proposed for 

antimicrobials (see Unit IX.D). 

Four new data requirements 

(activated sludge sorption isotherm 

study; ready biodegradability study; 

porous pot study; and modified 

activated sludge, respiration inhibition 

test) are proposed today for 

antimicrobials that are not included in 

the final rule for conventional 

pesticides. This is due to the nature of 

antimicrobial pesticides, which 

includes many down-the-drain uses, i.e. 

those discharged to public treatment 

systems, and is discussed in Units XII.B. 

and C. 

Most screening-level environmental 

fate assessments would be performed 

using the hydrolysis, photodegradation 

in water, activated sludge sorption 

isotherm, ready biodegradability, and 

modified activated sludge, respiration 

inhibition tests. For wood preservatives, 

the results of the photodegradation in 

soil study may also be considered in the 

screening-level assessment. If the 

porous pot study is triggered based on 

the results of the ready biodegradability 

study, then those results would also be 

considered. 

EPA notes that its proposed approach 

for performing a screening-level fate 

assessment could potentially result in 

the submission of higher-tiered studies. 

There are seven higher-tiered 

environmental fate studies, that could 

be triggered based on a weight-ofevidence evaluation of the results of the 

screening-level studies. For example, if 

the screening-level assessment were to 

indicate that a down-the-drain chemical 

would partition to sludge, soil, or 

sediment, then higher-tiered 

environmental fate studies such as the 

aerobic and anaerobic soil metabolism 

studies may be required. If the chemical 

would partition to water then highertiered ecotoxicity studies such as the 

fish early life stage may be required. 

Thus, the higher-tiered studies that 

could be triggered include both the 

environmental fate and ecotoxicity 

scientific disciplines. 

While not a new data requirement, 

subchronic dermal testing of end-use 

products has not been routinely 

required and therefore would be 

considered a new testing requirement. 

The circumstances for requiring the 

testing is the same as for conventional 

chemicals. (See Unit VIII). 

Each data requirement proposed in 

Units, VIII, IX, X, XII, XIII, and XIV is 

described as ‘‘new,’’ ‘‘current practices,’’ 

or ‘‘existing.’’ ‘‘New’’ means that the 

data requirement has never been 

required or has rarely been required on 

a case-by-case basis, and has not been 

routinely considered during the 

Agency’s evaluation of the data needed 

for the purpose of risk assessment. 

‘‘Current practices’’ encompasses the 

data that is typically required to register 

an antimicrobial pesticide product. This 

would include existing data 

requirements that are codified in part 

161 as well as those that are not codified 

in part 161 and are now being proposed 

for codification in part 158, subpart W. 

It would also include any study that has 

been routinely required on a case-bycase basis, or any study that is routinely 

considered during the Agency’s 

evaluation of the data needed for the 

purpose of risk assessment but is 

infrequently required because the 

triggers for that study are infrequently 

met. 

‘‘Existing’’ requirements are a subset 

of ‘‘current practices.’’ This particular 

subset means that the data requirement 

is codified in part 161 and being 

transferred to part 158, subpart W either 

‘‘as is’’ or with specified changes to the 

test notes, to the Rs, CRs, and NRs, or 

to the use patterns for which required. 

If there are proposed revisions to an 

existing data requirement, then 

clarifications on these proposed 

revisions are included in the preamble. 

Such revisions include proposing 

changes such as a change from 

conditionally-required to required, a 

change in the number of test species, or 

expanding the number of use patterns 

for which the test is required. 

As previously discussed, there are 

frequently consultations to discern data 

requirements for certain of the 

antimicrobial use patterns. These 

consultations have led to general 

understandings as to the data required 

for a particular use pattern. For certain 

use patterns, all of the studies are 

considered to be the Agency’s current 

practices. As an example, for the wood 

preservative use patterns, there is not a 

good fit to any of the part 161 use 

patterns in the tables and therefore the 

data needed to register a wood 

preservative is difficult to interpret from 

those tables. Given these circumstances, 


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EPA developed a series of requirements 

developed specifically for wood 

preservatives. These requirements are 

not codified in CFR, but the applicants 

understand that these are the data 

needed for wood preservatives and they 

routinely provide these studies to EPA. 

F. Tiered Data Requirements 

The Agency has organized the 

proposed requirements for antimicrobial 

pesticide products to support a tiered 

testing approach. Under such an 

approach the Agency prescribes a 

specific subset of ‘‘lower tier’’ studies 

that are conducted first. The results of 

this first- or lower-tiered testing are then 

used in conjunction with exposure data 

or other information to determine the 

need for more complex ‘‘higher tier’’ 

studies. The risk assessment must 

provide sufficient information to make 

the risk management decisions needed 

to register the product or establish a 

tolerance. This is a significant factor in 

the tiering process. 

Data requirements have been tiered 

when EPA believes it can adequately 

conduct a risk assessment using a tiered 

approach. The conditions for 

‘‘triggering’’ these higher tiered studies 

are specified in the test notes to the 

tables in proposed subpart W. A tiered 

data submission process is intended to 

allow the Agency to assess a pesticide’s 

risk without requiring the applicant to 

conduct and submit studies that may 

not be needed for the regulatory 

decision. For certain chemicals, data 

from lower tiered requirements may be 

sufficient in and of themselves or in 

combination with other data to address 

the Agency’s risk concerns without 

submission of higher tiered data 

requirements. In other cases, data from 

lower tiered requirements may indicate 

that higher tiered data need to be 

provided. The Agency expects 

applicants to consult with the Agency, 

as needed, to determine when 

submission of higher tiered data may be 

required. 

The Agency has tiered the data 

requirements based on an 

understanding of the potential exposure 

for a specific use pattern. As an 

example, for toxicology studies used to 

support human health risk assessments, 

the high human exposure grouping 

specifies 19 toxicology studies as 

required at the lower tier. The low 

human exposure grouping specifies 13 

toxicology studies as required. The 

Agency considered the frequency, 

duration, and/or magnitude of the 

exposure to determine the lower tier of 

toxicology testing requirements for both 

the high and low human exposure 

groupings. 

For ecotoxicity data requirements, the 

Agency requires a first tier of required 

data for all antimicrobials regardless of 

the use pattern. The need for higher 

tiered data depends not only on the 

frequency, duration, or magnitude of the 

exposure, but also on the results of the 

first tier of the data. 

Such a flexible approach allows EPA 

to require enough data, but not more 

than enough, to make the required 

safety finding. Such an approach is the 

same as that used for other pesticides; 

however, for antimicrobials the 

progression from lower to higher tier 

requirements may differ from that of 

conventional pesticides because the 

uses and expected exposures are 

different. 

G. Impact of this Proposal on Future 

and Existing Registrations 

This proposal concerns prospective 

data requirements for future 

registrations of antimicrobial pesticides. 

That is, these proposed data 

requirements, once final, would apply 

to all new applications for registration 

of antimicrobial pesticides submitted 

after the effective date of the rule. The 

new data requirements would also 

apply to applications of antimicrobial 

pesticides that are undergoing Agency 

review when the new regulation goes 

into effect. EPA believes that there may 

be a need for some type of a limited 

transition ‘‘window’’ for certain 

antimicrobial registration applications. 

EPA anticipates applicants of 

applications that were submitted, but 

not yet approved when the new 

regulations go into effect, may need to 

discuss with EPA the specifics of their 

application and whether additional time 

may be needed to complete generation 

of certain studies that may then be 

required to fulfill new data 

requirements. The Agency specifically 

requests comment on implementing the 

effective date of the final rule for 

antimicrobials with regards to future 

registrations of antimicrobials. 

The Agency does not intend to apply 

these requirements automatically or 

routinely to all existing pesticide 

registrations. While EPA intends a 

flexible approach to imposing the new 

requirements upon existing products, 

the Agency may find it necessary to callin data on certain existing registrations, 

for example, as warranted by emerging 

risks of concern for particular pesticides 

or as a result of possible future 

programmatic changes and priorities on 

existing pesticides, or during 

registration review. 

However, EPA notes that issuance of 

this proposed rule provides notice to 

applicants of potential new data 

requirements and of potential expansion 

of existing data requirements to 

additional antimicrobial use patterns. 

Applicants and potential applicants for 

new registrations as well as registrants 

of existing products may wish to 

evaluate their products in light of the 

proposed requirements. As always, the 

Agency encourages applicants to 

consult with EPA, if they have any 

questions regarding data requirements. 

H. Weight-of-Evidence Approach 

The weight-of-evidence (WOE) 

approach is referenced in several 

subpart W test notes. Such an approach 

requires a critical analysis of the entire 

body of available data for consistency 

and biological plausibility. Some 

considerations in this approach are 

listed below: 

• 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 higher 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. 

•Corroborative information. 

Supplementary information relevant to 

the conclusions reached in the 

assessment is incorporated, e.g., studies 

demonstrating agreement between 

model predictions and observed effects. 

WOE considers the kinds of evidence 

available, how that evidence fits 

together in drawing conclusions, and 

significant issues/strengths/limitations 

of the data and conclusions. WOE is not 

simply tallying the number of positive 

or negative studies. 

I. Use Patterns in Subpart W 

The general use pattern groups 

described in subpart B of part 158 are 

not used as the bases for describing 

antimicrobial data requirements. Those 

general use patterns were developed for 

and are appropriate to conventional 

pesticide chemicals. 

Some years ago, 12 use categories 

were developed specifically for 

antimicrobials. At that time the 

Agency’s data requirements for all 

pesticide chemicals were specified by 

use patterns developed for and 

appropriate to conventional pesticide 

chemicals. To fit antimicrobial uses into 

this agricultural scheme, the 

antimicrobial use categories referred 

back to the then-existing use patterns. 

With the Agency’s intention to establish 

specific data requirements for 


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antimicrobials in subpart W, this 

referral is no longer needed. 

Therefore, the Agency is proposing 

that the use categories employed in 

recent years to generalize the range of 

uses for individual antimicrobial 

pesticide chemicals, now constitute the 

use patterns for specifying the 

antimicrobials data requirements in the 

tables in proposed subpart W. 

Additionally, EPA is proposing to 

codify in § 158.2201 the specific use 

patterns for antimicrobials. 

FIFRA section 3(h)(3)(A)(ii)(I) requires 

that EPA ‘‘define the various classes of 

antimicrobial use patterns.’’ For 

antimicrobial pesticides, the Agency 

proposes to structure its requirements 

by using a system of 12 use patterns 

based on similarity of use, purpose, 

pesticidal function, the nature of the 

exposure, and, in some cases, 

application methods. Today’s proposal 

meshes with the statutory mandate to 

identify classes of antimicrobial use 

patterns by defining for each use pattern 

the data requirements that apply. EPA 

requests comment not only on the 12 

antimicrobial use patterns described in 

this Unit, but also on the usefulness of 

these use patterns. EPA also requests 

comment on whether or not any 

different/additional use patterns should 

be codified by splitting or recombining 

the existing use patterns to make 

separate and distinct use patterns. 

Antimicrobial use patterns also reflect 

environmental concerns for indoor 

versus outdoor use, as well as food 

versus nonfood-use, and high versus 

low human exposure. The 12 general 

use patterns for antimicrobial pesticides 

are described below. Examples within 

each use pattern are provided: 

1. Agricultural premises and 

equipment. This use pattern includes 

many indirect food uses with mostly 

indoor use sites. 

• Farm and farm animal premises such 

as animal houses and pens (including 

milk houses), parlors, stalls, and barns. 

•Transportation vehicles used to 

transport animals. 

• Equipment such as forks, shovels, 

scrapers; halters, ropes, other restraining 

equipment; racks, mangers, feeders, 

waterers, troughs, and fountains. 

• Food-handling equipment such as 

milking equipment. 

2. Food-handling/storage 

establishments, premises, and 

equipment. This use pattern also 

includes many indirect food uses due to 

the treatment of food contact surfaces 

and the resultant human exposures. All 

use sites are indoor. 

• Food or feed processing plants. 

• Eating establishments such as 

restaurants and cafeterias. 

• Food storage or distribution 

facilities. 

•Commercial transportation vehicles, 

shipping, and storage containers. 

• Food or feed stores and markets. 

• Vending machines. 

3. Commercial, institutional and 

industrial premises and equipment. 

This use pattern includes nonfood 

contact areas of commercial sites. 

Typically, antimicrobial pesticides 

would be applied to ceilings, doors, 

doorknobs, fixtures, floors, light 

switches, stairs, walls, windows, and 

woodwork as part of routine cleaning 

practices. Included within this use 

pattern are residential school and 

daycare institutions. 

This use pattern includes both indoor 

and outdoor uses. Some of the uses have 

the potential for significant exposure 

due to the repetitive nature of certain 

exposures and therefore may be 

considered as high human exposure. 

4. Residential and public access 

premises. This use pattern includes 

mostly nonfood areas, although it 

includes food-handling areas in homes. 

Some of the uses have the potential for 

significant exposure due to the 

repetitive nature of certain exposures 

and therefore may be considered as high 

human exposure. Most uses are indoor. 

• Premises, contents, and equipment 

of homes, apartments, mobile homes 

and shelters, including home-based 

daycare. 

• Public areas, public buildings, and 

public rooms. 

•Commercial kennels, or living 

quarters of pets, zoo animals, race 

horses, or laboratory animals. 

5. Medical premises and equipment. 

Medical waste is defined as any solid 

waste that is generated in the diagnosis, 

treatment, or immunization of human 

beings or animals, in research pertaining 

thereto, or in the production of 

biologicals including, but not limited to, 

culture and stocks, pathological wastes, 

human blood and blood products, and 

sharps. This use pattern is considered to 

be indoor nonfood. Some of the uses 

have the potential for repeated exposure 

and therefore may be considered as high 

human exposure. 

• Hospital or medical environments 

such as clinics, dental offices, nursing 

homes, sick rooms, morgues, and 

veterinary clinics. 

• Non-critical medical equipment 

such as bedpans, basins, and furniture. 

6. Human drinking water systems. 

Human drinking water systems include 

any methods used to provide potable 

water from raw water supplies. This use 

pattern is considered to be high human 

exposure due to the potential for human 

exposures via drinking water, as well as 

dermal exposures to the treated water. 

• Public water systems. 

• Individual water systems. 

• Emergency water systems. 

• Water purifier units. 

• Private water systems of individual 

homes, farms, institutions, camps, 

resorts, and industrial plants. 

• Emergency water systems for the 

public, campers, travelers, military, and 

fishermen. 

7. Materials preservatives. Materials 

preservatives are antimicrobial 

chemicals added during industrial 

processes to prevent the growth of 

microorganisms. Examples of such uses 

include paints, coatings, adhesives, 

textiles, and paper. This use pattern 

includes food and nonfood, and mostly 

indoor uses. 

8. Industrial processes and water 

systems. Certain antimicrobial 

chemicals, known as microbiocides, are 

used to control the growth of bacteria, 

fungi, and algae in circulating water 

systems. There are two types of systems: 

‘‘once-through’’ and ‘‘recirculating.’’ 

For ‘‘once-through’’ systems, the 

water is not re-used and is therefore 

released into the aquatic environment or 

a wastewater treatment plant after a 

single cycle through the system. Oncethrough uses have the potential for 

significant environmental exposure 

when the treated water is released to the 

environment. Large volumes of water (as 

much as millions of gallons per minute) 

may be released directly to a river, 

estuary, or marine environment within 

minutes or hours of adding the 

antimicrobial to the system. In addition 

to the potential for environmental 

exposure after release, there is the 

potential for high human exposure via 

drinking water if the intake pipe for a 

drinking water treatment plant is 

downstream. Also, the water could be 

used in crop and/or livestock 

production thus providing for 

additional human exposure. 

However, for many uses of water in 

industrial plants the treated water is reused repeatedly within the system, 

‘‘recirculating’’ in the system multiple 

times until released into the aquatic 

environment or a wastewater treatment 

plant. EPA has assumed that the 

releases are scheduled as the 

antimicrobial has been ‘‘used-up.’’ 

Given the lower frequency of release, 

resulting in lower volumes released to 

the environment, recirculating uses are 

likely to have less environmental 

exposure than that of once-through 

systems. 

As will be explained later in Unit XI, 

for the purposes of determining data 

requirements for environmental fate and 


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ecological effects, the industrial 

processes and water systems use pattern 

will be subdivided. Because of the 

distinct differences between the oncethrough 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. 

9. Antifoulant paints and coatings. 

Antifoulants are coatings and paints 

applied to boat hulls and bottoms, crab 

and lobster pots, and underwater 

structures or equipment to control the 

growth of freshwater or marine fouling 

organisms. Antifoulant coatings have 

the potential for high environmental 

exposure most particularly for marine 

(both freshwater and saltwater) 

environments. 

Also included within this use pattern 

is ballast water, that is, the water that is 

pumped in and out of ballast tanks as 

a ship’s weight changes due to loading 

and unloading of cargo. Ballast water 

provides needed stability for safe 

operation of marine vessels. In recent 

years there have been significant 

concerns about transport of marine 

species from one marine environment to 

another in ballast water. When 

discharged into a new environment, the 

new species may become invasive and 

disrupt the native ecology. Ballast water 

treatments (such as adding an 

antimicrobial to the ballast water before 

discharge) are intended to prevent this. 

The Agency has reviewed few 

applications for ballast water 

treatments, presumably because 

treatment of ballast water to prevent the 

transfer of microorganisms from one 

marine environment to another is 

relatively new. Since ballast water 

treatments also have the potential for 

high exposure to the aquatic (both 

freshwater and seawater) environment, 

EPA has grouped the ballast water 

treatment pesticide chemicals with the 

antifoulant coating pesticide chemicals. 

10. Wood preservatives. Wood 

preservative products are those which 

claim to control wood degradation 

problems due to fungal rot or decay, 

sapstain, molds, or wood-destroying 

insects. This use pattern has the 

potential for high exposure for both 

humans and the environment with 

mostly outdoor use sites. Certain uses 

can be food-uses. The types of wood and 

the products that can be manufactured 

with this treated wood are: 

• Freshly cut logs or lumber. 

• Seasoned building materials. 

• Utility poles, fence posts and rails. 

• Structural members. 

• Structures and dwellings. 

•Transportation vehicles (truck beds 

and support structures). 

•Crop containers. 

• Lawn furniture and decks. 

• Playground equipment. 

• Garden/landscape timbers. 

• Log homes. 

11. Swimming pools. Products in this 

use pattern are used to prevent/control 

the growth of bacteria or algae in the 

water systems of swimming pools, 

Jacuzzis, and hot tubs. This use pattern 

is considered to be high human 

exposure. Under routine use little or no 

environmental exposure is expected, as 

the water in swimming pools, Jacuzzis, 

or hot tubs is considered to be separated 

from the natural environment. However, 

when draining is needed, depending on 

the volume of water and the location of 

the pool or hot tub, it is most likely that 

discharge would be down-the-drain to a 

wastewater treatment plant, to a storm 

drain that discharges to a stream, or 

directly to soil. 

12. Aquatic areas. Products in this use 

pattern are designed to control or kill 

slime-forming bacteria, fungi, or algae in 

lakes, ponds, streams, drainage ditches, 

and other bodies of water. In addition to 

the potential for environmental 

exposure, there is 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 

water could be used in crop and/or 

livestock production thus providing for 

additional human exposure. 

J. Use Site Index 

As part of this action, the Agency is 

proposing to place on its website an 

Antimicrobial Use Site Index similar to 

the existing Pesticide Use Site Index at 

http://www.epa.gov/pesticides/ 

regulating/usesite/index.htm. 

Information similar to that which would 

be included on the Antimicrobial Use 

Site Index is included in the docket for 

this action (Ref. 41). The existing 

Pesticide Use Site Index will be retitled, the Pesticide Use Site Index for 

Conventional, Biochemical, and 

Microbial Pesticides to distinguish it 

from the Antimicrobial Use Site Index. 

K. Request for Comments 

The Agency invites the public to 

provide its views and suggestions for 

changes on all of the various proposals 

in this document. Specifically included 

within the Agency’s request for 

comments are the following proposals: 

• SAR white paper. 

• Four case studies. 

• 12 general use patterns, suggestions 

for different/additional use patterns, 

and their utility. 

• Proposed new down-the-drain 

requirements. 

Additionally, in other parts of this 

proposed rule, EPA is specifically 

requesting comments on certain issues. 

As appropriate during the 

development of this proposal, EPA has 

occasionally shared information with 

the regulated community on the data 

requirements that were under 

consideration. Commenters are 

encouraged to comment on such sharing 

of information as part of the 

administrative process of developing 

this proposed rule. 

The Agency welcomes comments on 

the following topics of particular 

interest to the Agency: 

• All aspects of the administrative 

process used to develop this proposed 

rule including outreach activities. 

•The need for, value of, and any 

alternatives to, the data requirements 

described in this document. 

•The scientific basis of this proposed 

rule. 

•The clarity of the proposed data 

requirements for antimicrobial 

pesticides and the relationship between 

the proposed data requirements and 

EPA’s statutory determinations. 

•The economic analysis of the 

proposed rule, as well as on its 

underlying assumptions, economic data, 

and high- and low-cost options and 

alternatives. 

Commenters are encouraged to 

present any data or information that 

should be considered by EPA during the 

development of the final rule. Describe 

any assumptions and provide any 

technical information and data used in 

preparing your comments. Explain 

estimates in sufficient detail to allow for 

them to be reproduced for validation. 

EPA’s underlying principle in 

developing the proposed revisions has 

been to strike an appropriate balance 

between the need for adequate data to 

make the statutorily mandated 

determinations and informed risk 

management decisions, while 

minimizing data collection burdens on 

applicants. 

V. Product Chemistry 

The Agency proposes to apply the 

product chemistry data requirements for 

conventional pesticide chemicals, in 

subpart D, to antimicrobial products. 

These requirements were promulgated 

in the final rule on October 26, 2007, (72 

FR 60934). Product chemistry 

requirements identify the basic identity, 

and chemical and physical 

characteristics of a pesticide chemical. 


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These data, to a limited extent, are used 

to determine if a pesticide contains 

contaminants which are of toxicological 

or environmental concern and are 

necessary to determine proper label 

precautions. Product chemistry 

requirements are generally not 

dependent on a pesticide’s intended use 

pattern, and therefore it is appropriate 

to apply the same requirements to 

antimicrobial pesticides as required for 

conventional pesticides. If 

circumstances particular to 

antimicrobial pesticides should arise, 

then the Agency has the authority to 

require the appropriate product 

chemistry data on a case-by-case basis. 

VI. Product Performance Data 

Requirements 

EPA is not proposing to revise 

product performance data requirements 

(§ 158.2220) at this time. At this time 

there are nearly identical product 

performance data requirements for 

antimicrobial chemicals in both 

§ 158.400 and part 161. EPA proposes to 

transfer the contents of the existing 

product performance data requirements 

for antimicrobial pesticides into subpart 

W, specifically § 158.2220. The table is 

transferred essentially unchanged. EPA 

is also proposing to delete the 

duplicative data requirements for 

antimicrobials from the table in 

§ 158.400. After the publication of the 

final rule, all product performance data 

requirements for antimicrobials will be 

contained in § 158.2220. 

In the Federal Register of September 

17, 1999, (64 FR 50726), EPA published 

a proposed rule entitled, ‘‘Registration 

Requirements for Antimicrobial 

Pesticide Products and Other Pesticide 

Regulatory Changes.’’ In that proposed 

rule, EPA proposed various definitions 

for public health pesticides. Today, the 

Agency is re-proposing definitions for 

the following terms: disinfectant, 

fungicide, microbiological water 

purifier, sanitizer, sterilant, 

tuberculocide, and virucide. These 

proposed definitions are identical to 

those in the 1999 proposal. The Agency 

is also re-proposing the 1999 criteria 

that EPA would use to consider whether 

a product makes a public health claim. 

The comments that were received on the 

1999 proposed rule were considered for 

today’s proposed rule. 

The current regulations in part 161 

require that each applicant must ensure 

through testing that its products are 

efficacious when used in accordance 

with label directions and commonly 

accepted practices. The requirement to 

submit product performance data is 

directly linked to making a public 

health claim. Today’s proposal makes 

explicit what antimicrobial claims 

would be considered public health 

claims for purposes of product 

performance data submission. 

At the time of application, EPA 

requires the submission of product 

performance data for products making a 

public health claim. An application will 

not be approved in the absence of 

acceptable data substantiating a public 

health claim. EPA requires the 

development of product performance 

data for all other (non-public–health) 

products, but does not review or 

approve such data as part of a new or 

amended registration. If, after the 

product has been registered, EPA has 

reason to review such data (for example, 

there are indications that the product 

does not perform as claimed), then EPA 

will require the registrant to submit 

such data within a reasonable time. A 

request for submission of product 

performance data after product 

registration is not required to be done 

under the Data Call-In provisions of 

FIFRA section 3(c)(2)(B), but is instead 

authorized by regulation. 

Accordingly, if an antimicrobial 

product makes a claim to control 

microorganisms that pose a threat to 

human health, the applicant is then 

required to submit product performance 

data to support its registration. The 

types of product performance data 

required by the Agency to support 

registration of an antimicrobial are 

determined by the types of claims made 

on the product’s label (e.g., sanitizer, 

disinfectant) and the intended use site 

for the product (e.g., hard surface, 

fabric). 

VII. Human Health Risk Assessment 

The data needed to conduct a human 

health risk assessment include both 

toxicology and exposure data. 

Toxicology studies are used to assess 

hazards of pesticides to humans and 

domestic animals, and include a variety 

of acute, subchronic, and chronic 

toxicity studies; developmental/ 

reproductive tests; and tests to assess 

mutagenicity and pesticide metabolism. 

To assess human health risk, there must 

be sufficient information to select the 

appropriate doses and end-points, i.e., 

the Agency must know the level of 

exposure at which an adverse effect is 

observed. This requires a toxicological 

database that is not only complete in the 

endpoints it covers, but is also of 

acceptable quality. The duration of the 

toxicity study approximates the 

estimated duration of the human 

exposure, while considering species 

differences in maturational milestones 

and overall life span. The toxicology 

data requirements are discussed in Unit 

VIII of this preamble. 

For EPA to assess the potential risks 

that antimicrobial products pose to 

humans, it is necessary not only to 

assess the hazard of the antimicrobial 

active ingredient based on toxicology 

information, but also to estimate human 

exposures to the antimicrobial based on 

the product use patterns. For 

antimicrobials, three types of exposure 

data are required: applicator, postapplication, and residue chemistry 

(which includes exposure via food and 

water). 

Applicator and post-application 

exposure data are used to evaluate 

exposures to persons in occupational 

and non-occupational settings, 

including residential, commercial, 

institutional, and recreational sites. 

Exposure data include: dermal and 

inhalation exposure data for applicators, 

post-application residue data, postapplication monitoring data, use 

information, and human activity 

information. Applicator and postapplication data requirements are 

discussed in Unit IX of this preamble. 

Residue chemistry information is 

used to establish tolerances for residues 

of pesticide chemicals (and any 

metabolites of concern) in/on food 

crops, processed foods, and animal 

products consumed by humans when 

the animal consumes a feed item 

derived from these crops. The Agency 

estimates the dietary exposure of the 

general population and various 

population subgroups to pesticide 

residues in food by using the residue 

data as inputs to the dietary modeling. 

The dietary exposure is then used in 

conjunction with toxicity data to 

determine risk. Residue chemistry data 

requirements are discussed in Unit X. 

VIII. Toxicology Data Requirements 

A. Toxicology Data Requirements for 

Antimicrobials 

EPA proposes to adapt the basic 

toxicology data types as listed in 

subpart F of current part 158 to support 

applications for antimicrobial products. 

However, EPA also proposes to modify 

the applicability of those requirements 

to reflect the differing risks of and levels 

of exposure to antimicrobials. 

As with conventional pesticides, the 

types of toxicology studies required for 

antimicrobials can include acute, 

subchronic, and chronic toxicity 

studies, as well as carcinogenicity, 

prenatal developmental toxicity, 

reproductive toxicity, mutagenicity, 

neurotoxicity, immunotoxicity, and 

other studies. 


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1. Acute toxicity studies provide 

information that serves as a basis for 

classification and precautionary labeling 

and the need for child resistant 

packaging. 

2. Subchronic toxicity studies provide 

information that can be used to assess 

human health hazards that may result 

from repeated exposures to a pesticide 

over a limited period of time. These data 

also provide information for selecting 

proper dose levels for chronic/ 

carcinogenicity studies. 

3. Chronic toxicity studies are used to 

assess potential hazards resulting from 

prolonged and repeated exposures to a 

pesticide over a significant portion of 

the life span. 

4. Prenatal developmental toxicity 

studies are designed to assess the 

potential of a pesticide to induce effects 

in offspring as the result of exposure of 

the mother during pregnancy. 

5. Multigeneration reproduction 

studies are designed to provide 

information concerning the general 

effects of a pesticide on overall 

reproductive capability. 

6. Mutagenicity studies assess the 

ability of the pesticide to interact 

directly or indirectly with cellular DNA, 

RNA, proteins, or chromosomes and the 

potential for adverse effects on cellular 

genetic material. 

7. Neurotoxicity studies evaluate the 

potential of the pesticide to adversely 

affect the structure and functions of the 

nervous system. 

8. Immunotoxicity studies evaluate 

the potential of the pesticide to 

adversely impact the immune system. 

9. Metabolism studies evaluate the 

absorption, distribution, 

biotransformation, and excretion of the 

pesticide. 

B. The History of Toxicology 

Requirements for Antimicrobials 

By 1984, the Agency had reconsidered 

its toxicology data requirements for all 

pesticides, including antimicrobials. For 

instance, it had become clear that 

exposure to antimicrobial pesticides 

might well be long-term and frequent 

since many antimicrobials were used 

indoors in close proximity to humans. 

Occupational users often were exposed 

to concentrated antimicrobial products 

while mixing and diluting the product 

for use, and might be exposed to an 

antimicrobial pesticide for large 

portions of their working lifetimes. In 

response to the reregistration program 

initiated under the 1988 amendments to 

FIFRA, EPA concluded that additional 

data were needed to properly evaluate 

the potential hazards associated with 

antimicrobial pesticides. Consequently, 

the Agency began to require more 

toxicity data for antimicrobials. In 1987, 

based on its evolving understanding of 

antimicrobial uses, the Agency issued 

an Antimicrobial Toxicology Data CallIn (DCI) Notice (52 FR 595, January 7, 

1987) (Ref. 24), which specified a tiered 

approach for submission of toxicology 

and human exposure data. 

The 1987 Antimicrobial Toxicology 

DCI divided antimicrobial pesticides 

into three exposure categories: low, 

medium, and high. The toxicology data 

required was tiered according the 

amount of exposure. The first tier 

toxicology data requirements (low 

exposure) were the standard acute 

studies, a 90–day dermal or inhalation 

study, a prenatal developmental toxicity 

study in one species, and a battery of 

mutagenicity studies. The second tier 

(medium exposure) included the firsttier toxicology studies and a subchronic 

feeding study, a prenatal developmental 

study in a second species, and a dermal 

absorption study. The third tier (high 

exposure) included the first- and 

second-tier studies and the chronic 

feeding, carcinogenicity, reproduction, 

and metabolism studies. All food-use 

antimicrobials were considered high 

exposure. 

Applicants could fulfill the toxicology 

data requirements by submitting the 

appropriate toxicity studies or by 

submitting a combination of toxicity 

studies and exposure data. The Agency 

used the exposure data and submitted 

toxicology data to determine whether 

and which additional toxicology studies 

were needed to assess the hazard of the 

antimicrobial. 

In proposing part 158, subpart W, the 

Agency is specifying the toxicology data 

requirements it believes are appropriate 

for specific antimicrobial use categories, 

drawing upon EPA’s experience since 

1987. EPA is now proposing two 

groupings: Low- and high-exposure. In 

practice, the submission, review, and 

evaluation of toxicity data merged the 

low- and medium-exposure categories. 

Therefore, the low- and mediumexposure categories from the 1987 DCI 

were combined to create what is today 

the low exposure category. 

Today’s proposed approach 

conceptually follows the tiering 

approach used in 1987. Generally, data 

requirements proceed in a tiered 

manner from simpler to more complex 

studies considering the frequency, 

duration, and magnitude of exposure as 

well as the dermal absorption of the 

pesticide. Knowledge gained from 

results of assessments performed using 

these lower tiered studies is used to 

indicate if any higher tiered studies are 

required. The Agency does not prescribe 

a required sequence of toxicological 

testing. There are many factors that 

could affect the testing progression. 

Rather, decisions regarding the 

sequence in which the tests are 

conducted are left up to the applicant. 

Thus, the applicant has flexibility to 

determine the sequence of testing, as 

best suited for their particular chemical. 

Early consultation with the Agency is 

recommended to attain a common 

understanding of the sequencing that 

should be used. 

C. Groupings for Antimicrobial 

Toxicology Data Requirements 

1. Overview. This proposal divides the 

antimicrobial uses into two groups, high 

human exposure and low human 

exposure uses. Because high human 

exposure uses may pose higher risks, 

more toxicology studies are required 

than for uses with less exposure. For the 

purpose of determining toxicology data 

requirements, high human exposure is 

defined as that resulting in human 

exposures over a considerable portion of 

the human lifespan. Exposure to food 

and water, which occurs throughout the 

human life span, is therefore a high 

human exposure. For other exposures 

such as occupational and residential, 

the Agency has considered the 

frequency, duration, or magnitude of the 

exposure to determine in its best 

professional judgment if the exposure is 

high. One or a combination of these 

parameters led the Agency to make the 

determination that the exposure is high. 

As an example, swimmers may swim 

daily or weekly, from several minutes to 

several hours with almost their entire 

body in the water. There are workers 

who manually pour concentrates into 

vessels for mixing (with water or other 

chemicals) in order to prepare dilute 

solutions for use. Such exposures can 

occur daily, weekly, monthly, or 

episodically as dictated by the 

circumstances of the job. Particularly in 

the absence of personal protective 

equipment, these workers have the 

potential for high dermal and inhalation 

exposures. Accordingly, for the 

purposes of defining data requirements, 

EPA proposes to categorize food and 

feed uses and certain nonfood-uses as 

high human exposure. 

As discussed, the Agency considers 

high human exposure uses to be those 

that could result in pesticide residues 

occurring in food or feed, or in drinking 

water. These would include, but are not 

limited to: 

• Human or animal drinking water. 

• Fruit and vegetable rinses. 

• Egg washes. 

• Outdoor aquatic uses in lakes, rivers, 

or streams which have the potential to 

contaminate potable water. 


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• Indirect food uses with residues 

equal to or greater than 200 parts per 

billion (ppb). 

• Any use that requires a tolerance or 

tolerance exemption (except for indirect 

food uses requiring a tolerance or 

tolerance exemption in which residues 

are less than 200 ppb). 

EPA also considers high human 

exposure uses to be those uses that 

could result in high exposure to 

applicators, and any other antimicrobial 

uses which could result in high 

exposure to humans. These would 

include but are not limited to: 

• Wood preservatives. 

• Metal cutting (metalworking) fluids. 

• Swimming pools. 

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 is proposing an approach 

that might allow an applicant for 

registration of a pesticide with low 

human exposure uses to generate fewer 

studies in total than would be required 

for high human exposure uses. Under 

this proposal, applicants with low 

human exposure antimicrobials may 

perform tests in a tiered fashion. As 

previously explained, for toxicology 

studies the high human exposure 

grouping specifies 19 toxicology studies 

as required, and for the low human 

exposure grouping, 13 toxicology 

studies as required. After the 13 

required studies for low human 

exposure are reviewed by the Agency, 

additional testing may be required for 

low-exposure uses based on the result(s) 

of the lower-tiered studies. These 13 

studies could indicate a low risk 

potential or could trigger the need for 

additional data. 

The table in proposed § 158.2230 

presents the toxicology data 

requirements. The proposed toxicology 

data requirements for the two groupings 

(high human exposure and low human 

exposure) are separated into two 

columns showing test by test whether it 

is typically required (shown as R) or 

conditionally required (shown as CR). 

The Agency recognizes that 

toxicology testing can represent a large 

burden on applicants and can involve 

significant animal testing. 

Consequently, the Agency works with 

applicants, the scientific community, 

and other stakeholders to ensure that 

data requirements produce the 

information needed to enable the 

Agency to make the safety findings 

required under FIFRA and FFDCA. The 

tiering process proposed within the 

toxicology data requirements requires 

fewer studies for lower exposures. The 

Agency also works to design study 

protocols that minimize the 

development burden and limit uses of 

test animals. Toxicity testing 

requirements may be satisfied in a 

combined study, such as combining the 

prenatal developmental and 

reproductive toxicity testing 

requirements in a single study. 

However, if this option is chosen, the 

protocol must be approved by the 

Agency prior to the initiation of the 

study. Details for developing protocols 

are available from the Agency. 

2. Data requirements for high human 

exposure uses. For high human 

exposure uses, EPA is proposing to 

require the following studies: Acute 

oral, dermal, and inhalation toxicity; 

primary eye and dermal irritation; 

dermal sensitization; subchronic studies 

in two species; mutagenicity studies; 

acute and subchronic neurotoxicity 

testing; prenatal developmental toxicity 

studies in two species; a two-generation 

reproduction study; a chronic feeding 

study in one species; carcinogenicity 

studies in two species; a mammalian 

metabolism study; and an 

immunotoxicity study. Based on a 

weight-of-evidence evaluation, a 

developmental neurotoxicity study may 

be required. If the Agency determines, 

based on use information that dermal 

exposure is the major route of exposure, 

then EPA may require dermal 

absorption testing or toxicological 

studies conducted by the dermal route. 

i. Wood preservatives. For wood 

preservatives, the Agency may require 

toxicity data on both the active 

ingredient which is incorporated into 

the wood and on transformation/ 

degradation products which occur in 

wood post-treatment. Such 

transformation/degradation products 

would include dislodgeable residues 

(i.e., residues that occur from hand 

contact with treated wood) or leachate 

residues (i.e., residues that occur in soil 

or water in contact with treated wood). 

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. If the use of the MWF 

is limited to ‘‘closed’’ systems only, the 

applicant clearly identifies the use as 

such, and the Agency agrees, then fewer 

toxicity studies would be required for 

that ‘‘closed’’ system. Based upon 

review and evaluation of the submitted 

toxicity studies and exposure data, EPA 

may determine that fewer additional 

toxicity studies than would generally be 

submitted are required. Upon request 

the Agency will provide written 

guidance concerning exposure, toxicity, 

and other data requirements for ‘‘open’’ 

and ‘‘closed’’ MWF systems. 

3. Data requirements for low human 

exposure uses. As previously discussed, 

the Agency proposes to apply a tiered 

system to toxicology testing 

requirements for low human exposure 

antimicrobials. The required data are: 

Acute oral, dermal, and inhalation 

toxicity; primary eye and dermal 

irritation; dermal sensitization; a 

subchronic toxicity study in the rodent; 

prenatal developmental toxicity studies 

in two species; a two-generation 

reproduction study; mutagenicity 

studies; and immunotoxicity testing. 

Based on the review of these studies, 

additional studies may be required if 

there is evidence of significant toxicity 

in the submitted studies. Evidence that 

could trigger concerns may include data 

indicating neurotoxicity, 

immunotoxicity, developmental, 

reproductive, or other systemic toxicity 

such as the presence of neoplastic 

growth or significant target organ 

toxicity. In such cases, appropriate 

studies to address the Agency’s hazard 

or risk concern would be required. The 

table in proposed § 158.2230 contains 

test notes that explain how these 

toxicology requirements are proposed to 

be applied to low human exposure 

antimicrobials. 

4. Data requirements for indirect food 

uses. For the purpose of determining 

toxicology data requirements, an 

antimicrobial use is considered an 

indirect food use when the 

antimicrobial pesticide is applied to a 

surface or incorporated into a material 

that may contact food, but is not applied 

directly to food. Residues of the 

pesticide or its degradates can be 

transferred to the food when it comes 

into contact with these treated surfaces 

and articles. Examples of antimicrobial 

uses which may result in residues in 

food, through normal use, are sanitizers 

and disinfectants, which may be used in 

food-handling areas, but not directly 

applied to the food. 

With the passage of the Food Quality 

Protection Act of 1996 (FQPA), as later 

modified by the Antimicrobial 

Regulation Technical Corrections Act of 

1998 (ARTCA), EPA currently has the 

responsibility for establishing tolerances 

or tolerance exemptions for all pesticide 

uses that result in residues in or on 

food, except for: 

•Residues that result from the use of 

antimicrobial substances on food or in 

water that comes into contact with food, 

if such substances are used where food 


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is prepared, packed, or held for 

commercial purposes. (For raw food 

commodities, this exclusion does not 

apply if the antimicrobial is applied in 

a facility where only such foods are 

treated and the treatment of the foods 

does not constitute food processing.) 

• Antimicrobial substances used as 

food contact substances in or on food, 

such as those used in the manufacture 

of food contact packaging. This 

exclusion does not apply to objects 

impregnated with a food contact 

substance (other than food packaging 

material) if the inclusion of the 

substance is intended to have an 

antimicrobial effect on the food contact 

surface of the object. 

FDA has the responsibility for 

regulating these antimicrobial 

substances as food additives under 

section 409 of the FFDCA. However, 

under the provisions of FIFRA section 

2(bb) prior to registration of a pesticide 

that may result in residues of that 

pesticide in or on food (including 

sanitizers, disinfectants, and 

slimicides), EPA must make a safety 

finding that the pesticide residue meets 

the standard set forth in section 408 of 

FFDCA. This applies even if FDA will 

establish a food additive regulation for 

the use of the antimicrobial substance 

under section 409 of the FFDCA. 

Since publication in 2002 of its final 

guidance for toxicology 

recommendations for food contact 

substances, FDA has used an approach 

with several tiers: residues less than 0.5 

ppb, between 0.5 and 50 ppb, between 

50 ppb and 1,000 ppb, and greater than 

1,000 ppb. EPA recognizes the historic 

usefulness of the FDA’s tiered approach 

and proposes to adopt it conceptually, 

but with a modification appropriate to 

antimicrobials (biocides). FDA’s 

guidance (Ref. 8) specifically 

recommends that a factor of 5 be used 

to account for the toxicity of biocides. 

Further modifications to this approach 

are needed for EPA to perform an 

assessment of risk that conforms to the 

FFDCA section 408 safety finding which 

now requires consideration of the ‘‘... 

special susceptibility of infants and 

children to the pesticide chemical 

residues....’’. Thus, additional studies 

are needed even for the lower exposures 

for which FDA historically would not 

have required data. 

Accordingly, EPA proposes to classify 

indirect food uses of antimicrobials 

which result in residues in or on food 

of less than 200 ppb as low human 

exposure uses for purposes of subpart 

W. Given FDA’s historical experience 

with biocides, EPA believes that the 200 

ppb (1,000 ppb divided by 5) 

benchmark is a reasonable delineation 

between high and low human 

exposures. Antimicrobials used in a 

manner which results in residues in 

food from an indirect use that are equal 

to or greater than 200 ppb would be 

considered high exposure uses. The 

Agency specifically requests comment 

on the use of 200 ppb residues in food 

as the differentiation between the high 

and low human exposure for the 

purposes of subpart W. 

For indirect food uses, the applicant 

should begin the process by collecting 

all available information. Since many 

indirect food uses were previously 

evaluated by FDA, there may be a 

petition that was submitted to FDA. For 

some chemicals, toxicity testing may 

have been conducted and reviewed in 

the open literature. After identifying the 

available reliable information, the 

applicant should compare this 

information to the data requirements in 

the appropriate column in the table in 

§ 158.2230. If the applicant believes that 

an existing study satisfies the data 

requirement, then this should be 

discussed with EPA. 

The applicant is also encouraged to 

review the approach discussed in Unit 

XVIII.A. of this preamble on the use of 

Structure-Activity-Relationship (SAR) 

assessments to ascertain if such 

techniques could provide useful 

information in preparing a submission 

to EPA. 

D. Acute Toxicity Studies for End-Use 

Products 

EPA proposes to add a test note to 

clarify that the currently required six 

acute toxicity studies are to be 

conducted on the product as formulated 

for sale and distribution. These 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. The applicant has 

the option of also conducting certain 

studies using the highest diluted 

concentration (i.e., the least diluted 

product) permitted by the labeling. This 

test note codifies EPA’s current 

practices. Consultation with the Agency 

is highly suggested to assure that the 

appropriate product and any 

appropriate dilutions are tested. 

E. Neurotoxicity 

EPA promulgated toxicity 

requirements for conventional pesticide 

chemicals, in which the data 

requirements for neurotoxicity were 

revised. The former test battery of three 

studies was revised to include only two 

studies. The rationale for those revisions 

was discussed in Unit XI of that 

proposed rule (March 11, 2005) (70 FR 

12276), and in the final rule preamble 

(October 26, 2007) (72 FR 60934). That 

rationale is also applicable to 

antimicrobial pesticide chemicals. 

EPA proposes to adopt the current 

conventional pesticide data 

requirements for neurotoxicity testing to 

antimicrobials. Adopting the battery of 

two neurotoxicity studies would codify 

the Agency’s current practices. 

The current adult neurotoxicity test 

battery for antimicrobials in part 161 

consists of three studies: Acute delayed 

neurotoxicity (hen), 90–day 

neurotoxicity (hen), and 90–day 

neurotoxicity (mammal). The mammal 

subchronic neurotoxicity study is 

required if the acute oral, dermal, or 

inhalation toxicity studies show 

neurotoxicity or neuropathy. The 

existing required data are inadequate for 

evaluating neurotoxic effects of some 

chemicals. 

The proposed battery of two studies 

in the rat is more sensitive than the 

neurotoxicity tests currently required in 

part 161. The objective of the proposed 

acute and subchronic neurotoxicity 

battery is to evaluate the incidence and 

severity of the functional and behavioral 

effects, the level of motor activity, and 

the histopathology of the nervous 

system following exposure to a pesticide 

chemical. 

Under this proposal, an adult 

neurotoxicity test battery of two studies 

would replace the current battery of 

three studies. The two studies are an 

acute and a subchronic 90–day 

neurotoxicity study in rats. The acute 

study would detect possible neurotoxic 

effects resulting from a single exposure. 

The subchronic study would detect 

possible effects resulting from repeated 

exposures. These studies were 

presented to the FIFRA SAP in 1994, 

which endorsed them, and the Agency 

has generally required them on a caseby-case basis since 1992 for all 

pesticides, including antimicrobial 

pesticides. 

The required parameters for a 

subchronic neurotoxicity study may be 

incorporated into the standard 90–day 

subchronic feeding study in rats. The 

acute and subchronic neurotoxicity 

studies in adult rats, in addition to 

providing data on the potential for 

adverse neurotoxic effects, may also 

provide a basis for comparing the 

potential for age-related differences in 

impacts on the nervous system if a 

developmental neurotoxicity study is 

triggered for the same chemical. 

For high human exposure uses, EPA 

proposes to require both the acute 

neurotoxicity and subchronic 

neurotoxicity studies in the rat. For low 

human exposure uses, both 


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neurotoxicity studies are proposed to be 

conditionally required (CR) and would 

be triggered if there is evidence of 

neurotoxic effects in the 90–day oral 

study in rodents or if other data show 

evidence of neurotoxicity. 

F. 90–Day Oral Studies 

EPA proposes to adopt the current 

conventional pesticide data 

requirements for subchronic (90–day) 

studies to antimicrobials. Oral 90–day 

toxicity studies in two species are 

currently required in part 161 for high 

human exposure uses and conditionally 

required in part 161 for low human 

exposure uses. The Agency is proposing 

to continue this existing requirement for 

high human exposure uses in part 158, 

subpart W. The Agency is proposing to 

require an oral 90–day study in one 

species (rodent) for low human 

exposure uses and to conditionally 

require testing in a second species (nonrodent). For low human exposure uses, 

this change from two conditionally 

required studies to one required and one 

conditionally required study would 

codify current practices. 

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 rangefinding studies in the mouse. 

Additionally, 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. Although the subchronic 

guidelines include the measurement of 

certain neurological endpoints, they do 

not meet the requirement for a 90–day 

neurotoxicity study. 

G. 21/28–day Dermal and 90–day 

Dermal Testing with End-Use Product 

Currently in part 161 there is a 

conditional requirement for 21–day 

and/or 90–day dermal toxicity studies 

for all use patterns. The Agency is 

proposing to continue to conditionally 

require 21/28–day and/or 90–day 

dermal toxicity studies for all 

antimicrobials. As determined by the 

Agency, based on the use pattern, 

frequency of exposure, and magnitude 

of exposure, the 21/28 day study may 

provide the appropriate information for 

risk assessment purposes. 

Just as with conventional pesticides, 

the Agency is proposing to require 

subchronic dermal testing of the enduse 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. Testing of an 

end-use (formulated) product in either 

of these studies has not been routinely 

required and therefore would be a new 

testing requirement for antimicrobials. 

A test note has been added to both of 

these existing data requirements to 

describe the triggers for end-use product 

testing. 

Currently, end-use products are 

required to be tested for acute dermal 

toxicity and dermal irritation. Without 

additional subchronic testing of the enduse product, risk from dermal exposure 

to an end-use product may be 

underestimated for those products that 

contain an inert ingredient that 

increases the dermal absorption of the 

active ingredient. An example of such 

an inert ingredient would be dimethyl 

sulfoxide. 

H. 90–day Dermal and 90–day 

Inhalation Testing for HVAC&R Uses 

Heating, ventilation, air conditioning, 

and refrigeration systems (collectively 

referred to as HVAC&R) refer to systems 

which refrigerate, exclusively air 

condition, or exclusively heat, as well as 

those in which one system provides 

both heating and cooling. HVAC&R 

systems are present in industrial, 

institutional, commercial, and 

residential establishments, and include, 

but are not limited to: air ducts, duct 

fittings, duct liners, fans, supply ducts, 

return ducts, exhaust ducts, intakes, 

outlets, louvers, diffusers, dampers, 

plenums, outdoor air intakes, air 

handling units, and any other ductwork 

and similar components. The Agency is 

concerned with potential exposures and 

risks from application of antimicrobial 

pesticide products used to treat the 

surfaces of HVAC&’s system 

components. An example of such 

treatment would be use of an 

antimicrobial as part of air duct 

cleaning. 

HVAC&R is a unique use site which 

must be specifically identified on the 

label of the antimicrobial product. The 

application of an antimicrobial product 

to an HVAC&R system represents a use 

pattern substantially different from 

other hard surface disinfection or 

sanitizer treatments. Application to 

HVAC&R systems may require that 

larger volumes of the antimicrobial be 

applied to both internal and external 

system components than would 

typically be used as a disinfection/ 

sanitizer application to a hard surface 

such as a desktop. Thus, there is a 

greater potential for the applicator to be 

exposed to large amounts of pesticide. 

In addition, many of the components of 

HVAC&R systems are typically 

inaccessible and could create unique 

exposure scenarios for applicators. Postapplication exposure to building 

occupants is also a concern. When the 

treated system resumes operation, the 

potential exists for the pesticide to be 

readily spread throughout the building. 

For these reasons, the Agency is 

proposing to modify the requirement for 

90–day subchronic studies to address 

HVAC&R uses. Specifically, the Agency 

is proposing to replace the 90–day oral 

toxicity test with two 90–day toxicity 

tests, one by the dermal route, and one 

by the inhalation route. These are the 

primary routes of exposure from 

HVAC&R uses, and such route-specific 

studies are intended to provide the 

Agency with the information needed to 

characterize the hazard for the risk 

assessment for HVAC&R uses of 

antimicrobial pesticides. 

I. Chronic Studies 

Currently in part 161 a chronic 

toxicity study in two species is required 

for all food-uses and conditionally 

required for all other use patterns. 

Today the Agency is proposing to 

continue this existing requirement by 

requiring a chronic study in the rodent 

for high human exposures and 

conditionally requiring the study for 

low human exposures. 

In its final rule for conventional 

pesticide chemicals, the Agency 

eliminated the requirement for an oral 

chronic study in a second, non-rodent 

species, usually the dog. Similarly, EPA 

is proposing to eliminate the 1–year dog 

study as a data requirement for 

antimicrobial pesticides. EPA’s 

reasoning is fully explained in the final 

rule (Unit X) for conventional pesticides 

(Refs. 36, 37, and 38). For antimicrobials 

EPA would adopt the same criteria (as 

set out in the applicable test note to the 

table in proposed § 158.2230) for the 

rare circumstances when a 1–year dog 

study might be required. 

J. Carcinogenicity Studies 

Currently in part 161 two 

carcinogenicity studies are required for 

all food-uses and conditionally required 

for all other use patterns. Today the 

Agency is proposing to continue this 

existing requirement by requiring 

carcinogenicity studies in two species 

for high human exposures and 

conditionally requiring the studies for 

low human exposures. 


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K. Prenatal Developmental Toxicity 

The Agency proposes to require two 

oral prenatal developmental toxicity 

studies (one in rodents and one in a 

non-rodent species) to support the 

registration of every antimicrobial 

pesticide product. This not only codifies 

the Agency’s current practices, but also 

harmonizes the requirements for 

antimicrobials with those of 

conventional pesticides. 

The Agency encourages applicants for 

registration to consider the use of 

combined study protocols in satisfying 

this requirement. A prenatal 

developmental toxicity study segment 

could be added to a two-generation 

reproduction study in rodents. By 

combining protocols, a single study 

could satisfy the requirement for both 

prenatal developmental and 

reproductive toxicity in the rodent. 

While it is recognized that the cost of 

the reproduction study would increase 

somewhat due to the additional work 

scope, the total cost of the combined 

study would be substantially less than 

that incurred by conducting the two 

studies separately. Moreover, a 

combined reproduction/developmental 

protocol should not require the use of 

additional animals and would increase 

the efficient utilization of the animals 

being studied. The second required 

prenatal developmental toxicity study 

in the non-rodent would then be 

performed separately. 

The Agency may require an additional 

prenatal developmental study by 

another route of exposure (usually 

dermal) if there is evidence of 

developmental toxicity in any of the 

available studies and the other route of 

exposure is, in the Agency’s judgment, 

a significant route of exposure (Refs. 3, 

18, and 35). Submission of such a study 

is an infrequent occurrence: only one 

dermal prenatal developmental toxicity 

study has been submitted for an 

antimicrobial. 

L. Reproduction 

The Agency proposes to require a 

reproductive toxicity study to support 

the registration of every antimicrobial 

pesticide product. This codifies the 

Agency’s current practices. 

For many years, for nonfood-uses, the 

Agency did not require a reproductive 

toxicity study for low human exposure 

antimicrobials. However, in 1997, it was 

suggested that, without a reproductive 

toxicity study, the Agency could be 

missing reproductive risks of concern. 

For example, the Pest Management 

Regulatory Agency (PMRA) of Canada, 

presented the results of a retrospective 

analysis during the public comment 

portion of the FIFRA SAP in June 1997 

(Ref. 13). Although the SAP did not 

comment on this analysis, the Agency 

determined that a reproductive toxicity 

study would ensure that it did not miss 

potential reproductive risks of concern. 

In making the safety finding under 

FFDCA, the Agency is required to 

consider the special susceptibility/ 

sensitivity of infants and children to 

pesticide chemical residues. EPA cannot 

adequately characterize the 

susceptibility of infants and children 

without a reproduction and fertility 

effects study that assesses the 

occurrence of biologically adverse 

effects on the male and female 

reproductive system, as well as on the 

developing organisms from exposure 

prior to conception (either parent), 

during prenatal development, or postnatally in the offspring up to the time 

of sexual maturation. Thus, to make the 

safety finding requires reproduction 

testing, since reproductive toxicity 

testing endpoints are not adequately 

assessed in the other required toxicity 

studies. Therefore, these other studies 

do not provide adequate ‘‘triggers’’ 

which would indicate the potential for 

reproductive toxicity. 

Today’s proposal harmonizes the 

requirements for antimicrobials with 

those of conventional pesticides. EPA 

has been requiring a reproductive 

toxicity study for all antimicrobials for 

the last several years. 

As noted in Unit VIII.K. of this 

preamble, the prenatal developmental 

and reproductive toxicity testing 

requirements may be combined in a 

single study. If the applicant does not 

choose this option, then separate 

developmental and reproductive 

toxicity studies must be conducted. 

M. Developmental Neurotoxicity (DNT) 

In practice, EPA evaluates each 

pesticide using all available 

toxicological information that might 

indicate a need for a developmental 

neurotoxicity study. The DNT study has 

been required on a case-by-case basis for 

certain conventional chemicals for fooduse and nonfood-use registrations since 

1991. 

Just as with conventional pesticide 

chemicals, the Agency is now proposing 

that DNT testing be conditionally 

required for all antimicrobial pesticides. 

This would be a new requirement for 

antimicrobial pesticides. The study is 

triggered based upon a weight-ofevidence evaluation of the toxicological 

database. The criteria involved in this 

weight-of-evidence evaluation are the 

same as those for conventional pesticide 

chemicals and are presented below: 

1. The antimicrobial pesticide causes 

treatment-related neurological effects in 

adult animal studies, such as: 

•Clinical signs of neurotoxicity. 

• Neuropathology. 

• Functional or behavioral effects. 

2. The antimicrobial pesticide causes 

treatment-related neurological effects in 

developing animals, following pre- or 

post-natal exposure such as: 

• Nervous system malformations or 

neuropathy. 

•Brain weight changes in offspring. 

• Functional or behavioral changes in 

the offspring. 

3. The antimicrobial pesticide elicits 

a causative association between 

exposures and adverse neurological 

effects in human epidemiological 

studies. 

4. The antimicrobial pesticide evokes 

a mechanism that is associated with 

adverse effects on the development of 

the nervous system, such as: 

• SAR relationship to known 

neurotoxicants. 

• Altered neuroreceptor or 

neurotransmitter responses. 

EPA proposes the addition of the 

developmental neurotoxicity study to 

the toxicology testing requirements as a 

conditional requirement. The two 

required developmental toxicity studies 

do not include an in-depth assessment 

of the development of the nervous 

system and therefore do not provide the 

same information as the DNT. In 

implementing this conditional 

requirement, applicants are encouraged 

to apply what is known about the 

chemical and its toxicity to develop a 

rational, science-based approach to this 

testing. 

N. Mutagenicity 

Mutagenicity testing is required in 

part 161; however, just as with 

conventional pesticide chemicals, the 

Agency is proposing to change the 

specific types of tests to be performed to 

satisfy the mutagenicity testing 

requirement (Refs. 4 and 26). A battery 

of mutagenicity tests is currently 

required in part 161 to assess the 

potential of the test chemical to 

adversely affect the genetic material in 

the cell and subsequently serve as part 

of the Agency’s weight-of-evidence 

approach for classifying potential 

human carcinogens. Mutagenicity data 

are also used to evaluate potential 

heritable effects in humans. 

Mutagenicity testing would no longer be 

subdivided into the categories of gene 

mutation, structural chromosomal 

aberrations, and other genotoxic effects, 

with selection from a wide range of 

mutagenicity tests satisfying these 

categories. 


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For conventional pesticides, the 

Agency requires in § 158.500 an initial 

battery for mutagenicity testing that 

consists of a bacterial reverse mutation 

assay with Salmonella typhimurium 

and Escherichia coli, an assay with 

mammalian cells in culture, and an in 

vivo cytogenetics assay. The Agency has 

selected the bacterial assay because it is 

a primary test for detecting intrinsic 

mutagenicity of many classes of 

biologically active chemicals. The 

genetics of each test strain of 

Salmonella and select strains of E. coli 

have been well-validated, and the assay 

is easy to perform, is used routinely 

throughout the world, and has an 

extensive data base of tested chemicals. 

The mammalian cells in culture assay 

will detect a wider spectrum of possible 

genetic endpoints not assayed in the 

bacterial test. The in vivo cytogenetics 

assay provides an important 

examination of the potential effect a test 

compound may have on an intact 

mammalian system. Data from this 

study provide information on in vivo 

metabolism, repair capabilities, 

pharmacokinetic factors (e.g., biological 

half-life, absorption, distribution, 

excretion) and target organ/tissue 

effects. 

EPA is proposing to modify the 

requirement for a bacterial reverse 

mutation assay conducted with 

Salmonella typhimurium and 

Escherichia coli. For antimicrobials, it is 

not always practical to test 

antimicrobials for mutagenicity in 

bacterial test systems such as the 

bacterial reverse mutation assay. Most 

antimicrobial pesticides are toxic to 

bacteria, and therefore can only be 

tested at very low doses in bacterial 

assays. This means that, for 

antimicrobials, negative results in 

studies done in bacterial test systems do 

not necessarily demonstrate nonmutagenicity. Given this limitation of 

bacterial reverse mutation assays such 

as the Ames test, EPA must carefully 

review Ames studies conducted using 

antimicrobials. 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. However, the 

Agency has previously accepted Ames 

tests for antimicrobials after review and 

evaluation indicates the validity of the 

results. If the results of the Ames tests 

are not valid, then the applicant would 

need to discuss other mutagenicity 

testing with the Agency, such as a 

forward mutation assay conducted using 

mouse lymphoma L5178Y cells. The test 

notes to the proposed mutagenicity 

requirements have been modified 

accordingly. 

Since there are many different 

mutagenicity tests available besides 

those in the initial battery, other types 

of testing may have been performed in 

the course of product research and 

development. In addition to the initial 

battery, data from such mutagenicity 

tests must be submitted to the Agency, 

along with a reference list of all studies 

and papers known to the applicant 

concerning the mutagenicity of the test 

chemical. Having this information at the 

beginning of a mutagenicity assessment 

will greatly facilitate EPA’s effort to 

provide a more accurate assessment of 

the mutagenicity of the antimicrobial 

pesticide in question. 

O. Immunotoxicity 

Just as with conventional pesticide 

chemicals, the Agency proposes to 

require immunotoxicity testing for all 

antimicrobial pesticides. This would be 

a new data requirement. 

Immunotoxicity testing is necessary to 

evaluate the potential of a chemical to 

produce adverse effects on the immune 

system. Immune system suppression has 

been associated with increased 

incidences of infections and neoplasia 

(abnormal and uncontrolled cell 

growth). In 1993, the National Research 

Council reviewed the technical 

literature and found that some 

pesticides are immunosuppressive (Ref. 

19). 

Because the immune system is highly 

complex, studies not specifically 

conducted to assess immunotoxic 

function are inadequate to characterize 

a pesticide’s potential immunotoxicity, 

even if some tissues subject to 

immunotoxic insult are examined. 

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. 

P. Metabolism and Pharmacokinetics 

Currently in part 161 a metabolism 

study is required for all food-uses and 

conditionally required for all other use 

patterns. Today the Agency is proposing 

to continue this existing requirement by 

requiring a metabolism and 

pharmacokinetics study for high human 

exposures and conditionally requiring 

the study for low human exposures. 

Q. Companion Animal Safety 

Currently in part 161 a domestic 

animal safety study is conditionally 

required. According to the test note in 

§ 161.340 this study would be required 

on a case-by-case basis. Today the 

Agency is proposing to continue this 

existing requirement by conditionally 

requiring the study for all antimicrobial 

use patterns. The test note specifies that 

the study would be triggered if the 

product’s use would result in exposure 

to domestic animals. 

R. Dermal Penetration 

Currently in part 161 a dermal 

penetration study is conditionally 

required for all antimicrobial use 

patterns. Today the Agency is proposing 

to continue this existing requirement by 

conditionally requiring a dermal 

penetration study for all antimicrobial 

use patterns. 

IX. Handler and Post-Application 

Exposure Data Requirements 

A. General 

Exposure data are used in the 

evaluation of the exposures to persons 

in occupational and non-occupational 

settings (§ 158.2260 and § 158.2270). For 

antimicrobials this includes residential, 

commercial and industrial, institutional, 

agricultural premises, and recreational 

sites. Data include dermal, inhalation, 

and non-dietary oral exposures. 

Most past exposure research with 

antimicrobial products has studied 

either handler exposure (i.e., exposure 

of people who mix, load, or apply 

antimicrobial pesticides in the course of 

the application process or through other 

work-related tasks) or post-application 

exposure of people to residues of 

antimicrobial pesticides after 

application, in treated areas or on 

treated surfaces. 

Handler exposure research may 

measure exposure to undiluted 

antimicrobial products as the products 

are mixed for application, or it may 

measure exposure to antimicrobial 

products diluted for use. Antimicrobial 

pesticide applicators may be industrial 

or other workers, professional 

applicators, or consumers using the 

product in or around their homes. 

EPA considers handler exposure data 

essential for fulfilling its mandate to 

protect human health from pesticide 

risk, including aggregate and cumulative 

risk, and is therefore proposing to 

require handler exposure studies for all 

antimicrobial products, when the 

toxicity and exposure criteria are 


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triggered. Codifying this requirement 

would assist applicants for registration 

of antimicrobial pesticides to determine 

which studies are required and then to 

design and conduct acceptable studies 

measuring handler exposure. 

Post-application exposure research 

measures exposures of people to 

residues of antimicrobial pesticides after 

their use or application, and thus does 

not involve the direct exposure that 

occurs during use. Of particular concern 

to EPA is the potential exposure of 

infants and children to post-application 

residues of products used in and around 

homes, daycare centers, or schools. 

The data requirements proposed here 

are based on the Agency’s current 

practice of requiring exposure data 

when certain toxicity and exposure 

criteria are met. These criteria are 

described in proposed § 158.2260 and 

§ 158.2270. Today’s proposal seeks to 

harmonize the exposure requirements 

for antimicrobials with those of 

conventional pesticides. The applicator 

(handler) exposure data requirements 

are the same as those codified for 

conventional pesticides. The postapplication data requirements are the 

same as conventionals, with the 

exception of one study (Dislodgeable 

Foliar Residue and Turf Transferable 

Residues) that is not needed for 

antimicrobials. 

The proposed requirement of such 

data for antimicrobial products when 

the toxicity and exposure criteria are 

triggered would allow the Agency to 

conduct more thorough exposure 

assessments for residential as well as 

occupational sites, and to cover all use 

and exposure scenarios for such sites. 

EPA presented the need for additional 

handler exposure data to the SAP in 

January 2007 (Ref. 39) and to the Human 

Studies Review Board (HSRB) in April 

2007 (Ref. 40). Both groups agreed that 

additional data are warranted. 

Research undertaken to address the 

proposed handler and post-application 

data requirements may involve 

intentional exposure of human subjects 

as those terms are defined in EPA’s 

rules at 40 CFR 26.1102, and if they do, 

protocols and supporting 

documentation as specified in that rule 

must be submitted for review by EPA 

and the HSRB before any subjects are 

enrolled in the research. If research 

involving intentional exposure of 

human subjects is initiated without 

EPA’s prior review, the resulting data 

will not be accepted in support of 

registration. Parties who are unsure 

whether proposed research involves 

intentional exposure are encouraged to 

consult with EPA before proceeding 

with the research. 

B. Use of Surrogate Data 

To support registration of an 

antimicrobial pesticide product, 

according to the proposed tables in 

§ 158.2260 and § 158.2270, applicants 

would generate needed exposure data 

with a typical end-use product. 

However, the Agency recognizes the 

need to minimize the economic burden 

of generating data to meet human 

exposure data requirements while 

obtaining sufficient data and 

information for exposure and risk 

assessments. Whenever appropriate, 

surrogate data may be used for the 

assessment of antimicrobial pesticides. 

The Agency is currently working with 

several industry Task Forces that are 

generating exposure monitoring data 

that may be able to be used as surrogate 

data sources. The Antimicrobial 

Exposure Assessment Task Force 

(AEATF-II) is developing handler 

exposure data for antimicrobial 

applications (such as mopping, wiping, 

aerosol sprays, painting, etc.). Task 

Force members can consider using this 

surrogate data, if determined by the 

Agency to be suitable, to assess 

antimicrobial handler risk instead of 

generating their own data. If surrogate 

data are inadequate for the Agency to 

adequately predict likely exposures and 

the resultant risks, then applicants 

would need to submit chemical-specific 

and/or product-specific data. 

C. Handler Exposure 

The Agency proposes to require data 

addressing handler exposure for 

antimicrobials when the toxicity and 

exposure criteria are triggered. As 

discussed in Unit IX.A., this not only 

codifies the Agency’s current practices, 

but also harmonizes the requirements 

for antimicrobials with those of 

conventional pesticides. EPA now 

proposes to codify these requirements in 

proposed § 158.2260 and set out 

explicitly in § 158.2260(b) the triggers 

describing the circumstances under 

which such data must be submitted. 

For handler exposure, the proposed 

data requirements are as follows: 

1. Dermal exposure studies. EPA 

proposes to require data for both 

outdoor and indoor dermal exposures to 

estimate the dermal exposure to persons 

directly handling pesticides. The 

number of exposure studies that may be 

required depends on the variety of use 

sites, their similarities, and whether the 

uses are indoor or outdoor. In the 

absence of surrogate data, generally, the 

selection of the appropriate testing 

site(s) is based on the exposure sites 

with the highest potential for exposure. 

Generally, this is determined based on 

the label uses and use rates. 

Consultation with the Agency is 

recommended for determining the 

appropriate use site(s) for testing. 

Studies of dermal exposure are often 

designed to concurrently measure 

inhalation exposure. 

2. Inhalation exposure studies. Just as 

with the dermal exposure studies, EPA 

proposes to require data for both 

outdoor and indoor inhalation exposure 

studies. In the absence of surrogate data, 

generally, the selection of the 

appropriate testing site(s) is based on 

the exposure sites with the highest 

potential for exposure. For inhalation 

exposure studies, the use sites with the 

potential for the highest exposure are 

almost always indoors. Based on its 

experience, the Agency believes 

potential exposure is highest indoors 

because the pesticide is confined in a 

closed area and therefore is less likely 

to be rapidly diffused or dispersed. This 

means that if the application rates are 

the same for an indoor scenario and an 

outdoor scenario, then the Agency may 

require only the indoor inhalation 

study, as that would have the highest 

potential exposure. Consultation with 

the Agency is recommended for 

determining the appropriate use site(s) 

for testing. Studies of inhalation 

exposure are often designed to 

concurrently measure dermal exposure. 

3. Biological monitoring. Biological 

monitoring is the only type of applicator 

exposure study proposed as a 

conditional requirement. Data from 

biological monitoring studies provide 

the Agency with estimates of the 

internal dose or amount of a pesticide 

in the body. EPA proposes to allow the 

submission of biological monitoring 

data in addition to, or in lieu of, dermal 

or inhalation exposure data, provided 

the human pharmacokinetics of the 

pesticide residue is sufficiently 

understood to permit the back 

calculation to determine the total 

internal dose, and providing further that 

there are adequate analytical methods 

available. Biological monitoring offers 

the advantage of assessing the internal 

dose, as opposed to the exposure or 

amount of chemical coming in contact 

with the surface of the skin or available 

for inhalation in the lungs as measured 

using passive dosimetry techniques. 

Because biological monitoring is 

necessarily specific to the material 

tested, generally it cannot be conducted 

using a surrogate chemical. 

4. Data reporting and calculations. 

EPA proposes to require applicants to 

submit data reporting and calculation 

information whenever applicator 

exposure data are submitted. These data 

are needed by Agency scientists for an 


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appropriate level of review and 

evaluation, and offer a submission 

format that the Agency has found 

useful. This information is important 

because it allows EPA to assess the 

quality and validity of the exposure 

study and thus the accuracy of the 

estimates and resultant exposure 

calculations derived from that study. 

The types of information that would be 

included under this data requirement 

include: 

•The chemical formulas used in the 

calculations. 

•The data used in the calculations, 

including the raw data manipulation/ 

correction used in order to calculate 

limits of detection/limits of 

quantification. 

•The statistical analyses required. 

•The quality control data for lab/field 

recovery and storage stability. 

•The actual calculations. 

Included within the data reporting 

and calculations requirement would be 

information on the ethical conduct of 

the research. EPA regulations at 40 CFR 

26.1303 require that the ethical conduct 

of all research involving human subjects 

be fully documented at the time of 

submission of the data resulting from 

the research. This requirement will 

apply to all exposure studies involving 

human subjects submitted to EPA under 

the pesticide laws, without regard to 

whether the research involves 

intentional exposure. Data from 

exposure studies not accompanied by 

the required documentation of ethical 

conduct will not be accepted for review. 

5. Product use information. EPA is 

proposing to require product use 

information for both occupational and 

residential use patterns. Product use 

information assists EPA to more 

accurately assess pesticide exposure to 

applicators by describing how the 

pesticide is actually used and applied. 

EPA requires this information because 

differences in use can translate to 

significant differences in exposure, and 

thus in risk. For applicator exposure, 

use information may include, but is not 

limited to, who applies the 

antimicrobial pesticide, the use sites, 

site locations, use directions, 

application rates and frequencies, 

application equipment and methods, 

protective equipment used, protective 

clothing worn, and other information 

that will determine exposure to 

antimicrobial pesticide handlers. 

The Agency acknowledges that the 

guideline for applicator product use 

information has not yet been finalized. 

However, the guideline for applicator 

product use information should be 

substantially similar to the one for postapplication. The guideline for postapplication product use information 

was presented to the FIFRA Science 

Advisory Panel (SAP) in March 1998. 

(The draft guideline is available at 

http://www.epa.gov/scipoly/sap/ 

meetings/1998/march/contents.htm.) 

The Agency will finalize both 

guidelines before publishing a final rule 

establishing antimicrobial data 

requirements. 

D. Post-Application Exposure 

The current data requirements for 

post-application exposure in § 161.390 

are focused on reentry to treated areas 

by agricultural workers. Since the 

promulgation of these requirements in 

1984, the Agency has become 

increasingly concerned about postapplication risks to persons 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. Under current practice, 

post-application exposure data are 

generally required for occupational and 

residential settings on a case-by-case 

basis when specific toxicity and 

exposure criteria have been met. 

Moreover, FFDCA mandates that EPA 

perform additional scientific analyses 

which before 1996 had not been a 

routine part of the Agency’s risk 

assessment process, including the 

assessment of aggregate exposures from 

multiple pathways including dietary 

and non-dietary routes of exposure. 

The Agency proposes to require data 

addressing post-application exposure 

for antimicrobials when the toxicity and 

exposure criteria are triggered. Two new 

exposure data requirements (soil residue 

dissipation and non-dietary ingestion 

exposure) are today proposed for 

antimicrobials. As discussed in Unit 

IX.A., this not only codifies the 

Agency’s current practices, but also 

harmonizes the requirements for 

antimicrobials with those of 

conventional pesticides. EPA now 

proposes to codify these requirements in 

proposed § 158.2270 and set out 

explicitly in § 158.2270(b) the triggers 

describing the circumstances under 

which such data must be submitted. 

For post-application exposure, the 

proposed data requirements are as 

follows: 

1. Soil residue dissipation. These data 

are needed to characterize exposures to 

residues of antimicrobials, and most 

particularly wood preservatives, that 

occur through contact with outdoor 

soils. This information is critical for 

assessing risks to children who play 

around and are in contact with treated 

wood structures such as decks, play 

sets, and gazebos, and the surrounding 

soils. This would be a new data 

requirement for antimicrobials. 

Protocols must be approved by the 

Agency prior to the initiation of the 

study. Details for developing protocols 

are available from the Agency. 

2. Indoor surface residue dissipation. 

The Agency proposes to require the 

indoor surface residue dissipation study 

(sometimes known as a surface wipe 

sampling study). This study supplies 

information on residue dissipation from 

treated areas and articles such as 

carpets, hardwood floors, and counter 

tops, after antimicrobial pesticides have 

been used. It is also used to determine 

residue dissipation from decks and 

other structures manufactured from 

treated wood. 

These data would quantify residue 

loads and characterize the dissipation 

rate (i.e., how fast pesticide residues 

disperse over time following 

application) of antimicrobial pesticides 

on indoor surfaces. The Agency could 

then assess the magnitude and duration 

of human exposure to antimicrobials 

present as surface residues. Without 

such data, the Agency has no precise 

means of calculating human exposures 

to such substances from contacting 

surfaces over time. This requirement 

would not apply to uses that are not 

surface treatments, e.g., aquatic areas, 

swimming pools, antifoulant coatings 

and paints. 

The draft guideline for indoor surface 

residue dissipation is available at http:// 

www.epa.gov/scipoly/sap/meetings/ 

1998/march/contents.htm. This draft 

guideline was externally peer-reviewed 

before presentation to the SAP in 1998. 

An examination of the FIFRA SAP 

website since 1998 to the present will 

show many presentations to the SAP on 

assessing occupational and residential 

exposures. Science has evolved in this 

area. 

EPA notes that it has reviewed and 

accepted many studies, on a case-bycase basis, that were not conducted in 

accordance with current guidelines, but 

which serve its needs and provide 

suitable information for risk assessment 

purposes. The guidelines themselves do 

not impose mandatory requirements. 

Instead, they present recognized 

standards for conducting acceptable 

tests, guidance on evaluating and 

reporting data, definition of terms, and 

suggested study protocols. The draft 

guideline, therefore, serves as a starting 

point for pre-protocol submission 

meetings where the Agency’s scientists 

can provide guidance to registrants or 

task forces on aspects of study design. 


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The Agency’s scientists are always 

willing to work with individual 

registrants to develop study designs to 

fulfill data requirements. The Agency 

will finalize this guideline before 

publishing a final rule establishing 

antimicrobial data requirements. 

For wood preservatives, EPA has 

worked with the Consumer Product 

Safety Commission (CPSC) to develop 

methodologies for conducting surface 

wipe sampling studies on wood. 

Protocols for wood preservative treated 

surface wipe sampling studies must be 

approved by the Agency prior to the 

initiation of the study. Details for 

developing protocols are available from 

the Agency. 

3. Dermal exposure. EPA proposes to 

require dermal exposure data for both 

outdoor and indoor dermal exposures to 

estimate the dermal exposure to persons 

exposed after the pesticide application 

has been completed. The discussion in 

Unit IX.C. of this preamble for handler 

dermal studies is also applicable to 

post-application exposures. 

4. Inhalation exposure. EPA proposes 

to require inhalation exposure data for 

both outdoor and indoor inhalation 

exposures to estimate the inhalation 

exposure to persons exposed after the 

pesticide application has been 

completed. The discussion in Unit IX.C. 

of this preamble for handler inhalation 

studies is also applicable to postapplication exposures. 

5. Biological monitoring. A 

conditional requirement for biological 

monitoring data was discussed in Unit 

IX.C. That discussion is also applicable 

to the proposed conditional requirement 

for biological monitoring for postapplication exposure which codifies the 

Agency’s current practices. 

6. Product use information. EPA 

proposes to require product use 

information for all antimicrobials. Such 

information has been routinely 

submitted to EPA by applicants and is 

now being codified as a separate and 

distinct requirement. For postapplication exposure, required product 

use information includes information on 

reapplication rates and frequencies, 

post-application entry restrictions, reentry intervals, rinsing and other 

residue removal practices, and other use 

data relevant to exposure after 

application. The draft guideline for 

post-application product use 

information is available at http:// 

www.epa.gov/scipoly/sap/meetings/ 

1998/march/contents.htm. The Agency 

will finalize this guideline before 

promulgating a final rule establishing 

antimicrobial data requirements. 

7. Description of human activity. For 

post-application exposure the Agency is 

proposing to require a description of 

human activities. Information on those 

persons who may enter treated areas 

after the application is complete has 

been routinely submitted to EPA by 

applicants and is now being codified as 

a separate and distinct requirement 

These data will allow for a more 

accurate evaluation of the exposure 

potential associated with use of an 

antimicrobial pesticide. The description 

of human activity data would define the 

activity patterns that affect exposures 

(e.g., defining the exposed populations 

in commercial/institutional and 

residential settings, the application 

sites, site-specific information on 

exposure time per activity, type of 

protective clothing worn, and any other 

relevant use activity data). The 

description of human activity 

information would be used with the use 

information (both application and postapplication), to help the Agency 

determine whether the exposure 

potential for humans is likely to be 

significant, and if additional data will 

be needed. 

8. Data reporting and calculations. 

EPA proposes to require applicants to 

submit data reporting and calculation 

information whenever post-application 

exposure data are submitted. Such 

information has been routinely 

submitted to EPA by applicants as part 

of any submission of exposure data and 

is now being codified as a separate and 

distinct requirement. The discussion in 

Unit IX.C. of this preamble for handler 

data reporting and calculations is also 

applicable to post-application 

exposures. Note in particular the 

discussion of the requirement at 40 CFR 

26.1303 for full documentation of the 

ethical conduct of all submitted 

research involving human subjects, 

whether or not they were intentionally 

exposed. 

9. Non-dietary ingestion exposure. 

The Agency proposes to require a nondietary ingestion exposure study for 

residential types of exposures only. This 

study is not required for occupational 

exposures since the primary concern for 

adult workers is exposure via the 

dermal and inhalation routes. This 

would be a new data requirement that 

evaluates the potential oral exposures to 

humans, particularly children, from 

antimicrobial pesticide residues from 

sources other than food. 

Note that EPA regulations at 40 CFR 

26.1203 prohibits, without exception, 

conduct of any research intended for 

submission to EPA under the pesticide 

laws which involves intentional 

exposure of children under 18. Thus, 

any study of potential exposure of 

children, oral or by any other pathway, 

to antimicrobial pesticide residues must 

only be an observational study, 

involving no intentional exposure of 

children. 

Incidental oral exposure via hand-tomouth, object-to-mouth and direct 

mouthing/ingestion is an important 

exposure pathway for infants and 

toddlers. The results from these studies 

will be used to assess the risks 

associated with the incidental ingestion 

of antimicrobial pesticides by children 

following antimicrobial pesticide 

applications in residential or public 

settings, or exposure to treated surfaces 

(e.g., carpets, toys, wood structures). 

This study would be required for uses 

in and around the home, daycare 

centers and schools. 

The Agency is primarily concerned 

with non-dietary exposures immediately 

following application of the 

antimicrobial pesticide; therefore, 

dissipation studies alone would not 

provide the information needed to 

assess risks from non-dietary ingestion. 

Information such as frequency/duration 

of hand-to-mouth activities and surface 

area mouthed are often needed as input 

values for the calculations that are 

performed to assess non-dietary 

ingestion exposure. When appropriate, 

EPA’s Exposure Factors Handbooks (see 

http://cfpub.epa.gov/ncea/cfm/ 

recordisplay.cfm?deid=20563) can be 

used as the source of this frequency/ 

duration information. However, the data 

in these Handbooks cannot replace 

chemical-specific information from 

studies of treated articles/surfaces that 

quantifies the amount of pesticide 

residue on such surfaces. 

Non-dietary ingestion may also occur 

through hand-to-mouth or object-tomouth transfer of antimicrobial 

pesticide residues during activities 

performed by children (e.g., crawling) 

that put them in close proximity with 

treated surfaces. Non-dietary ingestion 

exposure would be expected in 

residential or public (e.g., schools, 

daycare) settings following exposures to: 

• Soils in contact with, or adjacent to, 

preservative-treated wood structures 

such as play structures. 

• Outdoor surfaces such as decks. 

• Indoor surfaces such as 

antimicrobial pesticide-treated paint 

chips, or antimicrobial-sprayed floors or 

walls. 

• Antimicrobial-treated textiles, 

polymers, or other items (e.g., clothing, 

bedding, carpets, or toys). 

Non-dietary ingestion studies would, 

for example, monitor the amounts of 

pesticide residues in the rinsate from 

hand washing, and thus allow the 

Agency to develop science-based 

models or formulas to estimate 


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inadvertent exposure. The draft 

guideline for non-dietary ingestion is 

available at http://www.epa.gov/scipoly/ 

sap/meetings/1998/march/ 

contents.htm. This draft guideline was 

externally peer-reviewed before 

presentation to the SAP in 1998. An 

examination of the FIFRA SAP website 

since 1998 to the present will show 

many presentations to the SAP on 

assessing occupational and residential 

exposures. Science has evolved in this 

area. 

EPA notes that it has reviewed and 

accepted many studies, on a case-bycase basis, that were not conducted in 

accordance with current guidelines, but 

which serve its needs and provide 

suitable information for risk assessment 

purposes. The guidelines themselves do 

not impose mandatory requirements. 

Instead, they present recognized 

standards for conducting acceptable 

tests, guidance on evaluating and 

reporting data, definition of terms, and 

suggested study protocols. The draft 

guideline, therefore, serves as a starting 

point for pre-protocol submission 

meetings where the Agency’s scientists 

can provide guidance to registrants or 

task forces on aspects of study design. 

The Agency’s scientists are always 

willing to work with individual 

registrants to develop study designs to 

fulfill data requirements. The Agency 

will finalize this guideline before 

publishing a final rule establishing 

antimicrobial data requirements. 

X. Residue Chemistry Data 

Requirements 

A. General 

EPA proposes to adapt the basic 

residue chemistry data requirements 

(§ 158.2290) as listed in subpart O of 

current part 158 to support applications 

for antimicrobial products. However, 

EPA also proposes to modify the 

applicability of those requirements to 

reflect the differing risks and levels of 

exposure of antimicrobials. Residue 

chemistry data are used by the Agency 

to estimate dietary exposure to pesticide 

residues from food. If there are no direct 

or indirect food uses for the 

antimicrobial, then no residue 

chemistry data are required. 

The proposed changes will allow EPA 

to better estimate human dietary 

exposure to antimicrobial residues in or 

on food or feed, to more accurately 

assess tolerances and tolerance 

exemptions, and to provide additional 

tools for the enforcement of pesticide 

residue tolerances to ensure that food 

entering the commercial market meets 

the ‘‘reasonable certainty of no harm’’ 

standard under FFDCA. 

The residue chemistry database is 

designed to determine the composition 

of the pesticide residue and how much 

of that residue is present in food or 

animal feed. Residue chemistry studies 

include those which define: 

•The nature of the residue, i.e., 

metabolism studies. 

•The magnitude of the residue, i.e., 

those studies which measure how much 

of the residue of concern is present in 

food, feed, and water. 

Food-use pesticides require both 

types of studies. Both plant and 

livestock metabolism studies are needed 

to determine the breakdown of the 

pesticide chemical in a living system, 

that is, whether the chemical stays 

intact or is converted into metabolites. 

Occasionally, the metabolites are toxic 

and are included in the analyses as a 

residue of concern. Magnitude of the 

residue (MOR) studies are performed to 

determine the level of residues of 

concern in food. Data collection residue 

analytical methods are reviewed by EPA 

as part of the validation of the 

metabolism and MOR studies which are 

used to establish tolerances. 

In addition to dietary risk 

assessments, residue chemistry data are 

used to establish pesticide tolerances, 

the maximum level of pesticide residue 

that may remain on food. Because these 

are legal limits enforced by FDA, 

enforcement methods for detecting the 

presence and amount of the residue are 

needed, and are used by FDA, USDA, 

and the States for food inspection 

purposes. 

There are distinct differences between 

the residue chemistry requirements of 

conventional pesticides that are applied 

to crops in a field setting and those of 

antimicrobials that are more likely to be 

applied in a confined setting such as a 

food processing plant. Those differences 

are reflected in the data requirements. 

For example, no migration studies are 

required for terrestrial food and feed 

uses in part 158, subpart O, and no 

rotational crop studies are required for 

any antimicrobial uses. Certain test 

notes in part 158, subpart O and in 

subpart W are also different. As 

expected, the differences result from the 

different use patterns. 

Units X.B. and C. of this preamble 

discuss the two main categories of fooduses for the purpose of antimicrobial 

residue chemistry data requirements, 

direct and indirect. Units X.D. through 

Q. of this preamble explain changes to 

specific residue chemistry data 

requirements appropriate to 

antimicrobials. For the purpose of 

determining antimicrobial residue 

chemistry data requirements, most 

antimicrobial pesticides will be 

classified as either direct or indirect 

food uses, which are generally 

delineated in Units X.B. and C. of this 

preamble. For the purposes of defining 

the residue chemistry data requirements 

for antimicrobials, the table in proposed 

§ 158.2290 further delineates direct and 

indirect uses into four categories: direct 

and indirect food uses, agricultural 

premises, and aquatic uses. Applicants 

should consult with the Agency on the 

appropriate category(ies) for their 

product. 

B. Direct Food Uses 

If the antimicrobial is applied directly 

to food or water, it is a direct food use. 

Such uses would include, but are not 

limited to: 

• Livestock. 

• Livestock feed. 

• Drinking water for humans, livestock 

and/or poultry. 

• Egg washes. 

• Fruit and vegetable rinses. 

• Aquatic areas that have the potential 

to contaminate potable water. 

• Post-harvest applications that occur 

in the field, at a treatment facility (such 

as a packing shed), during transport, 

and while in storage, until the 

processing of the raw agricultural 

commodity begins. 

No currently registered antimicrobial 

products are applied to agricultural field 

crops. Should an application for such an 

antimicrobial product be submitted to 

EPA, then the Agency would likely 

require the same data as specified in 

part 158, subpart O for other field-use 

pesticides applied to crops, as the test 

notes more accurately reflect the 

conditionalities of a terrestrial use 

pattern. 

C. Indirect Food Uses 

For the purpose of determining 

residue chemistry data requirements, an 

antimicrobial use is considered an 

indirect food use when the 

antimicrobial pesticide is applied to a 

surface or incorporated into a material 

that will subsequently contact food, that 

is, the pesticide is not applied directly 

to the food. Residues of the pesticide or 

its degradates can be transferred to the 

food when it comes into contact with 

these treated surfaces and articles. 

Antimicrobial products labeled for 

treatment of hard non-porous surfaces 

which may come into contact with food 

(e.g., food area premises and equipment) 

are classified as indirect food contact 

uses. Sanitizers and disinfectants which 

remain on the surface of food-handling 

or processing equipment are indirect 

food uses. Sanitizers incorporated into 

articles (e.g., plastic products such as 

coffee cups or cutting boards) intended 


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for food contact are also indirect food 

uses. 

Hard surfaces are considered to be 

food surfaces when food is prepared for 

consumption, either commercially or 

residentially on such surfaces. Examples 

of hard surfaces are eating utensils, 

dinnerware, pots and pans, cutting 

boards, food preparation surfaces, 

countertops, refrigerator shelves, 

refrigerator bins, ice trays, dining table 

tops, and cabinet shelves. Wood treated 

with an antimicrobial pesticide product 

could be used to construct or maintain 

a bee hive, a cattle trough or feeding 

station. These and other indirect 

contacts with food or feed are assessed 

to evaluate the need for a tolerance or 

tolerance exemption. 

For the purpose of conducting a risk 

assessment for a sanitizer (an 

antimicrobial not rinsed from foodcontact surfaces), the Agency uses the 

directions on the antimicrobial product 

label in combination with modeled data 

to determine the amount of the sanitizer 

remaining. Under this approach, EPA 

will initially assume that all of the 

sanitizer residues remain on the surface 

and thus have the potential to enter the 

food. This is a worst-case or screeninglevel assumption. EPA will then use this 

modeled estimate in combination with 

toxicity data to determine if there is a 

risk of concern and/or whether to 

establish a tolerance or tolerance 

exemption. If there are risk concerns 

and if scientifically appropriate, EPA 

may refine the estimate of residues 

remaining on the surface using more 

realistic model assumptions. If no risks 

of concern are identified using these 

refined assumptions, then most likely 

EPA would not require higher-tiered, 

measured surface residue data. Of 

course, as an alternative to the Agency’s 

use of these screening-level or refined, 

modeled estimates, the applicant may 

provide data that measures the actual 

amount of sanitizer remaining on the 

treated surface or transferring to food. 

For disinfectants (antimicrobials with 

potable water rinses) EPA proposes to 

generally follow the risk assessment 

approach outlined for sanitizer 

solutions. EPA would disregard the 

potable water rinsing and assume that 

worst-case residues (estimated using the 

sanitizer model) are available for 

entering food items. Alternatively, the 

applicant can provide data measuring 

the actual amount of disinfectant 

remaining on the surface or transferring 

to food after rinsing the treated surface. 

If the antimicrobial is to be 

incorporated into products with food 

contact uses and bears a claim of surface 

sanitizing activity, the Agency will 

generally, in the absence of data, 

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. Alternatively, the applicant 

may submit migration studies to 

demonstrate the rate or amount of 

transference of the antimicrobial into 

food items. 

D. Chemical Identity 

Currently in part 161, information on 

chemical identity is required for all use 

patterns. Today the Agency is proposing 

to continue this existing requirement by 

requiring information on chemical 

identity for all antimicrobial use 

patterns. 

E. Directions for Use 

Currently in part 161, directions for 

use are required for all use patterns. 

Today the Agency is proposing to 

continue this existing requirement by 

requiring this information for all 

antimicrobial use patterns. 

F. Proposed Tolerance 

Currently in part 161, a proposed 

tolerance is required for all food-use 

patterns. Today the Agency is proposing 

to continue this existing requirement by 

requiring a proposed tolerance for all 

antimicrobial food-use patterns. 

G. Reasonable Grounds in Support of 

Petition 

Currently in part 161, reasonable 

grounds in support of petition is 

required for all food-use patterns. Today 

the Agency is proposing to continue this 

existing requirement by requiring this 

information for all antimicrobial fooduse patterns. 

H. Submittal of Analytical Reference 

Standards 

Currently in part 161, submittal of 

analytical reference standards is 

required for all food-use patterns. Today 

the Agency is proposing to continue this 

existing requirement by requiring 

submittal of these standards for all 

antimicrobial food-use patterns. 

I. Nature of the Residue in Plants 

The Agency proposes to continue to 

require a nature of the residue study in 

plants for aquatic uses and direct food 

contact uses. The Agency proposes to 

continue to conditionally require this 

study to support agricultural premise 

uses. 

J. Nature of the Residue in Livestock 

The Agency proposes to continue to 

require a nature of the residue in 

livestock study to support agricultural 

premise uses. The Agency is also 

proposing to continue to conditionally 

require a nature of the residue in 

livestock study to support direct food 

contact uses and aquatic areas. As with 

the data requirements for conventional 

pesticide chemicals EPA is proposing to 

change the chemical substance with 

which the test is performed. This would 

codify existing practices. 

For antimicrobials used to treat 

animal drinking water, or to treat wood 

in contact with animals or animal feed, 

or in aquatic areas, the Agency proposes 

to change the test substance for the 

nature of the residue in livestock study 

from ‘‘pure active ingredient, 

radiolabeled (PAIRA) and plant 

metabolites’’ to ‘‘PAIRA or radiolabeled 

plant metabolite.’’ The test substance 

‘‘metabolites’’ will be changed to 

‘‘metabolite’’ to clarify that dosing with 

more than one compound in any one 

study is not acceptable. This is needed 

because in studies involving 

simultaneous dosing with both the 

active ingredient and plant metabolites, 

it is impossible to determine the amount 

of metabolite due to active metabolism 

from that introduced through 

intentional dosing. Simultaneous dosing 

with the active ingredient and any 

metabolites may not produce useful 

results, because the active ingredient 

and metabolites may have different 

metabolic pathways that cannot be 

differentiated. In most cases dosing with 

only the parent compound is necessary. 

However, in cases where plant and 

animal metabolites are found to differ, 

separate studies in which livestock are 

dosed separately with each unique plant 

metabolite may also be required. 

The Agency proposes to specify in the 

test note that the livestock metabolism 

study would be required when an 

antimicrobial is applied directly to 

livestock, to livestock premises, to 

livestock drinking water, to livestock 

feed, or to crops used for livestock feed. 

This would also include antimicrobial 

uses to treat wood in contact with 

animals or animal feed, or in aquatic 

areas given the potential use for crop 

and livestock production. Such 

applications may result in both oral and 

dermal exposure of animals to the 

pesticide and, depending on the results, 

may necessitate magnitude of the 

residue studies to quantify the residues 

in meat, milk, poultry, and eggs. 

K. Residue Analytical Methods 

EPA proposes to require development 

and submission of analytical methods 

whenever a numerical tolerance is 

established. Residue analytical methods 

have two primary purposes: 

•To collect residue data for 

establishing tolerance levels and 


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conducting dietary exposure 

assessments. 

•To enforce the tolerances established 

by EPA in 40 CFR part 180. 

Residue analytical methods are 

currently required in part 161, and EPA 

proposes to continue this requirement. 

These methods are required only if a 

numerical tolerance is established and 

since numerical tolerances are rarely 

established for antimicrobials, 

submission of this data should be a rare 

occurrence. 

In part 158, subpart W, EPA is 

proposing to create separate entries in 

the proposed table in § 158.2290 for 

these two types of residue analytical 

methods to clearly indicate the need for 

both types of methods, or a method that 

can be used for both data collection and 

enforcement purposes. EPA believes 

that the separation of the combined 

requirement into separate and distinct 

requirements will provide clarity to 

applicants. 

The enforcement method has the 

following characteristics: 

• Analyzes for the residues of 

regulatory concern, i.e., those named in 

the established tolerance. 

• Is reasonably rapid (typically one 

day or less). 

• Uses readily available equipment 

and reagents. 

• Must be clearly and completely 

described in a stepwise manner such 

that laboratory personnel competent 

using similar procedures can 

successfully perform the procedure on 

the first trial. 

• Is subject to an independent 

laboratory validation. 

• Has a mechanism to confirm the 

results. 

The data collection method has the 

following characteristics: 

• Analyzes for all residues of 

toxicological concern. 

• No limitation on duration of 

procedure. 

• May use specially-developed and 

very expensive equipment. 

• Validation is subject only to internal 

laboratory controls. 

If the applicant can develop one 

method and the Agency finds that this 

one method satisfies the criteria for both 

the enforcement and the data collection 

method, then only one method needs to 

be submitted. Otherwise, two methods 

must be submitted. For the proposed 

table in § 158.2290 the ‘‘Rs’’ and ‘‘CRs’’ 

specified in the residue analytical 

method data requirements reflect the 

Agency’s best professional estimate of 

the likelihood of a numerical tolerance 

being established for an antimicrobial 

pesticide chemical and thus resulting in 

the requirement to submit the data. 

As with the data requirements for 

conventional pesticide chemicals, the 

Agency proposes to change the chemical 

substance for residue analytical 

methods from ‘‘TGAI and metabolites’’ 

to ‘‘residue of concern.’’ This would 

codify existing test practices. 

As with conventional pesticide 

chemicals (subpart O of part 158), the 

Agency is proposing to require an 

independent laboratory validation (ILV) 

of residue analytical methods to ensure 

the accuracy and reproducibility of data 

used for tolerance enforcement 

purposes. Codifying this current (since 

1988) practice (Ref. 28) would promote 

development of clearly written, 

complete descriptions of analytical 

methods that can be used by Federal 

and State enforcement agencies. 

L. Multiresidue Method Testing 

The current requirement in 40 CFR 

part 161 for residue analytical methods 

actually encompasses several 

submissions to the Agency. The first is 

the chemical-specific method(s) 

discussed in Unit X.K. of this preamble 

and the second is the multiresidue 

testing. In promulgating its part 158 

conventional pesticide data 

requirements, the Agency separated this 

combined requirement into separate and 

distinct requirements. EPA is proposing 

to do the same for antimicrobial 

pesticides. 

Today, the Agency is proposing to 

codify the requirement for testing the 

residue of concern of the antimicrobial 

pesticide using the FDA’s and the 

USDA’s multiresidue methods (MRM) 

as a separate data requirement. As 

above, the Rs and CRs in the proposed 

table in § 158.2290 reflect the Agency’s 

best professional estimate of the 

likelihood of a numerical tolerance 

being established. This testing is 

required only if a numerical tolerance is 

established and since numerical 

tolerances are rarely established for 

antimicrobials, submission of this data 

should be a rare occurrence. 

MRMs are important components of 

pesticide monitoring and enforcement 

programs. In food monitoring programs, 

such as those of FDA and USDA, it is 

not practical or feasible to test for each 

individual pesticide in a separate test. 

The MRMs are used to detect the 

presence of many pesticides, and then if 

needed, re-testing is done with the 

chemical-specific tolerance enforcement 

method. Since the residue analytical 

method requirement is intended to refer 

to a method that is specific for one 

pesticide (sometimes called a ‘‘single 

residue method’’) and the multiresidue 

methods currently in use are designed 

to measure as many pesticides as 

possible, it is clearer to list these as two 

separate data requirements. 

M. Storage Stability 

As with conventional pesticides, the 

Agency proposes to add a storage 

stability study as an explicit 

requirement to validate the results of the 

various magnitude of the residue 

studies. Such data have been required 

previously as a part of the magnitude of 

the residue study, but will now, as with 

conventional pesticides, be codified as a 

separate requirement. As discussed in a 

test note to the proposed table in 

§ 158.2290 storage stability 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 know to be 

volatile or labile. This test note would 

clarify when storage stability data are 

needed and also harmonizes the 

requirements for antimicrobials with 

those of conventional pesticides. 

Magnitude of the residue studies 

address how levels of pesticide residues 

in samples of human foods and 

livestock feeds are determined. These 

samples are often stored for extended 

periods of time prior to analysis. Since 

tolerances are based on residues at the 

time of harvest (or sample collection) 

and the residues may be lost by 

processes such as degradation and 

volatilization during storage prior to 

analysis, storage stability data 

predicting the pattern of degradation, if 

any, of residues during this period are 

critical to understanding the results of 

the field trial studies. 

N. Magnitude of Residue (MOR) Studies 

As with conventional pesticides, the 

Agency proposes to change the test 

substance from EP (end-use product) to 

TEP (typical end-use product) for the 

following types of MOR studies: Crop 

field trials, processed food or feed, 

potable water, fish, irrigated crops, and 

food handling studies. 

Residue data are needed for only one 

TEP of each formulation type used on a 

given commodity or site. When newer 

or other types of formulations are 

proposed for use, either additional 

residue data can be submitted to show 

that the use of these new or different 

formulations result in residues 

comparable to those arising from the 

original formulation for which residue 

chemistry data already exist, or side-byside bridging studies can be conducted 

for the different types of formulations. If 

the new formulation results in residues 

higher than those from use of the 

original formulation, then the same 

number of trials would generally be 


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required for the new formulation as was 

required for the original formulation. 

This would codify a longstanding 

practice at EPA for various MOR 

studies. The Rs and CRs reflect the 

likelihood of the need for MOR studies 

in the Agency’s best professional 

judgment. Test notes to the table in the 

proposed § 158.2290 describe the 

specific circumstances in which MOR 

studies may be required for an 

antimicrobial. 

O. Magnitude of Residue in Meat, Milk, 

Poultry, and Eggs 

Similar to the livestock metabolism 

study, the Agency proposes to change 

the test substance for the meat/milk/ 

poultry/egg (M/M/P/E) MOR studies. 

Due to the difficulties in interpreting 

results of studies in which a mixture is 

fed, the Agency is currently 

discouraging the feeding of mixtures 

and is instead requesting the feeding of 

isolated compounds in livestock 

studies. Hence, to codify current 

practice, the test substance will be 

changed to read a single plant 

metabolite instead of metabolites in the 

plural. Provided that plant and animal 

metabolites are the same, the parent 

compound must be the test substance in 

livestock feeding studies. If any plant 

metabolite exists that is not also an 

animal metabolite, a separate feeding 

study may be required involving dosing 

with that unique plant metabolite. The 

Agency will inform the applicant when 

this additional testing is required. It is 

expected that this study will be rarely 

requested. 

The Agency proposes to continue the 

conditional requirement for M/M/P/E 

MOR studies for agricultural premises, 

indirect food uses, direct food uses and 

aquatic uses. There are three types of M/ 

M/P/E MOR studies: livestock feeding 

studies, direct livestock treatments, and 

agricultural premise treatments. The 

Agency proposes to clarify that livestock 

feeding studies generally are not 

required when (1) residues are not 

found in/on feed items or (2) livestock 

metabolism studies indicate minimal 

transfer of the pesticide residue to 

tissues, milk or eggs. For those 

pesticides which leave non-detectable 

or low residues in feed items and for 

which the livestock metabolism study 

shows little transfer of radioactivity to 

tissues, the Agency may be able to 

conclude that data on the level of 

residues in livestock and their 

byproducts are not necessary. Livestock 

premise treatment studies are required 

for those antimicrobials used to clean or 

otherwise treat livestock premises such 

as feedlots. These are expected to be the 

most common studies applicable to 

antimicrobials. 

P. Anticipated Residues 

The term ‘‘anticipated residue’’ (AR) 

refers to exposure data that would 

permit significant refinement of dietary 

exposure estimates. Refinement means 

that the Agency would estimate very 

realistic dietary exposure estimates after 

first using the screening-level estimates 

that allow EPA to perform a very quick, 

but conservative dietary risk 

assessment. 

As previously discussed, no currently 

registered antimicrobial products are 

applied to agricultural field crops. 

Generally, for antimicrobial direct fooduses, when performing the initial, 

screening-level dietary risk assessment, 

EPA uses the antimicrobial tolerances as 

the input values for dietary modeling. If 

there are risk concerns and if 

scientifically appropriate, EPA may 

refine (that is to be more realistic) the 

input values by using data showing the 

pesticide residues in food closer to the 

point of consumption. Market basket 

surveys are an example of one source of 

residue data that could be used to 

generate more realistic dietary exposure 

estimates for direct food-uses. 

Anticipated residue data would be 

required when estimates of risk using 

residues at the tolerance level result in 

a risk of concern, and a more realistic 

estimate is needed. 

However, antimicrobials also include 

indirect food uses such as sanitizers and 

disinfectants which remain on the 

surface of food-handling or processing 

equipment. For these indirect food-uses, 

generally when performing the initial, 

screening-level dietary risk assessment, 

EPA uses several high-end (overestimated) assumptions as the input 

values for dietary modeling. In such an 

assessment, the same assumptions are 

used for every dietary assessment. Such 

an assessment can be performed 

quickly, and if there are no risk 

concerns, then the dietary assessment is 

considered to be complete. However, if 

there are risk concerns and as 

scientifically appropriate, EPA would 

begin a process of using the available 

information and data to refine, that is to 

be more realistic, in estimating input 

values. 

Since the screening-level risk 

assessment did not consider the 

particular use pattern of the 

antimicrobial chemical, as a first 

refinement, EPA would modify the 

assumptions to account for the 

particular use pattern of the chemical. 

Refinements to the assumptions can also 

be made if measured data such as a 

migration study were available. 

AR data would be required when 

estimates of risk have been refined using 

information and any measured data 

initially available to EPA, and these 

refined risks result in a risk of concern. 

Taking samples from treated hard 

surfaces is an example of one source of 

residue data that could be used to 

generate more realistic dietary exposure 

estimates for an indirect food-use. 

If there is no food-use, then AR data 

would not be submitted to EPA. AR data 

would be a conditional requirement that 

is triggered only when estimates of risk 

conducted using residues at the 

tolerance level may result in a risk of 

concern. This means that AR data 

would be required only for a food-use, 

and only if a numerical tolerance is 

established, and then only if the risk 

assessment conducted at tolerance level 

results in a risk of concern. This would 

be an infrequent occurrence for 

antimicrobials. Establishing this data 

requirement for antimicrobials not only 

codifies the Agency’s current practices, 

but also harmonizes the requirements 

for antimicrobials with those of 

conventional pesticides. 

Q. Food Migration Studies 

This study is unique to antimicrobials 

and this proposal codifies current 

practices. EPA is proposing to 

conditionally require a migration study 

for indirect food uses when modeled 

estimates of the amount of antimicrobial 

residues transferred to the food or feed 

may result in a risk of concern. This 

study would not be required for any 

other uses. 

A migration study is performed to 

determine the amount of a chemical 

substance that can enter a food 

commodity through contact with a 

treated surface. There are two basic 

types of migration studies. The first type 

includes sanitizing and disinfecting 

solutions that are applied to equipment 

in a food-processing facility. The second 

type includes matrices such as wood, 

plastic, paper, cloth, or rubber which 

may be impregnated with antimicrobial 

pesticides. The migration of the 

antimicrobial into the food occurs when 

the food commodity comes into contact 

with the treated surface or the 

impregnated matrix. 

As previously discussed, the Agency 

believes that it is possible to model a 

worst-case estimate of the amount of the 

antimicrobial chemical that migrates 

into the food commodity. If the worstcase estimates do not result in a risk of 

concern, then the applicant would not 

need to submit a migration study. As an 

alternative to these worst-case estimates, 

the applicant may provide data for the 


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amount of sanitizer/disinfectant 

remaining on the surface. 

There is no Agency guideline for 

conducting a migration study. EPA 

routinely accepts studies performed 

according to FDA’s food migration 

protocol/guidance. Applicants are 

encouraged to use existing FDA 

methodologies. Information that could 

be of value to applicants developing 

protocols is on the FDA website (Refs. 

7, 9, 10, and 11). Protocols must be 

approved by the Agency prior to the 

initiation of the study. However, if a 

migration study has been reviewed and 

accepted by FDA, then this fact should 

be included in the submission to EPA, 

along with the migration study. 

XI. Environmental Risk Assessment 

A. General 

Environmental fate studies evaluate 

the mobility, distribution and 

dissipation of a pesticide in various 

compartments of the environment, such 

as water, soil, air, and sediment. These 

studies are designed to identify which 

dissipation processes are likely to occur 

when the pesticide is released into the 

environment and characterize the 

significant degradates likely to result 

from these processes. Data from these 

studies are used as inputs in exposure 

models, and, in conjunction with 

ecological effects studies, are used to 

assess whether a pesticide has the 

potential to cause adverse effects to 

wildlife, fish, plants, and humans. 

Environmental fate studies are 

discussed in Unit XII. of this preamble. 

Ecological effects data are used by the 

Agency to determine the toxicological 

hazards of pesticides to various 

nontarget organisms, such as birds, 

mammals, fish, bees, terrestrial and 

aquatic invertebrates, and plants. These 

tests include short-term acute, subacute, 

reproduction, simulated field, and full 

field studies arranged in a tiered system 

that progresses from the basic laboratory 

tests to the applied field tests. 

Ecological effects testing for nontarget 

organisms are discussed in Unit XIII, 

and nontarget plants in Unit XIV of this 

preamble. 

These data provide a foundation for 

an environmental risk assessment. The 

results of the environmental fate 

assessment are evaluated in conjunction 

with the results of the ecological effects 

data to determine the potential of the 

pesticide to cause harmful effects to 

nontarget organisms and plants. 

The Agency has divided the 

antimicrobial pesticides into two groups 

for determining environmental fate and 

ecotoxicity data requirements: the low 

environmental exposure grouping and 

high environmental exposure grouping 

as discussed in Unit XI.B. 

B. Determination of the Two Groupings: 

Low and High Environmental Exposure 

1. Factors considered in determining 

the groupings. As previously discussed, 

EPA is proposing to establish its 12 

antimicrobial use patterns in § 158.2201. 

EPA examined these use patterns and 

identified those that occur outdoors, 

discharge effluent directly to the 

outdoors, or result in materials treated 

with antimicrobials (i.e., wood 

preservatives and antifoulants) being 

placed in the environment. Given this 

direct link to the environment, and 

correspondingly higher exposure 

potential, there is a greater potential for 

concern. In fact, EPA has been requiring 

more data for such use patterns than for 

other antimicrobial use patterns. 

2. The high environmental exposure 

grouping. The Agency believes that the 

potential for environmental exposure is 

high for three of the use patterns and 

part of a fourth use pattern. For the 

purposes of requiring data, the 

following use patterns represent the 

high environmental exposure grouping 

for environmental fate (§ 158.2280) and 

ecotoxicity (§ 158.2240 and § 158.2250) 

data requirements: 

• Once-through industrial processes 

and water systems (part of the industrial 

processes and water systems use 

pattern). 

• Antifoulant paints and coatings. 

• Wood preservatives. 

• Aquatic areas. 

The data that have been typically 

required for the use patterns now 

included in the high environmental 

exposure grouping are used to calculate 

estimated environmental concentrations 

(EECs) of the pesticide in different 

environmental media. These EECs are 

needed to conduct quantitative 

environmental and ecological risk 

assessments. These data would also 

have applicability to drinking water 

exposure assessments that are used in 

human health risk assessments. 

3. The low environmental exposure 

grouping. The low environmental 

exposure grouping is defined as those 

use patterns that are not included in the 

high environmental exposure grouping. 

For the purposes of requiring data, the 

following use patterns represent the low 

environmental exposure grouping for 

environmental fate (§ 158.2280) and 

ecotoxicity (§ 158.2240 and § 158.2250) 

data requirements: 

• Agricultural premises and 

equipment. 

• Food-handling and 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. 

• Swimming pools. 

•Recirculating industrial processes 

and water systems (part of the industrial 

processes and water systems use 

pattern). 

C. Data Requirements for Wood 

Preservatives 

As discussed previously in this 

proposal, wood preservatives are 

considered to be an antimicrobial use 

pattern with high expectation of 

environmental exposure. Wood that has 

been treated with a wood preservative 

product is placed directly into the 

outdoor environment, thus leading to 

the potential for significant release of 

the wood preservative into the 

environment. The data required to 

register a wood preservative product 

depend on the use site of the treated 

wood, which can be land-only, aquaticonly or both. For instance, a wood 

preservative product which would be 

used in or near water will usually have 

more data requirements concerning the 

effects of the pesticide on aquatic 

organisms than a product that is not 

used in or near water. 

Therefore, if a product specifies that 

wood that has been treated with that 

product cannot be used in areas with 

the potential for that wood coming into 

contact with water, then EPA believes 

that the potential for exposure is 

decreased. Accordingly, it is current 

EPA practice to require fewer 

environmental fate and ecological 

effects studies for such products. In 

practice it is difficult to assure that 

wood treated with a wood preservative 

that is for land-use only will not come 

in contact with water. 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. The 

Agency does not know if or how often 

this kind of diversion occurs. However, 

the Agency notes that in the United 

States, wood preservatives are 

categorized using the American Wood 

Preservers’ Association Use Category 

system. These categories describe the 

exposure conditions which treated 

wood products can be subjected to 

when in service. The categories, 

although general, provide some measure 

of control over how treated wood 

products are used. 


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A concern that has been raised to EPA 

is the difference in how different 

countries regulate wood preservative 

products. This could present a challenge 

for joint reviews of wood preservatives 

since different data requirements and 

differing programmatic objectives could 

result in different regulatory decisions. 

Today’s proposed data requirements 

are based on EPA’s current practice of 

determining the data required for a 

wood preservative product dependent 

on the usage (land-only versus land and 

aquatic). The Agency requests 

comments on the regulation of wood 

preservative products, and based on the 

comments received could continue with 

the split usage or determine to no longer 

have such a split usage. 

XII. Environmental Fate Data 

Requirements 

A. Environmental Fate Data 

Requirements for Antimicrobials 

The Agency proposes to adapt the 

basic environmental fate data types 

(§ 158.2280) as listed in subpart N of 

current part 158 to support applications 

for antimicrobial products. EPA also 

proposes to modify the applicability of 

those requirements to antimicrobials to 

reflect differing risks and levels of 

exposure. Moreover, new types of data 

are needed to evaluate the risks 

associated with use patterns more 

typically associated with antimicrobials, 

such as discharge through sewer 

systems and wastewater treatment 

plants to the environment. As discussed 

in this Unit, such studies could include: 

Activated sludge sorption isotherm, 

ready biodegradability, and modified 

activated sludge, respiration inhibition 

test. 

Fate studies characterize how a 

pesticide chemical dissipates once it is 

released into the environment, and 

identify the significant transformation 

products likely to result from these 

processes. Fate studies include both 

laboratory and field studies. Such 

studies can provide input parameters 

needed in simulation modeling. Under 

a tiered testing scheme, a specified set 

of laboratory studies determined by the 

use patterns is performed first, and then 

a preliminary, qualitative environmental 

fate and transport assessment is 

developed from the results of those 

lower-tiered studies and the modeling. 

This assessment could determine that 

no additional studies are needed. Or, 

this assessment could trigger highertiered laboratory-based studies, and/or 

to design or trigger appropriate field 

studies. Fate studies can also be used as 

triggers for determining which 

ecological effects data will be needed to 

support registration. 

Once the higher-tiered studies have 

been reviewed and evaluated, then the 

Agency would use all these data to 

develop quantitative environmental fate 

and drinking water exposure 

assessments, and to calculate estimated 

environmental concentrations of the 

pesticide in different media (such as 

water, sediment, or soils) under various 

pesticide application and site scenarios. 

The Agency uses these estimates of 

exposure in conjunction with toxicity 

data to assess whether a pesticide has 

the potential to cause adverse effects on 

human health via exposure through 

drinking water and the environment via 

exposures through both water and soil. 

B. History of Environmental Fate Data 

Requirements for Antimicrobials 

In 1984, at the time of promulgation 

of the original part 158 data 

requirements, there were no 

environmental fate data requirements 

for the indoor use pattern. At that time, 

EPA assumed that many of the indoor 

uses went down-the-drain to a 

wastewater treatment plant (WWTP), at 

which point dilution and degradation, 

or removal by WWTP processes would 

mitigate environmental concerns. Thus, 

currently, in part 161, there are no 

environmental fate data requirements 

for the indoor use pattern. 

In 1997, the Agency presented a draft 

of the antimicrobial data requirements 

to the FIFRA Science Advisory Panel 

(SAP) (Ref. 29). As part of its 

presentation EPA explained its intent to 

divide antimicrobial uses into two 

groupings based on the potential for 

environmental exposure (high 

environmental exposure and low 

environmental exposure). In 1997, the 

Agency defined the low environmental 

exposure grouping as the following 

eight use scenarios: Agricultural 

premises and equipment; foodhandling/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. For these eight use 

scenarios for environmental fate data 

the Agency intended to require a very 

reduced data set (hydrolysis data). 

In its report, the SAP expressed its 

concerns about ‘‘the lack of chemical 

fate data,’’ indicated that hydrolysis 

would be an important pathway of 

concern for only a subset of 

antimicrobial chemicals, and stated that 

both biodegradation data, and microbial 

data should also be required. According 

to the SAP, this was ‘‘to ensure the 

safety of environmental discharge but 

also for protection of publicly owned 

treatment works (POTWs) and other 

treatment systems which often rely on 

microbial treatment processes.’’ In 

response to the SAP’s concerns, the 

Agency reexamined the need for 

environmental fate data other than 

hydrolysis. As a result of this 1997 

reexamination, the Agency determined 

to conditionally require data on 

photodegradation in water for low 

environmental exposures. At that time, 

the Agency determined not to require 

biodegradation or microbial data. 

More recently, as part of its 

development of this proposed rule, EPA 

re-evaluated the 1997 SAP 

recommendations concerning the data 

requirements for environmental fate, 

and nontarget plant and organisms. The 

reason for this re-evaluation was, in 

part, due to certain comments that were 

received in response to the 2005 

proposed rule for conventional pesticide 

chemicals (70 FR 12276, March 11, 

2005). Additionally, the Agency was 

also becoming increasingly aware of 

detections of antimicrobial chemicals in 

various environmental compartments. 

The Agency received comments from 

four California water treatment 

authorities and from environmental 

agencies from two cities in California. 

The comments centered on their strong 

recommendations that FIFRA data 

requirements should be equivalent to 

the data required to develop water 

quality criteria (WQC) under the Clean 

Water Act (CWA) and should consider 

water quality issues related to urban 

pesticide use. California water-treatment 

authorities questioned the adequacy of 

the Agency’s assessment of risks with 

regard to water quality considerations 

including: Use of aquatic toxicity data, 

surface water quality studies, and urban 

uses of pesticides, particularly when 

these uses result in pesticide residues in 

receiving waters from storm sewers or 

sewage treatment plants. 

EPA believes that even though these 

comments were received in response to 

the conventional pesticide chemicals 

proposed rule, the submitted 

information on receiving waters for 

wastewater treatment plants is 

particularly applicable to 

antimicrobials, many of which are used 

indoors. This means that the 

antimicrobial goes down-the-drain and 

eventually reaches a wastewater 

treatment plant. Therefore, in its 

response to comments document for the 

final rule for conventional pesticide 

chemicals, EPA agreed that pesticide 

discharge into municipal sewage 

systems is an important issue 


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particularly for those antimicrobial 

pesticides which are typically rinsed 

down the drain. EPA stated it would 

consider the issue of down-the-drain 

chemicals in the proposed rule for 

antimicrobials. 

As a first step toward re-evaluating its 

processes and procedures for 

conducting a risk assessment for an 

antimicrobial chemical that goes downthe-drain, the Pesticide Program 

discussed these issues with EPA’s Office 

of Water (OW). The Agency is becoming 

increasingly aware of detections of 

antimicrobial pesticide chemicals in 

various environmental compartments, 

including surface water. An example of 

a chemical with such detections is 

triclosan (Refs. 12, 17, 22, and 23). The 

detection of such chemicals in surface 

water indicates that the antimicrobial 

(or its degradate) is moving from the 

area of application, down-the-drain to a 

WWTP, and then into the environment 

via the treated effluent. Certain 

chemicals can pose a risk even at low 

levels. Based on the Agency’s concerns 

about the potential effects of 

antimicrobials on the biological 

treatment processes used in WWTPs, 

concerns about potential 

bioconcentration of antimicrobials after 

release, and possible effects on 

nontarget species, the Agency now 

believes that new environmental fate 

data requirements are needed for downthe-drain antimicrobial uses. 

Therefore, EPA is proposing to require 

data to address environmental fate 

(degradation), biodegradation data, and 

microbial data, for the low 

environmental exposure grouping (as 

defined in Unit XI.B. and once-through 

industrial processes and water systems. 

These data reflect the Agency’s concern 

about the potential movement of 

antimicrobials and their degradates from 

the indoor environment to the outdoor 

environment. Additionally, these lowertiered data will allow EPA to conduct 

screening-level environmental fate 

assessments which can then indicate the 

need for higher-tiered fate and 

ecotoxicity studies and higher-tiered 

environmental assessments. 

EPA specifically requests comments 

on the Agency’s rationale for requiring 

data to perform a screening assessment 

on down-the-drain antimicrobial uses, 

the potential for performing highertiered studies based on the results of the 

screening assessment, and the cost and 

burden of performing the studies. 

EPA also notes that three use patterns, 

wood preservatives, antifoulants, and 

aquatic uses are not considered downthe-drain use patterns. As previously 

discussed, these uses either occur 

outdoors and thus discharge directly to 

the environment, or result in materials 

treated with antimicrobials being placed 

in the environment. Since these use 

patterns are unlikely to go down-thedrain, a screening-level environmental 

fate assessment is not needed. 

C. Today’s Proposal for Low 

Environmental Exposure Antimicrobials 

The Agency believes that 

environmental exposures from the use 

patterns discussed in Unit XI.B.3. of this 

preamble are likely to be small, because 

(1) the sites where these uses occur are 

not rapidly or directly connected to 

aquatic environments, (2) some of the 

applications occur on a very infrequent 

basis and other applications involve 

very small amounts of the antimicrobial, 

and (3) in many cases wastewaters 

containing these antimicrobials are 

processed in WWTPs. The indirect 

movement of antimicrobials from the 

use sites into the outdoor environment 

occurs mostly through water. In many 

cases, leachates, rinsates, and flushes 

are released down-the-drain, and 

eventually reach a WWTP. WWTPs 

degrade chemicals in their influent, 

although the degree of degradation 

varies widely depending on the 

chemical, the treatment process and 

other factors (e.g., ambient temperature). 

After treatment, the effluent (the treated 

water and any chemicals remaining in 

that water) is released into the aquatic 

environment, or to the terrestrial 

environment via land application of 

sewage sludge. 

Given the expectation of low 

exposures to the environment, EPA 

proposes to use a tiered system of data 

requirements to determine the type of 

environmental fate assessment needed 

for the low environmental exposure 

grouping. A screening-level assessment 

would be used to determine the 

potential of the antimicrobial chemical 

to directly harm the microbial treatment 

processes present in wastewater 

treatment systems, the environmental 

compartment(s) that the antimicrobial is 

likely to partition to, and the amount of 

antimicrobial that could be present in 

the effluent that the treatment plant 

releases to the environment. The 

presence of antimicrobials in an effluent 

release means that an ecological 

assessment could be required to 

evaluate risks to endangered species. It 

is also possible that estimation of 

concentrations to use in a drinking 

water assessment could be required. 

The lower-tiered environmental fate 

studies being proposed for the 

screening-level assessment for the low 

environmental exposure grouping are 

discussed in detail in Units XII.E. – K. 

of this preamble. The higher-tiered 

studies that would be triggered are 

based on a weight-of-evidence 

evaluation of the results of the lowertiered studies are discussed in Units 

XII.L. – Q. EPA’s proposal to 

conditionally require these data for the 

low environmental exposure grouping 

would for these studies expand the 

number of use patterns for which the 

test is conditionally required. 

It may be possible to model some of 

the needed parameters. The applicant is 

encouraged to review the approach 

discussed in Unit XVIII.A. of this 

preamble on the use of StructureActivity-Relationship (SAR) 

assessments to ascertain if such 

techniques could provide useful 

information in preparing their 

submission to EPA. 

EPA is proposing to conduct the 

screening-level of its fate assessment for 

these low environmental exposure 

antimicrobials with non-direct, delayed 

environmental connections in a threepronged approach. The three prongs are 

designed to (1) estimate the number of 

days per year of exceedance of the 

antimicrobial surface water 

concentration of concern to aquatic 

organisms in a surface water body 

downstream of a treatment plant, (2) 

determine any negative effect of the 

antimicrobials in the influent on the 

activated sludge biomass in biological 

wastewater treatment systems, and (3) 

determine the potential for the 

antimicrobial to accumulate in sediment 

or in organisms downstream from the 

WWTP release, or for there to be 

negative impacts on nontarget 

organisms in the receiving water body. 

For the first prong, modeling would 

be used to estimate a screening-level 

exposure concentration of the 

antimicrobial in a surface water body 

that receives effluent from a WWTP. 

EPA anticipates using the Down-theDrain model with the Probabilistic 

Dilution Model (PDM) option in the 

Exposure and Fate Assessment 

Screening Tool (E-FAST) (Version 2.0) 

available from the Agency’s website (see 

http://www.epa.gov/oppt/exposure/ 

pubs/efast.htm). This model option uses 

readily available data as inputs to 

estimate conservative (i.e., high-end) 

exposure concentrations. E-FAST has 

been independently peer-reviewed by 

EPA’s Science Advisory Board. 

Comments from that peer review have 

been incorporated into Version 2.0 of EFAST. 

The PDM option of E-FAST can 

predict downstream chemical 

concentrations from an industrial 

discharge and from disposal of 

consumer products into household 

wastewater. The module uses a simple 


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mass balance approach that uses 

probability distributions as inputs. The 

concentration of the chemical in the 

receiving surface water body is also 

calculated as a probability distribution 

of the ratio of WWTP effluent flow and 

stream flow immediately downstream of 

the WWTP. The Down-the-Drain Model 

can be run with or without the PDM 

option. 

The Down-the-Drain Model requires 

as an input value the production 

volume of the chemical. If this 

information cannot be supplied by the 

applicant, then the Agency would need 

to estimate the volume. The production 

volume would be used as if the entire 

volume of the chemical were expected 

to go down the drain. However, the 

Agency would be able to modify the 

production volume to account for the 

percentage of the chemical that is 

expected to actually go down the drain. 

As an example, almost all of a toilet 

bowl cleaner can be reasonably 

expected to go down the drain, but a 

hard surface cleaner could also vaporize 

into the air, dry on the surface, or be 

disposed of on paper towels into the 

trash. Therefore it may be reasonable to 

adjust the production volume used as an 

input to the Down-the-Drain model. The 

model estimates human exposure from 

ingestion of drinking water and fish, 

and concentrations of chemicals in 

surface waters downstream of WWTPs. 

The PDM option estimates the number 

of days of exceedance of a concentration 

of concern for aquatic organisms. 

Concentrations of concern are based on 

measurements of acute and/or chronic 

effects to aquatic organisms. 

For the second prong of the 

assessment, EPA intends to require five 

environmental fate studies to determine 

the potential of the antimicrobial to 

harm the microbial treatment processes 

in wastewater treatment systems, and to 

determine the potential amount of 

antimicrobial present in the effluent that 

the treatment plant releases to the 

environment. Higher-tiered studies 

would be triggered based on a weightof-evidence evaluation of the results of 

the following lower tiered studies: 

Hydrolysis; photodegradation in water; 

modified activated sludge, respiration 

inhibition test; activated sludge sorption 

isotherm; and ready biodegradability. 

These tests are discussed in Units XII.E., 

F., H., I., and K. of this preamble. 

•The data from the hydrolysis study 

would allow EPA to determine if the 

antimicrobial hydrolyzes in water 

during transport to the WWTP, and also 

after release to the environment. These 

data are routinely used to understand 

the persistence of a chemical in the 

environment, and when the hydrolysis 

breakdown products should also be 

considered in the environmental fate 

assessment. 

•The data from the photodegradation 

in water study would allow EPA to 

determine if the antimicrobial degrades 

in shallow water due to exposure to 

sunlight. These data are used to 

understand the persistence of a 

chemical in surface water. 

•The modified activated sludge, 

respiration inhibition test would allow 

EPA to identify antimicrobials which 

could harm the microorganisms found 

in biological wastewater treatment 

systems and would also indicate 

suitable antimicrobial concentrations for 

use in the ready biodegradability test. 

•The activated sludge sorption 

isotherm study would allow EPA to 

assess the distribution of the 

antimicrobial between the sludge and 

aqueous phases. 

•The ready biodegradability study 

would allow the Agency to determine 

whether the chemical tested achieves 

‘‘pass levels’’ for ready biodegradability. 

These screening tests are so stringent 

that it is assumed that the chemicals 

that meet the pass levels will rapidly 

and completely biodegrade in aquatic 

environments under aerobic conditions. 

Modeling could also be used to 

predict the removal of a chemical in a 

sewage treatment plant. STPWINTM is 

part of the EPI SUITE modeling 

available via the Agency’s website (see 

http://www.epa.gov/oppt/exposure/ 

pubs/episuite.htm). STPWINTM can 

predict values not only for the total 

removal but also three contributing 

processes: Biodegradation, sorption to 

sludge, and stripping to air. 

The third prong of the fate assessment 

would use the available product 

chemistry data (for example octanol/ 

water partition coefficient, vapor 

pressure, or solubility in water) or 

predicted/modeled data to determine 

the potential for the antimicrobial to 

bioconcentrate. This is consistent with 

the approach used in the Agency’s PBT 

profiler, an assessment tool that 

estimates environmental persistence (P), 

bioconcentration potential (B), and 

aquatic toxicity (T) of a chemical based 

on its molecular structure. (see http:// 

www.epa.gov/oppt/pbtprofiler.) 

The Agency would then use the 

results of all three prongs to conduct a 

screening-level environmental fate 

assessment. It is also possible that 

information from open literature could 

be useful to the Agency for its 

assessment. By combining the modeled 

exposure estimates with information on 

the persistence of the antimicrobial, its 

distribution in the environment, and its 

ability to harm the microorganisms 

found in a biological WWTP, the 

Agency could determine if there are risk 

concerns. Based on the concerns, EPA 

would be able to determine if a more indepth risk assessment would be 

required for certain environmental 

media. Higher-tiered data could be 

required to support such a risk 

assessment. The specific data would 

depend on the environmental medium 

in which the antimicrobial and its 

transformation products reside, and on 

the concentrations in the environment. 

• If the antimicrobial is completely 

degraded to non-toxic degradates, then 

it is likely that no higher-tiered 

environmental fate data would be 

required. 

• If the antimicrobial is not completely 

degraded by the WWTP and is in the 

effluent released to surface water, then 

depending on the concentrations that 

then occur in the environment, an 

assessment similar to that of an 

antimicrobial with high environmental 

exposure could be needed. 

• If the antimicrobial partitions to 

water, then the possible higher-tiered 

environmental fate studies would 

include: Leaching and adsorption/ 

desorption, and aerobic and anaerobic 

aquatic metabolism. 

• If the antimicrobial is likely to 

partition to sludge, soil, or sediment, 

then possible higher-tiered 

environmental fate studies would 

include aerobic and anaerobic soil 

metabolism studies, and sediment 

studies. EPA has considered that 

antimicrobials may be present in 

biosolids (sewage sludge) that are land 

applied. While soil and sediment data 

would be required for an antimicrobial 

risk assessment, these data may also be 

useful to EPA’s Biosolids Program 

conducted under 40 CFR part 503. 

The Agency specifically seeks 

comment on this proposed approach for 

performing a screening-level 

environment fate assessment and the 

potential for triggering higher-tiered 

studies. 

D. Case Studies 

To assess whether the proposed 

approach provides the data needed to 

assess exposure and risk of 

antimicrobial pesticides released to the 

environment via down-the-drain use 

patterns, the Agency has conducted four 

case studies. All of the models used for 

the case studies are peer-reviewed, and 

publicly available. These case studies, 

entitled ‘‘Four Case Studies of 

Antimicrobial Pesticides in the Downthe-Drain Screening Model, Using the 

Proposed Approach for a ScreeningLevel Environmental fate Assessment’’ 

(Ref. 42) reflect a particular integration 


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of the modeling results specific to the 

needs of antimicrobials. 

Four antimicrobial pesticides that 

have completed scientific review in the 

reregistration process were selected to 

represent a range of influent volumes to 

WWTPs, and general environmental fate 

and transport properties. Antimicrobials 

undergoing reregistration were chosen 

because they have fairly complete 

supporting data bases, and are well 

understood; that is, they allow a 

comparison of the proposed approach 

with real-world information. 

In selecting these four chemicals, the 

Agency attempted to select at least one 

chemical that should trigger higher tier 

data requirements and one that should 

trigger no higher tier data requirements. 

The environmental fate and transport 

characteristics considered during the 

case studies were environmental 

persistence, biodegradability, hydrolytic 

stability, and sorption potential. 

Although not intended to represent all 

possible combinations of chemical 

characteristics, use scenarios, and usage 

volumes, the four antimicrobials 

selected for the case studies were 

intended to include a sufficiently broad 

range of possible outcomes to credibly 

assess the proposed approach. 

•Chemical A was intended to 

represent a chemical with a high 

loading (mass) within the WWTP’s 

influent, high toxicity to fish and 

aquatic invertebrates, high hydrolytic 

stability, relatively high potential to 

biodegrade during wastewater 

treatment, and low to moderate 

potential to adsorb to activated sludge. 

This chemical was picked as a ‘‘worstcase’’ example. 

•Chemical B was intended to 

represent a chemical with a relatively 

low to moderate loading (mass) within 

the WWTP’s influent, high toxicity to 

fish and aquatic invertebrates, high 

hydrolytic stability, and no available 

data on biodegradability during 

wastewater treatment or the potential to 

adsorb to activated sludge. 

•Chemical C represents a ‘‘best-case’’ 

example. It is an organic acid that has 

a high loading (mass) within the 

WWTP’s influent, potential to 

bioaccumulate, high water solubility, no 

environmental fate data, and no 

ecotoxicity data. This chemical was 

selected as a case study because it 

degrades quickly and would be 

expected to have little potential for 

ecotoxicity. 

•Chemical D represents a mixture of 

two organic chemicals with relatively 

low loading (mass) within the WWTP’s 

influent volume, high resistance to 

biodegradation during wastewater 

treatment, low potential to sorb to 

activated sludge, and fairly low toxicity 

to fish and aquatic invertebrates. 

The specific identities of the 

antimicrobials have been ‘‘blinded’’ to 

focus those who may wish to comment 

on the proposed approach, and not what 

the result ‘‘should’’ be for a particular 

chemical. 

Many, but not all, of the values 

selected for input data for the case 

studies were based on measured or 

estimated values for existing 

antimicrobial pesticides. In some 

instances, values for input data needed 

to run models to assess exposure and 

risk from down-the-drain releases were 

not available. In those instances, 

hypothetical values were used. 

Hypothetical values were also 

sometimes selected to enable the cases 

to have sufficiently different key 

environmental fate and transport 

properties to be able to more rigorously 

test the proposed tiered approach for 

assessing exposure and risk to 

chemicals that are released down-thedrain. 

TABLE 1.—CASE STUDIES

Study Results 

Chemical A: A 

Chemical that 

Does Not Hydrolyze and Only Partially Biodegrades 

The proposed approach indicated 

Chemical A has 

considerable potential to pose ecological concerns. 

Aerobic and anaerobic soil metabolism studies 

are needed to refine environmental 

fate and dissipation, and highertier ecotoxicity 

studies are needed to determine 

risk to nontarget 

species. 

Chemical B: A 

Chemical Which Is 

Stable to Hydrolysis, But There Is 

No Data on the 

Potential to Biodegrade During 

Wastewater Treatment or Adsorb to 

Activated Sludge 

The proposed approach indicated 

that the lower 

tiered environmental fate studies are needed to 

determine Chemical B’s dissipation 

rate in wastewater 

treatment plants. 

Several higher 

tiered ecotoxicity 

studies are needed to determine 

risk to nontarget 

species. 

TABLE 1.—CASE STUDIES—Continued 

Study Results 

Chemical C: An Organic Acid that is 

Highly Soluble in 

Water 

There are no data to 

show that Chemical C would harm 

microorganisms 

found in biological 

wastewater treatment systems. 

Chemical D: A Mixture of Chemicals Chemical D does 

not appear to 

pose ecological 

risks at the assumed production 

levels. However, 

the potential for 

biodegradation 

and any potential 

impacts on waste 

water treatment 

plant organisms 

could not be 

ascertained with 

the available information. Therefore, 

the proposed new 

lower tiered environmental fate 

studies are required. 

From these case studies the Agency 

concludes that the proposed approach 

produces the results desired by the 

Agency. The proposed approach 

effectively distinguishes between 

chemicals that will require more indepth review and therefore higher-tiered 

studies versus chemicals that require 

only the lower tiered environmental fate 

and ecotoxicity studies to determine 

that no or few additional higher tiered 

studies are needed. 

The Agency specifically seeks 

comment on the case studies (Ref. 42) 

performed, including the assumptions 

used as model inputs. EPA will consider 

comments specific to the case studies 

along with comments on the proposed 

approach, as the Agency evaluates the 

use of the proposed approach for downthe-drain antimicrobials in the final rule 

for antimicrobial data requirements. 

E. Hydrolysis Study 

EPA proposes to require a hydrolysis 

study for all antimicrobial pesticides. In 

40 CFR part 161, hydrolysis studies are 

currently required for all use patterns 

except indoor. (The indoor part 161 use 

pattern is being considered by EPA to be 

similar to the low environmental 

exposure grouping.) Accordingly, EPA 

proposes to continue to require 

hydrolysis studies for all of the high 

environmental exposure use patterns 

(once-through industrial processes and 

water systems, antifoulant paints and 

coatings, wood preservatives, and 


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aquatic areas) and to codify the 

requirement for all other antimicrobial 

use patterns. In practice, hydrolysis 

studies have been required for all 

antimicrobial chemicals for over 10 

years. 

As previously discussed, EPA intends 

to require the hydrolysis study as part 

of the lower tier of environmental fate 

data requirements for down-the-drain 

chemicals. Chemicals that hydrolyze 

rapidly to less toxic chemicals may need 

few higher tiered studies. This study 

will allow EPA to determine how fast 

the antimicrobial breaks down in the 

presence of water and what degradates 

are formed. 

F. Photodegradation in Water 

In 40 CFR part 161, the 

photodegradation in water study is 

required for aquatic use patterns. The 

Agency proposes to continue its existing 

requirement for a photodegradation in 

water study for the antimicrobial 

aquatic areas use pattern. The Agency 

also proposes to require the study for all 

other antimicrobial uses. This would 

expand the number of use patterns for 

which this study is required. 

This study will allow EPA to 

determine the degradation of the 

pesticide in shallow water bodies as a 

result of exposure to sunlight. 

Chemicals that degrade quickly in the 

environment may need few higher tier 

studies. As with the data requirements 

for conventional pesticide chemicals, 

EPA intends to clarify in a test note 

certain conditions when 

photodegradation testing would not be 

required. Data on photodegradation in 

water would not be required when the 

electronic absorption spectra, measured 

at pHs 5, 7, and 9 of the chemical and 

its hydrolytic products, if any, do not 

show absorption or tailing between 290 

and 800 nanometers. If no absorption or 

tailing occurs in this range, it is unlikely 

that photodegradation occurs (Refs. 25 

and 27). 

G. Photodegradation in Soil 

The Agency is proposing to require 

the photodegradation in soil study for 

wood preservatives only. Leaching of 

wood preservatives (both the parent or 

transformation products) from 

preservative-treated wood could 

contaminate the surrounding soils. This 

would be a new data requirement which 

would provide data on the dissipation, 

nature and persistence of wood 

preservative degradation products 

formed by soil surface catalyzed 

photolysis. Using these data the Agency 

can assess the extent and duration of 

human (e.g., children playing below 

decks) and/or nontarget organism 

exposures to soils adjacent to 

preservative-treated wood structures. 

Such soils may contain the parent 

compound and/or transformation 

products, which could include those 

formed via photodegradation processes. 

H. Activated Sludge Sorption Isotherm 

The activated sludge sorption 

isotherm study would be a new data 

requirement. EPA is proposing to 

require this study only for the low 

environmental exposure grouping and 

the once-through industrial processes 

and water systems. This study is not 

required for wood preservatives, 

antifoulants, or aquatic areas. 

For antimicrobial chemicals that go 

down-the-drain and reach a WWTP, as 

part of its screening-level environmental 

fate assessment, EPA will analyze the 

potential impact of the antimicrobial 

chemical on the microorganisms in the 

typical biological treatment processes of 

a WWTP. The activated sludge sorption 

isotherm study would allow EPA to 

assess the distribution of the 

antimicrobial between the sludge and 

aqueous phases. This information is 

important in determining the method 

used in the ready biodegradability test 

and the higher-tiered studies that may 

be required. Antimicrobials that are 

predominantly in the water column and 

do not sorb to sludge may not need 

testing that focuses on sediment and 

soils, such as the aerobic and anaerobic 

soil metabolism studies. Antimicrobials 

that predominantly sorb to the sludge, 

soil, and sediment may not need testing 

that focuses on water, such as the 

aerobic and anaerobic aquatic 

metabolism studies. 

I. Ready Biodegradability 

The ready biodegradability study 

would be a new data requirement. EPA 

is proposing to require this study only 

for the low environmental exposure 

grouping and the once-through 

industrial processes and water systems. 

This study is not required for wood 

preservatives, antifoulants, or aquatic 

areas. 

For antimicrobial chemicals that go 

down-the-drain and reach a WWTP, as 

part of its screening-level environmental 

fate assessment, EPA will analyze the 

potential impact of the antimicrobial 

chemical on the microorganisms in the 

biological treatment processes of a 

WWTP. Biodegradation is an important 

environmental pathway in which the 

antimicrobial is broken down into 

‘‘smaller’’ chemicals by bacteria. This 

study supplies information on the rate 

of breakdown and the completeness of 

the degradation to carbon dioxide and 

water. A ready biodegradability study 

would allow the Agency to determine 

whether the chemical achieves ‘‘pass 

levels’’ for ready biodegradability (e.g., 

70% removal of dissolved organic 

carbon). These screening tests are so 

stringent that it is assumed that 

antimicrobials that ‘‘pass’’ will rapidly 

and completely biodegrade in aquatic 

environments under aerobic conditions. 

Chemicals that degrade quickly and 

completely may need few higher tiered 

studies. 

J. Porous Pot Test 

The Agency is proposing to 

conditionally require the porous pot 

study for antimicrobials based on the 

results of the ready biodegradability 

test. This would be a new data 

requirement. EPA is proposing to 

require this study only for the low 

environmental exposure grouping and 

the once-through industrial processes 

and water systems. This study is not 

required for wood preservatives, 

antifoulants, or aquatic areas. 

The porous pot study simulates the 

processes in the aeration basin of the 

activated sludge sewage treatment 

process. It is therefore a more realistic 

test than the biodegradability test. A 

chemical that did not ‘‘pass’’ the 

biodegradability test could degrade 

(partially or completely) under different 

conditions. The porous pot study would 

provide a measure of the extent of 

biodegradation or removal likely to 

occur during sewage treatment. An 

antimicrobial that degrades quickly and 

completely in a typical wastewater 

treatment plant may need few higher 

tiered studies. 

K. Modified Activated Sludge, 

Respiration Inhibition Test 

The modified activated sludge, 

respiration inhibition test would be a 

new data requirement. EPA is proposing 

to require this study only for the low 

environmental exposure grouping and 

the once-through industrial processes 

and water systems. This study is not 

required for wood preservatives, 

antifoulants, or aquatic areas. 

For antimicrobial chemicals that go 

down-the-drain and reach a WWTP, as 

part of its screening-level environmental 

fate assessment, EPA will analyze the 

potential impact of the antimicrobial 

chemical on the microorganisms in the 

biological treatment processes of a 

WWTP. The modified activated sludge, 

respiration inhibition test would allow 

EPA to identify antimicrobials which 

could harm the microorganisms found 

in WWTPs and thus impair the ability 

of these bacteria to carry out their 

intended function. Additionally, this 

study would also indicate suitable 


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concentrations for use in the ready 

biodegradability test. 

L. Leaching and Adsorption/Desorption 

In 40 CFR part 161, leaching and 

adsorption/desorption studies are 

required for all use patterns except the 

indoor. Accordingly, EPA proposes to 

continue to require the leaching and 

adsorption/desorption studies for all of 

the high environmental exposure use 

patterns: Once-through industrial 

processes and water systems, 

antifoulant paints and coatings, wood 

preservatives, and aquatic areas. 

EPA is also proposing to conditionally 

require these data for the low 

environmental exposure grouping. This 

would expand the number of use 

patterns for which the test is 

conditionally required. For the low 

environmental exposure grouping, the 

leaching and adsorption/desorption 

study is considered to be a higher-tiered 

study that would be triggered based on 

a weight-of-evidence evaluation of the 

results of the hydrolysis, 

photodegradation in water, activated 

sludge sorption isotherm, ready 

biodegradability, and modified activated 

sludge, respiration inhibition tests. 

The leaching and adsorption/ 

desorption study would provide 

information on the mobility of the 

antimicrobial pesticide in soils. The 

antimicrobial pesticide may or may not 

be transported to surface water and/or 

ground water bodies used for drinking 

water. The presence of an antimicrobial 

pesticide in drinking water sources 

could contribute to exposure via 

drinking water. 

M. Aerobic Soil Metabolism 

The Agency proposes to adapt its 

current requirement in 40 CFR part 161 

for an aerobic soil metabolism study to 

the specific needs of antimicrobial 

chemicals. Currently, 40 CFR part 161 

requires this study for terrestrial and 

outdoor types of uses. 

The aerobic soil metabolism study 

would be conditionally required for the 

low environmental exposure grouping, 

and once-through industrial processes 

and water systems. This would expand 

the number of use patterns for which 

the test is conditionally required. The 

aerobic soil metabolism study is 

considered to be a higher-tiered study 

that would be triggered based on a 

weight-of-evidence evaluation of the 

results of the hydrolysis, 

photodegradation in water, activated 

sludge sorption isotherm, ready 

biodegradability, and modified activated 

sludge, respiration inhibition tests. 

For aquatic areas, data would be 

required only for use sites that are 

intermittently dry. This would codify 

current practices for aquatic areas. 

For wood preservatives, the Agency 

proposes to require an aerobic soil 

metabolism study. This would codify 

current practices for wood 

preservatives. 

The aerobic soil metabolism study 

would allow EPA to better understand 

the antimicrobial pesticide’s 

degradation under aerobic (oxygen-rich) 

conditions in the laboratory. The results 

of the study would help to determine 

how fast the antimicrobial degrades in 

the presence of microorganisms in 

different natural soils, and what 

metabolites are formed. Chemicals that 

degrade quickly in soil are likely to have 

lower exposure estimates. 

N. Anaerobic Soil Metabolism 

Due to a printing error, the data 

requirement for an anaerobic soil 

metabolism study was inadvertently 

omitted from the data tables (now in 40 

CFR part 161) in 1991, and subsequent 

publications of the CFR. EPA asserts 

that this requirement is still in 

existence: This data requirement was 

never intentionally removed from the 

CFR by notice and comment 

rulemaking, and is not considered a new 

requirement. Therefore, EPA proposes 

to adapt its current requirement for an 

anaerobic soil metabolism study to the 

specific needs of antimicrobial 

chemicals by conditionally requiring the 

study for the low environmental 

exposure grouping, and wood 

preservatives. 

EPA is expanding the number of use 

patterns for which the test is 

conditionally required. For the low 

environmental exposure grouping, the 

anaerobic soil metabolism study is 

considered to be a higher-tiered study 

that would be triggered based on a 

weight-of-evidence evaluation of the 

results of the hydrolysis, 

photodegradation in water, activated 

sludge sorption isotherm, ready 

biodegradability, and modified activated 

sludge, respiration inhibition tests. 

For wood preservatives, the anaerobic 

soil metabolism study would be 

required if treated wood is used in 

aquatic environments or in soils which 

may become flooded or waterlogged. 

This would codify current practices for 

wood preservatives. 

The anaerobic soil metabolism study 

would facilitate a better understanding 

of the antimicrobial pesticide’s 

degradation under anaerobic (oxygenpoor) conditions in the laboratory. The 

results of the study would help to 

determine how fast the antimicrobial 

degrades in the presence of 

microorganisms in different natural 

soils, and what metabolites are formed. 

Chemicals that degrade quickly in soil 

are likely to have lower exposure 

estimates. 

O. Aerobic and Anaerobic Aquatic 

Metabolism 

In 40 CFR part 161 both the aerobic 

and anaerobic aquatic metabolism 

studies are required for aquatic uses. For 

antimicrobial chemicals, the Agency 

considers this to include the following 

uses: Once-through industrial processes 

and water systems, antifoulant paints 

and coatings, and aquatic areas. 

Therefore, the Agency proposes to 

continue its current requirement for 

aerobic and anaerobic aquatic 

metabolism studies for these uses. For 

wood preservatives these studies have 

been required on a case-by-case basis; 

therefore, this proposal would codify 

current practices. 

EPA is also proposing to conditionally 

require these two studies for the low 

environmental exposure grouping. This 

would expand the number of use 

patterns for which the test is 

conditionally required.. 

Anaerobic aquatic metabolism studies 

describe and measure the formation of 

pesticide residues in the water column 

or sediment under low-oxygen 

conditions. Aerobic aquatic metabolism 

studies determine the effects that 

exposure to aerobic, or oxygen-rich 

conditions in the water column or 

sediment can have on a pesticide when 

it is dispersed through the aquatic 

environment. Since the degradation or 

dissipation pathways of pesticides in 

aquatic environments are almost always 

different from those of terrestrial 

systems, soil metabolism studies may 

not clearly define the paths of 

degradation found in aquatic 

environments. For the low 

environmental exposure grouping, the 

aerobic and anaerobic aquatic 

metabolism studies are considered to be 

higher-tiered studies that would be 

triggered based on a weight-of-evidence 

evaluation of the results of the 

hydrolysis, photodegradation in water, 

activated sludge sorption isotherm, 

ready biodegradability, and modified 

activated sludge, respiration inhibition 

tests. Chemicals that degrade quickly in 

water or sediment are likely to have 

lower exposure estimates. 

P. Aquatic Sediment Studies 

Aquatic sediment studies are required 

for aquatic use patterns in 40 CFR part 

161. Accordingly, the Agency proposes 

to continue its current requirement for 

aquatic sediment studies for the 

antimicrobial aquatic areas use pattern. 

EPA is also proposing to conditionally 


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require an aquatic sediment study for all 

other antimicrobial use patterns based 

on the antimicrobial’s potential for 

aquatic exposure. 

For the low environmental exposure 

grouping, the aquatic sediment study is 

considered to be a higher-tiered study 

that would be triggered based on a 

weight-of-evidence evaluation of the 

results of the hydrolysis, 

photodegradation in water, activated 

sludge sorption isotherm, ready 

biodegradability, and modified activated 

sludge, respiration inhibition tests. This 

would expand the number of use 

patterns for which the test is 

conditionally required. 

For the once-through industrial 

processes and water systems, 

antifoulant paints and coatings, and 

wood preservatives, data would be 

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. 

This would codify current practices. 

The aquatic field dissipation study is 

used to determine the nontarget fate of 

a terrestrially applied pesticide that has 

a high potential to enter aquatic 

environments and to substantiate 

laboratory findings. The laboratory 

studies address one environmental fate 

process at a time. The aquatic field 

dissipation study examines pesticide 

loss or movement in water and 

sediment. Under field conditions 

degradation/dissipation processes can 

proceed differently from how they 

occurred under laboratory conditions. 

Data from this study can reduce the 

potential overestimation to both 

exposure and risk that can result from 

having only laboratory generated data. 

Protocols must be approved by the 

Agency prior to the initiation of the 

study. Details for developing protocols 

are available from the Agency. 

Q. Monitoring of Representative U.S. 

Waters 

The Agency is proposing to 

conditionally require monitoring of 

representative U.S. waters for all 

antimicrobial use patterns. This would 

include freshwater, saltwater, 

surfacewater, and groundwater. This 

would codify current practices. 

The Agency would use a weight-ofevidence approach taking into account 

factors such as available monitoring 

data; the vulnerability of the freshwater, 

estuarine, or marine water resources; 

and the persistence and fate of the 

pesticide active ingredient (or 

degradate). Protocols must be approved 

by the Agency prior to the initiation of 

the study. Details for developing 

protocols are available from the Agency. 

Based on past experience, the Agency 

believes that these monitoring data 

would be required only for a very small 

number of antimicrobial pesticide 

registrations. Monitoring for tributyltin 

antifoulants of the near coastal waters of 

the United States including the Great 

Lakes was required under the Organotin 

Anti-fouling Paint Control Act of 1988. 

In 1989, pesticide registrants were 

required to provide these monitoring 

data under FIFRA section 3(c)(2)(B). 

These tributyltin antifoulants data are 

the only monitoring of representative U. 

S. waters that has been required for an 

antimicrobial to date. 

R. Special Leaching Study 

The Agency is proposing to require 

special leaching studies for antifoulant 

paints and coatings, and wood 

preservatives. Part 161 is not explicit in 

the data that are currently required 

because those use patterns are not 

delineated sufficiently for antimicrobial 

pesticide chemicals. This proposal 

would codify the Agency’s current 

practices. These studies are needed 

because leaching from treated materials 

is the primary source of environmental 

exposure to antifoulants and wood 

preservatives. These studies would 

provide basic information about the 

availability of the pesticide to the 

environment, and would be used to 

perform exposure and risk assessments. 

There is no OPPTS Harmonized 

guideline for these studies. The 

applicant may perform the study with a 

protocol of their choice, or may use the 

American Wood Preservers’ 

Association’s (AWPA) Standard Method 

of Determining the Leachability of 

Wood Preservatives (AWPA E11–97), 

AWPA’s Standard Method for 

Determining the Leachability of Wood 

Preservatives in Soil Contact (AWPA 

E20–04), and the American Society for 

Testing and Materials (ASTM) Standard 

Test Method for Organotin Release Rates 

of Antifouling Coating Systems in Sea 

Water (ASTM D5108–90), or their 

equivalents. As stated in the test notes 

to the table in proposed § 158.2280, 

prior approval by the Agency of studies 

conducted according to AWPA E11–97 

or ASTM D5108–90 is not required. 

However, all studies that would be 

conducted according to other protocols 

must be approved by the Agency prior 

to the initiation of the study. Details for 

developing protocols are available from 

the Agency. 

XIII. Nontarget Organisms Data 

Requirements 

A. Nontarget Organisms Data 

Requirements for Antimicrobials 

EPA proposes to adapt the basic 

nontarget organism data types 

(§ 158.2240) as listed in subpart G of 

current part 158 to support applications 

for antimicrobial products. EPA 

proposes to modify the applicability of 

those requirements to antimicrobials to 

reflect differing risks and levels of 

exposure. Part 161 is not explicit in the 

data that are currently required because 

those use patterns are not delineated 

sufficiently for antimicrobial pesticide 

chemicals. The proposed table, in 

§ 158.2240, will provide greater 

transparency and clarity. 

Ecological effects testing includes 

short-term, acute, subacute, chronic, 

and reproduction studies, which 

progress from laboratory tests to applied 

field tests. These data allow the Agency 

to determine if the standard for 

registration is met and whether 

precautionary label statements 

concerning toxicity or potential adverse 

effects to nontarget organisms are 

necessary. 

The Agency is proposing to use a 

tiered system of ecological effects 

testing to assess the potential risks of 

pesticide uses to nontarget animals 

(aquatic and terrestrial vertebrates and 

invertebrates) for antimicrobial 

pesticide chemicals. For the first tier of 

testing EPA proposes to require for all 

antimicrobial pesticides three types of 

acute ecological effects studies. 

• Avian acute oral LD50. 

• Acute freshwater fish LC50. 

• Acute freshwater invertebrates EC50. 

These acute studies measure toxicity 

in representative species of the 

nontarget species most likely to be 

adversely affected and allow EPA to 

develop precautionary labeling. Such 

labeling includes statements such as 

‘‘This product is extremely toxic to 

birds’’ or ‘‘This product is toxic to fish.’’ 

These statements provide needed 

information in case of unintended or coincident exposure to antimicrobials, 

such as a transportation accident. And, 

in fact, these studies are currently 

required for an application for 

registration. 

These first tier data would be required 

for all antimicrobial use patterns and 

performed with the technical grade 

active ingredient (TGAI). Higher-tiered 

data would be required when the 

appropriate trigger in § 158.2240 is met. 

For instance, results from these first tier 

studies may indicate the need for acute 

toxicity testing in an additional species, 

or higher-tiered studies to assess hazard 


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to other species or in other parts of the 

environment. Other factors, such as, 

toxicity, persistence, and/or potential 

for bioaccumulation, may indicate the 

need for higher-tiered ecological effects 

and environmental fate data. All typical 

end-use product (TEP) testing is 

considered to be higher tier. An 

applicant must carefully consider 

whether studies listed in the higher tier 

data requirements are required for 

registration of his product and should 

consult with the Agency, as needed. 

The Agency has divided the 

antimicrobial pesticides into two groups 

for determining ecological effect data 

requirements, based on their expected 

environmental exposure. The two 

groupings are the same groupings used 

for environmental fate data 

requirements: Low and high 

environmental exposure groupings. (see 

Unit XI.B of this preamble.) 

B. The Low Environmental Exposure 

Grouping 

The use patterns within this grouping 

are the same as those described in Unit 

XI.B. of this preamble for environmental 

fate data requirements. As previously 

discussed in this Unit, EPA proposes to 

require a first tier of three ecological 

effects studies for all antimicrobials. 

These three acute ecotoxicity studies in 

combination with the screening-level 

environmental fate assessment proposed 

to be required for assessing the impacts 

of antimicrobial pesticides on WWTPs, 

are the initial studies for environmental 

modeling for risk assessment purposes. 

For the low environmental exposure 

grouping, higher-tiered ecotoxicity 

studies are conditioned on a weight-ofevidence evaluation of the results of the 

tier one ecotoxicity studies and/or the 

results of the screening-level 

environmental fate assessment. Thus, 

the studies described in Unit XIII.F., G., 

I., J., K., L., and M. could be triggered. 

C. The High Environmental Exposure 

Grouping 

As with the environmental fate data 

requirements, the high exposure 

environmental group consists of the 

once-through industrial processes and 

water systems, antifoulant paints and 

coatings, aquatic areas, and wood 

preservatives. These uses either occur 

outdoors, discharge effluent directly to 

the outdoors, or result in materials 

treated with antimicrobials (e.g., wood 

preservatives and antifoulants) being 

placed in the environment, thereby 

leading to potentially significant 

environmental exposure. For the high 

environmental exposure grouping, EPA 

proposes to require three first tier 

ecological effects studies and depending 

on the use pattern, other ecotoxicity 

studies such as avian studies and TEP 

testing. The Agency may require 

additional ecotoxicity studies based on 

the results of these studies or on other 

information. 

D. Acute Avian Oral Toxicity 

In 40 CFR part 161 acute avian studies 

are conditionally required for ‘‘indoor’’ 

uses of antimicrobials, and are required 

for aquatic uses of antimicrobials. (The 

indoor part 161 use pattern is being 

considered by EPA to be similar to the 

low environmental exposure grouping.) 

The Agency is proposing to require 

submission of acute avian LD50 toxicity 

studies for all antimicrobial use 

patterns. These studies are needed as 

part of the tier one ecotoxicity testing, 

and as previously explained are used to 

develop precautionary labeling. 

Testing in one avian species is 

required for the low environmental 

exposure grouping. The shift from CR to 

R for the low environmental exposure 

grouping would expand the number of 

use patterns for which this study is 

required. 

For antimicrobial chemicals, the 

Agency considers the aquatic use 

pattern in part 161 to include the 

following antimicrobial use patterns: 

Once-through industrial processes and 

water systems, antifoulant paints and 

coatings, and aquatic areas. Therefore, 

the Agency proposes to continue its 

current requirement for acute avian oral 

acute toxicity studies for these uses. For 

wood preservatives these studies have 

been required on a case-by-case basis; 

therefore, this proposal would codify 

current practices. 

As with the data requirements for 

conventional pesticide chemicals, the 

Agency is proposing to change the 

testing requirement from one species to 

two species for all antimicrobial use 

patterns except the low environmental 

exposure grouping. The change to two 

species is consistent with the Agency’s 

current practices. 

The species proposed in this proposal 

differ from those in the requirements for 

conventional pesticides. Many 

conventional chemicals are applied 

outdoors and are considered to be 

terrestrial uses. For antimicrobials the 

Agency is proposing that the testing be 

conducted with a waterfowl species and 

an upland game bird species. The 

selection of waterfowl and upland game 

species is consistent with the current 

submissions by registrants of 

antimicrobial products and reflects the 

data needed for the many indoor and 

aquatic uses of antimicrobials. 

E. Acute Aquatic Toxicity Studies 

The Agency is proposing to require 

acute aquatic toxicity studies (LC50 fish 

and EC50 invertebrate) for all 

antimicrobial uses. These studies are 

needed as part of the tier one ecotoxicity 

testing, and as previously explained are 

used to develop precautionary labeling. 

1. Tier 1 testing. In part 161, acute 

aquatic toxicity studies are 

conditionally required for ‘‘indoor’’ uses 

of antimicrobials, and are required for 

aquatic uses of antimicrobials. 

For antimicrobial chemicals, the 

Agency considers the aquatic use 

pattern in part 161 to include the 

following uses: Once-through industrial 

processes and water systems, 

antifoulant paints and coatings, and 

aquatic areas. Therefore, the Agency 

proposes to continue its current 

requirement for two acute aquatic fish 

toxicity studies (one warm water and 

one cold water species) and one 

invertebrate toxicity study for these use 

patterns. For wood preservatives these 

three studies have been required on a 

case-by-case basis; therefore, this 

proposal would codify current practices. 

For the low environmental exposure 

grouping, the Agency is proposing to 

require the acute freshwater fish toxicity 

study in one species, either a warm 

water or a cold water species. 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 than 1 part per million (ppm) 

or 1 milligram/liter (mg/L). This would 

codify existing practices. Additionally, 

the shift from CR to R for the low 

environmental exposure grouping 

(which contains many of the ‘‘indoor’’ 

uses) would also codify current 

practices. 

2. TEP testing. Typical End-Use 

Product (TEP) testing is proposed for 

both the acute freshwater fish and 

invertebrate toxicity studies. This is an 

existing requirement according to the 

test notes to the table in § 161.490. 

F. Avian Dietary Toxicity 

Currently in part 161 an avian dietary 

LC50 study is conditionally required for 

the greenhouse and indoor use patterns 

and required for all other use patterns. 

Today the Agency is proposing to 

continue this existing requirement by 

requiring the avian dietary study for 

aquatic areas and conditionally 

requiring the study for all other 

antimicrobial use patterns. 

G. Avian Reproduction 

The Agency has adapted the current 

data requirements in part 161 for avian 


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reproduction testing to determine the 

avian reproduction data requirements 

for antimicrobial chemicals. An avian 

reproduction study is conditionally 

required for aquatic uses in part 161. 

The Agency is proposing to require 

the avian reproduction study for the 

antimicrobial aquatic areas use pattern. 

The proposed change from 

conditionally required to required is 

consistent with the Agency’s current 

practices. 

For all other antimicrobial use 

patterns, the Agency is proposing to 

conditionally require the avian 

reproduction study. For wood 

preservatives this study has always been 

considered when EPA made its case-bycase determinations on the data needed 

for risk assessment; therefore, this 

proposal would codify the current 

practices used for wood preservatives. 

Since part 161 conditionally requires 

this testing for ‘‘aquatic uses,’’ the 

Agency’s proposal continues the 

existing data requirement for the oncethrough industrial processes and water 

systems. Since the testing is also 

proposed to be conditionally required 

for the low environmental exposure 

grouping, this would expand the 

number of use patterns for which these 

studies are conditionally required. 

H. Acute Estuarine and Marine Study 

Acute estuarine and marine toxicity 

studies are performed on three species: 

An estuarine/marine mollusk, an 

estuarine/marine invertebrate, and an 

estuarine/marine fish. These studies 

measure toxicity in representative 

estuarine and marine species of the 

nontarget species most likely to be 

adversely affected. 

1. TGAI testing. The Agency is 

proposing to require these three acute 

estuarine and marine studies for 

antifoulant paints and coatings, and 

conditionally require these studies for 

wood preservatives. This would codify 

the Agency’s current practices. 

Testing for all other antimicrobial use 

patterns would also be conditionally 

required. The Agency is proposing in 

part 158, subpart W to use the same 

conditionalities (as described in the test 

notes) for requiring these studies as in 

part 161, i.e. the testing is required if 

residues from the parent compound 

and/or transformation products are 

likely to enter the estuarine/marine 

environment. 

Part 161 conditionally requires this 

testing for ‘‘aquatic uses.’’ Therefore, the 

Agency’s proposal continues the 

existing data requirement for the oncethrough industrial processes and water 

systems, and aquatic areas. Since the 

testing is also proposed to be 

conditionally required for the low 

environmental exposure grouping, this 

would expand the number of use 

patterns for which these studies are 

conditionally required. 

2. TEP testing. For the acute estuarine 

and marine studies, TEP testing is 

proposed to be conditionally required 

for the low environmental exposure 

grouping, once-through industrial 

processes and water systems, and 

aquatic areas. This is an existing 

requirement according to the table in 

§ 161.490. 

I. Fish Early Life Stage and Aquatic 

Invertebrate Life-Cycle Study 

The Agency proposes in § 158.2240 to 

require both a fish early life stage and 

an aquatic invertebrate life-cycle study 

for once-through industrial processes 

and water systems, antifoulant paints 

and coatings, and aquatic areas. For 

these use patterns this would codify 

current practices. 

The Agency also proposes to 

conditionally require both studies for 

the low environmental exposure 

grouping. This would expand the 

number of use patterns for which the 

test is conditionally required. 

The Agency proposes to conditionally 

require both studies for wood 

preservatives. The studies would be 

required if pesticide residues from 

treated wood would be likely to enter 

freshwater or estuarine/marine 

environments, as determined by the 

Agency. 

Currently, in part 161 only one of 

these studies is conditionally required. 

Part 161 requires the submission of 

either the fish early life stage or the 

aquatic invertebrate life-cycle study, 

based on the more sensitive of the two 

species, as determined by the acute 

ecotoxicity studies. However, since both 

fish and invertebrates may be exposed 

when an antimicrobial pesticide enters 

natural waters, the Agency now believes 

both studies are needed. Neither study 

would adequately substitute for the 

other. While data from acute 

invertebrate and acute fish studies 

would be available, EPA does not 

believe that these acute studies would 

predict chronic sensitivity. 

For the low environmental exposure 

grouping the requirements are triggered 

if antimicrobial pesticide residues from 

the parent compound and/or 

transformation products are likely to 

enter freshwater or estuarine/marine 

environments, as determined by the 

Agency. For wood preservatives the 

requirements are triggered if 

antimicrobial 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. 

J. Fish Life Cycle 

Currently, this existing data 

requirement is conditionally required 

for all antimicrobials except ‘‘indoor’’ 

uses in part 161. The Agency is now 

proposing to expand this conditional 

requirement to all antimicrobial use 

patterns. 

The fish life cycle study is a two 

generation reproductive study in fish 

that can characterize a number of 

sensitive life stages. Just as with 

conventional pesticide chemicals, it is 

triggered on the results of the fish earlylife stage or invertebrate life cycle test, 

or other information indicating the 

reproductive physiology of fish may be 

affected. For the low environmental 

exposure grouping, the screening-level 

fate assessment would also inform the 

determination to require this study. If 

the antimicrobial is not degraded by the 

processes in the WWTP and is in the 

effluent released to surface water, then 

this study may be required. 

K. Aquatic Organisms, Bioavailability, 

Biomagnification Toxicity Tests 

This data requirement is composed of 

three studies: The oyster 

bioconcentration factor, the fish 

bioconcentration factor, and the aquatic 

food chain transfer. All three studies are 

not needed for every antimicrobial. The 

most commonly submitted study is the 

fish bioconcentration factor. 

Currently, these studies are 

conditionally required for all 

antimicrobials except ‘‘indoor’’ uses in 

part 161. The Agency is now proposing 

to expand this conditional requirement 

to all antimicrobial use patterns. For the 

low environmental exposure grouping, 

the screening-level fate assessment 

would also inform the determination to 

require this study. If the antimicrobial is 

not degraded by the processes in the 

WWTP and is in the effluent released to 

surface water, then this study may be 

required. 

For antimicrobials that have the 

potential to reach freshwater or 

saltwater, these studies are needed to 

identify those antimicrobials that could 

concentrate in various aquatic taxa. EPA 

is proposing to clarify in the test notes 

the three specific circumstances under 

which the study is not required. These 

three circumstances are the same as in 

the final rule for conventional pesticide 

chemicals. 


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L. Simulated or Actual Field Testing for 

Aquatic Organisms 

For all antimicrobial use patterns, the 

Agency is proposing to conditionally 

require simulated or field studies for 

aquatic organisms. These studies would 

be triggered when under actual use 

conditions significant impairment of 

nontarget aquatic organisms is likely to 

occur in the natural environment. This 

proposal would codify current practices. 

The Agency currently determines 

whether simulated or field studies are 

required for antimicrobials on a case-bycase basis, considering information such 

as: 

•The pesticide’s intended use. 

•The pesticide’s use rates. 

•The pesticide’s toxicity. 

•The pesticide’s physical and 

chemical properties. 

•The parent compound’s 

environmental fate characteristics and 

transformation products (such as 

metabolites and degradation products). 

• Nontarget organisms likely to be 

exposed. 

• Likelihood of exposure. 

As with conventional pesticides, the 

Agency is proposing to require 

independent laboratory validation of the 

environmental chemistry methods used 

to generate the data associated with this 

study. 

M. Sediment Testing 

The Agency is proposing to require 

acute invertebrate sediment testing, both 

freshwater and marine, for antifoulant 

paints and coatings and to conditionally 

require these studies for once-through 

industrial processes and water systems, 

wood preservatives, and aquatic areas. 

This would codify current practices. 

Additionally, EPA proposes to expand 

the conditional requirement to all other 

antimicrobial use patterns. This study 

would be triggered based on the 

antimicrobials presence in the water 

column (for example when released 

from a WWTP), the potential to sorb to 

sediment, and the persistence of the 

antimicrobial. 

The Agency is proposing to 

conditionally require chronic 

invertebrate sediment testing, both 

freshwater and marine, for all 

antimicrobial use patterns. This study is 

triggered by the same criteria as the 

acute sediment study, but would be of 

longer duration as determined by the 

persistence of the antimicrobial. This 

conditional requirement would codify 

current practices for the high 

environmental exposure grouping, and 

would then expand the requirement to 

the low environmental exposure 

grouping. 

Testing of aquatic organisms exposed 

to treated sediments allows EPA to 

assess the effects of sediment-bound 

pesticide residues in aquatic 

environments. The effects of sedimentbound pesticides (or their degradates) 

on aquatic environments cannot be 

accurately assessed from bioassays on 

compounds suspended in the water 

column alone. For example, lipophilic 

or hydrophobic chemicals can dissipate 

from the water column, but may remain 

in the aquatic environment adsorbed to 

sediment. As discussed in the proposed 

rule for conventional pesticides (70 FR 

12275) sediment-bound pesticides may 

differ significantly from pesticides in 

solution, showing different physical, 

chemical, and biological properties, 

chemical partitioning, bioavailability, 

concentrations in interstitial or pore 

water, exposure from sediment 

ingestion and possible manifestations of 

food chain effects. By serving as a 

potential pesticide sink, exposure to 

these compounds may lead to 

significant environmental risk to a wide 

variety of fish and aquatic invertebrates 

which live and feed at the bottom of a 

lake or stream. Sediment toxicity testing 

is needed to assess the bioavailability of 

a sediment-bound compound and to 

characterize the possible impact to 

sediment-dwelling benthic organisms. 

Once the Agency determines or 

extrapolates that the use pattern has the 

likelihood for chemical exposure to an 

aquatic system, then the available 

information on the adsorption of the 

chemical is reviewed. If the Agency 

determines that the antimicrobial meets 

one or more of the criteria for 

adsorption, then the available 

information on persistence of the 

chemical is reviewed. If one or more of 

the criteria for persistence are met, then 

a sediment study is required. 

Persistence (half-life of the pesticide in 

sediment) drives the decision regarding 

whether the acute or chronic study is 

conducted. 

Before designing the protocol, 

consultation with the Agency is needed 

if the applicant is uncertain as to which 

length of study is appropriate. For 

certain antimicrobials that are highly 

persistent, only the chronic study may 

be required. Protocols must be approved 

by the Agency prior to the initiation of 

the study. Details for developing 

protocols are available from the Agency. 

N. Honeybee Protection 

The current data requirements for 

testing pesticide toxicity to honeybees at 

§ 161.590 require the honeybee acute 

contact LD50 study when honeybees are 

likely to be exposed. The Agency 

proposes to conditionally require the 

acute study for wood preservatives and 

the low environmental exposure 

grouping. Since the study would be 

required only for uses involving 

treatment of beehives, empty or 

occupied, and since there are few such 

uses for antimicrobials, this study 

would be infrequently required. This 

study may not be required if the use 

pattern (as described on the label) 

prohibits fumigating or spraying 

beehives. 

Since beehives can be constructed of 

materials that have been treated with 

antimicrobials, the Agency proposes to 

conditionally require a study to 

determine the toxicity of treated wood 

and other materials to bees. This study 

must be conducted in a manner similar 

to that of the Honey Bee Toxicity of 

Residues on Foliage. This would codify 

current practices. Protocols must be 

approved by the Agency prior to the 

initiation of the study. Details for 

developing protocols are available from 

the Agency. 

XIV. Plant Protection Data 

Requirements 

A. Plant Protection Data Requirements 

EPA proposes to adapt the basic 

nontarget plant protection data types as 

listed in 40 CFR part 158, subpart G to 

support applications for antimicrobial 

products. EPA proposes to modify the 

applicability of those requirements to 

antimicrobials to reflect differing risks 

and levels of exposure. Part 161 is not 

explicit in the data that are currently 

required because those use patterns are 

not delineated for antimicrobial 

pesticide chemicals. The proposed table 

in § 158.2250 will provide greater 

transparency and clarity. 

Plants represent the most basic 

component of any functioning 

ecosystem by providing oxygen and a 

food source for aquatic and terrestrial 

animals. Therefore, it is important to 

determine the toxicity of the 

antimicrobial to plants. The data 

obtained from these studies will be used 

to conduct nontarget plant risk 

assessments. For aquatic environments 

such an assessment could include an 

effluent from a wastewater treatment 

plant being released into the 

environment. For terrestrial 

environments such an assessment could 

include wood preservatives in contact 

with soil, land-application of biosolids, 

or antimicrobials that partition to soil 

and sediment. 

B. Requirement for Tier II Testing for 

Antimicrobials 

The Agency’s guidelines for 

conducting nontarget plant protection 


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studies specify two types of tests: 

Single-dose studies (referred to in the 

guidelines as Tier I tests) and multipledose studies (Tier II). Usually, the 

applicant would conduct the singledose studies first, and then, based on 

the results of the single-dose studies, 

proceed to the multiple-dose studies, 

which evaluate the effects of multiple 

dosage levels on plant growth and are 

used to determine acute toxicity levels 

in comparison with environmental 

concentrations. Such studies are used to 

estimate the risk to nontarget plants and 

endangered plant species. 

Many antimicrobial pesticides are 

used to control plant pests such as algae 

in industrial processes (paper making, 

cooling towers, wastewater, sewage 

water treatment), and residential uses 

(swimming pools, ornamental ponds, 

moss growing on roofs). Some 

antifoulants, ballast water treatments, 

and wood preservatives are also 

intended to control plant pests. 

Therefore, antimicrobial pesticides used 

for plant pest control are expected to be 

phytotoxic to nontarget plants once 

released into terrestrial or aquatic 

environments. 

Accordingly, for all antimicrobial use 

patterns, the Agency is proposing only 

to require multiple-dose studies, which 

is consistent with the testing of certain 

phytotoxic conventional chemicals such 

as herbicides which also start at Tier II. 

In part 161, for most plant studies, the 

Tier II study is conditionally required 

and the Tier I study is required. For 

antimicrobials, EPA believes that the 

nontarget plant studies have been 

interpreted in the context of, and 

consistent with other phytotoxic 

chemicals, and this proposal would 

codify the shift from the use of the Tier 

I study to a Tier II study. 

If the applicant is in possession of 

single-dose studies that the applicant 

believes provide sufficient information, 

then the applicant is encouraged to 

consult early in the application process 

with EPA. The Agency can evaluate the 

information and inform the applicant as 

to the sufficiency, or the need for 

multiple-dose studies. If the applicant 

does not have any studies, then 

multiple-dose studies must be 

conducted. 

C. The Low Environmental Exposure 

Grouping 

The use patterns within this grouping 

are the same as those described in the 

Unit XI.B. of this preamble for 

environmental fate data requirements. 

D. The High Environmental Exposure 

Grouping 

The use patterns within this grouping 

are the same as those described in the 

Unit XI.B. of this preamble for 

environmental fate data requirements. 

E. Seedling Emergence (Tier II – DoseResponse) 

This terrestrial plant toxicity test is 

designed to evaluate toxicity to 

germinating seedlings and their ability 

to survive after chemical uptake from 

the surrounding soil. The Agency is 

proposing to require this study for the 

high environmental exposure grouping. 

This proposal would codify the shift 

from the use of the Tier I study to a Tier 

II study and thereby would codify 

current practices. 

The Agency is also proposing to 

conditionally require the Tier II study 

for low environmental exposure 

grouping based on the results of the 

algal study. This would expand the 

number of use patterns for which this 

study is conditionally required. 

F. Vegetative Vigor (Tier II – DoseResponse) 

This terrestrial plant toxicity test is 

designed to evaluate toxicity to young 

plants. The antimicrobial is applied to 

the foliage to evaluate uptake of the 

antimicrobial from the exposed green 

tissue. The Agency is proposing to 

require this study for wood 

preservatives and aquatic areas. For 

wood preservatives, this would codify 

current practices. For aquatic areas, this 

would codify the shift from the use of 

the Tier I study to a Tier II study and 

thereby would codify current practices. 

The Agency is also proposing to 

conditionally require this study for the 

low environmental exposure grouping, 

and industrial processes and water 

systems (once-through). This would 

expand the number of use patterns for 

which this study is conditionally 

required. 

G. Aquatic Plant Growth (Lemna gibba) 

(Tier II – Dose-Response) 

The Agency is proposing to require 

the Aquatic Plant Growth (Lemna gibba) 

(Tier II – Dose-Response) study for the 

high environmental exposure grouping. 

This would codify the shift from the use 

of the Tier I study to a Tier II study and 

thereby would codify current practices. 

The Agency is also proposing to 

conditionally require the Tier II study 

for low environmental exposures based 

on the results of the algal study. This 

would expand the number of use 

patterns for which this study is 

conditionally required. 

Lemna gibba or duckweed is an 

important wildfowl food source and is 

used in wastewater reclamation. 

Therefore, it is important to understand 

the impact of an antimicrobial on this 

food source. 

H. Aquatic Plant Growth (Tier II – DoseResponse) 

The Agency is proposing to require 

one or more of the Aquatic Plant Growth 

(Tier II – Dose-Response) studies for all 

antimicrobial use patterns. As with the 

aquatic plant study discussed in the 

previous section, part 161 requires the 

Tier I study and conditionally requires 

the Tier II study. For the high 

environmental exposure grouping, this 

would codify the shift from the use of 

the Tier I study to a Tier II study and 

thereby would codify current practices. 

Testing is required for four species 

representing green algae, freshwater 

cyanobacteria, a freshwater diatom and 

a marine diatom. These four species are 

used to represent hundreds of different 

species. 

Testing is required in only one 

species (green algae) for the low 

environmental exposure grouping. This 

would expand the number of use 

patterns for which this study is 

required. 

Green algae produce oxygen, serve as 

a food source for aquatic animals, and 

provide the basic energy needs of any 

aquatic ecosystem. The results of the 

green algae study will allow the Agency 

to determine if the other three aquatic 

plant growth studies are required for the 

low environmental exposure grouping. 

I. Terrestrial and Aquatic Field Studies 

The Agency is proposing to 

conditionally require Terrestrial and 

Aquatic Field Studies for all 

antimicrobial use patterns. Field studies 

provide more realistic information on a 

pesticide’s impacts than laboratory 

studies which focus only on one 

parameter, because field studies 

consider all potential impacts on plant 

growth. The need for these higher tier 

studies would be based on the results of 

the lower tier plant protection studies, 

adverse incident reports, intended use 

pattern, and environmental fate 

characteristics that indicate potential 

exposure. 

These two studies are conditionally 

required in part 161 for three use 

patterns. Due to the use patterns 

currently used in part 161, there is not 

sufficient delineation for comparison to 

the antimicrobial use patterns proposed 

today. While EPA routinely considers 

the need for these studies in 

determining the data needed for its risk 

assessments, it has required these 


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studies based on case-by-case 

circumstances on a very infrequent basis 

for antimicrobials. 

Since the testing is proposed to be 

conditionally required for all 

antimicrobial pesticide use patterns, 

this would expand the number of use 

patterns for which these studies are 

conditionally required. Additionally, 

this would harmonize the requirements 

for antimicrobials with those of 

conventional pesticides. 

XV. Peer Review 

A. National Research Council 

Recommendations 

The National Academy of Sciences 

issued a report in 1993 entitled, 

‘‘Pesticides in the Diets of Infants and 

Children’’ (Ref. 19). The study, 

conducted by the National Research 

Council (NRC), was initiated to address 

the question of whether the current 

regulatory system adequately protected 

infants and children from pesticide 

residues in food. The Council reviewed 

EPA’s then-current practices and data 

requirements related to dietary risk 

assessment as well as testing 

modifications planned by the Agency. 

The panel of experts concluded that, at 

that time, EPA approaches to data 

requirements and risk assessments 

emphasized the evaluation of the effects 

of pesticides in mature animals and, in 

general, there was a lack of data on 

pesticide toxicity in developing 

organisms. 

The Council’s recommendations with 

respect to regulatory needs for data 

development included the following: 

• Discussed the need to investigate the 

effects of pesticide exposure on 

immunotoxic responses in infants and 

children. 

• Supported the need for acute and 

subchronic neurotoxicity testing and 

encouraged the Agency to have these 

studies as part of the required data for 

all food-use pesticides. 

• Encouraged further work in the area 

of developmental neurotoxicity. 

Many of the NRC recommendations 

were incorporated into the data 

requirements that were promulgated for 

conventional pesticides (72 FR 60933), 

and for biochemical and microbial 

pesticides (72 FR 60988). By 

deliberately building on the foundation 

of these promulgated rules, and 

harmonizing to the extent practicable 

considering the differences in use 

patterns, many of the NRC 

recommendations, such as 

immunotoxicity testing, are 

incorporated into this proposed rule for 

antimicrobial pesticides. 

B. FIFRA Scientific Advisory Panel 

(SAP) 

1. 1994 meeting. In 1994, EPA held a 

2–day meeting of the SAP to review the 

Agency’s proposed amendments to the 

data requirements for pesticide 

registrations contained in 40 CFR part 

158, which covered antimicrobials. The 

SAP was asked to comment on each 

data requirement and identify, in their 

scientific opinion, which requirements 

were necessary to fully and thoroughly 

evaluate the potential hazard of a 

chemical compound and which were 

not intrinsically useful in providing 

practical scientific information. The 

revisions presented to the Panel, i.e., the 

changes to the data requirements 

presented in this document, were 

generally endorsed. A very complete 

discussion of the 1994 SAP meeting was 

presented in the proposed rule for 

conventional pesticides (70 FR 12276). 

2. June 1997 meeting: A set of 

scientific issues being considered by the 

Agency to determine antimicrobial 

issues. On June 3, 1997, the Agency 

presented an early version of the part 

158, subpart W proposal in an open 

meeting to the SAP. The Agency asked 

for specific comments in five areas 

covered by proposed 158W data 

requirements: Toxicology; residue 

chemistry, ecological effects and 

environmental fate, human exposure, 

and efficacy. The SAP’s full comments 

are found in the docket for this action 

(Ref. 29) and are summarized here. 

i. Toxicology. The Agency asked if its 

division of antimicrobial pesticide uses 

into high human exposure and low 

human exposure groups, with extensive 

data requirements for high exposure 

uses and tiered data requirements for 

low exposure uses, was an acceptable 

approach. The SAP agreed that the 

Agency’s tiered approach was 

reasonable, and made several 

suggestions to improve the proposal. 

Two of these suggestions were 

‘‘unambiguous trigger points indicating 

next Tier level of toxicity testing,’’ and 

‘‘to continue dialogue with Canadian 

counterparts to harmonize, clearly 

define trigger points, and improve the 

guidelines.’’ 

The Agency has worked to provide 

clear, unambiguous triggers in the test 

notes to the toxicology data 

requirements tables. EPA is also 

committed to dialogue with its 

Canadian counterpart. PMRA has 

routinely received updates on the status 

of the draft antimicrobial data 

requirements, and has been actively 

engaged throughout the development of 

this proposal. 

ii. Residue chemistry. The Agency 

asked the SAP if the scientific approach 

to obtaining dietary residue information 

in general, but specifically for indirect 

food contact sanitizers, was reasonable. 

The SAP agreed that the scientific 

approach was reasonable, and remarked 

extensively on the residue chemistry 

data requirements for indirect food uses 

such as sanitizers. They noted that such 

products had generally been of low 

toxicity or low persistence, and their 

belief that a tolerance or tolerance 

exemption for such uses was 

unnecessary, based on FDA’s practice 

with such products. The SAP also 

suggested the use of default surface 

residue values for estimating sanitizer 

residues to obviate the need for 

measured data. 

Although the SAP believes that a 

tolerance or tolerance exemption is 

unnecessary, under FFDCA, EPA is 

required to establish either a numerical 

tolerance, or an exemption from the 

requirement of a tolerance for indirect 

food uses. To obviate the need for 

measured data, EPA uses modeling and 

‘‘worst-case’’ estimates, as appropriate. 

As discussed in Unit X. of this 

preamble, if such estimates when paired 

with the toxicity data do not indicate a 

concern, then it is unlikely that 

measured surface residue data would be 

required. 

iii. Human exposure. The Agency 

asked the SAP if the approaches 

presented were reasonable and if the 

Agency had adequately accounted for 

all antimicrobial use and exposure 

scenarios. Additionally, the Agency 

asked if multiple exposure scenarios for 

one pesticide product would be better 

accounted for by data for all applicable 

exposure scenarios or a subset of 

applicable scenarios. 

•The SAP agreed that the Agency’s 12 

use categories for antimicrobials were a 

reasonable approach to organizing 

exposure data requirements, and were, 

in fact, similar to the approaches used 

by PMRA and the California EPA. EPA 

is proposing that these use categories be 

codified in § 158.2201 as the 

antimicrobial use patterns. 

•The SAP also advised that initially, 

all applicable exposure scenarios should 

be considered for a single antimicrobial 

product. The Agency accepted this 

recommendation which is now part of 

its standard exposure assessment 

practices. 

•The SAP expressed concern that 

post-application exposure might be too 

narrowly defined, and noted some 

possible exposure scenarios involving 

persons not in the 1997 presentation. In 

response, the Agency has broadened the 

scope of post-application exposure to 


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include persons who may come in 

contact with materials after treatment. 

This includes contact with impregnated 

materials and children’s exposure to 

treated wood. In response, the Agency is 

proposing to require the indoor surface 

residue dissipation study and the nondietary ingestion exposure study for 

residential uses to address this concern. 

iv. Ecological effects and 

environmental fate. For the 1997 

presentation to the SAP, EPA divided 

the antimicrobial use sites into two 

groupings: high expected environmental 

exposure and low expected 

environmental exposure. The Agency 

asked if a tiered data set to support an 

ecological risk assessment for uses with 

high expected environmental exposure 

was appropriate. The SAP agreed that a 

tiered data set to support an ecological 

risk assessment would be appropriate. 

EPA also asked if ecological risk 

assessments were necessary for the low 

expected environmental exposure 

grouping. In its presentation EPA stated 

its intention to require a very reduced 

data set suitable for developing 

precautionary labeling for 

manufacturing and certain end-use 

products. At that time EPA considered 

that ‘‘indoor’’ uses had minimal 

environmental exposures or releases of 

pesticide residues to the environment. 

The SAP commented that the reduced 

data set could be justified only if data 

available from other programs within 

EPA and elsewhere were adequate to 

assess ecological risk. As a result of the 

SAP’s concerns, the Pesticide Program 

discussed these issues with EPA’s Office 

of Solid Waste and Office of Water. 

As a result of these discussions in the 

late 1990s, the Pesticide Program 

continued to believe that 

• ‘‘Indoor’’ residential uses of 

antimicrobials with the rinses going 

down-the-drain had minimal 

environmental exposures or releases of 

pesticide residues to the environment, 

• Industrial effluents that could 

possibly contain antimicrobials would 

be adequately regulated via the 

permitting process under the National 

Pollutant Discharge Elimination System 

Program of the Clean Water Act and 

wastes possibly containing 

antimicrobials would be adequately 

regulated under the Resource 

Conservation and Recovery Act. 

Therefore, in 1997, the Agency 

determined not to require 

biodegradation or microbial data. 

More recently, as part of its 

development of this proposed rule, EPA 

re-evaluated its belief that ‘‘indoor’’ 

residential uses had minimal 

environmental exposures. EPA is now 

proposing to require the environmental 

fate and ecological effects data for 

conducting an ecological risk 

assessment for down-the-drain 

antimicrobials. The rationale for this 

decision is discussed in Unit XII.B. of 

this preamble. 

The SAP expressed its concerns about 

‘‘the lack of chemical fate data,’’ and 

also stated that biodegradation data 

(both aerobic and anaerobic) should be 

required. 

• In response to the SAP, EPA 

reexamined the need for environmental 

fate data other than hydrolysis, and as 

a result of this 1997 reexamination, the 

Agency determined to conditionally 

require data on photodegradation in 

water for these low expected 

environmental exposures. EPA is now 

proposing to require the 

photodegradation in water study for all 

antimicrobial chemicals, including the 

low environmental exposure grouping. 

• Initially, in 1997, the Agency 

determined to not require 

biodegradation data. EPA has 

reconsidered this 1997 decision and 

today is proposing to require an 

activated sludge sorption isotherm, a 

ready biodegradability test, and a 

modified activated sludge, respiration 

inhibition study for the low 

environmental exposure grouping. 

The SAP also questioned why 

microbial data to protect publicly 

owned treatment works (POTWs) and 

other treatment systems which often 

rely on microbial treatment processes 

were not required. The Agency 

investigated this possibility, but could 

not in the early 1990s determine a 

satisfactory set of data that would then 

be useful in protecting the highly 

variable conditions of specific POTWs. 

EPA is proposing as part of its 

environmental fate data requirements, to 

require the data that would allow EPA 

to assess the impacts of antimicrobials 

on wastewater treatment plants. 

The SAP questioned the use of 

precautionary labeling to protect fish 

and wildlife from improper use of 

antimicrobials, especially considering 

that some use categories would pose 

exposure via sewage systems. As a 

result, EPA prepared sample labeling to 

reduce this source of exposure: ‘‘This 

product is toxic to fish and aquatic 

invertebrates. Do not discharge effluent 

containing this product into lakes, 

streams, ponds, estuaries, oceans, or 

public water unless this product is 

specifically identified and addressed in 

a NPDES permit. Do not discharge 

effluent containing this product to 

sewer systems without previously 

notifying the sewage treatment plant 

authority.’’ This type of labeling is still 

in use today. 

The SAP cautioned that although 

wildlife exposure to antimicrobials via 

water was the most likely source of 

exposure, terrestrial exposure is also 

possible. The Agency concurred, and is 

proposing to require for the aquatic 

areas use pattern and to conditionally 

require for all other use patterns, the 

avian dietary and avian reproductive 

studies for performing such an 

assessment. 

Finally, the SAP expressed concern 

that antimicrobial metabolites may be 

more toxic than their parent 

compounds, and therefore may also 

need to be tested. The Agency agrees, 

and has revised many of the test notes 

in this proposal to clarify the need for 

data on metabolites when the available 

information demonstrate that the 

metabolites are more toxic or otherwise 

pose environmental risks. 

3. 1998 and 1999 meetings. Data 

requirements, as related to the 

application of the newly mandated 

FFDCA safety factor (required under the 

FQPA amendments) were presented to 

the SAP in 1998 and 1999. Copies of 

documents prepared for the 1998 and 

1999 SAP meetings and the final reports 

from each of the meetings are in the 

docket for this action (Refs. 30, 31, 32, 

and 33) and can be found on EPA’s web 

site at http://www.epa.gov/scipoly/sap. 

A summary of the issues specific to the 

proposed antimicrobial data 

requirements follows: 

i. Toxicology. In December 1998, EPA 

presented the SAP an issues paper on 

the use of the FQPA safety factor to 

address the special sensitivity of infants 

and children to pesticides. The 

discussion on the developmental 

neurotoxicity study was specifically 

discussed in the context of the 

appropriateness of using an additional 

safety factor. At that time, the SAP did 

not reach a consensus recommendation 

on whether this study should be 

routinely or conditionally required. The 

issue of what is a complete and reliable 

data set was brought before the SAP 

again in May 1999. The majority of the 

Panel supported the Agency’s approach 

to applying data requirements but 

advised the Agency to revisit the first 

tier of required toxicity studies every 

few years to update data requirements 

as needed. The Panel also agreed with 

the Agency on the need to require the 

neurotoxicity battery of studies, 

including developmental neurotoxicity 

testing, for high exposure pesticides 

such as food-use pesticides. The SAP’s 

recommendations are reflected in 

today’s proposed antimicrobial data 

requirements for developmental 

neurotoxicity and immunotoxicity. This 

also harmonizes the data requirements 


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for conventional pesticides and for 

antimicrobials. 

ii. Post-application exposure. 

Working in collaboration with Health 

Canada and the Organization for 

Economic Cooperation and 

Development (OECD), EPA drafted 

guidelines for post-application 

exposures studies. They were internally 

peer-reviewed and shared with the 

California Department of Pesticide 

Regulation, representatives from 

academia, and the American Crop 

Protection Association. The Agency 

presented its post-application exposure 

guidelines and standard operating 

procedures to the SAP in 1998 and 

again in 1999. In 1999, the SAP 

commended the Agency for making 

significant strides toward developing 

scenario-based residential and nonoccupational exposure assessments that 

are sufficiently conservative as to not 

underestimate exposures. The data 

requirements proposed for postapplication exposure to antimicrobials 

are drawn from this body of work. 

4. 2000 meeting. In its response to an 

April 2000 presentation on certain 

scientific issues concerning 

probabilistic ecological risk assessment, 

the SAP was asked for 

recommendations on sediment toxicity 

testing. The SAP stated that the extent 

to which a compound partitions from 

the aqueous phase to the sediment is a 

key consideration in determining the 

need for testing benthic organisms. 

There was a consensus among SAP 

members that compounds with high 

Kocs (organic carbon-water partition 

coefficient) or Kows (octanol-water 

partition coefficient) required sediment 

testing for benthic fish or invertebrates. 

A copy of the final report is in the 

docket for this action (Ref. 34) and can 

be found on EPA’s web site at http:// 

www.epa.gov/scipoly/sap. Based on this 

meeting, the guidelines for sediment 

testing were developed. For 

antimicrobials, acute and chronic 

sediment testing are proposed to be 

required or conditionally required. 

XVI. International Activities 

EPA actively works through 

international and regional organizations 

and directly with other countries to 

develop common or compatible 

international approaches to pesticide 

registration, including data 

requirements. Joint reviews and work 

sharing are two of the approaches used 

by EPA to increase the harmonization of 

pesticide regulatory programs. EPA 

believes that making pesticide 

regulatory programs more consistent 

internationally will: 

• Maintain high standards for the 

protection of human health and the 

environment. 

• Increase the efficiency of the 

registration process by lessening the 

resource burden on governments and 

the regulatory community. 

• Provide more equal access to pest 

management tools. 

• Strengthen the regulatory process. 

• Facilitate the registration of 

alternative pest control tools. 

• Minimize trade problems. 

Harmonization activities are 

increasing and evolving as agencies and 

applicants build upon their experiences. 

A. Joint Data Reviews and Evaluations 

EPA is working closely with other 

countries toward greater uniformity in 

testing, reviewing and evaluating all 

pesticides. The benefits of international 

regulatory cooperation on 

antimicrobials are potentially great: 

Improved science through greater 

information exchange, and reduced 

regulatory and resource burdens on 

national governments and regulated 

parties through harmonized pesticide 

regulatory review. Over the last several 

years, substantial progress has been 

made toward international cooperation 

on pesticide regulatory review. Member 

countries of the Organization for 

Economic Cooperation and 

Development (OECD), including the 

United States, have agreed upon 

harmonized guidance for the formats of 

industry data submissions (dossiers) 

and country data review reports 

(monographs). Countries now frequently 

exchange pesticide reviews or consult 

with one another on key technical 

aspects of a review. 

Under the North American Free Trade 

Act (NAFTA), EPA has worked 

cooperatively with Canada and/or 

Mexico, dividing up detailed evaluation 

work on a number of pesticides. The 

Agency has also entered into similar 

information exchange and comparative 

review arrangements with other 

countries. There have been multiple 

bilateral joint reviews and/or work 

sharing with member countries of the 

European Union. Trilateral joint reviews 

and workshares have been performed 

with Canada and Australia. A global 

joint review is being conducted among 

six countries (the United States, 

Australia, New Zealand, Canada, 

Ireland, and the United Kingdom.) The 

peer reviewers will be four other EU 

countries. The primary objective of all 

of these arrangements has been to use 

resources in the most efficient way 

possible. 

Concerning antimicrobials, since 

2000, Health Canada’s Pest Management 

Regulatory Agency (PMRA), the USEPA 

and California’s EPA have been 

cooperating on a joint review for the reevaluation/reregistration of the 

following three heavy-duty wood 

preservatives: Pentachlorophenol, 

creosote, and chromated copper 

arsenate. The review of submitted data, 

writing of the risk assessments, and peer 

review activities are being shared. 

Exposure data used in the preliminary 

risk assessment were collected from 

both U.S. and Canadian wood-treatment 

facilities. Both PMRA and EPA are 

contributing to the public comment 

process. The cooperative activities 

continue as both EPA and PMRA work 

toward issuance of their decision 

documents in September 2008. 

B. Harmonization of Data Requirements 

As the international regulatory 

community works toward greater 

harmonization on pesticide review, 

attention has also focused on the data 

requirements, how the requirements 

compare from one country to another, 

and what can or should be done to 

establish common requirements. To the 

extent that data requirements for 

pesticide registration are similar, 

sharing reviews and comparing 

evaluations is easier and more 

meaningful. Requirements that differ 

considerably from one country to 

another can mean that applicants who 

are looking to register a pesticide in 

more than one country may have to 

conduct many different studies to 

satisfy all the various national 

requirements. Therefore, from the 

perspective of the applicant, 

establishing similar requirements also 

can reduce the resources that must be 

spent to conduct testing. 

OECD Member countries have had 

discussions about harmonizing 

pesticide data requirements within the 

OECD community. The pesticide 

industry took on the complex task of 

looking at data requirement differences 

among Member countries to identify 

areas that might benefit from 

harmonization. Preliminary findings 

presented to the OECD Working Group 

on Pesticides Meeting in June 2001, 

reported, consistent with the positions 

of scientific reviewers in OECD Member 

countries, that toxicology data 

requirements are quite similar across 

countries. This does not mean that there 

is no room for additional harmonization 

work on toxicology data requirements, 

but rather that there are other testing 

areas where there is much less 

consistency on data requirements across 

countries. 

Ecotoxicological and environmental 

fate studies present a particular 


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challenge for harmonization. Data 

requirements in these areas can differ 

considerably from one country to 

another depending upon how countries’ 

tiered approaches to data requirements 

are applied. National data requirements 

must be tied to national use patterns 

and environmental and ecological 

conditions. A reliable environmental 

hazard assessment, for example, must be 

based on studies that accurately reflect 

the climate, soil types and agricultural 

practices of the country doing the 

assessment. Because ecological and 

environmental studies must be 

representative of national conditions to 

adequately support national risk 

assessments, harmonization of data 

requirements for these types of studies 

can be difficult. Harmonization can 

require extensive dialogue between 

scientists to determine which data 

requirements can act as common 

requirements. Such dialogue can also 

include discussions of test 

‘‘conditionalities,’’ that are reflected in 

the test notes to the tables for the 

proposed data requirements. 

Since 1995, the United States and 

Canada under the NAFTA Technical 

Working Group on Pesticides, 

Harmonization of the Evaluation of 

Antimicrobial Pesticides Project have 

worked together to harmonize data 

requirements for antimicrobials. These 

harmonization activities represent two 

efforts. EPA coordinates with Canada’s 

PMRA on harmonization activities for 

all disciplines except efficacy. For 

harmonization activities for efficacy 

requirements EPA coordinates with 

Health Canada’s Therapeutic Product 

Directorate (TPD). 

EPA and PMRA approach 

antimicrobial data requirements 

differently. EPA uses a tiered testing 

strategy, while PMRA bases its data 

requirements on a defined use pattern 

approach. EPA and PMRA’s data 

requirements have been carefully 

compared. TPD and EPA recently 

completed a crosswalk of EPA and TPD 

efficacy data requirements, which is 

being used for planning purposes to 

explore future harmonization activities. 

The data requirements proposed in this 

document for antimicrobials represent 

U.S. national requirements but they 

reflect extensive consultation with 

Canada. The data requirements are 

harmonized to a high degree. The two 

countries plan to continue to work 

together to keep data requirements for 

all disciplines as similar as possible. 

OECD has not conducted any activity 

specifically aimed at harmonizing data 

requirements for biocides. In 1997– 

1998, the OECD Pesticide Program 

conducted a survey to collect 

information on the existing 

requirements across countries. The 

survey served two purposes: (1) To 

improve OECD’s understanding of how 

Member countries regulate biocides, and 

(2) to provide information that could be 

used to prepare the way for future 

efforts to increase international cooperation in biocide regulation. The 

survey shows great variability. At this 

time OECD has no plans to work toward 

harmonizing these data requirements, 

but instead has worked at harmonizing 

tools and methodologies in order to 

reduce duplication and harmonize 

review procedures for possible work 

sharing. 

C. Protocol/Guideline Harmonization 

Harmonization can also involve 

protocol/guideline development or 

revisions so that the studies produced 

can meet common data requirements. 

Issues can arise because the study 

protocols or guidelines used to generate 

the studies to meet the requirements can 

be different. In other words, a particular 

data requirement might be the same 

from one country to the next, but the 

study submitted to meet the 

requirement can run into acceptance 

problems if done according to a protocol 

that is acceptable in one country, but 

not in another. There is significant 

commonality in protocol design for 

toxicology studies among various 

countries, but less for ecotoxicology and 

environmental fate studies. Information 

on how to satisfy data requirements is 

specified in § 158.70. This section 

provides for both the recommended use 

of EPA Guidelines and for the 

acceptability of OECD protocols with 

certain caveats. Section 158.80 allows 

for the use of data developed in foreign 

countries, again with certain caveats to 

ensure that the data will meet EPA’s 

needs under FIFRA and FFDCA. 

D. Ballast Water Treaty 

Both domestically and 

internationally, an emerging significant 

use of antimicrobials is the treatment of 

ballast water. Ballast water provides 

needed stability for safe operation of 

marine vessels. It is the water that is 

pumped in and out of the ship’s ballast 

tanks to ensure safe operation, such as 

compensating for the ship’s weight 

changes due to loading and unloading of 

cargo. In recent years there have been 

significant concerns about transport of 

marine species from one marine 

environment to another, via ballast 

water. Ballast water treatments are 

intended to kill the marine species prior 

to discharge. When discharged into a 

new environment, a new species may 

become invasive and disrupt the native 

ecology. 

The International Convention for The 

Control and Management of Ships’ 

Ballast Water and Sediments, 2004 (also 

referred to as the Ballast Water 

Convention) was adopted by consensus 

at a diplomatic conference in London on 

February 13, 2004. The U. S. delegation 

was led by the Coast Guard with 

participation by EPA and other Federal 

agencies. The treaty opened for 

signature on June 1, 2004, and will enter 

into force 12 months after ratification by 

30 countries representing 35% of the 

world’s merchant shipping tonnage. 

Once in force, the treaty will require 

that ships manage their ballast water to 

meet discharge standards according to a 

schedule in the treaty. In order to meet 

those discharge standards, ships will 

need to install equipment to treat their 

ballast water, including disinfection. To 

date, ten countries representing 3.42% 

of the world shipping tonnage have 

become Parties to the treaty. 

Although the United States has not 

signed the treaty, ballast water 

discharges in U.S. waters are already 

regulated by the Coast Guard under the 

Nonindigenous Aquatic Nuisance 

Prevention and Control Act, as amended 

(16 U.S.C. 4701 et seq.) The existing 

Coast Guard ballast water management 

regulations can be found at 33 CFR part 

151, subparts C and D. At present, the 

Coast Guard is engaged in further 

rulemaking that would set a 

performance standard for the quality of 

ballast water discharged in U.S. waters 

and which will further foster 

development of ballast water treatment 

technologies. 

The Agency has reviewed few 

applications for ballast water 

treatments, presumably because such 

treatments and technologies are 

relatively new. Therefore, for the 

purpose of determining data 

requirements EPA determined to group 

ballast water treatments with antifoulant 

paints and coatings since both have the 

potential for exposure to marine 

organisms. OECD has not developed 

data requirements for ballast water. 

XVII. Research Involving Human 

Subjects 

Research with human subjects which 

is conducted or supported by the U. S. 

government is subject to regulations for 

the protection of human subjects 

referred to as the Common Rule. EPA 

was one of many federal departments 

and agencies who jointly promulgated 

the Common Rule in 1991. EPA’s 

codification of the Common Rule 

appears at 40 CFR part 26, subpart A. 


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On February 6, 2006, EPA published 

in the Federal Register (71 FR 6138) a 

final rule amending 40 CFR part 26 by 

adding nine new subparts. These 

amendments extend regulatory 

protection to human subjects of research 

involving intentional exposure and 

intended for submission to EPA under 

the pesticide laws, when the research is 

conducted not by the Federal 

government but by private parties with 

no support from Federal Common Rule 

departments or agencies. As 

subsequently amended effective August 

22, 2006 (71 FR 36171), this rule (1) 

forbids both EPA and third parties who 

intend to submit the research to EPA to 

conduct new research involving 

intentional exposure of pregnant or 

nursing women or of children; (2) 

extends the substantive provisions of 

the Common Rule to third-party human 

research involving intentional exposure 

of non-pregnant adults that is intended 

for submission to EPA under the 

pesticide laws; (3) requires submission 

to EPA of protocols and related 

information about covered human 

research before it is initiated; (4) 

establishes an independent Human 

Studies Review Board to review both 

proposals for new research and reports 

of covered human research on which 

EPA proposes to rely under the 

pesticide laws; and (5) forbids EPA to 

rely, in its actions under the pesticide 

laws, on research involving intentional 

exposure of pregnant or nursing women 

or of children, or which otherwise fails 

to meet criteria for acceptance, except in 

narrowly defined circumstances. 

The provisions of this amended rule 

directly affecting third-party research 

intended for submission to EPA are 40 

CFR part 26, subparts K, L, and M. 

Subpart K extends the substantive 

provisions of the Common Rule to thirdparty research involving intentional 

exposure of non-pregnant adult subjects 

that is intended for submission to EPA 

under the pesticide laws. Subpart K also 

requires submission to EPA of proposals 

for any covered research for review by 

EPA staff and the Human Studies 

Review Board before it is initiated, and 

specifies the range of information 

required to support any such proposal. 

Subpart L prohibits conduct of any new 

third-party research intended for 

submission to EPA involving intentional 

exposure of pregnant or nursing women 

or of children. Subpart M specifies the 

range of information required to be 

submitted with every report of 

completed research with human 

subjects to document its ethical 

conduct. 

Studies required under proposed 40 

CFR part 158, subpart W which involve 

intentional exposure of human subjects 

are also subject to subparts K, L, and M 

of 40 CFR part 26. The following data 

requirements in proposed § 158.2260 

and § 158.2270 call for studies likely to 

involve intentional exposure of human 

subjects: 

•Biological monitoring studies. 

• Mixer/loader or applicator exposure 

studies. 

• Post-application exposure studies. 

If any studies undertaken to address 

these requirements involve intentional 

exposure of a human subject (as defined 

at 40 CFR §26.1102(i)), then the study 

must not be initiated before submission 

of protocols and supporting 

documentation for review by EPA and 

the Human Studies Review Board. The 

requirements for protocol submissions 

are specified at 40 CFR 26.1125. It may 

be possible to design some studies 

responsive to the proposed data 

requirements for antimicrobials so that 

they do not meet the regulatory 

definition of research involving 

intentional exposure of a human 

subject. 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. 

XVIII. Alternative Testing Paradigms 

As with conventional pesticide 

chemicals, the Agency is committed to 

moving towards a more efficient and 

refined testing/risk assessment 

paradigm for antimicrobial pesticide 

chemicals. 

A. Structure Activity Relationship (SAR) 

EPA must rely upon information of 

appropriate quality and reliability for 

each decision made by the Agency. In 

the Office of Pesticide Programs (OPP), 

the evaluation process for a pesticide 

chemical traditionally begins with the 

applicant’s submission of a set of 

studies conducted with the specific 

pesticide chemical of interest. 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, as well as 

the dose and endpoints at which an 

adverse effect can occur in various 

animal species. 

Today, there is significant interest in 

determining alternative testing 

paradigms that could offer more 

flexibility in the design of an integrated 

approach in which the selection of the 

required studies as well as the design of 

the study protocols is influenced by the 

existing, reliable information about the 

chemical. 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. 

EPA is charged with developing a 

pesticide regulatory program that is 

protective of human health and the 

environment. Other factors that also 

deserve consideration in the 

implementation of such a program are 

efficiency and effectiveness. 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 alternative 

methods of determining which 

chemicals could be evaluated in a 

scientifically rigorous manner using 

means other than measured data. From 

the Agency’s perspective an alternative 

testing paradigm may also allow for a 

stream-lined review process for 

chemicals of potential lower toxicity, 

thus freeing resources for more indepth, complex reviews of higher 

toxicity chemicals. 

An integrated approach would focus 

on using all relevant, credible 

information on the chemical of interest. 

Applicants are cautioned that such an 

approach will require a different type of 

thought process which will incorporate 

significantly more planning and ‘‘data 

mining’’ types of activities than making 

arrangements to conduct the required 

studies. However, it could also offer a 

flexibility that is not always present 

under the currently-used, guidelinedriven (study-by-study) approach. 

Both SAR and QSAR techniques play 

a critical role in an integrated approach. 

In the SAR process, a chemical’s 

molecular structure is compared to that 

of other chemicals for which data are 

available. These structural similarities 

are then used to make predictive 

judgments about a chemical’s physical, 

chemical, and biological properties. 

Thus, the chemical’s physical, chemical, 

and biological properties are a function 

of (or directly related to) the chemical’s 

molecular structure. Quantitative SAR is 

referred to as QSAR. To develop a 

QSAR, a selected set of measured data 

on a single physical, chemical, or 

biological property are used to derive a 

model (an equation) to predict the value 

of that property. 


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EPA’s Office of Pollution Prevention 

and Toxics administers two programs, 

the Interagency Testing Committee (ITC) 

and the New Chemicals Program (NCP) 

under the Toxic Substances Control Act, 

that have been using various forms of 

SAR and QSAR since the late 1970s. 

The ITC is an independent advisory 

committee that screens chemicals or 

classes of chemicals and prioritizes 

them for testing. The NCP uses an 

expert judgment SAR process to assess 

human health and has developed QSAR 

models to evaluate physical, chemical 

and environmental fate properties and 

ecological effects. 

Additionally, other agencies (both 

U.S. and non-U.S.) are investigating 

how to use these alternative techniques. 

OECD has devoted a significant amount 

of time and effort to coordinating model 

development and model validation for 

such an integrated approach. EPA has 

participated on these workgroups. 

During the last 6 years, OPP has made 

increasing use of SAR as part of its 

regulatory decision-making process. 

Documents to establish tolerance 

exemptions, documents to support 

tolerance reassessment, and 

Reregistration Eligibility Decision 

Documents have incorporated the use of 

SAR, when appropriate. 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. Over time, OPP has 

progressed from using SAR techniques 

to support a dataset of guideline type 

studies to, for certain assessments, 

relying on SAR techniques as an 

acceptable source of information on the 

chemical. OPP is now considering when 

and how to codify in subpart A of 

current part 158 that information 

derived from SAR assessments and/or 

QSAR modeling could be acceptable for 

fulfilling a data requirement. The 

submitter of such information would be 

expected to supply a rationale 

describing the utility of the information 

and provide documentation on the 

scientific validity of the information. 

The determination that the predicted 

data fulfills the data requirement would 

be at the sole discretion of the Agency. 

The Agency seeks comment on the use 

of predictive techniques to fulfill the 

part 158 subpart W data requirements, 

and specifically on when and if the use 

of SAR and QSAR should be codified in 

part 158, subpart A. Codification in part 

158, subpart A means that SAR and 

QSAR techniques would be applicable 

to conventional, biochemical and 

microbial, and antimicrobial pesticide 

chemicals. The Agency specifically 

seeks comment on this issue. Comments 

will be used in the further development 

of SAR and QSAR approaches for 

fulfilling data requirements, but will not 

be addressed in the final rule for 

antimicrobial data requirements. 

Those applicants considering use of 

SAR and QSAR as part of a submission 

package to OPP should realize SAR and 

Quantitative SAR (QSAR) modeling 

results can sometimes be used instead of 

measured data, but modeled data cannot 

be preferentially substituted for wellconducted studies (measured data). If 

measured data are available for a 

particular endpoint, then the measured 

data should carry the greatest weight for 

hazard and risk assessment purposes. 

Applicants are cautioned that if the 

Agency determines that the SAR and/or 

QSAR do not fulfill the data 

requirement, then the registration may 

be delayed while a study (measured 

data) is generated according to part 158 

requirements. 

At this time, the Agency intends to 

continue its initial explorations and 

begin the process to shift from the 

current guideline-driven (study-bystudy) approach to a more integrated 

approach in which the use of predicted 

data, generated using validated models, 

is considered along with information 

from open literature and studies 

specifically generated under part 158 

data requirements. All relevant 

information would be considered as part 

of a weight-of-evidence evaluation. 

The shift to an integrated approach 

would occur over some time. OPP has 

deliberately chosen to begin this shift 

with antimicrobial pesticide chemicals 

instead of conventional pesticide 

chemicals for two reasons: First, most 

conventional pesticide chemicals are 

deliberately created for their biological 

activity and many require complex risk 

assessments. Few conventional 

pesticides have non-pesticidal uses. 

Second, antimicrobials also have 

biological activity, but are more likely to 

have non-pesticidal uses and, in fact, 

may have been assessed by other 

regulatory agencies. The ready 

availability of published literature and 

publicly-available assessments offer a 

unique opportunity for the applicant to 

use the available information as a 

starting point for fulfilling data 

requirements, and offering the possible 

option, when appropriate, of SAR and 

QSAR for those data requirements that 

are not yet fulfilled by measured data. 

It should be realized that just as 

measured data have uncertainties, 

predicted data also have uncertainties. 

Use of different models (developed 

using different sets of data) would 

necessarily have trade-offs. Therefore, 

QSAR models must be used with 

caution. Expert judgment is required to 

determine the appropriate model to use 

and if the results of the model strike the 

correct balance of accuracy and 

precision, with the potential for few 

false negatives or false positives. 

At this time, EPA believes that for 

certain endpoints, especially physical/ 

chemical and fate properties, that SAR 

and QSAR might be effectively utilized 

to fulfill these data requirements for 

many antimicrobial pesticide chemicals. 

When considering biological properties, 

EPA believes that SAR and QSAR can 

be most effectively utilized in the 

evaluation of chemicals that exhibit 

lower toxicity for human health and/or 

ecotoxicity parameters. This is 

appropriate because the risk assessment 

for lower toxicity chemicals can be 

streamlined, i.e., through use of a 

screening-level assessment procedure 

rather than multiple tiers of assessments 

with progressively more data 

requirements. 

As appropriate, OPP will consider the 

use of SAR and/or QSAR predictive 

techniques as part of the hazard 

assessment, and eventually the dose and 

endpoint selection process for 

antimicrobial chemicals. Under a 

QSAR-based approach an applicant 

could provide the Agency with an 

analysis that could frame the actual data 

required to register the antimicrobial 

pesticide chemical. For some 

antimicrobials, applicants may have the 

option of characterizing certain of the 

active ingredient properties via 

predictive techniques. It is the 

responsibility of the applicant to 

provide sufficient information to 

conduct a risk assessment that can be 

used to support a risk management 

decision. If the applicant believes that a 

SAR assessment and/or QSAR model 

would provide scientifically credible 

information that would be useful to 

EPA, then it is the responsibility of the 

applicant to provide to the Agency a 

rationale on the appropriateness of SAR 

or QSAR for that particular endpoint 

and sufficient documentation on how 

the assessment and/or model is 

scientifically valid. Without such 

information OPP cannot judge the 

validity of the model and therefore the 

acceptability of the results of the model 

for OPP’s decision-making purposes. 

At this time, the use of SAR is not yet 

a standardized approach in OPP, and is 

being handled on a case-by-case basis. 

Therefore, OPP has not yet developed a 

standardized format for submission of 

such information. Further information 

on OPP’s current thinking on how SAR 


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and QSAR modeling can be used as part 

of an integrated approach to hazard and 

risk assessment to support a regulatory 

decision-making process and guidance 

on submission formats is contained in 

the support document, ‘‘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’’ which 

is contained in the docket for this 

proposed rule (Ref. 43). The Agency 

specifically seeks comment on this 

support document. 

B. International Life Sciences Institute 

and Health and Environmental Sciences 

Institute Approaches 

In both the proposed (70 FR 12276) 

and final (72 FR 60934) rules for 

conventional pesticide chemicals, EPA 

discussed the relevance and importance 

of the ILSI/HESI project. There have 

been discussions on alternative testing 

paradigms with the International Life 

Sciences Institute (ILSI) Health and 

Environmental Sciences Institute (HESI) 

under the Agricultural Chemical Safety 

Assessment (ACSA) Technical 

Committee, since 2001 (Ref. 14). The 

focus of this effort has been toxicity 

testing for agricultural chemicals, but 

the results would also be applicable to 

antimicrobial pesticides. 

This project, with the participation of 

EPA scientists, represents an evolution 

of the current paradigm of animal (in 

vivo) toxicity testing toward a more 

integrated tiered testing approach for 

pesticide chemicals. Under this 

integrated approach, both the selection 

of studies that would be required, as 

well as the design of the tests 

themselves, could be influenced by 

other substantive and reliable 

information about the pesticide. 

The goals being pursued by EPA for 

this next generation of toxicity testing 

are to: 

• Incorporate advances in science and 

technology in an expeditious manner. 

• Identify cost effective and 

scientifically sound alternatives to 

current animal tests. 

• Define a transparent, step wise plan 

that leads to an evolution, not 

revolution, in testing and assessment. 

• Define a clear and credible process, 

with external peer-review and 

stakeholder participation. 

All available information would be 

considered: Not only toxicity and doseresponse 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 age-related 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. 

ACSA represents the first 

comprehensive effort to scientifically redesign the toxicology animal-testing 

framework for pesticide chemicals. A 

series of reports authored by HESI/ILSI 

were published in a special edition of 

the Journal of Critical Reviews in 

Toxicology in January 2006 (Refs. 1, 2, 

3, and 6). These four articles 

summarized the initial findings and 

recommendations. 

The ACSA proposal is consistent with 

EPA’s direction and goals to develop a 

more efficient and reliable testing 

paradigm. The ACSA approach departs 

significantly from the current 

standardized list of hazard studies used 

by many national and international 

authorities to assess pesticides. Some 

studies could be eliminated while 

endpoint coverage might be increased in 

redesigned studies based on responses 

observed in a core set of toxicity tests. 

Thus, it will be essential to conduct 

retrospective and prospective data 

analyses to determine whether this new 

testing paradigm will meet EPA’s risk 

assessment needs. 

The first retrospective analysis has 

been completed for the 1–year chronic 

dog study. Based on this retrospective 

analysis, which was reviewed by the 

FIFRA SAP, the 1–year chronic dog 

study is no longer required for 

conventional pesticide chemicals and is 

not proposed as a data requirement for 

antimicrobial chemicals. Another 

retrospective analysis on the 2- 

generation reproductive toxicity study is 

underway. To this end, the Office of 

Pesticide Programs is currently working 

with EPA’s National Center for 

Computational Toxicology to populate a 

Toxicological Reference Database 

(ToxRef) with data from the rat 2- 

generation reproductive study, prenatal 

developmental toxicity and systemic 

toxicity studies on hundreds of 

pesticides that represent different 

classes, modes of action, and toxicity 

profiles. EPA will use this relational 

database to determine the value of 

endpoints currently evaluated in risk 

assessment (i.e., the F1 versus F2

responses). 

From these analyses the Agency will 

gain other information critical for 

gaining scientific consensus. Such 

information would be the triggers, that 

is, the points at which a concern is 

indicated and thus a higher level of 

testing is needed. The retrospective 

analyses will aid the Agency in 

confirming the proposed ACSA triggers 

or in determining new ones. Once the 

analysis is complete, EPA will be able 

to complete draft guidance on testing. 

EPA plans to request SAP review and 

public comment of the analyses and 

draft guidance in 2008. 

Additionally, there are plans to 

conduct several case studies using the 

ACSA tiered testing proposal. It is 

essential to test how the ACSA scheme 

works in practice. From such case 

studies, EPA will be able to assess the 

feasibility of a testing laboratory’s 

ability to perform such a complex study, 

and will have the opportunity to 

evaluate the ability of the approach and 

its parameters to characterize known 

toxicants and address risk assessment 

needs. 

In considering regulatory changes to 

reflect the results of EPA’s consideration 

of ACSA, the Agency will develop 

scientific position papers on the new 

approach and recommendations for 

internal and external review. Internal 

review includes review by the FIFRA 

SAP and opportunities for public 

comment. External peer review and 

acceptability by other national and 

international regulatory authorities are 

considered before implementation of 

any new testing paradigm and data 

requirements. Harmonization of data 

requirements with our NAFTA and 

OECD partners is also an important 

factor. International regulations 

currently require studies that were 

omitted in ACSA. If EPA had 

requirements that were significantly 

different from those of the international 

community, then there could be 

significant problems for applicants in 

trying to satisfy multiple and different 

requirements world-wide. 

Thus, as these analyses and the 

needed peer reviews are completed, 

EPA will have the opportunity to 

determine if the new testing paradigm 

will meet its risk assessment needs. EPA 

will then be able to determine what 

revisions to current data requirements 

and testing guidelines may be 

appropriate. 

C. Computational Toxicology 

EPA’s Office of Research and 

Development (ORD) established the 

National Center for Computational 

Toxicology (NCCT) in 2005. The NCCT 

is developing computational tools for 

interpreting data from computational 

chemistry, high-throughput screening 


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(HTS) and genomic technologies as 

follows: 

•Computational chemistry is the 

integration of modern computing and 

information technology with 

information on molecular biology and 

chemistry to predict bioactivity profiles. 

• HTS is a system to rapidly and 

efficiently test large batches of 

chemicals for bioactivity utilizing 

robotics and automation applied to 

molecular biology and assay methods. 

• Genomics is the study of all the 

genes of a cell or tissue, and their 

function. 

EPA’s ToxCastTM Program began in 

2006. The underlying hypothesis for 

ToxCastTM is that an organism’s 

toxicological response is driven by 

interactions between chemicals and 

biomolecular targets. ToxCastTM also 

includes model development to predict 

the potential toxicity of environmental 

chemicals based on bioactivity profiles. 

These models will identify predictive 

signatures, derived from the bioassay 

data. This means that EPA under 

ToxCastTM will develop methods of 

prioritizing chemicals for further 

screening and testing to assist the 

Agency’s programs in the management 

and regulation of environmental 

contaminants (Ref. 5). 

There are three phases to the 

development of ToxCastTM: 

1. The proof-of-concept phase of 

ToxCastTM will examine more than 300 

chemicals, with rich toxicological 

databases, in over 400 different HTS 

bioassays. Predictive signatures will be 

created by correlating the HTS bioassay 

data to the known toxicity of the 300 

chemicals. 

2. A signature evaluation and 

expansion phase will focus on testing 

and extending the ToxCastTM predictive 

signatures, through the generation of 

HTS data on over 1,000 additional 

chemicals. 

3. The application phase of ToxCastTM

will be expanded to include a variety of 

high-priority chemicals that are either 

regulated and/or considered for 

regulation by EPA and potentially 

thousands of environmental chemicals 

requiring prioritization. ToxCastTM is 

envisioned as delivering an affordable, 

science-based system for categorizing 

chemicals. 

In 2007 the NCCT awarded nine 

contracts for the generation of HTS and 

genomics data as part of the ToxCastTM

chemical prioritization research 

program, in order to develop the ability 

to predict, or forecast toxicity based on 

bioactivity profiling. State-of-the-art 

HTS and genomic approaches 

developed by the pharmaceutical 

industry provide information on the 

impact of chemicals on biological 

pathways critical for the function of 

systems such as the heart, lungs, brain, 

or reproductive organs quickly and in a 

cost-efficient manner. Thus, results from 

these bioassays will provide a 

comprehensive and detailed overview of 

the potential impact of environmental 

chemicals upon key cellular activities. 

As the ToxCastTM database grows so 

will confidence in the models 

developed from that data, as well as the 

resultant predictions of toxicity and 

potential mechanisms of action derived 

from the models. This could result in 

changing and/or reducing the use and 

numbers of animals in toxicity testing. 

This could also result in fewer in vivo 

tests being conducted as scientists and 

regulators learn how to interpret and 

use ToxCastTM predictions to then 

determine the chemicals that must be 

tested using traditional toxicity testing. 

Results from the first phase of 

ToxCastTM are anticipated by the 

summer of 2008. However, significant 

effort will be needed as ToxCastTM

transitions from proof-of-concept to a 

useful prioritization tool. 

D. National Academy of Sciences (NAS) 

Report Concerning Toxicity Testing and 

Assessment of Environmental Agents 

EPA asked NAS to undertake a 

comprehensive review of established 

and emerging toxicity-testing methods 

and strategies. In response to this 

request NAS convened the Committee 

on Toxicity Testing and Assessment of 

Environmental Agents. EPA asked the 

Committee to conduct their assessment 

in two parts. Part I is a review 

document, discussing current and nearterm methods and strategies for 

collecting information for human health 

risk assessment. Part II is a long-range 

vision and strategic plan for changes to 

human health risk assessment 

paradigms. 

In June 2006, NAS released Toxicity 

Testing for Assessment of 

Environmental Agents: Interim Report 

(Ref. 20). This report fulfills EPA’s Part 

I request. In conducting its research 

NAS considered numerous documents 

and resources such as (1) current 

toxicity testing protocols and various 

testing strategies using these protocols, 

(2) impediments to the use of human 

data, (3) strategies that rank or screen 

chemical substances, and (4) human 

health risk assessment guidance 

documents. The Part I report identified 

four objectives that EPA should strive to 

meet as it works to evolve its current 

paradigm of toxicity testing: 

• Depth, providing the most accurate, 

relevant information possible for hazard 

identification and dose-response 

assessment. 

• Breadth, providing data on the 

broadest possible universe of chemicals, 

endpoints, and life stages. 

• Animal welfare, causing the least 

animal suffering possible and using the 

fewest possible animals. 

•Conservation, minimizing the 

expenditure of money and time on 

testing and regulatory review. 

The report acknowledged that it was 

difficult to simultaneously meet all four 

objectives. 

In 2007 NAS released its Part II report 

entitled ‘‘Toxicity Testing in the 21st 

Century: A Vision and a Strategy’’ (Ref. 

21). According to NAS, toxicity testing 

is approaching a ‘‘scientific pivot 

point.’’ Today, there are advances in the 

biological sciences that are already 

impacting how toxicity testing is 

conducted. NAS concluded that a 

paradigm shift would be needed to 

transform the current testing system but 

that ‘‘the result will be a more efficient, 

informative and less costly system for 

assessing the hazards posed by 

industrial chemicals and pesticides.’’ 

E. Next Steps 

EPA will undertake rule-makings on a 

timely basis as the science progresses 

and changes to the data requirements 

are appropriate. 

XIX. Animal Welfare Concerns 

The Agency understands many 

people’s concern about the use of 

animals for research and data 

development purposes. In both the 

proposed rule (70 FR 12276) and in the 

final rule (72 FR 60934) for 

conventional pesticide chemicals, EPA 

discussed its commitment to the 

development and use of alternative 

approaches to animal testing. 

Taking into consideration principles 

of sound science and the requirements 

of FIFRA to protect humans and the 

environment, the Agency is committed 

to avoiding unnecessary or duplicative 

animal testing. As a result, the Agency 

has invested significant resources to 

investigate more integrated testing 

approaches that include, in silico, in 

vitro, and focused in vivo testing. The 

Agency’s long-term goal is to create a 

testing paradigm so that chemicals are 

tested in animals only for those 

endpoints most relevant to each 

chemical’s exposure or intended use. 

The Agency acknowledges that 

substantial work remains to achieve this 

long-term goal, but the Agency is also 

working on the important short-term 

goal to make the existing animal testing 

paradigm more efficient, reliable, and 


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responsive to its risk assessment and 

management needs. 

As a result of the Agency’s activities 

to move towards a more efficient animal 

paradigm, EPA is proposing to eliminate 

the existing requirement for the 1–year 

chronic dog study for antimicrobial 

pesticide chemicals. 

XX. Potential Rule-Makings of the 

Future for Endangered Species 

EPA is charged with protecting 

endangered and threatened species from 

potential harm from pesticide use. 

Under the Endangered Species Act, EPA 

must ensure that the registered uses of 

pesticides 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 or National 

Marine Fisheries Service. Accordingly, 

in its proposed and final rules for both 

conventional pesticide chemicals, and 

biochemical and microbial pesticide 

chemicals, the Agency discussed the 

possibility of future data and 

information needs to develop and/or 

refine risk assessments for endangered 

and threatened species. As a result of 

those proposed rules, EPA received 

comments. For the present, EPA will 

consider those comments in the context 

of its ongoing risk assessments, 

including those for antimicrobials. If 

EPA finds that it needs to amend 

subpart W of part 158 to normalize 

endangered species data requirements, 

it will consider those comments and any 

comments submitted in response to this 

proposed rule in the development of a 

future proposed rule. 

For agricultural pesticides, there is 

generally greater specificity relative to 

where a pesticide may be used. If 

adequate geographic delineation of the 

use site is possible, then overlap with 

the locations of an endangered or 

threatened species may also be possible. 

However, antimicrobial pesticides are 

different from agricultural pesticides. 

The Agency expects that most 

antimicrobial uses with potential for 

environmental exposure (e.g., wood 

preservatives, antifoulant paints, 

industrial wastewater discharges, ballast 

water discharges) could impact 

geographic areas of the United States 

that are less well defined. For example, 

vessels treated with antifoulant paints 

can occur in freshwater, estuarine, or 

marine areas within the U.S. (such as 

lakes and rivers) and in coastal waters. 

Wood preservatives could be used in 

locations that may result in an impact 

to terrestrial and/or aquatic organisms 

depending on the use of the wood, 

which could occur throughout the 

United States. Antimicrobial use sites 

will be much more difficult to delineate, 

and overlay with endangered or 

threatened species locations. 

The Agency seeks comment on: 

1. The types of data that could be 

useful for conducting the assessment 

required. 

2. Projections of how long it would 

take to generate the needed data. 

3. Whether antimicrobial use sites can 

be adequately correlated with 

endangered species locations, and 

suggested methods for doing so. 

XXI. References 

1. Barton, A, Pastoor, TP, Baetcke, K, 

Chambers, JE, Diliberto, J, Doerrer, NG, 

Driver, JH, Hastings, CE, Iyengar, S, 

Krieger, R, Stahl, B, and Timchalk, C. 

2006. The acquisition and application of 

absorption, distribution, metabolism, 

and excretion (ADME) data in 

agricultural chemical safety 

assessments. Critical Reviews in 

Toxicology. 36, 9–35. 

2. Carmichael, NG, Barton, HA, 

Boobis, AR, Cooper, RL, Dellarco, VL, 

Doerrer, NG, Fenner-Crisp, PA, Doe, JE, 

Lamb, JC, and Pastoor, TP. 2006. 

Agricultural chemical safety assessment: 

a multi-sector approach to the 

modernization of human safety 

requirements. Critical Reviews in 

Toxicology. 36, 1–7. 

3. Cooper, RL, Lamb, JC, Barlow, SM, 

Bentley, K, Brady, AM, Doerrer, NG, 

Eisenbrandt, DL, Fenner-Crisp, PA, 

Hines, RN, Irvine, L, Kimmel, CA, 

Koeter, H, Li, AA, Makris, SL, Sheets, L, 

Speijers, GJA, and Whitby, K. 2006. A 

tiered approach to life stages testing for 

agricultural chemical safety assessment. 

Critical Reviews in Toxicology. 36, 69– 

98. 

4. Dearfield, KL, Auletta, AE, Cimino, 

MC, and Moore, MM. 1991. 

Consideration in the U. S. 

Environmental Protection Agency’s 

Testing Approach for Mutagenicity. 

Mutation Research. 258, 259–283. 

5. Dix, DJ, Houck, KA, Martin, MT, 

Richard, AM, Setzer, RW, Kavlock, RJ. 

2007. The ToxCast Program for 

Prioritizing Toxicity Testing of 

Environmental Chemicals; Toxicological 

Sciences 95(1), 5–12 (accessed July 2, 

2008) http://toxsci.oxfordjournals.org/ 

cgi/content/abstract/95/1/5. 

6. Doe, JE, Boobis, AR, Blacker, A, 

Dellarco, VL, Doerrer, NG, Franklin, C, 

Goodman, JI, Kronenberg, JM, Lewis, R, 

McConnell, EE, Mercier, T, Moretto, A, 

Nolan, C, Padilla, S, Phang, W, Solecki, 

R, Tilbury, L, van Ravenswaay, B, and 

Wolf, DC. 2006. A tiered approach to 

systemic toxicity testing for agricultural 

chemical safety assessment. Critical 

Reviews in Toxicology. 36, 37–68. 

7. Food and Drug Administration 

(FDA) (January 1993). Sanitizing 

Solutions: Chemistry Guidelines for 

Food Additive Petitions. (accessed July 

2, 2008) http://www.cfsan.fda.gov/ 

~dms/opa-cg3a.html. 

8. FDA (April 2002a). Guidance for 

Industry: Preparation of Premarket 

Notifications for Food Contact 

Substances: Toxicology 

Recommendations. (accessed July 2, 

2008) http://www.cfsan.fda.gov/~dms/ 

opa2pmnt.html. 

9. FDA (April 2002b). Guidance For 

Industry: Preparation of Food Contact 

Notifications and Food Additive 

Petitions for Food Contact Substances: 

Chemistry Recommendations. Final 

Guidance. (accessed July 2, 2008) http:// 

www.cfsan.fda.gov/~dms/ 

opa2pmnc.html. 

10. FDA (August 2006) Estimating 

Dietary Intake of Substances in Food 

(accessed July 2, 2008) http:// 

www.cfsan.fda.gov/~dms/opa2cg8.html 

11. FDA (December 2007) Guidance 

for Industry: Preparation of Premarket 

Submissions for Food Contact 

Substances: Chemistry 

Recommendations. (accessed July 2, 

2008) http://www.cfsan.fda.gov/~dms/ 

opa3pmnc.html 

12. Halden, R, and Paull, D. 2005. CoOccurrence of Triclocarban and 

Triclosan in U.S. Water Resources. 

Environmental Science and Toxicology. 

39: 6, 1420–1426. 

13. Health Canada, Pesticide 

Management Regulatory Agency: 

Memorandum from Don Grant, Director 

Health Evaluation Division: 

Reproductive Toxicity Testing in 

Proposed 40 CFR 158, Subdivision W - 

Data Requirements for Antimicrobial 

Pesticides. December 1, 1997. 

Attachment to Memorandum: The 

Assessment of Reproductive Toxicity for 

Antimicrobial Pesticides: The Tiered 

Approach of USEPA and Proposals for 

Change; November 1997 draft. 

14. International Life Sciences 

Institute, Health and Environmental 

Sciences Institute Developing strategies 

for agricultural chemical safety 

evaluation, a report from an April 22– 

23, 2001 workshop. (September 2001) 

15. Luster et al. 1992. Risk 

Assessment in Immunotoxicology I. 

Sensitivity and Predictability of 

Immune Tests, Fundamental and 

Applied Toxicology. 18: 200–210. 

16. Luster et al. 1993. Risk 

Assessment in Immunotoxicology II. 

Relationships Between Immune and 

Host Resistance Tests, Fundamental and 

Applied Toxicology. 21: 71–82. 

17. McAvoy, D, Schatowitz, B, Jacob, 

M, Hauk, A, and Eckhoff, W. 2002. 

Measurement of Triclosan in 


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59426 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 

Wastewater Treatment Systems. 

Environmental Toxicology and 

Chemistry, 21: 7, 1323–29. 

18. Marzulli, F. and Maibach, H. 

Dermatotoxicology (5th ed.). page 284. 

19. National Research Council, 

‘‘Pesticides in the Diets of Infants and 

Children,’’ National Academy Press, 

Washington, D.C., 1993. 

20. National Research Council 2006. 

Executive Summary: Toxicity Testing 

for Assessment of Environmental 

Agents: Interim Report. (Note: click on 

download free executive summary) 

(accessed July 1, 2008) http:// 

www.nap.edu/catalog/11523.html. 

21. National Research Council 2007. 

Executive Summary: Toxicity Testing in 

the 21st Century: A Vision and a 

Strategy (Note: click on download free 

executive summary) (accessed July 1, 

2008) http://www.nap.edu/catalog/ 

11970.html. 

22. Santa Clara Basin Watershed 

Management Initiative. 2006. White 

Paper: Environmental Emergence of 

Triclosan.(accessed July 2, 2008) http:// 

www.scbwmi.org/PDFs/ 

WMI_Triclosan_FinalJan06.pdf. 

23. Singer, H, Muller, S. Tixiewr, C., 

and Pillonel, L. 2002. Triclosan: 

Occurrence and Fate of a Widely Used 

Biocide in the Environment: Field 

Measurements in Wastewater Treatment 

Plants, Surface Waters, and Lake 

Sediments. Environmental Science and 

Toxicology. 36: 23, 4998–5004. 

24. USEPA Federal Register Notice. 

Toxicology Data Call-In for 

Antimicrobial Pesticides (January 7, 

1987) (FRL–3136–3). 

25. USEPA (March 9, 1992). 

Environmental Fate and Effects Division 

Policy Note 1–2: Waiver of the 

Photodegradation in Water Data 

Requirement Based on the Electronic 

Absorption Spectra of the Pesticide 

(Henry Jacoby). 

26. USEPA (August 5, 1991). 

Memorandum: Revised Mutagenicity 

Guideline and Requirement – 

Explanation, from Kerry L. Dearfield, 

Science Analysis and Coordination 

Branch. 

27. USEPA (September 1993). 

Pesticide Reregistration Rejection Rate 

Analysis – Environmental Fate (EPA 

738–R–93–010). 

28. USEPA (February 7, 1996). 

Pesticide Registration (PR) Notice 96–1. 

Tolerance Enforcement Methods — 

Independent Laboratory Validation by 

Petitioner. (accessed July 1, 2008) http:// 

www.epa.gov/opppmsd1/PR_Notices/ 

pr96–1.html. 

29. USEPA Federal Insecticide, 

Fungicide and Rodenticide Act (FIFRA) 

Scientific Advisory Panel (SAP) Meeting 

of June 1997: A Set of Scientific Issues 

Being Considered by the Agency to 

Determine Antimicrobials Issues 

(accessed July 1, 2008) http:// 

www.epa.gov/scipoly/sap/meetings/ 

1997/june/antimicr.htm. 

30. USEPA FIFRA SAP Meeting of 

December 1998: A Retrospective 

Analysis of Twelve Developmental 

Neurotoxicity Studies (Draft 11/12/98) 

(accessed July 1, 2008) http:// 

www.epa.gov/scipoly/sap/meetings/ 

1998/december/neuro.pdf. 

31. USEPA FIFRA SAP Report No. 

99–01B: II - A Retrospective Analysis of 

Twelve Developmental Neurotoxicity 

Studies (January 22, 1999) (accessed 

July 1, 2008) http://www.epa.gov/ 

scipoly/sap/meetings/1998/december/ 

final2.pdf. 

32. USEPA FIFRA SAP Meeting of 

December 1998: Toxicology Data 

Requirements for Assessing Risks of 

Pesticide Exposure to Children’s Health. 

(Draft—November 30, 1998). http:// 

www.epa.gov/scipoly/sap/meetings/ 

1998/december/10xreq.pdf. 

33. USEPA FIFRA SAP Meeting of 

May 1999: Toxicology Data 

Requirements for Assessing Risks of 

Pesticide Exposure to Children’s Health. 

(Draft—April 28, 1999). (accessed July 1, 

2008) http://www.epa.gov/scipoly/sap/ 

meetings/1999/may/10xtx428.pdf. 

34. USEPA FIFRA SAP Meeting of 

April 2000: Implementation Plan for 

Probabilistic Ecological Assessment 

(August 2, 2000). (accessed July 2, 2008) 

http://www.epa.gov/oscpmont/sap/ 

meetings/2000/april/ 

freportapril572000.pdf. 

35. USEPA (November 28, 2001). 

General Principles for Performing 

Aggregate Exposure and Risk 

Assessments (page 16) (accessed July 2, 

2008) http://www.epa.gov/oppfead1/ 

trac/science/aggregate.pdf. 

36. USEPA FIFRA SAP Meeting May 

2005: A Comparison of the Results of 

Studies on Pesticides from 12– or 24– 

Month Dog Studies with Dog Studies of 

Shorter Duration (accessed July 2, 2008) 

http://www.epa.gov/scipoly/sap/ 

meetings/2005/may2/ 

dogstudymay05.pdf. 

37. USEPA FIFRA SAP Meeting 

Minutes No. 2005–03: A Set of 

Scientific Issues Being Considered by 

the Environmental Protection Agency 

Regarding: A Comparison of the Results 

of Studies on Pesticides from 12– or 24– 

Month Dog Studies with Dog Studies of 

Shorter Duration (accessed June 30, 

2008) http://www.epa.gov/scipoly/sap/ 

meetings/2005/may5/ 

meetingminutesmay5_6_2005.pdf. 

38. USEPA (March 20, 2006). Length 

of Dog Toxicity Study(ies) that is 

Appropriate for Chronic RfD 

Determinations of Pesticide Chemicals. 

Health Effects Division/Office of 

Pesticide Programs. 

39. USEPA (January 2007) FIFRA SAP 

Meeting Minutes (accessed June 25, 

2008) http://www.epa.gov/scipoly/sap/ 

meetings/2007/january/ 

january2007finalmeetingminutes.pdf. 

40. USEPA (April 2, 2007) Human 

Studies Review Board Meeting Minutes 

(EPA-HSRB–07–02) (accessed June 25, 

2008) http://www.epa.gov/OSA/hsrb/ 

files/ 

April2007HSRBMtgFinalReport.pdf. 

41. USEPA (February 5, 2007) 

Appendix B – Antimicrobial Product 

Use Sites and Categories Index. USEPA, 

Antimicrobials Division, Office of 

Pesticide Programs. 

42. USEPA (December 31, 2007). Four 

Case Studies of Antimicrobial Pesticides 

in the Down-the-Drain Screening Model, 

Using the Proposed Approach for a 

Screening-Level Environmental Fate 

Assessment. USEPA, Antimicrobials 

Division, Office of Pesticide Programs. 

43. USEPA (December 17, 2007). 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. 

44. USEPA (2008). Economic Analysis 

of the Proposed Data Requirements for 

Antimicrobial Pesticides, EAB/BEAD/ 

OPP. 

45. USEPA (August 26, 2008). 

Supporting Statement for an 

Information Collection Request (ICR), 

Data Requirements for Antimicrobial 

Pesticides (Proposed Rule), EPA ICR No. 

2318.01, OMB Control No. 2070–(new). 

XXII. FIFRA Review Requirements 

Under FIFRA section 25(a), EPA has 

submitted a draft of the proposed rule 

to the Secretary of the Department of 

Agriculture and the appropriate 

Congressional Committees. There were 

no comments in response to these 

submissions. 

Under FIFRA section 21(b) EPA 

submitted a draft of the proposed rule 

to the Secretary of Health and Human 

Services (HHS). Their comments on this 

proposed rule included requests for (1) 

clarification on the application of these 

new testing requirements to current 

registrants, (2) information about prions, 

(3) the possible effects of antimicrobial 

residues present in food on intestinal 

flora, and (4) the potential for 

antimicrobial resistance. 

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 


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promulgated. Once effective, EPA 

would use the promulgated data 

requirements as the standard for 

reviewing new applications. These same 

promulgated data requirements, once 

effective, would also be used during 

Registration Review, when the Agency’s 

scientists prepare the publicly available 

documentation on the data needed 

during Registration Review to complete 

the needed risk assessments. 

EPA also agrees that the criteria for 

determining the efficacy of proposed 

anti-prion agents have not yet been 

established. 

Concerning HHS’s Center for 

Veterinary Medicine’s (CVM) comment 

on intestinal flora, EPA believes that the 

studies proposed in this rule for use in 

a pesticide risk assessment are 

protective of human health. EPA has no 

specific information on effects on 

antimicrobial residues that would not be 

captured by the required health effects 

studies. 

HHS’s CVM is correct that this 

proposed rule does not address 

potential antimicrobial resistance as a 

result of the use of a pesticide product. 

While the Pesticide Program is aware of 

this issue, we have neither determined 

the extent of the problem nor how data 

requirements could be developed to 

address the issue. The Pesticide 

Program will continue to monitor efforts 

such as those of the CODEX ad hoc 

Intergovernmental Task Force on 

Antimicrobial Resistance and the 

Interagency Task Force on 

Antimicrobial Resistance, on which 

EPA is a participant (see http:// 

www.cdc.gov/drugresistance/ 

actionplan/). The research being 

conducted by the collaborating federal 

agencies, which is primarily focused on 

antibiotics, may eventually form the 

basis for the Pesticide Programs’ 

approach to potential resistance as a 

result of the use of pesticide products. 

We have the authority to require studies 

on a case-by-case basis and to revise our 

data requirements in the future, if 

appropriate. 

EPA requested that the SAP waive its 

review of this proposal based on the 

SAP’s 1997 review. The SAP waived its 

review of this proposal on February 19, 

2008. 

XXIII. Statutory and Executive Order 

Reviews 

A. Executive Order 12866 

Pursuant to Executive Order 12866, 

entitled Regulatory Planning and 

Review (58 FR 51735, October 4, 1993), 

the Office of Management and Budget 

(OMB) has determined that this 

proposed rule is a ‘‘significant 

regulatory action’’ because this action 

might raise novel legal or policy issues 

arising out of legal mandates, the 

President’s priorities, or the principles 

set forth in the Executive Order. 

Accordingly, as a result of this OMB 

determination, EPA submitted this 

proposed rulemaking to OMB for review 

under Executive Order 12866. Any 

changes made in response to OMB 

comments have been documented in the 

public docket for this rulemaking as 

required by section 6(a)(3)(E) of the 

Executive Order. 

EPA has prepared an economic 

analysis of the potential costs associated 

with this proposed action, entitled 

‘‘Economic Analysis of the Proposed 

Change in Data Requirements for 

Antimicrobial Pesticides.’’ It is noted 

that this analysis applies only to new 

antimicrobial pesticides submitted for 

registration, and to new uses of 

currently registered antimicrobial 

pesticides. For conducting its economic 

analysis, EPA considered a registration 

action as referring to an application for 

registration of a new product that 

contains an active ingredient that is not 

included in any currently registered 

product, an application for a new 

product that includes the addition of a 

use pattern that is not currently 

registered for one or more active 

ingredients contained in the product, 

and 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. 

A copy of the economic analysis (Ref. 

44) can be found in the public docket 

for this action, and is briefly 

summarized here. 

In the proposed rule, EPA is: 

• Proposing newly codified data 

requirements, which are not currently 

established in part 161, but are routinely 

considered in current practice. 

• Proposing changes to some of the 

existing data requirements such as a 

change from conditionally-required to 

required, a change in the number of test 

species, or expanding the number of use 

patterns for which the test is required. 

• Proposing new data requirements, 

which have never been required or have 

rarely been required on a case-by-case 

basis, and have not been routinely 

considered during the Agency’s 

evaluation of the data needed for the 

purpose of risk assessment. 

• Proposing to eliminate the 

requirement for the chronic nonrodent 

study currently established in part 161. 

To calculate the potential costs 

associated with this proposal, EPA first 

identified the studies that would 

generate the data to fulfill the proposed 

data requirements, and then gathered 

information on the price that 

laboratories might charge to conduct 

that study. To the extent possible, 

several cost estimates were compiled for 

each study. The low and high cost 

estimates provided by the various 

laboratories were averaged to account 

for price variations related to differences 

in the assumptions about the study 

performed (e.g., protocol, species used), 

and differences in the price charged by 

different laboratories. 

EPA assumed that each data 

requirement would always be fulfilled 

and therefore data would always need to 

be generated for each requirement. This 

assumption could lead to an 

overestimate of the burden of the 

proposal, because sometimes the data 

are already available because the firm 

generated it for their own use. In such 

cases, the firm would simply need to 

submit those data to EPA, which 

involves less burden and cost than 

generating it. Some firms may have 

surrogate data that could be used, while 

others may qualify for a waiver. Some 

firms may share the cost of generating 

the data. All of these would involve 

lower costs than generating the data 

anew. 

EPA then used historical data on 

antimicrobial pesticide registration 

actions that occurred from 2000 to 2005 

to identify the entities that sought 

pesticide registration actions in the past. 

The data required for each registration 

action depends on several factors, 

including the type of registration action 

(e.g., registration of a new active 

ingredient food-use, registration of a 

new active ingredient nonfood-use, 

registration and amendments to 

registrations involving a major new use); 

scientific discipline (e.g., toxicology, 

residue chemistry, human exposure), 

and use pattern. The percentage of time 

a particular test would be required was 

estimated from this information. For the 

new data requirements, the percentage 

of time was estimated by EPA scientists, 

based on their past experience in the 

program and their understanding of the 

need for and the use of the new data 

requirements. 

The Agency prepared an industry 

profile using the same historical data on 

pesticide registration actions to identify 

the companies involved in those 

actions, and based it on public 

information gathered about those 

companies. EPA also used this industry 

profile to analyze the potential impacts 

of the proposed rule on small 

businesses, the results of which are 

summarized in Unit XXIII.B below. 

Overall the potential impact of this 

proposal on businesses is small, and 


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therefore the Agency believes that a 

negative effect on the availability of 

antimicrobial pesticide products to 

users is unlikely. On balance, the 

Agency believes that the costs of the 

proposed rule are justified by the 

benefits from enhanced protection of 

human health and the environment. 

TABLE 2.—TOTAL ANTIMICROBIAL INDUSTRY COST PER YEAR

Total Industry Cost per Year 

($1000) 

Baseline (BL) 11,080 

Current Practices (CP) 11,726 

Proposed Rule (PR) 14,961 

Incremental Costs (PR – BL) 3,882 

Newly Imposed Costs (PR-CP) 3,236 

Thus, the difference between the 

baseline (the existing data requirements 

that were codified in 1984) and the 

Agency’s current practices in requiring 

data is $646,000 annually. The 

difference between the proposed data 

requirements and current practices is 

$3.2 million annually. The difference 

between the proposed data requirements 

and the existing data requirements is 

$3.9 million annually. The average cost 

per registration action of a new 

antimicrobial active ingredient is 

approximately $1 million to $4.5 

million. It is noted that this analysis 

applies only to new antimicrobial 

pesticides submitted for registration, 

and to new uses of currently registered 

antimicrobial pesticides. 

For existing chemicals, the proposed 

part 158 subpart W data requirements 

would be relevant to the registration 

review program which began to replace 

the reregistration program in 2006 as a 

means of systematically reviewing 

existing registrations against the 

standards of FIFRA. Data needs 

identified under registration review for 

existing chemicals must be imposed 

under the Agency’s Data Call-In (DCI) 

program. 

EPA has not evaluated the potential 

burden of the proposed data 

requirements on registrants of existing 

chemicals in this proposal. However, 

EPA anticipates that there will be 

additional costs associated with the 

proposed studies under Registration 

Review. For each chemical, EPA will 

evaluate the specific need for additional 

data, including studies proposed today. 

Stakeholders and the public have 

opportunities for input, consultation 

and involvement concerning individual 

pesticide cases throughout the 

registration review process. Although 

EPA has identified the schedule for 

which chemicals will be reviewed over 

the next few years, the evaluation of 

data needs has not been done. Thus, the 

costs are unknown. EPA will articulate 

the specific burden and costs associated 

with each DCI pursuant to the 

appropriate Information Collection 

Request (ICR) approvals under the 

Paperwork Reduction Act (PRA). 

B. Regulatory Flexibility Act 

Pursuant to section 605(b) of the 

Regulatory Flexibility Act (RFA), 5 USC 

601 et seq., the Agency hereby certifies 

that this action will not have a 

significant adverse economic impact on 

a substantial number of small entities. 

The factual basis for the Agency’s 

determination is presented in the small 

entity impact analysis prepared as part 

of the economic analysis for this 

proposed rule (Ref. 44), which is 

summarized in Unit XXIII.A., and a 

copy of which is available in the docket 

for this rulemaking. The following is a 

brief summary of the factual basis for 

this certification. 

Under the RFA, small entities include 

small businesses, small organizations, 

and small governmental jurisdictions. 

For purposes of assessing the impacts of 

today’s proposed rule on small entities, 

small entity is defined in accordance 

with the RFA as: (1) a small business as 

defined by the Small Business 

Administration’s (SBA) regulations at 13 

CFR 121.201, which is based on either 

the maximum number of employees or 

on the sales for small businesses in each 

industry sector, as defined by a 6–digit 

NAICS code; (2) a small governmental 

jurisdiction that is a government of a 

city, county, town, school district or 

special district with a population of less 

than 50,000; and (3) a small 

organization that is any not-for-profit 

enterprise which is independently 

owned and operated and is not 

dominant in its field. EPA has 

determined that this rulemaking does 

not impact any small governmental 

jurisdictions or any small not-for-profit 

enterprise because these entities are 

rarely pesticide applicants or 

registrants. 

Some of the small entities directly 

regulated by this rulemaking are in the 

pesticide and other agricultural 

chemical manufacturing industry sector 

(NAICS code 325320). Firms in this 

sector are considered small under the 

RFA definition if they employ 500 or 

fewer people. The economic analysis for 

this proposed rule specifies the NAICS 

code used for each of the firms 

analyzed. 

As detailed in the Economic Analysis, 

EPA estimates that 750 unique parent 

companies constitute the total universe 

of pesticide antimicrobial registrants. Of 

these, based on the SBA definition of a 

small business and the available sales 

data for these firms, EPA estimates that 

500, or approximately 67%, qualify as a 

small business. The available 

antimicrobial pesticide registration data 

for 2000–2005 indicates that only a 

small portion of the 500 registrants are 

likely to be impacted by the proposed 

regulation. Specifically, 64 firms with 

antimicrobial registrations would have 

incurred additional costs under the 

proposed rule. Of the 64 firms, EPA 

estimates that a total of 25 small 

pesticide registrants would have 

incurred additional costs under the 

proposed rule. 

The impacts to small antimicrobial 

registrants are measured as the per firm 

incremental cost, which is the 

difference between the existing data 

requirements in part 161 (the baseline) 

and those proposed in this rule. The 

impact of the regulation is expressed as 

the proportion of the average annual per 

firm incremental costs to the average 

annual firm sales. 

The Agency’s analysis of impacts on 

small businesses indicates that: 

• About 25 (5%) of the 500 small firms 

subject to the proposal are likely to 

experience some impact (greater than 

0%). 


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• About 22 (4.4%) of the 500 small 

firms are likely to experience an 

economic impact of 1% or more of gross 

sales. 

• About 14 (2.8%) of the 500 small 

firms are likely to experience an 

economic impact of 3% or more of gross 

sales. 

Based on the Agency’s small business 

impact analysis, the Agency does not 

anticipate that the additional costs to 

industry resulting from this proposed 

rule will cause a significant adverse 

economic impact on a substantial 

number of small entities because the 

additional costs are a small share of 

gross revenues for most firms and less 

than 5% of small firms are likely to 

experience some impact. 

EPA is particularly interested in 

receiving comment from small 

businesses as to the benefits, costs and 

impacts of this rule. Any comments 

should be submitted to the Agency in 

the manner specified under ADDRESSES. 

C. Paperwork Reduction Act 

The information collection 

requirements contained in this proposed 

rule have been submitted for approval to 

the Office of Management and Budget 

(OMB) under the Paperwork Reduction 

Act (PRA), 44 U.S.C. 3501 et seq. EPA 

has prepared a new Information 

Collection Request (ICR) document 

identified by EPA ICR No. 2318.01, a 

copy of which has also been placed in 

the docket for this proposed rule. (Ref. 

45). 

Under the PRA, ‘‘burden’’ is defined 

at 5 CFR 1320.3(b). In addition, an 

agency may not conduct or sponsor, and 

a person is not required to respond to 

an information collection request unless 

it displays a currently valid OMB 

control number, or is otherwise required 

to submit the specific information by a 

statute. The OMB control numbers for 

certain EPA regulations in 40 CFR, after 

appearing in the preamble of the final 

rule, are listed in 40 CFR part 9 and, if 

applicable, included with the related 

collection instrument (e.g., form or 

survey). 

The information collection activities 

related to the submission of data to EPA 

in order to register, amend or retain a 

new or existing pesticide product or 

obtain a tolerance for that product are 

already approved by OMB under the 

PRA. As such, this ICR only addresses 

the proposed changes to the data 

requirements that impact the 

information collection activities related 

to antimicrobial pesticides. The 

procedures for submitting data to EPA 

under FIFRA and the FFDCA are not 

changed in this proposal, and are 

already approved by OMB as follows: 

1. The data submission activities 

associated with the establishment of a 

tolerance are currently approved under 

OMB Control No. 2070–0024 (EPA ICR 

No. 0597); 

2. The data submission activities 

associated with the application for a 

new or amended registration of a 

pesticide are currently approved under 

OMB Control No. 2070–0060 (EPA ICR 

No. 0277); 

3. The data submission activities 

associated with the generation of data 

for reregistration are currently approved 

under OMB Control No. 2070–0107 

(EPA ICR No. 1504); and 

4. The data submission activities 

associated with the generation of data 

for special review or registration review 

are currently approved under OMB 

Control No. 2070–0057 (EPA ICR No. 

0922). 

These program activities are an 

integral part of the Agency pesticide 

program and the corresponding ICRs are 

regularly renewed every three years as 

required by the PRA. The total 

estimated average annual public 

reporting burden currently approved by 

OMB for these various activities range 

from 8 hours to approximately 3,000 

hours per respondent, depending on the 

activity and other factors surrounding 

the particular pesticide product. 

In the new ICR for this proposed rule, 

which is based on the Economic 

Analysis (Ref. 44), EPA estimates that 

the typical current annual paperwork 

burden for registrants per antimicrobial 

pesticide registration is 194 burden 

hours and $12,631. This represents the 

baseline antimicrobial pesticide 

registration burden and costs. When 

considering the potential increase in 

this estimated annual burden and cost 

resulting from the new data 

requirements in this proposed rule, the 

Agency estimated the incremental 

burden and cost to be 35% of the 

baseline burden and costs, i.e., 68 

burden hours and $4,421. Assuming an 

annual number of 15 antimicrobial 

pesticide registrations, the total annual 

registrant paperwork burden and costs 

for antimicrobial pesticide registrations 

are estimated to be approximately 3,929 

hours and $255,773.25, of which 1,019 

hours and $66,150 represent burden 

related to new data requirements, and 

$158.25 represents estimated delivery 

costs. 

Any comments on the Agency’s need 

for this information, the accuracy of the 

provided burden estimates, and any 

suggested methods for minimizing 

respondent burden, should be directed 

to the docket for this proposed rule, 

under Docket ID number EPA–HQ– 

OPP–2008–0110. See ADDRESSES 

section at the beginning of this 

document for where to submit 

comments to EPA. 

You may also submit a copy of your 

comments on the ICR directly to OMB. 

Comments to OMB should be sent to the 

Office of Information and Regulatory 

Affairs, Office of Management and 

Budget (OMB), 725 17th Street, NW, 

Washington, DC 20503, Attention: Desk 

Office for EPA. Since OMB is required 

to make a decision concerning the ICR 

between 30 and 60 days after October 8, 

2008, a comment to OMB is best assured 

of having its full effect if OMB receives 

it by November 7, 2008. 

In the final rule, the Agency will 

address any comments received 

regarding the information collection 

requirements contained in this proposal. 

In addition, after the ICR for the final 

rule is approved, EPA will incorporate 

the increased burden into the existing 

ICRs as appropriate. 

D. Unfunded Mandates Reform Act 

Under Title II of the Unfunded 

Mandates Reform Act of 1995 (UMRA) 

(Public Law 104– 4), EPA has 

determined that this action does not 

contain a Federal mandate that may 

result in expenditures of $100 million or 

more for State, local, and tribal 

governments, in the aggregate, or the 

private sector in any one year. As 

described in this document, the 

incremental costs for the proposed part 

158 subpart W data requirement 

changes for antimicrobial pesticides is 

estimated at nearly $3.9 million per year 

for the private sector, which is below 

the $100 million threshold. Since State, 

local, and tribal governments are rarely 

pesticide applicants, the proposed rule 

is not expected to significantly or 

uniquely affect small governments. 

Accordingly, this action is not subject to 

the requirements of sections 202 and 

205 of UMRA. 

E. Executive Order 13132 

Pursuant to Executive Order 13132, 

entitled Federalism (64 FR 43255, 

August 10, 1999), EPA has determined 

that this proposed rule does not have 

‘‘federalism implications,’’ because it 

will not have substantial direct effects 

on the states, on the relationship 

between the national government and 

the states, or on the distribution of 

power and responsibilities among the 

various levels of government, as 

specified in the Order. As indicated 

above, instances where a state is a 

registrant are extremely rare. Therefore, 

this proposed rule may seldom affect a 

state government. Thus, Executive 

Order 13132 does not apply to this 

proposed rule. In the spirit of the Order, 


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and consistent with EPA policy to 

promote communications between the 

Agency and State and local 

governments, EPA specifically solicits 

comment on this proposed rule from 

State and local officials. 

F. Executive Order 13175 

As required by Executive Order 

13175, entitled Consultation and 

Coordination with Indian Tribal 

Governments (65 FR 67249, November 

6, 2000), EPA has determined that this 

proposed rule does not have tribal 

implications because it will not have 

substantial direct effects on tribal 

governments, on the relationship 

between the Federal government and 

the Indian tribes, or on the distribution 

of power and responsibilities between 

the Federal government and Indian 

tribes, as specified in the Order. As 

indicated above, at present, no tribal 

governments hold, or have applied for, 

a pesticide registration. Thus, Executive 

Order 13175 does not apply to this 

proposed rule. In the spirit of the Order, 

and consistent with EPA policy to 

promote communications between the 

Agency and State and local 

governments, EPA specifically solicits 

comment on this proposed rule from 

tribal officials. 

G. Executive Order 13045 

This section is not subject to 

Executive Order 13045, entitled 

Protection of Children from 

Environmental Health Risks and Safety 

Risks (62 FR 19885, April 23, 1997) 

because it does not propose an 

environmental standard that is intended 

to have a negatively disproportionate 

effect on children. To the contrary, this 

action will provide added protection for 

children from pesticide risk. The 

proposed data requirements are 

intended to address risks that, if not 

addressed, could have a 

disproportionate negative impact on 

children. EPA will use the data and 

information obtained by this proposed 

rule to carry out its mandate under 

FFDCA to give special attention to the 

risks of pesticides to sensitive 

subpopulations, especially infants and 

children. 

H. Executive Order 12898 

This proposed rule does not have an 

adverse impact on the environmental 

and health conditions in low-income 

and minority communities because this 

proposed rule only impacts entities that 

intend to register or currently hold a 

registration for an antimicrobial 

pesticide. Therefore, under Executive 

Order 12898, entitled Federal Actions to 

Address Environmental Justice in 

Minority Populations and Low-Income 

Populations (59 FR 7629, February 16, 

1994), the Agency does not need to 

consider environmental justice-related 

issues. 

I. National Technology Transfer and 

Advancement Act 

Section 12(d) of the National 

Technology Transfer and Advancement 

Act of 1995 (NTTAA), 15 U.S.C. 272 

note) directs EPA to use voluntary 

consensus standards in its regulatory 

activities unless to do so would be 

inconsistent with applicable law or 

impractical. Voluntary consensus 

standards are technical standards (e.g., 

materials specifications, test methods, 

sampling procedures, etc.) that are 

developed or adopted by voluntary 

consensus standards bodies. NTTAA 

directs EPA to provide Congress, 

through OMB, explanations when the 

Agency decides not to use available and 

applicable voluntary consensus 

standards. This regulation proposes the 

types of data to be required to support 

antimicrobial pesticide registration but 

does not propose to require specific 

methods or standards to generate those 

data. 

This proposed regulation does not 

impose any technical standards that 

would require Agency consideration of 

voluntary consensus standards. The 

Agency invites comment on its 

conclusion regarding the applicability of 

voluntary consensus standards to this 

rulemaking. 

J. Executive Order 12630 

EPA has complied with Executive 

Order 12630, entitled Governmental 

Actions and Interference with 

Constitutionally Protected Property 

Rights (53 FR 8859, March 15, 1988), by 

examining the takings implications of 

this rule in accordance with the 

‘‘Attorney General’s Supplemental 

Guidelines for the Evaluation of Risk 

and Avoidance of Unanticipated 

Takings’’ issued under the Executive 

Order. 

K. Executive Order 12988 

In issuing this rule, EPA has taken the 

necessary steps to eliminate drafting 

errors and ambiguity, minimize 

potential litigation, and provide a clear 

legal standard for affected conduct, as 

required by section 3 of Executive Order 

12988, entitled Civil Justice Reform (61 

FR 4729, February 7, 1996). 

L. Executive Order 13211 

This rule is not subject to Executive 

Order 13211, entitled ‘‘Actions 

concerning Regulations that 

Significantly Affect Energy Supply, 

Distribution, or Use’’ (66 FR 28355, May 

22, 2001) because it is not likely to have 

any adverse effect on the supply, 

distribution, or use of energy. 

Lists of Subjects in 40 CFR Part 158 

Environmental protection, 

Administrative practice and procedure, 

Agricultural commodities, Pesticides 

and pests, Reporting and record keeping 

requirements. 

Lists of Subjects in 40 CFR Part 161 

Environmental protection, 

Administrative practice and procedure, 

Agricultural commodities, Pesticides 

and pests, Reporting and record keeping 

requirements. 

Dated: September 24, 2008. 

Stephen L. Johnson, 

Administrator. 

Therefore, it is proposed that 40 CFR 

part 158 and part 161 be amended as 

follows: 

1. The authority citation for part 158 

continues to read as follows: 

Authority: 7 U.S.C. 136–136y and 21 

U.S.C. 346a. 

2. Section 158.1(c)(4) is revised to 

read as follows: 

§ 158.1 Purpose and scope. 

* * * * * 

(c) * * * 

(4) Antimicrobial pesticides. Subparts 

A, B, C, D, and W apply to antimicrobial 

pesticides. 

3. Section 158.100 is amended by 

revising the heading of paragraph (a); by 

revising paragraph (b); by redesignating 

paragraph (c) as paragraph (e); and by 

adding new paragraphs (c) and (d) to 

read as follows: 

§ 158.100 Pesticide use patterns. 

(a). General use patterns for 

conventional, biochemical, and 

microbial pesticides. * * * 

(b) Pesticide use site index for 

conventional, biochemical, and 

microbial pesticides. The Pesticide Use 

Site Index for Conventional, 

Biochemical, and Microbial Pesticides is 

a comprehensive list of specific 

pesticide use sites. The index is 

alphabetized separately by site for all 

agricultural and all nonagricultural 

uses. The Pesticide Use Site Index 

associates each pesticide use site with 

one or more of the 12 general use 

patterns. It may be used in conjunction 

with the data tables to determine the 

applicability of data requirements to 

specific uses. The Pesticide Use Site 

Index for Conventional, Biochemical, 

and Microbial Pesticides, which will be 

updated periodically, is available from 


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the Agency or may be obtained from the 

Agency’s website at http:// 

www.epa.gov/pesticides. 

(c) Antimicrobial pesticide use 

patterns. The general use patterns for 

antimicrobial pesticides are described in 

§ 158.2201. 

(d) Pesticide use site index for 

antimicrobial pesticides. The Pesticide 

Use Site Index for Antimicrobial 

Pesticides is a comprehensive list of 

specific antimicrobial use sites. The 

index is alphabetized by antimicrobial 

use sites, and associates each 

antimicrobial use site with one or more 

of the antimicrobial use patterns. It may 

be used in conjunction with the data 

tables to determine the applicability of 

data requirements to specific uses. The 

Pesticide Use Site Index for 

Antimicrobial Pesticides, which will be 

updated periodically, is available from 

the Agency or may be obtained from the 

Agency’s website at http:// 

www.epa.gov/pesticides/regulating/ 

usesite/. 

(e) * * * 

§ 158.400 [Amended] 

4. The table in § 158.400(d) is 

amended by removing the category 

‘‘Efficacy of antimicrobial agents’’ and 

all of the entries under that category. 

5. Part 158 is amended by adding 

subpart W to read as follows: 

Subpart W—Antimicrobial Pesticide 

Data Requirements 

Sec 

§ 158.2200 Applicability. 

§ 158.2201 Antimicrobial use patterns. 

§ 158.2203 Definitions. 

§ 158.2210 Product chemistry. 

§ 158.2220 Product performance. 

§ 158.2230 Toxicology data. 

§ 158.2240 Nontarget organisms. 

§ 158.2250 Nontarget plant protection. 

§ 158.2260 Applicator exposure. 

§ 158.2270 Post-application exposure. 

§ 158.2280 Environmental fate. 

§ 158.2290 Residue chemistry. 

Subpart W—Antimicrobial Pesticide 

Data Requirements 

§ 158.2200 Applicability. 

Subpart W establishes data 

requirements for any pesticide product 

that is: 

(a) A pesticide that is intended for use 

as an ‘‘antimicrobial pesticide’’ within 

the meaning of FIFRA section 

2(mm)(1)(A), regardless of whether it 

also meets the criterion of FIFRA 

section 2(mm)(1)(B). That criterion 

excludes from the definition any 

antimicrobial product that is intended 

for a food-use requiring a tolerance or 

exemption under FFDCA section 408 or 

a food additive regulation under FFDCA 

section 409. EPA will apply this subpart 

to all products intended for an 

antimicrobial use, purpose or function; 

the exclusion in FIFRA section 

2(mm)(1)(B) does not exclude products 

from the data requirements of this 

subpart. 

(b) A product that bears both 

antimicrobial and non-antimicrobial 

uses or claims is subject to the data 

requirements for pesticides in subparts 

C – O, and U or V of this part with 

respect to its non-antimicrobial uses and 

claims, and to the requirements of this 

subpart W with respect to its 

antimicrobial uses and claims. 

(c) A wood preservative, including a 

product that is intended to prevent 

wood degradation problems due to 

fungal rot or decay, sapstain, or molds. 

(d) An antifoulant, including a 

product that is intended to kill or repel 

organisms that can attach to underwater 

surfaces, such as boat bottoms. 

§ 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. 

(b) Use site index. The Antimicrobial 

Use Site Index is a comprehensive list 

of specific antimicrobial use sites. The 

Index associates antimicrobial use sites 

with one or more of the 12 antimicrobial 

use patterns. It is to be used in 

conjunction with the data tables in this 

subpart to determine the applicability of 

data requirements to specific uses. The 

Antimicrobial Pesticide Use Site Index, 

which will be updated periodically, is 

available from the Agency or may be 

obtained from the Agency’s website at 

http://www.epa.gov/pesticides/ 

regulating/usesite/. 

(c) An applicant unsure of the correct 

use pattern(s) for his product should 

consult the Agency. 

§ 158.2203 Definitions. 

(a) Definitions. The following terms 

are defined for the purposes of this 

subpart: 

(1) Disinfectant means a substance 

that destroys or eliminates a specific 

species of infectious or other public 

health microorganism, but not 

necessarily bacterial spores, in the 

inanimate environment. 

(2) Fungicide means a substance that 

destroys fungi (including yeasts) and 

fungal spores pathogenic to man or 

other animals in the inanimate 

environment. 

(3) Microbiological water purifier 

means any unit, water treatment 

product or system that removes, kills or 

inactivates all types of disease-causing 

microorganisms from the water, 

including bacteria, viruses and 

protozoan cysts, so as to render the 

treated water safe for drinking. 

(4) 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. 

(5) Sterilant means a substance that 

destroys or eliminates all forms of 

microbial life in the inanimate 

environment, including all forms of 

vegetative bacteria, bacterial spores, 

fungi, fungal spores, and viruses. For 

purposes of this subpart, ‘‘sporicide’’ 

and ‘‘sterilant’’ are synonymous. 

(6) Tuberculocide means a substance 

that destroys or irreversibly inactivates 

tubercle bacilli in the inanimate 

environment. 

(7) Virucide means a substance that 

destroys or inactivates viruses in the 

inanimate environment. 

(b) Public health claim. An 

antimicrobial pesticide is considered to 

make a public health claim if 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. 

A product makes a public health claim 

if one or more of the following apply: 

(1) A claim is made for control of 

specific microorganisms or classes of 

microorganisms that are directly or 

indirectly infectious or pathogenic to 

man (or both man and animals). 

Examples of specific microorganisms 

include, but are not limited to, 

Mycobacterium tuberculosis, 

Pseudomonas aeruginosa, Eschericha 

coli (E. coli), human immunodeficiency 

virus (HIV), Streptococcus, and 

Staphylococcus aureus. Claims for 

control of microorganisms infectious or 

pathogenic only to animals (such as 

canine distemper virus or hog cholera 

virus) are not considered public health 

claims. 


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(2) A claim is made for the pesticide 

product 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. 

(3) A claim is made for the pesticide 

product as a fungicide against fungi 

infectious or pathogenic to man, or the 

product does not clearly state that it is 

intended for use only against non-public 

health fungi. 

(4) A claim is made for the pesticide 

product as a microbiological water 

purifier or microbial purification 

system. 

(5) A non-specific claim is made that 

the pesticide product will beneficially 

impact or affect public health at the site 

of use or in the environment in which 

applied (such as a ‘sanitary’ claim), and: 

(i) The pesticide product contains one 

or more ingredients that, under the 

criteria in 40 CFR 153.125(a), is an 

active ingredient with respect to a 

public health microorganism and 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 public health claims. 

§ 158.2210 Product chemistry. 

The product chemistry data 

requirements of subpart D of this part 

apply to antimicrobial products covered 

by this subpart. 

§ 158.2220 Product performance. 

(a) General. (1) 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. 

(2) Product performance data for each 

product that bears a public health 

claim. Each product that bears a public 

health claim, as described in 

§ 158.2203(b), must be supported by 

product performance data, as listed in 

the table in this paragraph. Product 

performance data must be submitted 

with the application for registration or 

amended registration. 

(3) Determination of data 

requirements. Subpart B of this part and 

§ 158.2201 describe how to use the table 

in paragraph (c) of this section to 

determine the product performance data 

requirements for antimicrobial pesticide 

products. 

(b) Key. R = Required; EP = End-use 

product; 

(c) Table. The following table shows 

the data requirements for product 

performance. 

TABLE — ANTIMICROBIAL PRODUCT PERFORMANCE DATA REQUIREMENTS

Guideline Number Data Requirement All Use Patterns Test Substance 

91–2 Products for use on hard surfaces R EP 

91–3 Products requiring confirmatory 

data 

R EP 

91–4 Products for use on fabrics and 

textiles 

R EP 

91–5 Air sanitizers R EP 

91–7 Products for control of microbial 

pests associated with human 

and animal wastes 

R EP 

91–8 Products for treating water systems R EP 

§ 158.2230 Toxicology data. 

(a) General. Subpart B of this part and 

§ 158.2201 describe how to use the table 

in paragraph (d) of this section to 

determine the toxicology data 

requirements for an antimicrobial 

pesticide product. Notes that apply to 

an individual test including specific 

conditions, qualifications, or exceptions 

are listed in paragraph (e) of this 

section. 

(b) 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. 

(1) High human exposure uses. For 

the purpose of determining data 

requirements, high 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. High 

human exposure uses of antimicrobials 

include but are not limited to: 

(i) Any use which requires a tolerance 

or tolerance exemption (except for 

indirect food uses requiring a tolerance 

or tolerance exemption in which 

residues are less than 200 ppb). 

(ii) Indirect food uses with residues 

equal to or greater than 200 ppb. 

(iii) Use in human or animal drinking 

water. 

(iv) Fruit and vegetable rinses. 

(v) Egg washes. 

(vi) Swimming pools. 

(vii) Outdoor aquatic uses in lakes, 

rivers or streams which have the 

potential to contaminate potable water. 

(viii) Wood preservatives. 

(ix) Metalworking fluids. 

(2) Low human exposure nonfood and 

low human exposure indirect food uses. 

Generally, low exposure uses are those 

not listed in paragraph (b)(1) of this 

section as high exposure uses. 

(3) Tiering of data requirements. 

Applicants for registration of 

antimicrobials may perform tests in a 

tiered fashion. After the initially 

required tests are conducted, additional 

testing may be required if results of the 

initial tests trigger the need for 

additional data. Conditions that trigger 

the need for additional data are given in 

the test notes in paragraph (e) of this 

section. 


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(c) Key. R = Required; CR = 

Conditionally required; NR = Not 

required; MP = Manufacturing-use 

product; EP = End-use product; TGAI = 

Technical grade of the active ingredient; 

TEP = Typical end-use product; PAI = 

Pure active ingredient; PAIRA = Pure 

active ingredient, radiolabeled; Choice = 

choice of several test substances 

depending on studies required. 

(d) Table. The following table shows 

the data requirements for toxicology. 

The test notes appear in paragraph (e) of 

this section. 

TABLE — ANTIMICROBIAL TOXICOLOGY DATA REQUIREMENTS

Guideline Number Data Requirement 

Use Pattern Test Substance to Support 

High Test Note No. 

Human20Exposure 

Uses 

Low 

Human 

Exposure 

Uses 

MP EP 

Acute Testing 

870.1100 Acute oral toxicity - rat R R MP and 

TGAI 

EP and 

TGAI 

1, 2 

870.1200 Acute dermal toxicity R R MP and 

TGAI 

EP and 

TGAI 

1, 2, 3 

870.1300 Acute inhalation toxicity - rat R R MP and 

TGAI 

EP and 

TGAI 

4 

870.2400 Primary eye irritation - rabbit R R MP and 

TGAI 

EP and 

TGAI 

1, 2, 3 

870.2500 Primary dermal irritation R R MP and 

TGAI 

EP and 

TGAI 

1, 2, 3 

870.2600 Dermal sensitization R R MP and 

TGAI 

EP and 

TGAI 

1, 2, 3, 5 

870.6200 Acute neurotoxicity - rat R CR TGAI TGAI 6 

Subchronic Testing 

870.3100 90–Day oral toxicity - rodent R R TGAI TGAI 7, 8, 9, 15 

870.3150 90–Day oral toxicity - nonrodent R CR TGAI TGAI 7, 10, 11, 15 

870.3250 21/28–Day dermal toxicity CR CR TGAI EP and 

TGAI 

12, 13 

870.2500 90–Day dermal toxicity CR CR TGAI EP and 

TGAI 

7, 13, 14, 15 

870.3465 90–Day inhalation - toxicity - rat CR CR TGAI TGAI 7, 15, 16, 17 

870.6200 90–Day neurotoxicity - rat R CR TGAI TGAI 6, 8 

Chronic Testing 

870.4100 Chronic oral toxicity - rodent R CR TGAI TGAI 18, 19, 20 

870.4200 Carcinogenicity - two rodent species 

- rat and mouse preferred 

R CR TGAI TGAI 19, 21, 22 

Developmental Toxicity and Reproduction 

870.3700 Prenatal developmental toxicity - rat 

and rabbit preferred 

R R TGAI TGAI 23, 24, 25, 26 

870.3800 Reproduction and fertility effects R R TGAI TGAI 26, 27, 28, 29 

870.6300 Developmental neurotoxicity CR CR TGAI TGAI 28, 29, 30 

Mutagenicity 

870.5100 Reverse mutation assay R R TGAI TGAI 31, 32 

870.5300 

870.5375 

In vitro mammalian gene mutation R R TGAI TGAI 31, 33 


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TABLE — ANTIMICROBIAL TOXICOLOGY DATA REQUIREMENTS—Continued 

Guideline Number Data Requirement 

Use Pattern Test Substance to Support 

High Test Note No. 

Human20Exposure 

Uses 

Low 

Human 

Exposure 

Uses 

MP EP 

870.5380 

870.5385 

870.5395 

In vivo cytogenetics R R TGAI TGAI 31, 34 

Special Testing 

870.7485 Metabolism and pharmacokinetics R CR PAI or 

PAIRA 

PAI or 

PAIRA 

35 

870.7200 Companion animal safety CR CR NR Choice 36 

870.7600 Dermal penetration CR CR Choice Choice 37 

870.7800 Immunotoxicity R R TGAI TGAI -- 

(e) Test notes. The following test 

notes apply to the data requirements in 

the table to paragraph (d) of this section: 

1. Not required if test material is a gas or 

highly volatile liquid. 

2. For the six acute toxicity studies 

conducted with the end-use product, the test 

must be conducted using the product as 

formulated for sale and distribution. 

However, if the end-use product is labeled 

that the product is to be diluted for use, the 

applicant may also conduct certain studies 

using the highest diluted concentration (i.e. 

the least diluted product) permitted by the 

labeling. The end-use dilution testing is in 

addition to the as- formulated-for-sale testing 

and used only for labeling purposes. 

Consultation with the Agency is highly 

suggested to assure that the appropriate 

product and any appropriate dilutions are 

tested. 

3. Not required if test material is corrosive 

to skin or has pH less than 2 or greater than 

11.5. 

4. Data are required when the product 

consists of, or under conditions of use will 

result in, a respirable material (e.g., gas, 

vapor, aerosol or particulates). 

5. Data are required if repeated dermal 

exposure is likely to occur under conditions 

of use. 

6. For low exposure uses, data are required 

if the neurotoxicity screen in the 90–day oral 

rodent study or other data indicate 

neurotoxicity. 

7. 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. 

8. 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. 

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, 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. 

10. A 1–year non-rodent study (i.e., 1–year 

dog study) may be required if the Agency 

finds that a pesticide chemical is highly 

bioaccumulating and is eliminated slowly. 

Thus it does not achieve steady state or 

sufficient tissue concentrations to elicit an 

effect during a 90–day study. EPA may 

require the appropriate tier II metabolism and 

pharmacokinetic studies to evaluate more 

precisely bioavailability, half life, and steady 

state to determine if a longer duration dog 

toxicity study is needed. 

11. 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). 

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. 

13. 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. 

14. 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. 

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. 

16. Data are required if there is the 

likelihood of significant repeated inhalation 

exposure to the pesticide as a gas, vapor, or 

aerosol. 

17. 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. 

18. 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. 

19. 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. 

20. 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. 


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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. 

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. 

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. 

23. Testing in two species is required for 

all uses. 

24. 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. 

25. Additional testing by other routes of 

exposure may be required if the pesticide is 

determined to be a prenatal developmental 

toxicant after oral dosing. 

26. The developmental toxicity study in 

rodents may be combined with the twogeneration reproduction study in rodents by 

using a second mating of the parental 

animals in either generation. Protocols must 

be approved by the Agency prior to the 

initiation of the study. Details for developing 

protocols are available from the Agency. 

27. A two-generation reproduction study is 

required. 

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. 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. 

29. 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. 

30. 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). 

31. To enhance the weight-of-evidence 

determination for the pesticide’s 

mutagenicity, the Agency requires 

submission of other mutagenicity test results, 

besides those specifically listed in this table, 

that may have been performed for other 

endpoints that may be predictive of 

mutagenicity. A reference list of all studies 

and papers known to the applicant 

concerning the mutagenicity of the test 

chemical must be submitted with the 

required studies. 

32. 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. 

33. For the in vitro mammalian gene 

mutation study, there is a choice of assays 

using either mouse lymphoma L5178Y cell 

thymidine kinase (tk) gene locus, maximizing 

assay conditions for small colony expression 

and detection; Chinese hamster ovary (CHO) 

or Chinese hamster lung fibroblast (v79) 

cells, hypoxanthine-guanine phosphoribosyl 

transferase (hgprt) gene locus, accompanied 

by an appropriate in vitro test for 

clastogenicity; or CHO cells strains AS52, 

xanthine-guanine phosphoribosyl transferase 

(xprt) gene locus. 

34. 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. 

35. 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. 

36. These data may be required if the 

product’s use will result in exposure to 

domestic animals through, but not limited to, 

direct application. 

37. A risk assessment assuming that dermal 

absorption is equal to oral absorption must be 

performed to determine if the dermal 

penetration study is required, and to identify 

the doses and duration of exposure for which 

dermal absorption is to be quantified. 

§ 158.2240 Nontarget organisms. 

(a) General. Subpart B of this part and 

§ 158.2201 describe how to use the table 

in paragraph (e) of this section to 

determine the terrestrial and aquatic 

nontarget organisms and nontarget plant 

protection data requirements for a 

particular antimicrobial pesticide 

product. Notes that apply to an 

individual test including specific 

conditions, qualifications, or exceptions 

are listed in paragraph (f) of this section. 

(1) Terrestrial and aquatic nontarget 

organism data are required to support 

the registration of most end-use and 

manufacturing-use antimicrobial 

products. 

(2) Data are generally not required to 

support end-use products of a gas, 

highly volatile liquid, highly reactive 

solid, or a highly corrosive material. 

(3) If the Agency determines that the 

transformation products of the 

parentcompound are more toxic, 

persistent, bioaccumulative, or have 

been shown to cause adverse effects in 

mammalian or aquatic reproductive 

studies, then data on those 

transformation products are required to 

support registration. 

(4) 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 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). 

(b) Low environmental exposures. For 

the purpose of determining data 

requirements, the low environmental 

exposure grouping of use patterns 

includes the following use patterns or 

partial use patterns: 

(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) Swimming pools. 

(9) Recirculating industrial processes 

and water systems in which the treated 

water is re-used repeatedly within the 

system. 

(c) High environmental exposures. For 

the purposes of determining data 

requirements, the high environmental 

exposure grouping of use patterns 

includes the following use patterns or 

partial use patterns: 

(1) Once-through industrial processes 

and water systems in which the water 

is not re-used, and is released after a 

single cycle through the system. 


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(2) Antifoulant paints and coatings. 

(3) Wood preservatives. 

(4) Aquatic areas. 

(d) Key. MP = Manufacturing use 

product; EP = End use product; R = 

Required; CR = Conditionally required; 

NR = Not required; TGAI = Technical 

grade of the active ingredient; TEP = 

Typical end-use product; PAIRA = Pure 

active ingredient radiolabeled; a.i. = 

active ingredient. 

(e) Table. The following table shows 

the data requirements for nontarget 

organisms. The test notes appear in 

paragraph (f) of this section. 

TABLE — ANTIMICROBIAL NONTARGET ORGANISM DATA REQUIREMENTS

Guideline 

Number 

Data Requirement 

Use Pattern Test Substance to 

Support 

Test Note 

No. Low Environmental 

Exposure 

High Environmental Exposure 

MP EP 

Industrial 

Processes and 

Water Systems(OnceThrough) 

Antifoulant 

Coatings 

and Paints 

Wood Preservatives Aquatic 

Areas 

Tier One Testing 

850.2100 Acute avian oral 

toxicity 

R R R R R TGAI TGAI 1 

850.1010 Acute freshwater invertebrates toxicity R R R R R TGAI TGAI 2 

850.1075 Acute freshwater fish toxicity R R R R R TGAI TGAI 3 

Higher Tier Testing 

Avian Testing 

850.2200 Avian dietary 

toxicity 

CR CR CR CR R TGAI TGAI 4, 5 

850.2300 Avian reproduction CR CR CR CR R TGAI TGAI 1, 6 

Aquatic Organisms Testing 

850.1010 Acute freshwater invertebrates toxicity CR R NR NR R --- TEP 2, 7 

850.1075 Acute freshwater fish toxicity CR R NR NR R --- TEP 7 

850.1025 

850.1035 

850.1045 

850.1055 

850.1075 

Acute estuarine 

and marine 

organisms 

toxicity 

CR CR R CR CR TGAI TGAI 8, 9 

Acute estuarine 

and marine 

organisms 

toxicity 

CR CR NR NR CR --- TEP 7, 8 

850.1400 Fish early-life 

stage 

CR R R CR R TGAI TGAI 10 

850.1300 

850.1350 

Aquatic invertebrate lifecycle CR R R CR R TGAI TGAI 10 

850.1500 Fish life-cycle CR CR CR CR CR TGAI TGAI 11, 12 


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TABLE — ANTIMICROBIAL NONTARGET ORGANISM DATA REQUIREMENTS—Continued 

Guideline 

Number 

Data Requirement 

Use Pattern Test Substance to 

Support 

Test Note 

No. Low Environmental 

Exposure 

High Environmental Exposure 

MP EP 

Industrial 

Processes and 

Water Systems(OnceThrough) 

Antifoulant 

Coatings 

and Paints 

Wood Preservatives Aquatic 

Areas 

850.1710 

850.1730 

850.1850 

Aquatic organisms, bioavailability, 

biomagnification, toxicity 

tests 

CR CR CR CR CR TGAI.PAI, 

degradate 

TGAI.PAI, 

degradate 

13 

850.1950 Simulated or actual field testing for aquatic 

organisms 

CR CR CR CR CR TEP TEP 14, 15, 16 

Sediment Testing 

850.1735 Whole sediment; acute 

freshwater invertebrates 

CR CR R CR CR TGAI TGAI 15, 17 

850.1740 Whole sediment; acute 

marine invertebrates 

CR CR R CR CR TGAI TGAI 15, 17, 19 

None Whole sediment; chronic 

invertebrates 

fresh-water 

and marine 

CR CR CR CR CR TGAI TGAI 15, 18, 19 

Insect Pollinator Testing 

850.3020 Honeybee acute 

contact 

CR NR NR CR NR TGAI TGAI 20 

850.3030 Toxicity of residues to honeybees CR NR NR CR NR TGAI TEP or 

treated 

wood 

21 

(f) Test notes. The following test notes 

apply to the data requirements in the 

table to paragraph (e) of this section: 

1. For low environmental exposures, data 

are required for one avian species. For 

industrial processes and water systems (oncethrough), antifoulant paints and coatings, 

wood preservatives, and aquatic areas, data 

are required for one waterfowl species and 

one upland game bird species. 

2. Data are required on one freshwater 

aquatic invertebrate species. 

3. For low environmental exposures, data 

are required on one species of fish, either one 

cold water species or a warm water species. 

Testing on a second species is required if the 

active ingredient or principal transformation 

products are stable in the environment and 

the LC50 in the first species is greater than 1 

ppm or 1mg/L. For all other use patterns, 

data are required on two species of fish, one 

cold water species and one warm water 

species. 

4. For low environmental exposures, 

industrial processes and water systems (oncethrough), antifoulant paints and coatings, and 

wood preservatives, data are required for one 

waterfowl species, if the avian acute oral 

LD50 (TGAI testing) is less than or equal to 

100 mg a.i./kg and a.i. residues or its 

principal transformation products are likely 

to occur in avian feed items. Data on one 

upland game bird species are required if the 

avian dietary LC50 in the first species tested 

is less than or equal to 500 ppm a.i. in the 

diet. 

5. For aquatic areas, data are required on 

one waterfowl species and one upland game 

bird species. 

6. For low environmental exposures, 

industrial processes and water systems (oncethrough), antifoulant paints and coatings, and 

wood preservatives, data are required if one 

or more of the following criteria are met: 

i. Birds may be subjected to repeated or 

continued exposure to the pesticide or any of 

its transformation products, especially 

preceding or during the breeding season. 

ii. The pesticide or any of its major 

metabolites or degradation products are 

stable in the environment to the extent that 

a potentially toxic amount may persist in 

avian feed. 

iii. The pesticide or any of its major 

metabolites or degradation products are 

stored or accumulated in plant or animal 

tissues, as indicated by the octanol/water 

partition coefficient (Kow is greater than or 

equal to 1,000), accumulation studies, 

metabolic release and retention studies, or as 

indicated by structural similarity to known 

bioaccumulative chemicals. 

iv. Any other information, such as that 

derived from mammalian reproduction 

studies that indicate that reproduction in 

terrestrial vertebrates may be adversely 

affected by the anticipated use of the 

pesticide product. 


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7. 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 onehalf the LC50/EC50 of the TGAI when the enduse 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. 

8. Data are required on one estuarine/ 

marine mollusk, one estuarine/marine 

invertebrate, and one estuarine/marine fish 

species. 

9. For low environmental exposures, 

industrial processes and water systems (oncethrough), 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. 

10. For low environmental exposures, data 

are required if pesticide residues from the 

parent compound or transformation products 

are likely to enter freshwater or estuarine/ 

marine environments, as determined by the 

Agency. For wood preservatives, data are 

required if pesticide residues from the parent 

compound, transformation products, and/or 

leachates from preservative-treated wood are 

likely to enter freshwater or estuarine/marine 

environments, as determined by the Agency. 

Testing should be conducted with the most 

sensitive organism (either freshwater or 

estuarine/marine vertebrates, or freshwater or 

estuarine/marine invertebrates), as 

determined from the results of the acute 

toxicity tests (acute EC50 freshwater 

invertebrates; acute LC50/EC50 estuarine and 

marine organisms; acute freshwater fish 

LC50.) 

11. 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. 

12. 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-effect 

concentration or no-observed-effect level 

(NOEC/NOEL) 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. 

13. 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. 

14. 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. 

15. Protocols must be approved by the 

Agency prior to the initiation of the study. 

Details for developing protocols are available 

from the Agency. 

16. Data are required if the intended use 

pattern, and the physical/chemical properties 

and environmental fate characteristics of the 

antimicrobial indicate significant potential 

exposure and based on the results of the 

acute and chronic aquatic organism testing 

significant impairment of nontarget aquatic 

organisms could result. 

17. Data are required if the half-life of the 

pesticide in the sediment is equal to or less 

than 10 days in either the aerobic soil or 

aquatic metabolism studies, and if one or 

more of the following conditions are met: 

i. The soil partition coefficient (Kd) is equal 

to or greater than 50. 

ii. The log Kow is equal to or greater than 

3. 

iii. The Koc is equal to or greater than 

1,000. 

18. Data are required if the EEC in 

sediment is > 0.1 of the acute LC50/EC50

values and if one or more of the following 

conditions are met: 

i. The soil partition coefficient (Kd) is equal 

to or greater than 50 L/kg. 

ii. The log Kow is equal to or greater than 

3. 

iii. The Koc is equal to or greater than 

1,000. 

19. 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. 

20. Data are required only for beehive 

applications when the beehive (empty or 

occupied) is treated. 

21. 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. 

§ 158.2250 Nontarget plant protection. 

(a) General. Subpart B of this part and 

§ 158.2201 describe how to use the table 

in paragraph (e) of this section to 

determine the nontarget plant protection 

data requirements for a particular 

antimicrobial pesticide product. Notes 

that apply to an individual test 

including specific conditions, 

qualifications, or exceptions are listed 

in paragraph (f) of this section. 

(b) Low environmental exposures. For 

the purpose of determining data 

requirements, the low environmental 

exposure grouping of use patterns 

includes the following use patterns or 

partial use patterns: 

(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) Swimming pools. 

(9) Recirculating industrial processes 

and water systems in which the treated 

water is re-used repeatedly within the 

system. 

(c) High environmental exposures. For 

the purposes of determining data 

requirements, the high environmental 

exposure grouping of use patterns 

includes the following use patterns or 

partial use patterns: 

(1) Once-through industrial processes 

and water systems in which the water 

is not re-used, and is released after a 

single cycle through the system. 

(2) Antifoulant paints and coatings. 

(3) Wood preservatives. 

(4) Aquatic areas. 

(d) Key. MP = Manufacturing use 

product; EP = End use product; R = 

Required; CR = Conditionally required; 

NR = Not required; TGAI = Technical 

grade of the active ingredient; TEP = 

Typical end-use product. 

(e) Table. The following table shows 

the data requirements for nontarget 

plant protection. The test notes appear 

in paragraph (f) of this section. 


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TABLE — NONTARGET PLANT PROTECTION DATA REQUIREMENTS

Guideline 

Number 

Data Requirement 

Use Pattern Test Substance to Support 

Test Note 

Low Environ- No. 

mental Exposure 

High Environmental Exposure 

MP EP 

Industrial 

Processes 

and Water 

Systems(OnceThrough) 

Antifoulant 

Coatings 

and Paints 

Wood 

Preservatives 

Aquatic 

Areas 

850.4225 Seedling 

emergence, 

Tier II - 

dose response 

CR R R R R TEP TEP 1, 2 

850.4250 Vegetative 

vigor, Tier 

II - dose 

response 

CR CR NR R R TEP TEP 1, 3 

850.4400 Aquatic plant 

growth 

(aquatic 

vascular 

plant) Tier 

II - dose 

response 

CR R R R R TGAI, TEP TGAI, TEP 2, 4 

850.5400 Aquatic plant 

growth 

(algal) Tier 

II (dose 

response) 

R R R R R TGAI, TEP TGAI, TEP 4, 5, 6 

850.4300 Terrestrial 

field 

CR CR CR CR CR TEP TEP 7, 8, 9 

850.4450 Aquatic field CR CR CR CR CR TEP TEP 7, 8, 9 

(f) Test notes. The following test notes 

apply to the data requirements in the 

table to paragraph (e) of this section: 

1. Data on only one plant species (rice, 

Oryza sativa) are required. 

2. 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. 

3. For low environmental exposures, and 

industrial processes and water systems (oncethrough), data are required if one or more of 

the following criteria are met: 

i. The octanol/water partition coefficient 

(Kow) for the active ingredient or principal 

transformation products ≥ 1,000 for the active 

ingredient or principal transformation 

products; 

ii. The hydrolysis half-life of the active 

ingredient or principal transformation 

products in water is > 4 days. 

iii. The results of the ready 

biodegradability study [§ 158.2280] indicate 

that the active ingredient or principal 

degradation products are not biodegradable 

in 28 days, i.e. the biodegradation curve has 

not reached a plateau for at least three 

determinations within the 28 days. 

4. 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. 

5. 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. 

6. For industrial processes and water 

systems (once-through), antifoulant coatings 

and paints, wood preservatives, and aquatic 

areas, Tier II (dose response) studies are 

required on four species (Anabaena flosaquae, Navicula pelliculosa, Skeletonema 

costatum, and Selenastrum capricornutum. 

7. Environmental chemistry methods used 

to generate data must include the results of 

a successful confirmatory method trial by an 

independent laboratory. 

8. 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. 

9. Protocols must be approved by the 

Agency prior to the initiation of the study. 

Details for developing protocols are available 

from the Agency. 

§ 158.2260 Applicator exposure. 

(a) General. Subpart B of this part and 

§ 158.2201 describe how to use the table 

in paragraph (d) of this section to 

determine the applicator exposure data 

requirements for antimicrobial pesticide 

products. Notes that apply to an 

individual test including specific 

conditions, qualifications, or exceptions 

are listed in paragraph (e) of this 

section. 

(1) If EPA determines that industrial 

standards, such as the workplace 

standards set by the Occupational Safety 

and Health Administration, provide 

adequate protection for a particular 

pesticide or a particular use pattern, 

applicator exposure data may not be 

required for that pesticide or the use 

pattern. Applicants should consult with 

the Agency on appropriate testing before 

the initiation of studies. 

(2) The Agency may accept surrogate 

exposure data estimations from other 

sources to satisfy applicator exposure 

data requirements if the data meet the 


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basic quality assurance, quality control, 

good laboratory practice, and other 

scientific requirements set by EPA. In 

order to be acceptable, the Agency must 

find that the surrogate exposure data 

estimations have adequate information 

to address applicator exposure data 

requirements and contain enough 

adequate replicates of acceptable quality 

to reflect the specific use prescribed on 

the label and the applicator activity of 

concern, including formulation type, 

application methods and rates, type of 

activity, and other pertinent 

information. The Agency will consider 

using such surrogate data for evaluating 

human exposure on a case-by-case basis. 

(3) Occupational uses include not 

only handlers, mixers, loaders, and 

applicators, but also commercial 

applications to residential sites. 

Residential uses are limited to nonoccupational, i.e., non-professional, 

antimicrobial applications. Both 

occupational and residential applicator 

data may be required for the same 

product. 

(b) Criteria for testing. Applicator 

exposure data described in paragraph 

(d) of this section 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. 

(1) Toxicity criteria. i. Evidence of 

potentially significant adverse effects 

have been observed in any applicable 

toxicity studies. 

ii. Scientifically sound 

epidemiological or poisoning incident 

data indicate that adverse health effects 

may have resulted from handling of the 

pesticide. 

(2) Exposure criteria. i. Dermal 

exposure may occur during use. 

ii. Respiratory exposure may occur 

during use. 

(c) Key. R = Required; CR = 

Conditionally required; TEP = Typical 

end-use product. 

(d) Table. The following table shows 

the data requirements for applicator 

exposure. The test notes appear in 

paragraph (e) of this section. 

TABLE — ANTIMICROBIAL APPLICATOR EXPOSURE DATA REQUIREMENTS

Guideline Number Data Requirements Occupational Residential Test Substance Test Note No 

875.1100 Dermal outdoor exposure R R TEP 1, 2, 3 

875.1200 Dermal indoor exposure R R TEP 1, 2, 3, 4 

875.1300 Inhalation outdoor exposure R R TEP 1, 2, 3 

875.1400 Inhalation indoor exposure R R TEP 1, 2, 3, 4 

875.1500 Biological monitoring CR CR TEP 1, 2, 3 

875.1600 Data reporting and calculations R R TEP 5 

875.1700 Product use information R R TEP — 

(e) Test notes. The following test 

notes apply to the data requirements in 

the table to paragraph (d) of this section: 

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 

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. For metal working fluids (MWFs), the 

Agency can provide written guidance 

concerning exposure, toxicity, and other data 

requirements for ‘‘open’’ and ‘‘closed’’ MWF 

systems. 

5. Data reporting and calculations are 

required when handler exposure data are 

required. 

§ 158.2270 Post-application exposure. 

(a) General. Subpart B of this part and 

§ 158.2201 describe how to use the table 

in paragraph (d) of this section to 

determine the post-application exposure 

data requirements for antimicrobial 

pesticide products. The data generated 

during these studies are used to 

determine the quantity of pesticide to 

which people may be exposed after 

application. Notes that apply to an 

individual test, including specific 

conditions, qualifications, or exceptions 

to the designated test, are listed in 

paragraph (e) of this section. 

(1) For all end-use products, postapplication exposure data are required 

when certain toxicity criteria are met 

and the human activities associated 

with the pesticide’s use pattern can lead 

to potential adverse exposures. 

(2) 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 studies. 

(3) 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, 

good laboratory practice, and other 

scientific requirements set by EPA. In 

order to be acceptable, the Agency must 

find that the surrogate exposure data 

estimations have adequate information 

to address applicator exposure data 

requirements and contain enough 

adequate replicates of acceptable quality 

to reflect the specific use prescribed on 

the label and the applicator activity of 

concern, including formulation type, 

application methods and rates, type of 

activity, and other pertinent 

information. The Agency will consider 

using such surrogate data for evaluating 

human exposure on a case-by-case basis. 


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(b) Criteria for Testing. Postapplication exposure data described in 

paragraph (d) of this section 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. 

(1) Toxicity criteria. (i) Evidence of 

potentially significant adverse effects 

have been observed in any applicable 

toxicity studies. 

(ii) Scientifically sound 

epidemiological or poisoning incident 

data indicate that adverse health effects 

may have resulted from handling of the 

pesticide. 

(2) Exposure criteria. (i) Outdoor uses. 

(A) Occupational human postapplication exposure to residues of 

antimicrobial pesticides could occur as 

the result of, but is not limited to, 

worker re-entry into treatment sites, 

clean-up and equipment maintenance 

tasks, handling wood preservativetreated wood, or other work-related 

activity. 

(B) Residential human postapplication exposure to residues of 

antimicrobial pesticides could occur 

following the application of 

antimicrobials pesticides to outdoor 

areas and spaces at residential sites, 

such as, but not limited to homes, 

daycare centers, and other public 

buildings. 

(ii) Indoor uses. (A) Occupational 

human post-application exposure to 

pesticide residues could occur following 

the application of the antimicrobial 

pesticide to indoor spaces or surfaces. 

(B) Residential human postapplication exposure to pesticide 

residues could occur following the 

application of the antimicrobial 

pesticide to indoor spaces or surfaces at 

residential sites, such as, but not limited 

to homes, daycare centers, hospitals, 

schools, and other public buildings. 

(c) Key. R = Required; CR = 

Conditionally required; NR = Not 

required; TEP = Typical end-use 

product. 

(d) Table. The following table shows 

the data requirements for postapplication exposure. The test notes 

appear in paragraph (e) of this section. 

TABLE — ANTIMICROBIAL POST-APPLICATION EXPOSURE DATA REQUIREMENTS

Guideline Number Data Requirement 

Use Sites 

Test Substance Test Note 

No. Occupational Residential 

875.2200 Soil residue dissipation CR CR TEP 1, 2, 3 

875.2300 Indoor surface residue dissipation R R TEP 1, 3, 4, 5, 6 

875.2400 Dermal exposure R R TEP 1, 3, 7, 8 

875.2500 Inhalation exposure R R TEP 1, 8, 9 

875.2600 Biological monitoring CR CR TEP 1, 8, 10 

875.2700 Product use information R R TEP --- 

875.2800 Description of human activity R R TEP --- 

875.2900 Data reporting and calculations R R TEP 11 

875.3000 Non-dietary ingestion exposure NR R TEP 1, 12 

(e) Test notes. The following test 

notes apply to the data requirements in 

the table to paragraph (d) of this section: 

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. 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. 

3. 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. 

4. For wood preservatives, data are 

required for treated wood surfaces where 

post-application contact with treated wood is 

anticipated. 

5. 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. 

6. 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). 

7. 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. 

8. 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. 

9. 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. 

10. Biological monitoring data are required 

when passive dosimetry techniques are not 

applicable for a particular exposure scenario 

(such as a swimmer/spa exposure) and 

exposure estimates from modeling 

techniques used in conjunction with the 

toxicity data indicate a risk of concern. 

11. Data reporting and calculations are 

required when any post-application exposure 

monitoring data are required. 

12. 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-tomouth transfer, and object-to-mouth transfer 

of surface residues). 


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§ 158.2280 Environmental fate. 

(a) General. Subpart B of this part and 

§ 158.2201 describe how to use the table 

in paragraph (e) of this section to 

determine the environmental fate data 

requirements for antimicrobial pesticide 

products. Notes that apply to an 

individual test including specific 

conditions, qualifications, or exceptions 

are listed in paragraph (f) of this section. 

(1) Environmental fate data are 

required to support the registrations of 

all end-use and manufacturing-use 

antimicrobial products. 

(2) 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. 

(3) 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). 

(b) Low environmental exposures. For 

the purpose of determining data 

requirements, the low environmental 

exposure grouping of use patterns 

includes the following use patterns or 

partial use patterns: 

(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) Swimming pools. 

(9) Recirculating industrial processes 

and water systems in which the treated 

water is re-used repeatedly within the 

system. 

(c) High environmental exposures. For 

the purposes of determining data 

requirements, the high environmental 

exposure grouping of use patterns 

includes the following use patterns or 

partial use patterns: 

(1) Once-through industrial processes 

and water systems in which the water 

is not re-used, and is released after a 

single cycle through the system. 

(2) Antifoulant paints and coatings. 

(3) Wood preservatives. 

(4) Aquatic areas. 

(d) Key. MP = Manufacturing use 

product; EP = End use product; R = 

Required; CR = Conditionally required; 

NR = Not required; TGAI = Technical 

grade of the active ingredient; TEP = 

Typical end-use product; PAIRA = Pure 

active ingredient radiolabeled. 

(e) Table. The following table shows 

the data requirements for environmental 

fate. The test notes appear in paragraph 

(f) of this section. 

TABLE—ANTIMICROBIAL ENVIRONMENTAL FATE DATA REQUIREMENTS

Guideline 

Number Data Requirement 

Use Pattern Test Substance to Support 

Test Note 

No. Low Environmental 

Exposure 

High Environmental Exposure 

MP EP 

Industrial 

Pro-cesses 

and Water 

Systems(OnceThrough) 

Antifoulant 

Coatings 

and Paints 

Wood 

Preservatives 

Aquatic 

Areas 

Degradation Studies - Laboratory 

835.2120 Hydrolysis R R R R R TGAI or 

PAIRA 

TGAI or 

PAIRA 

1 

835.2240 Photodegradation in 

water 

R R R R R TGAI or 

PAIRA 

TGAI or 

PAIRA 

2 

835.2410 Photodegradation in 

soil 

NR NR NR R NR TGAI or 

PAIRA 

TGAI or 

PAIRA 

-- 

Biodegradation Studies - Laboratory 

835.1110 Activated Sludge 

Sorption Isotherm 

R R NR NR NR TGAI TGAI -- 

835.3110 Ready 

Biodegradability 

R R NR NR NR TGAI TGAI 3 

850.6800 Modified Activated 

Sludge, Respiration 

Inhibition Test 

R R NR NR NR TGAI TGAI -- 

835.3220 Porous Pot Study CR CR NR NR NR TGAI TGAI 4 

Mobility Studies 

835.1230 

835.1240 

Leaching and adsorption/desorption CR R R R R TGAI or 

PAIRA 

TGAI or 

PAIRA 

5, 7 

Metabolism Studies - Laboratory 


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TABLE—ANTIMICROBIAL ENVIRONMENTAL FATE DATA REQUIREMENTS—Continued 

Guideline 

Number Data Requirement 

Use Pattern Test Substance to Support 

Test Note 

No. Low Environmental 

Exposure 

High Environmental Exposure 

MP EP 

Industrial 

Pro-cesses 

and Water 

Systems(OnceThrough) 

Antifoulant 

Coatings 

and Paints 

Wood 

Preservatives 

Aquatic 

Areas 

835.4100 Aerobic soil metabolism CR CR NR R CR TGAI or 

PAIRA 

TGAI or 

PAIRA 

5, 6, 8, 9 

835.4200 Anaerobic soil metabolism CR NR NR CR NR TGAI or 

PAIRA 

TGAI or 

PAIRA 

5, 8, 10 

835.4300 Aerobic aquatic metabolism CR R R CR R TGAI or 

PAIRA 

TGAI or 

PAIRA 

5, 8, 10 

835.4400 Anaerobic aquatic metabolism CR R R CR R TGAI or 

PAIRA 

TGAI or 

PAIRA 

5, 8, 10 

Dissipation Studies -- Field 

835.6200 Aquatic (sediment) CR CR CR CR R TEP TEP 5, 11, 12, 

13 

Ground and Surface Water Monitoring 

None Monitoring of representative U.S. waters CR CR CR CR CR residue of 

concern 

residue of 

concern 

11, 12, 

14 

Special Studies 

None Special leaching NR NR R R NR TGAI TEP 15, 16 

(f) Test notes. The following test notes 

apply to the data requirements in the 

table in paragraph (e) of this section: 

1. 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. 

2. 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. 

3. 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. 

4. Required if the pass criteria for the ready 

biodegradation study are not met. This means 

70% or greater removal of dissolved organic 

carbon and 60% or greater of theoretical 

oxygen demand or theoretical carbon 

dioxide. These pass values must be reached 

in a 10–day window within the 28–day 

period of the test. 

5. 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. 

6. For industrial processes and water 

systems (once-through), data are required 

based on a weight-of-evidence evaluation of 

the results of the hydrolysis, 

photodegradation in water, activated sludge 

sorption isotherm, ready biodegradability, 

and modified activated sludge, respiration 

inhibition tests. 

7. Adsorption and desorption using a batch 

equilibrium method is preferred. In some 

cases, as when the antimicrobial pesticide 

degrades rapidly, soil column leaching with 

unaged or aged columns may be more 

appropriate to fully characterize the potential 

mobility of the parent compound and major 

transformation products. 

8. The environmental media (soil, water, 

hydrosoil, and biota) to be utilized in these 

studies must be collected from areas 

representative of potential use sites. 

9. For industrial processes and water 

systems (once-through), and aquatic areas, 

data are required for use sites that are 

intermittently dry. 

10. For wood preservatives, data are 

required if treated wood is used in aquatic 

environments or in soils which may become 

flooded or waterlogged. 

11. Environmental chemistry methods used 

to generate data associated with this study 

must include results of a successful 

confirmatory method trial by an independent 

laboratory. 

12. Protocols must be approved by the 

Agency prior to the initiation of the study. 

Details for developing protocols are available 

from the Agency. 

13. For industrial processes and water 

systems (once-through), antifoulant paints 

and coatings, and wood preservatives, data 

are required based on the potential for 

aquatic exposure and if the 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. 

14. Data are required if the weight-ofevidence 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. 

15. For wood preservatives, an aquatic 

leaching study is required. A soil leaching 

study is required if human or environmental 

exposures are likely to occur from leachates 

that contain the active ingredient or principal 

transformation products from wood treated 

with a preservative product. For these 

studies, the Agency accepts the following 

methods or their equivalents: American 

Wood Preservers’ Association (AWPA) 

Method E11–97 (aquatic leaching), and 

AWPA Method E20–04 (soil leaching). Prior 

approval of studies conducted according to 

E11–97 is not required. All other protocols 


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59444 Federal Register / Vol. 73, No. 196 / Wednesday, October 8, 2008 / Proposed Rules 

must be approved by the Agency prior to the 

initiation of the study. Details for developing 

protocols are available from the Agency. 

16. 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. 

§ 158.2290 Residue chemistry. 

(a) General. Subpart B of this part and 

§ 158.2201 describe how to use the table 

in paragraph (f) of this section to 

determine the residue chemistry data 

requirements for antimicrobial pesticide 

products. 

(b) Residue chemistry data are 

required for products described in this 

paragraph. 

(1) Each end-use product bearing label 

directions for food-uses that require a 

tolerance or tolerance exemption, 

including, but not limited to the 

following: 

(i) Direct food uses such as 

antimicrobial products used to treat 

animal or poultry drinking water, for 

egg washing, or fruit and vegetable 

rinses. 

(ii) Indirect food uses such as 

antimicrobial products applied to a 

surface or incorporated into a material 

that may contact food or feed. Residues 

may be expected to transfer to such food 

or feed. Data are required regardless of 

whether the antimicrobial is applied or 

impregnated for the purpose of 

imparting antimicrobial protection to 

external surfaces of the substance or 

article, or for the purpose of protecting 

the substance or article itself. 

(iii) Aquatic uses that have the 

potential to result in residues in potable 

water, or in water used for livestock and 

poultry drinking water, irrigation of 

crops, or water containing fish that may 

be used for human food. 

(iv) Wood preservative or antifoulant 

products intended for treating wood that 

may be used for food purposes (e.g., 

lobster pots, fish cages, or fish farms). 

(2) Each manufacturing-use product 

bearing directions for formulation into 

an end-use product bearing food-uses 

described in paragraph (b)(1) of this 

section. 

(c) Except as described in paragraph 

(b) of this section, residue chemistry 

data are not required to support a 

tolerance exemption if dietary exposure 

estimates are not needed due to low 

toxicity of the active ingredient or 

theoretical (modeled) estimates of 

exposure are adequate to assess dietary 

risk. 

(d) Key. R = Required; CR = 

Conditionally required; NR = Not 

required; TGAI = Technical grade of the 

active ingredient; TEP = Typical enduse product; PAI = Pure active 

ingredient; PAIRA = Pure active 

ingredient radiolabeled; the residue of 

concern is determined by the Agency. 

(e) Table. The following table shows 

the data requirements for residue 

chemistry. The test notes appear in 

paragraph (f) of this section. 

TABLE — ANTIMICROBIAL RESIDUE CHEMISTRY DATA REQUIREMENTS

Guideline Number Data Requirement 

Use Pattern 

Test substance Test Note 

No. Agricultural 

Premises 

Indirect 

Food 

Uses 

Direct 

Food 

Contact 

Uses 

Aquatic 

Uses 

Supporting Information 

860.1100 Chemical identity R R R R TGAI -- 

860.1200 Directions for use R R R R -- -- 

860.1550 Proposed tolerance R R R R -- 1 

860.1560 Reasonable grounds in support of 

petition 

R R R R -- 1 

860.1650 Submittal of analytical reference 

standards 

R R R R PAI and residue of 

concern 

2 

Nature of the residue 

860.1300 Nature of the residue in plants CR NR R R PAIRA 3, 4, 5 

860.1300 Nature of the residue in livestock R NR CR CR PAIRA or radiolabeled 

plant metabolite 

6, 7, 8 

Analytical methods 

860.1340 Residue analytical methods for enforcement of tolerances CR CR R CR Residue of concern 9 

860.1340 Residue analytical methods for data 

collection 

CR CR R CR Residue of concern 10 

860.1360 Multiresidue method testing CR CR R CR Residue of concern 11 

Magnitude of the residue 

860.1380 Storage stability R R R R TEP or residue of 

concern 

12 


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TABLE — ANTIMICROBIAL RESIDUE CHEMISTRY DATA REQUIREMENTS—Continued 

Guideline Number Data Requirement 

Use Pattern 

Test substance Test Note 

No. Agricultural 

Premises 

Indirect 

Food 

Uses 

Direct 

Food 

Contact 

Uses 

Aquatic 

Uses 

860.1500 Crop field trials CR CR R R TEP 13, 14 

860.1520 Processed food or feed NR CR CR CR TEP 15 

860.1480 Meat/milk/poultry/eggs CR CR CR CR TGAI or plant metabolite 16, 17 

860.1400 Potable water R NR NR R TEP 18 

860.1400 Fish NR NR NR R TEP 19 

860.1400 Irrigated crops NR NR NR CR TEP 20 

860.1460 Food-handling NR CR R NR TEP 21 

860.1540 Anticipated residues CR CR CR CR Residue of concern 22 

None Migration studies NR CR NR NR TGAI 23 

(f) Test notes. The following test notes 

apply to the data requirements in the 

table to paragraph (e) of this section: 

1. A petition proposing a numerical 

tolerance or a tolerance exemption is 

required for any food or feed use subject to 

section 408 of the FFDCA if the use is not 

covered by an existing tolerance or tolerance 

exemption. 

2. An analytical reference standard is 

required for any food or feed use requiring 

a tolerance. Material safety data sheets must 

accompany analytical standards as specified 

by OSHA in 29 CFR 1910.1200. 

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. 

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. 

9. A residue analytical method suitable for 

enforcement purposes is required whenever 

a numeric tolerance is proposed. 

Enforcement methods must be supported by 

results of an independent laboratory 

validation. 

10. A residue analytical method suitable 

for collecting data to establish tolerances 

must quantitate all residues of concern, as 

determined by the Agency. 

11. Data are required to determine whether 

the FDA/USDA multiresidue methodology 

would detect and identify the antimicrobial 

active ingredient and its metabolites. 

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. 

13. Residue data are required if 

antimicrobial chemicals are to be applied to 

mushroom houses, empty or occupied 

beehives, wood used to construct beehives, 

or any use which could result in residues in 

food or feed. 

14. If the antimicrobial chemical is applied 

to growing crops in the field, then the 

requirements of 40 CFR part 158, subpart O 

(terrestrial food or feed use pattern) apply. 

15. Data on the nature and level of residues 

in processed food or feed are required if 

residues could potentially concentrate on 

processing, thus requiring the establishment 

of a separate tolerance higher than that of the 

raw agricultural commodity. 

16. Data are required when the pesticide 

use is a direct application to livestock. 

17. Data are required if livestock premises 

are treated or if pesticide residues are present 

in or on livestock feed items or intentionally 

added to drinking water. These studies, 

however, may not be required in cases where 

the livestock metabolism studies indicate 

negligible transfer of pesticide residues of 

concern to tissues, milk, and eggs at the 

maximum expected exposure level for the 

animals. 

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. 

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. 

20. Data are required for antimicrobial 

pesticides applied directly to water that 

could be used for irrigation or to irrigation 

facilities such as ditches. 

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. 

22. Data are required when estimates of 

risk using residues at the tolerance level may 

result in a risk of concern. These data may 

include washing, cooking, processing or 

degradation studies as well as market basket 

surveys for a more precise residue 

determination. 


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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. 

PART 161—[AMENDED] 

6. The authority citation for part 161 

continues to read as follows: 

Authority: 7 U.S.C. 136 – 136y. 

Part 161 [Removed] 

7. Part 161 is removed: 

[FR Doc. E8–23127 Filed 10–7–08; 8:45 am] 

BILLING CODE 6560–50–S 


sroberts on PROD1PC70 with PROPOSALS