
[Federal Register: October 8, 2008 (Volume 73, Number 196)]
[Proposed Rules]               
[Page 59381-59446]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr08oc08-31]                         


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Part III





Environmental Protection Agency





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40 CFR Parts 158 and 161



Data Requirements for Antimicrobial Pesticides; Proposed Rule


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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.

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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 e-
mail. 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 screening-level 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 down-the-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 Sec.  158.75 
and Sec.  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 Sec.  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 
food-use 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 
tolerance-setting 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 step-wise 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 Sec.  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

[[Page 59387]]

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-of-evidence 
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 higher-tiered 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-by-case 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,

[[Page 59388]]

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 call-in 
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

[[Page 59389]]

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 Sec.  
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. Once-through 
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 re-used 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

[[Page 59390]]

ecological effects, the industrial processes and water systems use 
pattern will be subdivided. Because of the distinct differences between 
the once-through and recirculating water systems, the once-through 
water system will be grouped with those use patterns with potential for 
higher environmental exposures and the recirculating water system with 
those use patterns with the potential for lower environmental 
exposures.
    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 re-
titled, 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.

[[Page 59391]]

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 (Sec.  158.2220) at this time. At this time there are 
nearly identical product performance data requirements for 
antimicrobial chemicals in both Sec.  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 Sec.  158.2220. The table is transferred essentially 
unchanged. EPA is also proposing to delete the duplicative data 
requirements for antimicrobials from the table in Sec.  158.400. After 
the publication of the final rule, all product performance data 
requirements for antimicrobials will be contained in Sec.  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, post-application, 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, post-application monitoring 
data, use information, and human activity information. Applicator and 
post-application 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.

[[Page 59392]]

    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 Call-In (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 
first-tier 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 
medium-exposure 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 Sec.  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 Sec.  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

[[Page 59394]]

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 Sec.  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 case-by-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

[[Page 59395]]

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 (non-rodent). 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 range-finding 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 end-use product if the product 
or any component of the product may increase dermal absorption of the 
active ingredient(s) or could potentiate toxic or pharmacologic 
effects. 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 end-use 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. Post-application 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 Sec.  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.

[[Page 59396]]

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 post-natally 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 food-use 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-
of-evidence 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.

[[Page 59397]]

    For conventional pesticides, the Agency requires in Sec.  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 non-mutagenicity. 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 Sec.  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 (Sec.  158.2260 
and Sec.  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

[[Page 59398]]

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 
Sec.  158.2260 and Sec.  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 post-
application 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 Sec.  158.2260 and Sec.  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 Sec.  158.2260 and set out explicitly in Sec.  
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

[[Page 59399]]

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 post-application. The guideline for post-application 
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 
Sec.  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 post-application 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 Sec.  158.2270 and set out 
explicitly in Sec.  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-by-case 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.

[[Page 59400]]

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 post-application 
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 post-application 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 post-application exposure, required 
product use information includes information on reapplication rates and 
frequencies, post-application entry restrictions, re-entry 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 post-application), 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 
non-dietary 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-to-mouth, 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-to-mouth 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

[[Page 59401]]

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-by-case 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 
(Sec.  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 food-uses 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 Sec.  
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

[[Page 59402]]

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 food-contact 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 screening-level 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 food-use 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

[[Page 59403]]

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 Sec.  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 
Sec.  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 Sec.  
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 Sec.  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-by-side 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

[[Page 59404]]

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 Sec.  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 food-uses, 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 (over-estimated) 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 worst-case 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

[[Page 59405]]

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 Sec.  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 (Sec.  158.2280) 
and ecotoxicity (Sec.  158.2240 and Sec.  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 (Sec.  158.2280) 
and ecotoxicity (Sec.  158.2240 and Sec.  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, aquatic-only 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.

[[Page 59406]]

    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 (Sec.  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 higher-tiered 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; food-handling/storage 
establishments premises and equipment; commercial, institutional and 
industrial premises and equipment; residential and public access 
premises; medical premises and equipment; human drinking water systems; 
materials preservatives; and swimming pools. 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

[[Page 59407]]

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 down-the-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 
down-the-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 lower-tiered 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 higher-tiered 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 down-the-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-the-drain, 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 lower-tiered 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 Structure-Activity-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 three-pronged 
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-the-Drain 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 E-FAST.
    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

[[Page 59408]]

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 
weight-of-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 in-depth 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 Down-the-Drain 
Screening Model, Using the Proposed Approach for a Screening-Level 
Environmental fate Assessment'' (Ref. 42) reflect a particular 
integration

[[Page 59409]]

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 ``worst-case'' 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-the-drain.

                         Table 1.--Case Studies
------------------------------------------------------------------------
                   Study                               Results
------------------------------------------------------------------------
Chemical A: A Chemical that Does Not        The proposed approach
 Hydrolyze and Only Partially Biodegrades    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 higher-
                                             tier ecotoxicity studies
                                             are needed to determine
                                             risk to nontarget species.
------------------------------------------------------------------------
Chemical B: A Chemical Which Is Stable to   The proposed approach
 Hydrolysis, But There Is No Data on the     indicated that the lower
 Potential to Biodegrade During Wastewater   tiered environmental fate
 Treatment or Adsorb to Activated Sludge     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.
------------------------------------------------------------------------
Chemical C: An Organic Acid that is Highly  There are no data to show
 Soluble in Water                            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 in-depth 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 down-the-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

[[Page 59410]]

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

[[Page 59411]]

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 (oxygen-poor) 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

[[Page 59412]]

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-
of-evidence indicates that the active ingredient or principal 
transformation products are likely to have the potential for 
persistence, mobility, nontarget aquatic toxicity or bioaccumulation. 
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-of-evidence 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 Sec.  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 
(Sec.  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 Sec.  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 co-incident 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 Sec.  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

[[Page 59413]]

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-of-
evidence 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 Sec.  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

[[Page 59414]]

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-by-case 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 once-through 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 once-through 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 Sec.  161.490.

I. Fish Early Life Stage and Aquatic Invertebrate Life-Cycle Study

    The Agency proposes in Sec.  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 early-life 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.

[[Page 59415]]

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-by-case 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 sediment-bound 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 Sec.  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 Sec.  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

[[Page 59416]]

studies specify two types of tests: Single-dose studies (referred to in 
the guidelines as Tier I tests) and multiple-dose studies (Tier II). 
Usually, the applicant would conduct the single-dose 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 - Dose-Response)

    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 - Dose-Response)

    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 - Dose-Response)

    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

[[Page 59417]]

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 Sec.  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

[[Page 59418]]

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 non-
dietary 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

[[Page 59419]]

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 non-occupational exposure assessments that are 
sufficiently conservative as to not underestimate exposures. The data 
requirements proposed for post-application 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 re-evaluation/
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

[[Page 59420]]

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 co-operation 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 Sec.  
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.

[[Page 59421]]

    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 third-party 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 Sec.  158.2260 and Sec.  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 
Sec. 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 in-depth, 
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, guideline-driven (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.

[[Page 59422]]

    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 well-
conducted 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-by-study) 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

[[Page 59423]]

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 dose-response data from other guideline or non-guideline studies, 
but also structure-activity relationships, data on the mechanism or 
mode of action of the chemical, pharmacokinetic data, studies that 
examine 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 
re-design 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

[[Page 59424]]

(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 near-term 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

[[Page 59425]]

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.

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    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

[[Page 59427]]

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

[[Page 59428]]

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%).

[[Page 59429]]

     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,

[[Page 59430]]

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:


Sec.  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:


Sec.  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

[[Page 59431]]

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 Sec.  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) * * *


Sec.  158.400  [Amended]

    4. The table in Sec.  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
Sec.  158.2200 Applicability.
Sec.  158.2201 Antimicrobial use patterns.
Sec.  158.2203 Definitions.
Sec.  158.2210 Product chemistry.
Sec.  158.2220 Product performance.
Sec.  158.2230 Toxicology data.
Sec.  158.2240 Nontarget organisms.
Sec.  158.2250 Nontarget plant protection.
Sec.  158.2260 Applicator exposure.
Sec.  158.2270 Post-application exposure.
Sec.  158.2280 Environmental fate.
Sec.  158.2290 Residue chemistry.

Subpart W--Antimicrobial Pesticide Data Requirements


Sec.  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.


Sec.  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.


Sec.  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.

[[Page 59432]]

    (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.


Sec.  158.2210  Product chemistry.

    The product chemistry data requirements of subpart D of this part 
apply to antimicrobial products covered by this subpart.


Sec.  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 Sec.  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 
Sec.  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      R                        EP
                                        hard surfaces
----------------------------------------------------------------------------------------------------------------
91-3                                   Products requiring       R                        EP
                                        confirmatory data
----------------------------------------------------------------------------------------------------------------
91-4                                   Products for use on      R                        EP
                                        fabrics and textiles
----------------------------------------------------------------------------------------------------------------
91-5                                   Air sanitizers           R                        EP
----------------------------------------------------------------------------------------------------------------
91-7                                   Products for control of  R                        EP
                                        microbial pests
                                        associated with human
                                        and animal wastes
----------------------------------------------------------------------------------------------------------------
91-8                                   Products for treating    R                        EP
                                        water systems
----------------------------------------------------------------------------------------------------------------

Sec.  158.2230  Toxicology data.

    (a) General. Subpart B of this part and Sec.  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.

[[Page 59433]]

    (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
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                    Use Pattern           Test Substance to Support
                                                                           ---------------------------------------------------------
              Guideline Number                      Data Requirement              High        Low Human                                 Test Note No.
                                                                            Human20Exposure   Exposure        MP            EP
                                                                                  Uses          Uses
--------------------------------------------------------------------------------------------------------------------------------------------------------
 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 -               R             R   MP and TGAI   EP and TGAI                    4
                                              rat
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.2400                                     Primary eye irritation -                  R             R   MP and TGAI   EP and TGAI              1, 2, 3
                                              rabbit
--------------------------------------------------------------------------------------------------------------------------------------------------------
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 -                    R              CR        TGAI          TGAI        7, 10, 11, 15
                                              nonrodent
--------------------------------------------------------------------------------------------------------------------------------------------------------
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 -             CR            CR        TGAI          TGAI        7, 15, 16, 17
                                               rat
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.6200                                     90-Day neurotoxicity - rat                R              CR        TGAI          TGAI                 6, 8
--------------------------------------------------------------------------------------------------------------------------------------------------------
 Chronic Testing........................................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.4100                                     Chronic oral toxicity -                   R              CR        TGAI          TGAI           18, 19, 20
                                              rodent
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.4200                                     Carcinogenicity - two rodent              R              CR        TGAI          TGAI           19, 21, 22
                                              species - rat and mouse
                                              preferred
--------------------------------------------------------------------------------------------------------------------------------------------------------
 Developmental Toxicity and Reproduction................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.3700                                     Prenatal developmental                    R             R          TGAI          TGAI       23, 24, 25, 26
                                              toxicity - rat and rabbit
                                              preferred
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.3800                                     Reproduction and fertility                R             R          TGAI          TGAI       26, 27, 28, 29
                                              effects
--------------------------------------------------------------------------------------------------------------------------------------------------------
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                                     In vitro mammalian gene                   R             R          TGAI          TGAI               31, 33
870.5375...................................   mutation
--------------------------------------------------------------------------------------------------------------------------------------------------------

[[Page 59434]]


870.5380                                     In vivo cytogenetics                      R             R          TGAI          TGAI               31, 34
870.5385...................................
870.5395...................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
 Special Testing........................................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.7485                                     Metabolism and                            R              CR PAI or PAIRA  PAI or PAIRA                  35
                                              pharmacokinetics
--------------------------------------------------------------------------------------------------------------------------------------------------------
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.

[[Page 59435]]

    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 two-generation reproduction study in rodents by using a 
second mating of the parental animals in either generation. 
Protocols must be approved by the Agency prior to the initiation of 
the study. Details for developing protocols are available from the 
Agency.
    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.


Sec.  158.2240  Nontarget organisms.

    (a) General. Subpart B of this part and Sec.  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.

[[Page 59436]]

    (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
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                 Use Pattern                                   Test Substance to
                                                                                  -------------------------------------------------------------------------         Support
                                                                                                                 High Environmental Exposure               ------------------------
                                                                                                 ----------------------------------------------------------                           Test Note
               Guideline Number                          Data Requirement               Low          Industrial                                                                          No.
                                                                                   Environmental   Processes and    Antifoulant       Wood        Aquatic       MP          EP
                                                                                      Exposure     Water Systems   Coatings and  Preservatives     Areas
                                                                                                   (Once-Through)     Paints
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Tier One Testing................................................................................................................................................................................
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.2100                                        Acute avian oral toxicity                    R                 R             R              R           R        TGAI        TGAI             1
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1010                                        Acute freshwater invertebrates               R                 R             R              R           R        TGAI        TGAI             2
                                                 toxicity
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
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                CR               R            NR             NR           R         ---         TEP          2, 7
                                                 toxicity
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1075                                        Acute freshwater fish toxicity                CR               R            NR             NR           R         ---         TEP             7
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1025                                        Acute estuarine and marine                    CR                CR           R               CR          CR      TGAI        TGAI          8, 9
850.1035......................................   organisms toxicity
850.1045......................................
850.1055......................................
850.1075......................................
                                               -------------------------------------------------------------------------------------------------------------------------------------------------
                                                Acute estuarine and marine                    CR                CR          NR             NR            CR       ---         TEP          7, 8
                                                 organisms toxicity
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1400                                        Fish early-life stage                         CR               R             R               CR         R        TGAI        TGAI            10
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1300                                        Aquatic invertebrate life- cycle              CR               R             R               CR         R        TGAI        TGAI            10
850.1350......................................
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1500                                        Fish life-cycle                               CR                CR            CR             CR          CR      TGAI        TGAI        11, 12
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

[[Page 59437]]


850.1710                                        Aquatic organisms,                            CR                CR            CR             CR          CR TGAI.PAI,   TGAI.PAI,            13
850.1730......................................   bioavailability,                                                                                           degradate   degradate
850.1850......................................   biomagnification, toxicity tests
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1950                                        Simulated or actual field testing             CR                CR            CR             CR          CR       TEP         TEP    14, 15, 16
                                                 for aquatic organisms
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                        Sediment Testing
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1735                                        Whole sediment; acute freshwater              CR                CR           R               CR          CR      TGAI        TGAI        15, 17
                                                 invertebrates
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1740                                        Whole sediment; acute marine                  CR                CR           R               CR          CR      TGAI        TGAI    15, 17, 19
                                                 invertebrates
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
None                                            Whole sediment; chronic                       CR                CR            CR             CR          CR      TGAI        TGAI    15, 18, 19
                                                 invertebrates fresh-water and
                                                 marine
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                    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            21
                                                                                                                                                                          treated
                                                                                                                                                                             wood
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

    (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 (once-
through), 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 (once-through), antifoulant paints and coatings, and 
wood preservatives, data are required for one waterfowl species, if 
the avian acute oral LD50 (TGAI testing) is less than or 
equal to 100 mg a.i./kg and a.i. residues or its principal 
transformation products are likely to occur in avian feed items. 
Data on one upland game bird species are required if the avian 
dietary LC50 in the first species tested is less than or 
equal to 500 ppm a.i. in the diet.
    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 (once-through), antifoulant paints and coatings, and 
wood preservatives, data are required if one or more of the 
following criteria are met:
    i. Birds may be subjected to repeated or continued exposure to 
the pesticide or any of its transformation products, especially 
preceding or during the breeding season.
    ii. The pesticide or any of its major metabolites or degradation 
products are stable in the environment to the extent that a 
potentially toxic amount may persist in avian feed.
    iii. The pesticide or any of its major metabolites or 
degradation products are stored or accumulated in plant or animal 
tissues, as indicated by the octanol/water partition coefficient 
(Kow is greater than or equal to 1,000), accumulation 
studies, metabolic release and retention studies, or as indicated by 
structural similarity to known bioaccumulative chemicals.
    iv. Any other information, such as that derived from mammalian 
reproduction studies that indicate that reproduction in terrestrial 
vertebrates may be adversely affected by the anticipated use of the 
pesticide product.

[[Page 59438]]

    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 one-half the 
LC50/EC50 of the TGAI when the end-use product 
is used as directed.
    ii. An ingredient in the end-use product other than the active 
ingredient is expected to enhance the toxicity of the active 
ingredient or to cause toxicity to aquatic organisms.
    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 (once-through), wood preservatives, and aquatic areas, 
data are required if the pesticide residues from the parent compound 
and/or transformation products are likely to enter the estuarine/
marine environment.
    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.


Sec.  158.2250  Nontarget plant protection.

    (a) General. Subpart B of this part and Sec.  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.

[[Page 59439]]



                                                                      Table -- Nontarget Plant Protection Data Requirements
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                              Use Pattern                                Test Substance to Support
                                                                               ----------------------------------------------------------------------------------------------------
                                                                                                                High Environmental Exposure
                                                                                                   ----------------------------------------------------
                                                                                                    Industrial                                                                        Test Note
               Guideline Number                        Data Requirement          Low Environmental   Processes                                                                           No.
                                                                                     Exposure        and Water  Antifoulant       Wood        Aquatic        MP            EP
                                                                                                      Systems     Coatings   Preservatives     Areas
                                                                                                      (Once-     and Paints
                                                                                                     Through)
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.4225                                       Seedling emergence, Tier II -                     CR         R            R             R            R           TEP           TEP          1, 2
                                                dose response
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.4250                                       Vegetative vigor, Tier II -                       CR          CR         NR             R            R           TEP           TEP          1, 3
                                                dose response
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.4400                                       Aquatic plant growth (aquatic                     CR         R            R             R            R     TGAI, TEP     TGAI, TEP          2, 4
                                                vascular plant) Tier II - dose
                                                response
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.5400                                       Aquatic plant growth (algal)                     R           R            R             R            R     TGAI, TEP     TGAI, TEP       4, 5, 6
                                                Tier II (dose response)
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
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 (once-through), data are required if one or more of 
the following criteria are met:
    i. The octanol/water partition coefficient (Kow) for 
the active ingredient or principal transformation products >= 1,000 
for the active ingredient or principal transformation products;
    ii. The hydrolysis half-life of the active ingredient or 
principal transformation products in water is > 4 days.
    iii. The results of the ready biodegradability study [Sec.  
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 flos-aquae, 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.


Sec.  158.2260  Applicator exposure.

    (a) General. Subpart B of this part and Sec.  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

[[Page 59440]]

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 non-occupational, 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          R                       R                      TEP                    1, 2, 3
                                      exposure
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.1200                             Dermal indoor exposure  R                       R                      TEP                    1, 2, 3, 4
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.1300                             Inhalation outdoor      R                       R                      TEP                    1, 2, 3
                                      exposure
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.1400                             Inhalation indoor       R                       R                      TEP                    1, 2, 3, 4
                                      exposure
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.1500                             Biological monitoring   CR                      CR                     TEP                    1, 2, 3
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.1600                             Data reporting and      R                       R                      TEP                    5
                                      calculations
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.1700                             Product use             R                       R                      TEP                    --
                                      information
--------------------------------------------------------------------------------------------------------------------------------------------------------

    (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.


Sec.  158.2270  Post-application exposure.

    (a) General. Subpart B of this part and Sec.  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, post-application 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.

[[Page 59441]]

    (b) Criteria for Testing. Post-application 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 
post-application 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 preservative-treated wood, or other work-related activity.
    (B) Residential human post-application 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 post-application 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 
post-application exposure. The test notes appear in paragraph (e) of 
this section.

                                           Table -- Antimicrobial Post-Application Exposure Data Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                               Use Sites
               Guideline Number                        Data Requirement        ----------------------------------------   Test Substance      Test Note
                                                                                   Occupational         Residential                              No.
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.2200                                       Soil residue dissipation                          CR                  CR               TEP       1, 2, 3
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.2300                                       Indoor surface residue                           R                   R                 TEP   1, 3, 4, 5,
                                                dissipation                                                                                           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 post-application 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 post-
application 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[deg] 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 non-dietary pathway(s) of 
interest. Data must be generated to consider all potential pathways 
of non-dietary ingestion exposure that are applicable (e.g., soil 
ingestion, hand-to-mouth transfer, and object-to-mouth transfer of 
surface residues).

[[Page 59442]]

Sec.  158.2280  Environmental fate.

    (a) General. Subpart B of this part and Sec.  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
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                          Use Pattern                              Test Substance to Support
                                              -----------------------------------------------------------------------------------------------
                                                                          High Environmental Exposure
                                                             ----------------------------------------------------
                                    Data                      Industrial                                                                       Test Note
      Guideline Number          Requirement         Low       Pro-cesses                                                                          No.
                                               Environmental   and Water  Antifoulant       Wood        Aquatic        MP            EP
                                                  Exposure      Systems     Coatings   Preservatives     Areas
                                                                (Once-     and Paints
                                                               Through)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Degradation Studies - Laboratory........................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
835.2120                      Hydrolysis                 R            R            R             R            R       TGAI or       TGAI or           1
                                                                                                                        PAIRA         PAIRA
--------------------------------------------------------------------------------------------------------------------------------------------------------
835.2240                      Photodegradatio            R            R            R             R            R       TGAI or       TGAI or           2
                               n in water                                                                               PAIRA         PAIRA
--------------------------------------------------------------------------------------------------------------------------------------------------------
835.2410                      Photodegradatio           NR           NR           NR             R           NR       TGAI or       TGAI or          --
                               n in soil                                                                                PAIRA         PAIRA
--------------------------------------------------------------------------------------------------------------------------------------------------------
 Biodegradation Studies - Laboratory....................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
835.1110                      Activated                  R            R           NR            NR           NR          TGAI          TGAI          --
                               Sludge
                               Sorption
                               Isotherm
--------------------------------------------------------------------------------------------------------------------------------------------------------
835.3110                      Ready                      R            R           NR            NR           NR          TGAI          TGAI           3
                               Biodegradabili
                               ty
--------------------------------------------------------------------------------------------------------------------------------------------------------
850.6800                      Modified                   R            R           NR            NR           NR          TGAI          TGAI          --
                               Activated
                               Sludge,
                               Respiration
                               Inhibition
                               Test
--------------------------------------------------------------------------------------------------------------------------------------------------------
835.3220                      Porous Pot                  CR           CR         NR            NR           NR          TGAI          TGAI           4
                               Study
--------------------------------------------------------------------------------------------------------------------------------------------------------
Mobility Studies........................................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
835.1230                      Leaching and                CR          R            R             R            R       TGAI or       TGAI or        5, 7
835.1240....................   adsorption/                                                                              PAIRA         PAIRA
                               desorption
--------------------------------------------------------------------------------------------------------------------------------------------------------
Metabolism Studies - Laboratory.........................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------

[[Page 59443]]


835.4100                      Aerobic soil                CR           CR         NR             R             CR     TGAI or       TGAI or   5, 6, 8, 9
                               metabolism                                                                               PAIRA         PAIRA
--------------------------------------------------------------------------------------------------------------------------------------------------------
835.4200                      Anaerobic soil              CR         NR           NR              CR         NR       TGAI or       TGAI or    5, 8, 10
                               metabolism                                                                               PAIRA         PAIRA
--------------------------------------------------------------------------------------------------------------------------------------------------------
835.4300                      Aerobic aquatic             CR          R            R              CR          R       TGAI or       TGAI or    5, 8, 10
                               metabolism                                                                               PAIRA         PAIRA
--------------------------------------------------------------------------------------------------------------------------------------------------------
835.4400                      Anaerobic                   CR          R            R              CR          R       TGAI or       TGAI or    5, 8, 10
                               aquatic                                                                                  PAIRA         PAIRA
                               metabolism
--------------------------------------------------------------------------------------------------------------------------------------------------------
Dissipation Studies -- Field............................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
835.6200                      Aquatic                     CR           CR           CR            CR          R           TEP           TEP   5, 11, 12,
                               (sediment)                                                                                                            13
--------------------------------------------------------------------------------------------------------------------------------------------------------
Ground and Surface Water Monitoring.....................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
None                          Monitoring of               CR           CR           CR            CR           CR  residue of    residue of   11, 12, 14
                               representative                                                                         concern       concern
                               U.S. waters
--------------------------------------------------------------------------------------------------------------------------------------------------------
Special Studies.........................................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
None                          Special                   NR           NR            R             R           NR          TGAI           TEP      15, 16
                               leaching
--------------------------------------------------------------------------------------------------------------------------------------------------------

    (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-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.
    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-of-evidence indicates that the active ingredient or principal 
transformation products are likely to have the potential for 
persistence, mobility, nontarget aquatic toxicity, or 
bioaccumulation.
    14. Data are required if the weight-of-evidence indicates that 
the active ingredient or principal transformation products are 
likely to occur in nontarget freshwater, estuarine, or marine waters 
such that human or environmental exposures are likely to occur. The 
Agency takes into account other factors such as the toxicity of the 
chemical(s), available monitoring data and the vulnerability of the 
freshwater, estuarine, or marine water resources in the 
antimicrobial use area.
    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

[[Page 59444]]

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.


Sec.  158.2290  Residue chemistry.

    (a) General. Subpart B of this part and Sec.  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 end-use 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
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                     Use Pattern
                                                                 --------------------------------------------------
                                                                                              Direct                                           Test Note
           Guideline Number                 Data Requirement      Agricultural   Indirect      Food       Aquatic        Test substance           No.
                                                                    Premises     Food Uses    Contact      Uses
                                                                                               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              R            R           R           R   --                                1
                                         support of petition
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1650                                Submittal of analytical            R            R           R           R   PAI and residue of                2
                                         reference standards                                                         concern
--------------------------------------------------------------------------------------------------------------------------------------------------------
Nature of the residue...................................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1300                                Nature of the residue in            CR         NR           R           R   PAIRA                       3, 4, 5
                                         plants
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1300                                Nature of the residue in           R           NR            CR          CR PAIRA or radiolabeled       6, 7, 8
                                         livestock                                                                   plant metabolite
--------------------------------------------------------------------------------------------------------------------------------------------------------
Analytical methods......................................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1340                                Residue analytical                  CR           CR         R            CR Residue of concern                9
                                         methods for enforcement
                                         of tolerances
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1340                                Residue analytical                  CR           CR         R            CR Residue of concern               10
                                         methods for data
                                         collection
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1360                                Multiresidue method                 CR           CR         R            CR Residue of concern               11
                                         testing
--------------------------------------------------------------------------------------------------------------------------------------------------------
Magnitude of the residue................................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1380                                Storage stability                  R            R           R           R   TEP or residue of                12
                                                                                                                     concern
--------------------------------------------------------------------------------------------------------------------------------------------------------

[[Page 59445]]


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.

[[Page 59446]]

    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
