Pesticides; Data Requirement for Conventional Chemicals

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Federal Register › Vol. 70 › 70 FR 12277

This text was captured on Aug 14, 2026. It is a snapshot, not a live feed, so check the official code before relying on it.

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ENVIRONMENTAL PROTECTION AGENCY 40 CFR Parts 152 and 158 [OPP-2004-0387; FRL-6811-2] RIN 2070-AC12 Pesticides; Data Requirement for Conventional Chemicals AGENCY:

Environmental Protection Agency (EPA).

ACTION:

Proposed rule.

SUMMARY:

EPA proposes to update and revise its data requirements for the registration of conventional pesticide products. These data requirements and those already codified in part 158 of title 40 of the Code of Federal Regulations (CFR), are intended to provide EPA with data and other information necessary for the registration of a conventional pesticide chemical. Since the data requirements in part 158 were first codified in 1984, information needed to support the registration of a pesticide chemical has evolved as the general scientific understanding of the potential hazards posed by pesticides has grown. Over the years, updated data requirements were developed by EPA using a process that involved public participation and extensive involvement by the scientific community, including peer review by the FIFRA Scientific Advisory Panel (SAP). Most of the data requirements contained in this proposal have been applied on a case-by-case basis to support individual applications, or imposed via Data Call-In (DCI) on all registrants of similar products. Although the data requirements imposed have progressed as scientific understanding and concerns have evolved, the codified data requirements have not been updated to keep pace. This proposal involves changes to the codified data requirements that pertain to product chemistry, toxicology, residue chemistry, applicator exposure, post-application exposure, nontarget terrestrial and aquatic organisms, nontarget plant protection, and environmental fate. Coupled with updating data requirements, EPA proposes to add a few new studies, reformat the requirements, and revise its general procedures and policies associated with data submission

nts that pertain to product chemistry, toxicology, residue chemistry, applicator exposure, post-application exposure, nontarget terrestrial and aquatic organisms, nontarget plant protection, and environmental fate. Coupled with updating data requirements, EPA proposes to add a few new studies, reformat the requirements, and revise its general procedures and policies associated with data submission. By codifying existing data requirements which are currently applied on a case-by-case basis, the pesticide industry, along with other partners in the regulated community, attain a better understanding and are better prepared for the pesticide registration process. This proposed rule does not apply to the data requirements for the registration of antimicrobial pesticide products; inert ingredients for pesticide products; spray drift, product performance (efficacy); or biochemical, and microbial pesticides.

DATES:

Comments must be received on or before June 9, 2005.

ADDRESSES:

Submit your comments, identified by Docket ID No. OPP-2004-0387, by one of the following methods:

• Federal eRulemaking Portal . http://www.regulations.gov. Follow the on-line instructions for submitting comments.

• Agency Web Site . http://www.epa.gov/edocket. EDOCKET, EPA's electronic public docket and comment system, is EPA's preferred method for receiving comments. Follow the on-line instructions for submitting comments.

• E-mail . opp-docket@epa.gov .

• Mail . Public Information and Records Integrity Branch (PIRIB) (7502C), Office of Pesticide Programs (OPP), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001.

• Hand Delivery . Public Information and Records Integrity Branch (PIRIB), Office of Pesticide Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1801 S. Bell St., Arlington, VA. Such deliveries are only accepted during the Docket's normal hours of operation, and special arrangements should be made for deliveries of boxed information.

Instructions

ngton, DC 20460-0001.

Instructions . Direct your comments to Docket ID No. OPP-2004-0387. EPA's policy is that all comments received will be included in the public docket without change and may be made available online at http://www.epa.gov/edocket , 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 EDOCKET, regulations.gov, or e-mail. The EPA EDOCKET and the federal regulations.gov websites are “anonymous access ” systems, 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 EDOCKET or regulations.gov, your e-mail address will be automatically captured and included as part of the comment that is placed in the public 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. For additional information about EPA's public docket visit EDOCKET on-line or see the Federal Register of May 31, 2002 (67 FR 38102)

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. For additional information about EPA's public docket visit EDOCKET on-line or see the Federal Register of May 31, 2002 (67 FR 38102). For additional instructions on submitting comments, go to Unit I.B. of the SUPPLEMENTARY INFORMATION section of this document.

Docket . All documents in the docket are listed in the EDOCKET index at http://www.epa.gov/edocket. Although listed in the index, some information is not publicly available, i.e. , 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 electronically in EDOCKET or in hard copy at the Public Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall #2, 1801 S. Bell St., Arlington, VA. This docket facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The docket telephone number is (703) 305-5805.

FOR FURTHER INFORMATION CONTACT:

Vera Au, Field and External Affairs Division (FEAD), Office of Pesticide Programs, Mailcode: 7506C, Environmental Protection Agency, 1200 Pennsylvania Ave. NW., Washington, DC 20460; telephone number: (703) 308-9069: fax number: 703-305-5884; e-mail address: au.vera@epa.gov .

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

e-mail address: au.vera@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 or registrant of a pesticide product, including agricultural, residential, and industrial pesticides, but not including antimicrobial, biochemical or microbial pesticides, or inert ingredients in pesticide products. This proposal also may affect any person or company who might petition the Agency for new tolerances, hold a pesticide registration with existing tolerances, or any person or company who is interested in obtaining or retaining a tolerance in the absence of a registration, that is, an import tolerance. This latter group may

Chemical Producers (NAICS 32532), e.g. , pesticide manufacturers or formulators of pesticide products, importers or any person or company who seeks to register a pesticide or to obtain a tolerance for 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 consult the appropriate Branch Chief in the Registration Division of the Office of Pesticide Programs at 703-305-5447.

B. What Should I Consider as I Prepare My Comments for EPA?

for EPA?

1. Submitting CBI. Do not submit this information to EPA through EDOCKET, regulations.gov or e-mail. Clearly mark the part or all of the information that you claim to be CBI. For CBI information in a disk or CD ROM that you mail to EPA, mark the outside of the disk or CD ROM as CBI and then identify electronically within the disk or CD ROM the specific information that is claimed as CBI. In addition to one complete version of the comment that includes information claimed as CBI, a copy of the comment that does not contain the information claimed as CBI must be submitted for inclusion in the public docket. Information so marked will not be disclosed except in accordance with procedures set forth in 40 CFR part 2.

2. Tips for Preparing Your Comments. When submitting comments, remember to:

• Identify the rulemaking by docket number and other identifying information (subject heading, Federal Register date and page number).

• 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.

• Explain why you agree or disagree; suggest alternatives and substitute language for your requested changes.

• Describe any assumptions and provide any technical information and/or data that you used.

• If you estimate potential costs or burdens, explain how you arrived at your estimate in sufficient detail to allow for it to be reproduced.

• Provide specific examples to illustrate your concerns, and suggest alternatives.

• Explain your views as clearly as possible, avoiding the use of profanity or personal threats.

• Make sure to submit your comments by the comment period deadline identified.

II. Organization of Preamble

This preamble is organized according to the outline in this unit.

I. General Information II. Organization of Preamble III. Statutory Authorities and Regulatory Framework IV. Background V. Purpose and Scope of this Proposal VI. Overview of Proposed Changes VII

ity or personal threats.

• Make sure to submit your comments by the comment period deadline identified.

II. Organization of Preamble

This preamble is organized according to the outline in this unit.

I. General Information II. Organization of Preamble III. Statutory Authorities and Regulatory Framework IV. Background V. Purpose and Scope of this Proposal VI. Overview of Proposed Changes VII. General Provisions of Part 158 (subpart A) VIII. How to Use the Data Tables (subpart B) IX. Product Chemistry Data Requirements (subpart D) X. Terrestrial and Aquatic Nontarget Organisms Data Requirements (subpart E) XI. Toxicology Data Requirements (subpart F) XII. Nontarget Plant Protection Data Requirements (subpart J) XIII. Post-Application Exposure Data Requirements (subpart K) XIV. Environmental Fate Data Requirements (subpart N) XV. Residue Chemistry Data Requirements (subpart O) XVI. Applicator Exposure Data Requirements (subpart U) XVII. Data Requirements Not Affected by this Proposal XVIII. Peer Review XIX. International Harmonization of Data Requirements XX. Research Involving Human Subjects XXI. ILSI Work on New Toxicity Paradigm XXII. Animal Welfare Concerns XXIII. Summary of Changes Being Proposed XXIV. Public Comments Sought XXV. References XXVI. FIFRA Review Requirements XXVII. Statutory and Executive Order Reviews III. Statutory Authorities and Regulatory Framework

EPA is authorized to regulate pesticides under two federal statutes. The Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) regulates the sale, distribution, and use of pesticide products through a licensing (registration) scheme. The Federal Food, Drug and Cosmetic Act (FFDCA), among other things, regulates the safety of pesticide residues in food and feed. Both FIFRA and FFDCA were amended in 1996 by the Food Quality Protection Act (FQPA) to strengthen the protections offered, with particular emphasis on protection of children.

This action is issued under the authority of secs. 3, 4, 5, 10, 12, and 25 of FIFRA (7 U.S.C

The Federal Food, Drug and Cosmetic Act (FFDCA), among other things, regulates the safety of pesticide residues in food and feed. Both FIFRA and FFDCA were amended in 1996 by the Food Quality Protection Act (FQPA) to strengthen the protections offered, with particular emphasis on protection of children.

This action is issued under the authority of secs. 3, 4, 5, 10, 12, and 25 of FIFRA (7 U.S.C. 136-136y) and sec. 408 of FFDCA (21 U.S.C. 346a). The data required for a registration, reregistration, experimental use permit, or tolerance are listed in 40 CFR part 158.

A. FIFRA

Under FIFRA, every pesticide product must be registered (or specifically exempted from registration under FIFRA sec. 25(b)) with EPA before it may be sold or distributed in the United States. To obtain a registration, an applicant or registrant 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, as defined in the statute, requires the Agency to consider the risk of the use of the pesticide and weigh this against its benefit. EPA must determine that the safety standard contained in FIFRA is met before granting a federal pesticide registration.

1. Registration. Section 3 of FIFRA contains the requirements for registration. Specifically, FIFRA sec. 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 registrants and applicants of pesticide products. An applicant for registration 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 efficacy in certain cases. Although the data requirements are imposed primarily as a part of initial registration, EPA is authorized under FIFRA sec

f pesticide products. An applicant for registration 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 efficacy in certain cases. Although the data requirements are imposed primarily as a part of initial registration, EPA is authorized under FIFRA sec. 3(c)(2)(B) to require a registrant to develop and submit additional data to maintain a registration. This post registration data call-in authority recognizes that the scientific underpinnings of risk assessment change, and is another means by which EPA may keep data for use in risk assessment current with evolving science.

2. Reregistration. FIFRA sec. 4 requires that EPA reregister each pesticide product first registered before November 1984. This date was chosen based upon the fact that pesticides registered since 1984 were subject to the part 158 requirements of the 1984 regulation. Additional data for older

3. Experimental use permits. Subject to some exceptions, FIFRA sec. 5 requires persons seeking experimental use of pesticides under field conditions to obtain an experimental use permit (EUP). An EUP allows limited use of a pesticide for specified experimental and data collection purposes intended to support future registration of the pesticide. Because an 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. For example, when performing crop field trials, a registrant may opt to destroy the treated crop rather than generate the needed residue chemistry data to establish a temporary tolerance. The regulations governing the issuance of EUPs are found in 40 CFR part 172.

B. FFDCA

FFDCA mandates EPA to determine that the level of pesticide chemical residues in food and feed will be safe for human consumption

mple, when performing crop field trials, a registrant may opt to destroy the treated crop rather than generate the needed residue chemistry data to establish a temporary tolerance. The regulations governing the issuance of EUPs are found in 40 CFR part 172.

B. FFDCA

FFDCA mandates EPA to determine that the level of pesticide chemical residues in food and feed will be safe for human consumption. An applicant must petition the Agency for a tolerance (maximum residue level) for a pesticide that is to be used in or around food or feed commodities, or could otherwise come in contact with food or feed. The safety standard set under FFDCA sec. 408(b) and (c) defines safe as “a reasonable certainty that no harm ” will result from exposures to pesticide chemical residues. In making this determination, EPA is directed to consider aggregate risks from multiple sources of pesticide exposure, including anticipated food, drinking water, and other non-occupational exposures for which there is reliable information. Under FFDCA sec. 408(b)(2)(C), EPA must make a separate finding of safety for infants and children. In addition, EPA must take into account a variety of other factors, enumerated in sec. 408(b)(2)(D), including the cumulative risks associated with pesticides having a common mechanism of toxicity. The combination of aggregate and cumulative exposure increases the nature and scope of EPA's risk assessment, and potentially the types and amounts of data needed to determine that the FFDCA safety standard is met.

ded to determine that the FFDCA safety standard is met.

1. Establishing tolerances. Under FFDCA sec. 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. As previously mentioned, in 1996, FQPA modified FFDCA to establish a single health-based standard for tolerance-setting and enhanced the risk assessment process to more clearly focus on pesticide risks to children. The new safety standard applies to tolerances in a number of regulatory situations, including:

• Permanent 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 sec. 18 emergency exemptions; and

• Temporary tolerances established for experimental use permits under FIFRA sec. 5.

2. Reassessing tolerances. Under FFDCA sec. 408(q), EPA must reassess each tolerance established before August 3, 1996, on a prescribed 10-year schedule. The Agency has reassessed many tolerances under its reregistration program. Numerous regulatory decisions have been made based upon available data and information required by the existing data requirements, and supplemented by additional data provided by registrants through data call-ins or voluntary submissions.

C. Linking FIFRA and FFDCA Safety Standards

FRA and FFDCA Safety Standards

Unless EPA is able to establish or maintain a needed tolerance or exemption under FFDCA, a pesticide cannot be registered under FIFRA for a food/feed use. FQPA created a specific linkage (FIFRA sec. 2(bb)) between the “unreasonable adverse effects” finding under FIFRA and the determination of pesticide residue safety of “reasonable certainty of no harm” under FFDCA. In essence, a pesticide that is inconsistent with, or does not meet, the FFDCA sec. 408 safety standard poses an unreasonable adverse effect that precludes new or continued registration. Thus, both FIFRA and FFDCA standards must be met for pesticides intended to be registered in the United States for food or feed uses.

Given this linkage between registration and tolerances, it makes sense for EPA to define data requirements for both purposes: the data required to support a determination of “reasonable certainty of no harm” under FFDCA are an integral part of the data needed for an “unreasonable adverse effects” determination under FIFRA. Consequently, when promulgated, these proposed data requirements would encompass the basic data requirements for both registration and tolerance-setting determinations. EPA will retain its authority to require additional data on a case-by-case basis.

IV. Background

A. Why does EPA Require Data for Pesticide Registrations?

Pesticide Registrations?

Under the FFDCA and the FIFRA, anyone seeking to register a pesticide product is required to provide information to EPA that demonstrates their products can be used without posing unreasonable risk to human health and the environment, and for food uses, that there is a reasonable certainty that no harm will result from exposures to the residues of their pesticide product. As appropriate for the particular pesticide product, EPA uses the information provided to evaluate the pesticide for a wide range of adverse human health effects, from eye and skin irritation to cancer and birth defects, and to assess how the pesticide affects animal and plant species, non-target insect species, and what happens to the pesticide in soil, water, and air.

B. What are the Data Requirements?

First promulgated in 1984, the data requirements in 40 CFR part 158 outline the kinds of data and related information typically needed to register a pesticide. The data requirements are organized by major pesticide type ( e.g. , conventional, antimicrobial, biochemical/microbial, etc.), scientific discipline ( e.g. , toxicology, etc.), and major use site ( e.g. , outdoor vs. indoor). Part 158 also outlines the associated procedures for submitting the data, requesting a waiver from a requirements, and other associated procedures. Since there is much variety in pesticide chemistry, exposure, and hazard, part 158 is designed to be flexible. Table notes to each data requirement explain under what conditions data are typically needed. The Agency also recognizes, however, that due to the particular nature and risk of some pesticides, registrants may seek to obtain data waivers or may suggest alternative approaches to satisfying requirements. Over the years since 1984, other data requirements have been implemented on a case-by-case basis

Table notes to each data requirement explain under what conditions data are typically needed. The Agency also recognizes, however, that due to the particular nature and risk of some pesticides, registrants may seek to obtain data waivers or may suggest alternative approaches to satisfying requirements. Over the years since 1984, other data requirements have been implemented on a case-by-case basis. The determination of what data or information is needed is based on a scientifically rigorous process that includes peer review by the FIFRA Scientific Advisory Panel (SAP), as well

In essence, the data requirements identify the questions that the registrant will need to answer regarding the safety of a pesticide product before the Agency can register it. The data requirements address both components of a risk assessment, i.e. , what hazards does the pesticide present, and what level of exposure. The answer to one question may inform the kind of information needed in others. For example, a pesticide that is persistent and toxicologically potent may require more extensive exposure data to help establish a safe level of exposure. If there is negligible exposure then there may be generally less need for extensive hazard data since any conceivable risk would be low.

1. The establishment of standardized data requirements. Until 1984, data requirements were based on longstanding requirements initially put in place when pesticides were regulated by the U.S. Department of Agriculture (USDA) and the Food and Drug Administration (FDA). However, because virtually all of EPA's decisions relating to the registration of pesticides or the establishment of tolerances depend on Agency evaluation of scientific studies, EPA has throughout the years developed standardized data requirements and test guidelines, and established evaluation procedures and peer review processes to ensure the quality and consistency of scientific studies.

The current provisions in part 158 were originally promulgated in October, 1984

on of pesticides or the establishment of tolerances depend on Agency evaluation of scientific studies, EPA has throughout the years developed standardized data requirements and test guidelines, and established evaluation procedures and peer review processes to ensure the quality and consistency of scientific studies.

The current provisions in part 158 were originally promulgated in October, 1984. Prior to this, data requirements for the registration of pesticides were contained in a variety of guidance documents, not in regulatory form. Part 158 was intended to be a concise presentation of what data were required and under what circumstances. Once codified, part 158 specified standard hazard and exposure studies required for registration and tolerance setting and also identified conditions under which more specialized studies might be required. Guidelines, i.e. , instructions and test methods on how to perform a study, had meanwhile been issued as a series of Pesticide Assessment Guidelines. These documents, updated in 1996, describe acceptable protocols, test conditions, and data reporting guidelines to ensure that EPA's regulatory decisions are based on sound scientific data.

2. Relationship between the harmonized test guidelines and part 158 requirements. EPA has established a unified library for test guidelines issued by the Office of Prevention, Pesticides and Toxic Substances (OPPTS) for use in testing chemical substances to develop data for submission to EPA under the Toxic Substances Control Act (TSCA), FFDCA or FIFRA. This unified library of test guidelines represents an Agency effort that began in 1991 to harmonize the test guidelines within OPPTS, as well as to harmonize the OPPTS test guidelines with those of the Organization for Economic Cooperation and Development (OECD) of the European Community

substances to develop data for submission to EPA under the Toxic Substances Control Act (TSCA), FFDCA or FIFRA. This unified library of test guidelines represents an Agency effort that began in 1991 to harmonize the test guidelines within OPPTS, as well as to harmonize the OPPTS test guidelines with those of the Organization for Economic Cooperation and Development (OECD) of the European Community. The process for developing and amending these test guidelines includes several opportunities for public participation and the extensive involvement of the scientific community, including peer review by the FIFRA SAP and the Science Advisory Board (SAB) and other expert scientific organizations.

The purpose for harmonizing these guidelines into a single set of OPPTS guidelines is to minimize variations among the testing procedures that must be performed to meet the Agency's data requirements under FIFRA and TSCA. 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. As such, pesticide registrants may use a non-guideline protocol to generate the data required by part 158. Typically the registrant will use the available guideline, in which case the study protocol would simply cite the relevant guideline. If the registrant deviates from these guidelines, or is asked to provide data where there isn't yet a final guideline available, the registrant will discuss the variation with EPA and will explain and justify the methods chosen in the study protocol. Non-guideline protocols are accepted, provided that the study protocol meets the purpose of the test standards specified in the guidelines, and provides data of suitable quality and completeness as typified by the protocols cited in the guidelines. More information about the unified library and these guidelines is available at http://www.epa.gov/opptsfrs/home/guidelin.htm .

the study protocol. Non-guideline protocols are accepted, provided that the study protocol meets the purpose of the test standards specified in the guidelines, and provides data of suitable quality and completeness as typified by the protocols cited in the guidelines. More information about the unified library and these guidelines is available at http://www.epa.gov/opptsfrs/home/guidelin.htm .

C. Why Have the Data Needs Changed Since 1984?

1. 1988 FIFRA amendments. In 1988, FIFRA was amended to ensure that older pesticides met the scientific standards of the day. Among other things, the amendments provided for the acceleration of the reregistration program by establishing statutory deadlines and new procedures. The 1988 changes to FIFRA are important because it was during this effort that EPA recognized that some of the 1984 data requirements were becoming out of date. The Agency then used the reregistration process to focus on needed changes.

2. The National Academy of Sciences 1993 Report. With increasing emphasis on protecting children's health, EPA began to examine its data requirements relative to evaluating the potential risks from pesticides to sensitive subpopulations. The Agency sought the advice of the National Academy of Sciences' National Research Council (NRC) to assess its risk assessment methodologies and to provide additional information on the extent to which children may be at risk given emerging scientific information and technologies. In their 1993 report entitled, “Pesticides in the Diets of Infants and Children,” (Ref. 1) NRC offered recommendations for further protecting infants and children from pesticides in their diet. The NRC called for the Agency to require more data and adopt better risk assessment methodologies. For example, the Council called for increased testing in the area of immune function, neurodevelopmental and reproductive testing, and neurotoxicity testing

Diets of Infants and Children,” (Ref. 1) NRC offered recommendations for further protecting infants and children from pesticides in their diet. The NRC called for the Agency to require more data and adopt better risk assessment methodologies. For example, the Council called for increased testing in the area of immune function, neurodevelopmental and reproductive testing, and neurotoxicity testing. NRC also suggested adding a thyroid screen to existing subchronic and chronic toxicity tests and additional tests on age-related physiological changes and pharmacokinetics in immature animals.

At the time the 1993 report was released, EPA had already begun work on many of the recommendations to improve the quality of its risk assessments. New testing guidelines and protocols were developed. Since then, many of the testing requirements recommended by the NRC have been incorporated into the Agency's standard evaluation requirements and practices. In addition, in line with the Council's recommendations and the FIFRA Scientific Advisory Panel's (SAP) advice, EPA recently expanded its neurotoxicity and developmental neurotoxicity study requirements. These updated requirements are contained in this proposal.

3. The Food Quality Protection Act of 1996 (FQPA). Passage of FQPA in 1996 reformed our nation's pesticide and food safety laws, resulting in changes in EPA's approach to protecting human health from risks associated with pesticide use. As mentioned, FQPA modified both FIFRA and FFDCA and established a single health-based standard for food-use pesticides and added protections for infants and children.

d, FQPA modified both FIFRA and FFDCA and established a single health-based standard for food-use pesticides and added protections for infants and children.

Throughout the 1990s, EPA has been continually working on improving data requirements. Under FFDCA, as amended by FQPA, EPA must reassess all existing pesticide tolerances and exemptions against the expanded and more rigorous safety standard. Beginning in 1994, and increasingly since the enactment of FQPA, EPA has changed aspects of its data requirements and risk assessment process to improve its ability to assess exposure more accurately and to strengthen its understanding of the potential pesticide risk to children. As mentioned, risk assessments must now consider data relating to aggregate exposure (exposure to pesticides from food, drinking water, and non-occupational routes such as home and garden uses) and cumulative risk (effects from exposures to multiple pesticides that share a common mechanism of toxicity). These measures necessitate collection of additional data on drinking water and non-occupational and residential exposure.

V. Purpose and Scope of this Proposal

A. What is the Scope of this Proposal?

This proposal applies only to conventional pesticides. In general, a conventional pesticide is considered as a synthetic chemical or a natural substance with a toxic mode of action. It is applicable to both manufacturing-use and end-use products. It does not include data requirements for antimicrobial, biochemical or microbial pesticides; inert ingredients; or changes to existing spray drift or product performance (efficacy) data requirements for conventional chemicals.

B. Why is EPA Proposing these Revisions?

EPA has a number of objectives in proposing this regulation to update and revise the data requirements in 40 CFR part 158. First, this proposal will update the requirements in part 158 to reflect changes that have occurred over time and which are generally applied already

ft or product performance (efficacy) data requirements for conventional chemicals.

B. Why is EPA Proposing these Revisions?

Second, this proposal will provide clarity on the data requirements themselves, with data requirements reformatted to promote efficiency in registration decision processes. Third, information developed in fulfilling these data requirements will improve the scientific basis supporting increasingly complex risk management decisions.

1. Updating the 1984 requirements. Although most of the specific requirements in part 158 have not changed since the data requirements were first published in 1984, there is information that is out-of date or may be unclear. The underlying science has advanced ( e.g. , NAS in 1993 suggested changes to better protect children). The Agency's legislative mandate has been broadened to address new concerns. For example, given the stricter mandates imposed by the 1988 FIFRA amendments (emphasis on exposure to population subgroups) and the 1996 FQPA amendments to FIFRA and FFDCA, EPA finds that it is more frequently requesting certain data, and the Agency believes it should detail more specifically the conditions under which these tests will be required. Thus the proposed change entails both new tests and broadened requirements for some current tests.

This regulation will reflect the changes in data requirement practices that have evolved through practice since the 1984 data requirement rule was promulgated and address data needed to meet requirements created by statutory amendments to FIFRA and FFDCA. In addition, the rule will eliminate redundant data submission requirements

both new tests and broadened requirements for some current tests.

EPA's underlying principle in development of this regulation is to strike an appropriate balance between the need for adequate data to make informed risk management decisions while minimizing the data collection burden.

Until this proposal is promulgated, the Agency will continue to use existing authority in 40 CFR part 158, to obtain these data on a case-by-case basis should they be necessary to support a registration.

2. Reorganizing part 158 to improve usability. EPA proposes to reorganize and reformat part 158 subpart A (General Provisions), and subpart B (How to Use Data Tables), and reorganize and renumber subpart D (Data Requirement Tables) into several individual subparts (see Table 1 in Unit VI). Each subpart would contain the data requirement tables for an individual scientific discipline and references to correlate with the Pesticide Assessment Guidelines. The Agency also proposes to remove from the regulations the current Appendix A, (a compendium of pesticide use sites and use categories), and create a separate Pesticide Use Index Guidance Document. Since the information contained in Appendix A only serves as reference material and is not being stated as a requirement, EPA believes that a guidance document format is easier to keep current and therefore better serves the regulated community. The information will be placed on EPA's website and made available to the public.

3. Improving the scientific basis for pesticide registration decisions

Since the information contained in Appendix A only serves as reference material and is not being stated as a requirement, EPA believes that a guidance document format is easier to keep current and therefore better serves the regulated community. The information will be placed on EPA's website and made available to the public.

3. Improving the scientific basis for pesticide registration decisions. In general, the information developed as a result of the revisions, if finalized as proposed today, is expected to increase scientific understanding of the health and environmental effects of pesticides to which individuals and the environment may be exposed. The revised requirements are expected to improve the scientific basis for the Agency's regulatory decisions about the human health and environmental risks of pesticide products. The improved scientific basis is also expected to benefit a wide range of parties, including consumers and the general public, workers, scientists, industry, governments, public health officials, and the medical community, as well as foreign parties. Discussed in more detail in the document entitled “Economic Analysis of the Proposed Change in Data Requirements Rule for Conventional Pesticides,” which is available in the public docket for this rulemaking, the following briefly highlights the various ways the improved data is expected to be used:

i. Better informed regulatory decisions allow preservation of important pesticide uses . The proposed revisions enable the Agency to make better informed regulatory decisions based on more complete data about the potential risks of pesticides. For example, the proposed changes better target needed data that take into account human and wildlife toxicological end points or routes of exposure not now adequately covered. The proposed rule would also require better information about the potential for pesticides to cause immunotoxic or developmental neurotoxic effects

isions based on more complete data about the potential risks of pesticides. For example, the proposed changes better target needed data that take into account human and wildlife toxicological end points or routes of exposure not now adequately covered. The proposed rule would also require better information about the potential for pesticides to cause immunotoxic or developmental neurotoxic effects. This information is expected to be valuable in assuring that pesticide residues in food or from other sources are safe for children as well as other consumers. These studies would allow the Agency to assess aggregated and cumulative risks to consumers, with special emphasis on children. The proposal also includes exposure data tailored specifically to address pesticide handlers is crucial in assessing their risk and thus adequately protecting their health.

ii. More refined exposure assessments mean clearing understanding of real risks. EPA's current application and post-application exposure data base is not comprehensive, especially regarding exposures to pesticides in some agricultural or nonagricultural settings. The new data that would be collected under this proposal would allow the Agency to conduct improved exposure

iii. Clarity and transparency to regulated community means savings. The enhanced clarity and transparency of the information presented in part 158 should enhance the ability of industry to avoid wasted time and effort. Registrants may save time and money by understanding when studies are needed. This should allow products to enter the market earlier, thus increasing profits. The addition of some data requirements is likely to further communicate to domestic and world-wide marketplaces that pesticide products and items treated with them are safer, thus enhancing the reputation of American agricultural products and registered pesticides as tools for public health, etc.

iv. Enhanced international harmonization means less duplication

et earlier, thus increasing profits. The addition of some data requirements is likely to further communicate to domestic and world-wide marketplaces that pesticide products and items treated with them are safer, thus enhancing the reputation of American agricultural products and registered pesticides as tools for public health, etc.

iv. Enhanced international harmonization means less duplication. Data generated as a result of the revised requirements in part 158 would generally be sufficient for the needs of the OECD countries because EPA has harmonized the FIFRA test guidelines with those OECD. As a result, assessments of pesticides that are developed using data under the revised part 158 can be shared worldwide, allowing companies to avoid duplicative efforts to meet the requirements of other countries where the company may also manufacture and sell certain pesticides. This should lead to cost savings for companies that operate in the international market.

However, since EPA continues to allow applicants to submit and use their own study protocols to generate data that they subsequently submit to EPA, and there are differences in the mandate and authorities between EPA and OECD countries, the data submitted to EPA under part 158 would be expected to satisfy OECD standards under most circumstances, but perhaps not in all cases.

v. Better informed users means 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 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 that should be read and understood before using a pesticide product, and how to dispose of that product

changes should also mean that the label will provide better information on the use of the 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 that should 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 pesticide products appropriate to their needs, and to use and dispose of products in a manner that is safe and environmentally sound. Farmers (as well as other applicators) 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 to people or the environment from residues on treated crops or through off-site movement.

vi. EPA information assists other communities in assessing pesticide risks. Scientific, environmental, and health communities find pesticide toxicity information useful to respond to a variety of needs. For example, medical professionals are concerned about the health of patients exposed to pesticides; poison control centers make use of and distribute information on toxicity and treatment associated with poisoning; and scientists use toxicity information to characterize the effects of pesticides and to assess risks of pesticide exposure. Similarly those responsible for protection of non-target wildlife need reliable information about 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. In turn, the companies will be able to improve their ability to make appropriate decisions and take useful actions.

s 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. In turn, the companies will be able to improve their ability to make appropriate decisions and take useful actions.

C. How Will this Proposal Affect Existing Registrations?

This proposal concerns prospective data requirements for future registrations of pesticides. That is, these proposed data requirements would apply to all new registrations of pesticides after the rule is finalized. The Agency does not intend to apply these requirements retrospectively to all existing pesticide registrations. While the intended future applicability of this proposed rule is to new applications, the Agency may find it necessary to call-in some data on certain existing registrations, as warranted by emerging risks of concern on particular pesticides or as a result of possible future programmatic changes and priorities on existing pesticides.

VI. Overview of Proposed Changes

A. Phased approach

This proposal is the first in a series of revisions aimed at comprehensively updating EPA's pesticide data requirements. The data requirements discussed in this proposal pertain to conventional pesticides. Future proposals will address data requirements for antimicrobial pesticides, biochemical and microbial pesticides, inert ingredients in pesticide products, and product performance data requirements.

osal is the first in a series of revisions aimed at comprehensively updating EPA's pesticide data requirements. The data requirements discussed in this proposal pertain to conventional pesticides. Future proposals will address data requirements for antimicrobial pesticides, biochemical and microbial pesticides, inert ingredients in pesticide products, and product performance data requirements.

B. Organizational changes

Part 158 is currently divided into four subparts:

• Subpart A, General Provisions

• Subpart B, How to Use Data Tables

• Subpart C, Product Chemistry Data Requirements

• Subpart D, Data Requirements Tables

EPA proposes to reorganize part 158 to more closely correspond with the Office of Prevention, Pesticides, and Toxic Substances (OPPTS) Harmonized Guidelines, primarily by creating a series of new subparts to replace subpart D. Each subpart will address an individual scientific discipline or data type. In this preamble, EPA will refer to the proposed new subpart and section designations when discussing the data requirements. Table 1 below provides a cross-reference between the current and proposed new subparts. Future new subparts are included for information.

Table 1.—Part 158: Proposed Change to Subpart Designations Current Regulation and Title Proposed Regulation and Title Subpart A: 158.20 General Provisions Subpart A: 158.1 General Provisions Subpart B: 158.100 How to Use Data Tables Subpart B: 158.100 How to Use Data Tables Subpart C: 158.150 Product Chemistry Subpart D: 158.300 Product Chemistry Subpart D: 158.240 Residue Chemistry Subpart O: 158.1200 Residue Chemistry Subpart D: 158.290 Environmental Fate Subpart N: 158.1100 Environmental Fate Subpart D: 158.340 Toxicology Subpart F: 158.500 Toxicology Subpart D: 158.390 Reentry Protection Subpart K: 158.800 Post-application Exposure Subpart D: 158.440 Spray Drift Subpart R: 158.1400 Spray Drift Subpart D: 158.490 Wildlife and Aquatic Organisms Subpart E: 158.400 Terrestrial and Aquatic Nontarget Organisms Subpart D: 158.590

.290 Environmental Fate Subpart N: 158.1100 Environmental Fate Subpart D: 158.340 Toxicology Subpart F: 158.500 Toxicology Subpart D: 158.390 Reentry Protection Subpart K: 158.800 Post-application Exposure Subpart D: 158.440 Spray Drift Subpart R: 158.1400 Spray Drift Subpart D: 158.490 Wildlife and Aquatic Organisms Subpart E: 158.400 Terrestrial and Aquatic Nontarget Organisms Subpart D: 158.590 Nontarget Insects Subpart D: 158.540 Plant Protection Subpart J: 158.700 Plant Protection Subpart D: 158.640 Product Performance Subpart G: 158.600 Product Performance Subpart D: 158.690 Biochemical Pesticides Subpart L: 158.900 Biochemical Pesticides Subpart D: 158.740 Microbial Pesticides Subpart M: 158.1000 Microbial Pesticides Subpart P: 158.1300 Pesticide Management and Disposal (Reserved) Subpart U: 158.1500 Applicator Exposure Subpart V: 158.1600 Inert Ingredients (Reserved) Subpart W: 158.1700 Antimicrobials Further, EPA proposes to remove the current Appendix A, which contains a compendium of pesticide use sites and use categories to help determine data requirements. This will be separately issued and maintained as a guidance document.

C. “New Requirement” Vs.“Newly Codified Requirement.”

FIFRA is a licensing statute, under which regulatory decisions on the registrability of an individual product is based upon data specific to the product and its uses. EPA is authorized to require the submission of data that it needs to make the registration decision in the context of any individual application for registration, amended registration or reregistration. EPA may also impose a data requirement after registration in order to maintain the registration, using specific Data Call-In (DCI) authority of FIFRA sec. 3(c)(2)(B).

Since 1984, when part 158 was first promulgated, EPA's data requirements have evolved as the general scientific understanding of the potential hazards posed by pesticides has grown

istration, amended registration or reregistration. EPA may also impose a data requirement after registration in order to maintain the registration, using specific Data Call-In (DCI) authority of FIFRA sec. 3(c)(2)(B).

Since 1984, when part 158 was first promulgated, EPA's data requirements have evolved as the general scientific understanding of the potential hazards posed by pesticides has grown. Most of the data requirements contained in this new proposal have been applied on a case-by-case basis to support individual applications, or imposed via a DCI on all registrants of similar products. Thus EPA's actual data requirements have progressed as scientific understanding and concerns have evolved, but part 158 data requirements have not been updated to keep pace.

The result of this regulatory lag is that EPA regards many data requirements in today's proposal to be “newly codified requirements,” routinely applied in practice on a case-by-case basis but simply not codified in the CFR. However, because they have not been codified, they are considered to be “new requirements” never before imposed on the regulated industry. For the purposes of this proposal, EPA has evaluated the costs and burdens of all proposed requirements, whether “new” or “newly codified ” against the data requirements as originally promulgated in 1984, termed “ existing requirements.” Many of these studies can be categorized as rarely to infrequently required.

In this preamble, EPA is proposing new and revised data requirements that encompass all three categories of requirements:

1. EPA is proposing “new requirements,” never before imposed on any registrant.

2. EPA is proposing “newly codified requirements,” which have been applied on a case-by-case basis, but are not in the CFR.

3. EPA is proposing revisions to “existing requirements.”

D. Types of Revisions Being Proposed

Part 158 is a massive and complex set of tables that describe pesticide data requirements

1. EPA is proposing “new requirements,” never before imposed on any registrant.

2. EPA is proposing “newly codified requirements,” which have been applied on a case-by-case basis, but are not in the CFR.

3. EPA is proposing revisions to “existing requirements.”

D. Types of Revisions Being Proposed

Part 158 is a massive and complex set of tables that describe pesticide data requirements. Each data requirement is currently established and its scope and applicability defined according to a number of parameters. Having comprehensively evaluated its data requirement parameters, EPA is proposing changes in all areas of data requirements. Some of these changes are clarifications or housekeeping changes without cost or burden, others have the effect of increasing or decreasing the burden of the data requirement. The types of changes may be broadly categorized as follows:

1. Substantive changes —i. Addition of a requirement . This encompasses both “new requirements” and “newly codified requirements.” For example, EPA is proposing a “new requirement” for immunotoxicity testing. On the other hand, data requirements for applicator exposure (subpart U) are entirely “newly codified.“

ii. Elimination of a requirement, sometimes with substitution of a new requirement . For example, EPA is wholly eliminating the requirement for seed germination testing. By contrast, the existing requirement for a battery of mutagenicity studies is being eliminated in favor of a specific set of mutagenicity studies.

iii. A change to the number or type of species that must be tested . For example, EPA proposes to require acute avian toxicity testing on an additional passerine species in some instances. EPA also proposes to require that certain toxicity studies be conducted routinely with two species instead of one.

iv. A change in the conditionality of the test requirement . For example, EPA is proposing to change a number of requirements from conditionally required to fully required, or vice versa

es to require acute avian toxicity testing on an additional passerine species in some instances. EPA also proposes to require that certain toxicity studies be conducted routinely with two species instead of one.

iv. A change in the conditionality of the test requirement . For example, EPA is proposing to change a number of requirements from conditionally required to fully required, or vice versa. In some cases, this change is a minor change in the actual frequency (and burden) of the requirement. In other cases, the change may represent a substantive increase in frequency of requirement.

v. A change to the use patterns to which a data requirement applies . As described elsewhere, EPA proposed to increase the number of use pattern descriptors from 9 to 15. In some cases, EPA proposes to extend requirements currently limited to food uses to nonfood uses, e.g. , prenatal developmental toxicity studies. A second example would be a proposed expansion of certain studies into greenhouse and indoor use patterns, for example, avian oral toxicity requirements.

vi. A change to the test substance to be used . Typical test substances include the technical grade of active ingredient (TGAI), the manufacturing-use product, the end-use product, and a “typical product.” For example, EPA proposes to require primary eye and primary dermal irritation, and dermal sensitization testing using the TGAI in addition to the end-use product.

vii. A clarification in the notes describing the test . For example, EPA is proposing in a test note that analytical methods for residue chemistry and environmental fate be validated by an independent laboratory.

2. Technical changes having no substantive effect —i. Relocation of a requirement . For example, EPA proposes to move the magnitude of residues in rotational crops data requirement from environmental fate requirements to residue chemistry requirements.

ii. A change to the title of a data requirement

methods for residue chemistry and environmental fate be validated by an independent laboratory.

ii. A change to the title of a data requirement. For example, EPA proposes to rename the “teratogenicity” data requirement to “prenatal developmental toxicity” to more accurately reflect the nature of the study.

iii. Subdividing an existing requirement to create two separate entries. For example, EPA proposes to separately list the storage stability requirement for residue samples. This requirement is currently included in the plant and animal metabolism data requirement. A change of this nature is intended to highlight an aspect of a test requirement for the regulated community.

iv. Merging two data requirements into a single requirement. For example, EPA proposes to merge the terrestrial field dissipation study with the long-term field dissipation study because both studies provide similar information.

Each data requirement for which a revision is proposed is discussed in detail in subsequent units of this preamble. Readers are referred to the table in Unit XXIII. for a line-by-line listing of every current and proposed data requirement and the types of changes proposed. If no change is proposed, the table contains a notation to that effect.

VII. General Provisions of Part 158 (Subpart A)

A. General

Subpart A serves as an introduction to the data requirements in part 158. As proposed, current material has been substantially revised to be more concise and easier to understand. EPA has eliminated much of the redundancy in current subpart A and streamlined the remaining material. Unless otherwise superseded by part 174, the regulations of this part apply to plant-incorporated protectants.

1. New material. New content has been added to subpart A

irements in part 158. As proposed, current material has been substantially revised to be more concise and easier to understand. EPA has eliminated much of the redundancy in current subpart A and streamlined the remaining material. Unless otherwise superseded by part 174, the regulations of this part apply to plant-incorporated protectants.

1. New material. New content has been added to subpart A. Specifically, EPA has added new § 158.3 containing definitions relevant to part 158 as a whole. In this proposal, EPA has referred to statutory definitions in FIFRA and FFDCA, and has included only a single new definition, that of “applicant.” This definition is intended to provide an inclusive term that covers all persons who submit data to the Agency for any purpose, including applicants for registration, reregistration, or experimental use permit under FIFRA, petitioners for tolerance or exemption under FFDCA, and registrants who are required to submit data to maintain registration. The term “applicant” is proposed to be used for all such persons. The definition is drawn from the definition of “application for research or marketing permit,” in 40 CFR 160.3, which also relates to data development. EPA requests comment on whether additional definitions are needed.

2. Disposition of current subpart A material. The following sections of current subpart A are proposed to be deleted or substantially revised. The following Table 2 explains each section.

Table 2.—Disposition of Current Subpart A Material Section Title Disposition 158.20 Overview Paragraph (a) deleted Paragraph (b). Content contained in proposed § 158.1, Purpose and Scope. Paragraph (c) deleted. 158.25 Applicability of data requirements Deleted as redundant or unnecessary. Applicability of this part to various regulatory actions is contained in proposed § 158.5 158.30 Timing of the imposition of data requirements Deleted as unnecessary and not relevant

tion 158.20 Overview Paragraph (a) deleted Paragraph (b). Content contained in proposed § 158.1, Purpose and Scope. Paragraph (c) deleted. 158.25 Applicability of data requirements Deleted as redundant or unnecessary. Applicability of this part to various regulatory actions is contained in proposed § 158.5 158.30 Timing of the imposition of data requirements Deleted as unnecessary and not relevant. This section addresses approval of registration actions, which is properly covered in part 152, and is not relevant to data requirements. 158.32 Format of data submissions. Retained and revised. Discussed in Unit VII.B. 158.33 Procedures for claims of confidentiality of data. Retained and revised. Discussed in Unit VII.C. 158.34 Flagging of studies for potential adverse effects. Retained. Criteria revised. 158.35 Flexibility of the data requirements Deleted as redundant. Mainly contains cross-references to similar material elsewhere in part 158. 158.40 Consultation with the Agency. Deleted. Consultation with the Agency is encouraged in several sections of proposed part 158. 158.45 Waivers Retained and revised. Discussed in Unit VII.E. 158.50 Formulator's exemption Information to be relocated to 40 CFR 152.85, which covers the formulator's exemption. 158.55 Agricultural vs. Non-agricultural pesticides Deleted as unnecessary. Material is covered in individual subparts of proposal, which are organized by agricultural and no-agricultural use patterns. 158.60 Minor uses Deleted as unnecessary. Definitions and minor use policies are largely governed by statutory mandates and priorities, not regulatory policies. 158.65 Biochemical and microbial pesticides Deleted. Material will be considered for inclusion in future revisions of biochemical and microbial data requirements. 158.70 Acceptable protocols Revised. 158.75 Requirements for additional data Paragraph (a) retained. Paragraph (b) deleted as unnecessary. This material is covered by paragraph (a)

tutory mandates and priorities, not regulatory policies. 158.65 Biochemical and microbial pesticides Deleted. Material will be considered for inclusion in future revisions of biochemical and microbial data requirements. 158.70 Acceptable protocols Revised. 158.75 Requirements for additional data Paragraph (a) retained. Paragraph (b) deleted as unnecessary. This material is covered by paragraph (a). 158.80 Acceptability of data Paragraph (a) moved to § 158.70(a) - now refers to “cited.” Paragraph (b) deleted. Paragraph (c) retained. Paragraph (d) revised. 158.85 Revision of data requirements and guidelines Deleted as unnecessary. Guideline references are contained in tables in each subpart. B. Format of Data Submissions

EPA proposes to reorganize for clarity the data submission requirements of § 152.32. EPA would eliminate descriptions of EPA assignment of MRID numbers, as this internal action does not bear upon applicant requirements. Applicants would continue to format data submissions in support of regulatory actions according to current Agency procedures. The proposed rule makes clear that administrative non-data elements of a submission (forms, labels, and correspondence) are not subject to formatting requirements.

The Agency also proposes to eliminate specific media and copy requirements from the regulatory text because these requirements are subject to change as the Agency implements new strategies to reduce the paperwork burden on data submitters and to simplify the submission process. The Agency intends to provide updated guidance in a new PR Notice that will supersede PR Notice 86-5. EPA has a web page that provides guidance for both paper and electronic data submission.

ds to provide updated guidance in a new PR Notice that will supersede PR Notice 86-5. EPA has a web page that provides guidance for both paper and electronic data submission.

After a series of pilots EPA has developed a standard for electronic submission of data using Adobe Acrobat Portable Document Format and related tools for pesticide data submitters to create electronic versions of documents. Extensive guidance has been developed and posted on the EPA web page dedicated to electronic submissions( http://www.epa.gov/oppfead1/edsgoals.htm ). As experience is gained, and in consultation with stakeholders, EPA intends to refine its guidance.

Registrants should note that regulations in part 159 concerning FIFRA sec. 6(a)(2) submissions require that such data be formatted according to the requirements of this section.

C. Confidential Business Information

EPA proposes to clarify its policies on confidentiality claims asserted by submitters and on the release of information by the Agency. Section 158.33 discusses information that may be claimed as confidential and the procedures for asserting such a claim. It also discusses information that may be released by EPA, and circumstances under which such information can be released. Any release of information by EPA would be in accordance with FIFRA sec. 10, FFDCA sec. 408, and EPA regulations under the Freedom of Information Act (5 U.S.C. 552) found in 40 CFR part 2. The revisions to procedures for asserting confidentiality claims would not apply to data submitted to the Agency before the date of promulgation of this rule. Further regulatory provisions regarding confidentiality can be found at 40 CFR part 2.

omulgation of this rule. Further regulatory provisions regarding confidentiality can be found at 40 CFR part 2.

1. Confidentiality of 408 information. EPA also proposes to implement the revised confidentiality provisions in FFDCA sec. 408(i). Prior to the changes made in FFDCA by FQPA in 1996, confidentiality of information submitted in support of a tolerance or exemption was governed by old sec. 408(f), which made all such information confidential until publication of a regulation establishing a tolerance or exemption (unless the submitter explicitly waived confidential protection). This section was replaced in 1996 by current sec. 408(i), which provides in part, “Data and information that are or have been submitted to the Administrator under this section or sec. 348 of this title in support of a tolerance or an exemption from a tolerance shall be entitled to confidential treatment for reasons of business confidentiality and to exclusive use and data compensation to the same extent provided by secs 3 and 10 of the Federal Insecticide, Fungicide, and Rodenticide Act.” EPA has never formally interpreted the meaning of sec. 408(i) with respect to confidential information.

The likely intent of Congress was to accord information submitted in support of a tolerance or exemption the same confidentiality protections that apply to data submitted under FIFRA, especially considering the extent to which FIFRA and FFDCA were intertwined more closely by FQPA. Treating information submitted under the two statutes identically means that they are subject to the same protections ( e.g. , restrictions on disclosure of entire studies to multinational corporations in accordance with FIFRA sec. 10(g)) and the same disclosure requirements ( e.g. , mandatory public availability of safety and efficacy information in accordance with FIFRA 10(d)(1))

losely by FQPA. Treating information submitted under the two statutes identically means that they are subject to the same protections ( e.g. , restrictions on disclosure of entire studies to multinational corporations in accordance with FIFRA sec. 10(g)) and the same disclosure requirements ( e.g. , mandatory public availability of safety and efficacy information in accordance with FIFRA 10(d)(1)). In fact, this discussion may be largely academic, because EPA expects that nearly all data submitted under part 158 in support of a tolerance or exemption will also be information submitted under FIFRA. The only exception would pertain to import tolerances or exemptions for pesticides that are not used in the United States, submissions which are uncommon. All references in this preamble to FIFRA sec. 10 are therefore intended to apply equally to information submitted pursuant to FFDCA 408.

2. Safety and efficacy information. Information pertaining to the safety and efficacy of registered pesticides must in most cases be made available to the public. The existing provisions in 40 CFR 158.33 regarding the confidentiality of safety and efficacy information have in some cases been unclear to registrants and applicants, resulting in confusion regarding what information is claimed as confidential. EPA seeks to clarify these provisions, and to clear up some long-standing misconceptions as to the eligibility of inert ingredient and process information for confidential treatment.

FIFRA sec

regarding the confidentiality of safety and efficacy information have in some cases been unclear to registrants and applicants, resulting in confusion regarding what information is claimed as confidential. EPA seeks to clarify these provisions, and to clear up some long-standing misconceptions as to the eligibility of inert ingredient and process information for confidential treatment.

FIFRA sec. 10(d)(1) provides that “information concerning the objectives, methodology, results, or significance of any test or experiment performed on or with a registered or previously registered pesticide or its separate ingredients, impurities, or degradation products, and any information concerning the effects of such pesticide on any organism or the behavior of such pesticide in the environment, including, but not limited to, data on safety to fish and wildlife, humans and other mammals, plants, animals, and soil, and studies on persistence, translocation

Excepted from that mandatory disclosure requirement is certain information pertaining to manufacturing and quality control processes and to inert ingredients, which is given qualified protection under FIFRA secs. 10(d)(1)(A), (B), or (C). This exception has been frequently misinterpreted to mean that all such information is made categorically confidential by sec. 10(d)(1). In fact, as decided by the District Court for the District of Columbia in NCAP v. Browner , 941 F.Supp. 197, 201 (D.D.C. 1996), the statute makes information subject to FIFRA sections 10(d)(1)(A), (B), or (C) neither categorically confidential nor categorically public. Instead, the information may be entitled to confidential treatment, but only if it meets the requirements of sec. 10(b) (generally, trade secrets and information whose disclosure is likely to cause substantial harm to the competitive position of the submitter)

e statute makes information subject to FIFRA sections 10(d)(1)(A), (B), or (C) neither categorically confidential nor categorically public. Instead, the information may be entitled to confidential treatment, but only if it meets the requirements of sec. 10(b) (generally, trade secrets and information whose disclosure is likely to cause substantial harm to the competitive position of the submitter).

EPA believes that, with the exception of information pertaining to a pesticide that has never been registered, all information submitted in accordance with part 158 (including information submitted in connection with an application for a tolerance or exemption) constitutes safety and efficacy information subject to sec. 10(d)(1). All of the information subject to part 158 concerns “the effects of such pesticide on any organism or the behavior of such pesticide in the environment.” This includes not only studies regarding hazard and fate, but also information such as product chemistry, which is collected by the Agency for the very purpose of determining the effects of the pesticide on organisms and its behavior in the environment.

In addition to providing submitters with an opportunity to designate information as subject to one of the exceptions in FIFRA secs. 10(d)(1)(A), (B), or (C) (a feature also contained in the current version of § 158.33), EPA proposes to include a provision that all information that has not been so designated and that pertains to a registered or previously registered pesticide be deemed non-confidential by operation of law, without further notice to the submitter (subject to the requirements of sec. 10(g) regarding disclosure to multinational entities). This provision would not apply to information that was submitted prior to May 4, 1988, the effective date of the current regulation contained in § 158.33, and thus the first time that claims under sec. 10 (d)(1)(A), (B), or (C) were required to be identified.

3. Information pertaining to unregistered pesticides

ct to the requirements of sec. 10(g) regarding disclosure to multinational entities). This provision would not apply to information that was submitted prior to May 4, 1988, the effective date of the current regulation contained in § 158.33, and thus the first time that claims under sec. 10 (d)(1)(A), (B), or (C) were required to be identified.

3. Information pertaining to unregistered pesticides. Although safety and efficacy information (which by definition pertains only to registered or previously registered pesticides) is made publicly available by statute, if the information pertains to unregistered pesticides (including both applications for new active ingredients and import tolerances for pesticides used only outside the United States) it is not subject to the same mandatory disclosure requirement. Such information may be entitled to confidential treatment if it meets the requirements of sec. 10(b). In practice, EPA believes that information relating to the effects of unregistered pesticides that is not within one of the exceptions in FIFRA sec. 10(d)(1)(A), (B), or (C) will seldom meet this test. Much of the information in studies is valuable only to the extent that it can be used for registration/tolerance purposes, and protection from unauthorized submission or citation of a study by persons other than the submitter is provided by the FIFRA and FFDCA data compensation provisions and by FIFRA sec. 10(g). Moreover, because such information becomes publicly available once the pesticide is registered, competitors will eventually be able to get access to the information. Thus, confidentiality should normally be appropriate only when disclosure of the information prior to registration would give competitors an advance look at information that they could use to their advantage.

At the same time, the period prior to registration is of special importance for public participation in the registration process. Under FIFRA sec

y be able to get access to the information. Thus, confidentiality should normally be appropriate only when disclosure of the information prior to registration would give competitors an advance look at information that they could use to their advantage.

At the same time, the period prior to registration is of special importance for public participation in the registration process. Under FIFRA sec. 3(c)(4), EPA publishes a Federal Register notice announcing receipt of an application for registration of a product involving a new active ingredient or changed use pattern, and gives the public an opportunity to comment on the application. Implicit in the opportunity to comment is the availability of sufficient information to evaluate the risks and benefits of the product. Although requests for pre-registration information may be made under the Freedom of Information Act, the amount of time involved in contacting the submitter to clarify claims, obtaining substantiation of the confidentiality claim, and making a final determination on the claim make it very difficult for the public to get access to important information on a timely basis.

Because of the possibility that some pre-registration information may be legitimately confidential, EPA does not believe that it can categorically determine all such information to be non-confidential. The provisions in this proposal requiring the submitter to specify which information is claimed as confidential will simplify access to information not so claimed, but EPA is soliciting comment on other mechanisms to facilitate public access to pre-registration information.

access to information not so claimed, but EPA is soliciting comment on other mechanisms to facilitate public access to pre-registration information.

4. Confidentiality claims for plant-incorporated protectant information. Part 174 was incorporated into 40 CFR effective September 17, 2001. The regulations in part 158 apply to plant-incorporated protectants unless otherwise superseded by part 174. In addition to complying with the requirements of § 158.33, any confidentiality claims for information subject to 40 CFR part 174 (plant-incorporated protectants) must be substantiated at the time of submission as described in § 174.9.

5. Disclosure of data to multinational entities. Also included is a proposed provision governing the release of data to foreign or multinational pesticide companies. Under sec. 10(g) of FIFRA, EPA requires that any person requesting information from the Agency affirm that he or she is not an “entity engaged in the production, sale, or distribution of pesticides in countries other than the United States or in addition to the United States” and that the information will not be disclosed to such an entity. The requirement for such an affirmation applies to all data received by the Agency under FIFRA (and FFDCA) and is not limited to confidential business information.

In Class Determinations 3-85 (50 FR 48833, November 27, 1985) and 1-99 (64 FR 70019, December 15, 1999) EPA elucidated the criteria for determining whether information and documents derived from studies or reports submitted to the agency are subject to the restrictions of FIFRA sec. 10(g). In order to be outside the scope of sec. 10(g), documents must not (1) “contain or consist of any complete unpublished report submitted to EPA ” or (2) “contain or consist of excerpts or restatements of any such report which reveal the full methodology and complete results of the study, test, or experiment, and all explanatory information necessary to understand the methodology or interpret the results.” (50 FR 48834)

e the scope of sec. 10(g), documents must not (1) “contain or consist of any complete unpublished report submitted to EPA ” or (2) “contain or consist of excerpts or restatements of any such report which reveal the full methodology and complete results of the study, test, or experiment, and all explanatory information necessary to understand the methodology or interpret the results.” (50 FR 48834). Although the application of these class determinations is limited to data reviews created by the Agency (3-85) and information regarding unreasonable adverse effects of

6. Release to state and foreign governments with consent. EPA also is including in this proposal a provision to facilitate the release and exchange of information with State and foreign regulatory agencies. In an effort to promote harmonization and to conserve resources through work share programs, the exchange of data often is beneficial and desirable. Applicants would have the option of signing a statement authorizing the Agency to release information contained in their documents for such purposes. Although most governments provide protection for confidential information, EPA cannot guarantee how a particular government would treat specific information disclosed to it. Consequently, the submitter should be aware of any risk involved before granting consent to disclosure. However, EPA would not view disclosure to a government that protected confidential information as otherwise waiving confidential treatment for the information.

D. Flagging Criteria

EPA proposes to revise the flagging requirements of § 158.34, established in 1985, without changing the substance of the requirement. Currently, applicants for registration and amended registration, and submitters of data under FIFRA sec. 3(c)(2)(B) are required to flag certain toxicology studies that show results potentially indicating an adverse effect. EPA proposes to make minor revisions to update and clarify the criteria to encompass the new types of toxicology studies being proposed today

the substance of the requirement. Currently, applicants for registration and amended registration, and submitters of data under FIFRA sec. 3(c)(2)(B) are required to flag certain toxicology studies that show results potentially indicating an adverse effect. EPA proposes to make minor revisions to update and clarify the criteria to encompass the new types of toxicology studies being proposed today. Specifically, EPA proposes to:

1. Reduce the number of study criteria from 11 to 7 by combining certain studies under one criterion. The new criteria would eliminate distinctions between subchronic and chronic studies in most cases.

2. Combine reproductive, prenatal developmental toxicity and developmental neurotoxicity studies under one criterion to better focus on effects on children and infants.

3. Consolidate the criteria that address the No-Observed-Adverse-Effect Levels (NOAEL) into a single criterion covering all studies from which NOAELs are derived. In so doing, EPA would change references to cholinesterase inhibition to “acute toxicity.” This change acknowledges that NOAELs are now derived for a number of acute toxicity effects, not just cholinesterase inhibition. In a similar vein, EPA would eliminate the specific “less than 10X” and “less than 100X” triggers for NOAEL study flagging in favor of a more general description of “less than the current NOAEL.” Both of these changes could result in more studies being flagged.

4. Update the guidelines references, and terminology, e.g. , teratogenicity studies are now called prenatal developmental toxicity studies; the ADI is now referred to as the RfD. EPA believes that these revisions to the criteria will simplify the application of the criteria by submitters, even though additional studies may be required to be flagged.

E. Waivers

EPA proposes to reformat its waiver process, currently contained in § 158.45, but to retain its provisions

ty studies are now called prenatal developmental toxicity studies; the ADI is now referred to as the RfD. EPA believes that these revisions to the criteria will simplify the application of the criteria by submitters, even though additional studies may be required to be flagged.

E. Waivers

EPA proposes to reformat its waiver process, currently contained in § 158.45, but to retain its provisions. This proposal retains the flexibility of the current provisions for applicants to request, and EPA to evaluate, the need for data on a case-by-case basis depending on individual chemicals and use patterns. One of the benefits of updating part 158 as proposed today is that the improvements in clarity and transparency of the data requirements will greatly assist both the Agency and applicants in addressing data waivers.

1. Waiver requests submitted as part of an application for registration. Waiver requests submitted in conjunction with an application for registration, amended registration, experimental use permit, or petition for tolerance are considered in the context, and in the same time frame, as the application is considered, based upon the application review period in FIFRA sec. 33. The review periods currently range from 90 days for minor amendments to as much as 3 years for new chemical applications. Consideration of waiver requests (and there may be multiple requests in a single application) is done by Agency scientists when the application is reviewed scientifically.

2. Waiver requests submitted in response to Data Call-Ins for studies that are required in part 158

33. The review periods currently range from 90 days for minor amendments to as much as 3 years for new chemical applications. Consideration of waiver requests (and there may be multiple requests in a single application) is done by Agency scientists when the application is reviewed scientifically.

2. Waiver requests submitted in response to Data Call-Ins for studies that are required in part 158. In the case of DCIs for data requirements that are contained in part 158, EPA believes that it will be able to make waiver decisions in a reasonably prompt timeframe since the need for the data has been established, the criteria upon which the data are required (use pattern, exposure pattern, chemical characteristics, etc.) have been elaborated, and the conditionalities associated with its imposition have been carefully considered in the development of this proposal. In other words, much of the evaluative process associated with a data waiver has already been done. Thus EPA will be able to judge an adequately supported waiver request against these existing factors to determine whether a waiver can be granted.

Moreover, the improved transparency of the requirements and conditions in new part 158 means that an applicant will be able to ascertain with reasonable certainty the likelihood that EPA would consider favorably a waiver request. EPA believes that improved clarity will also reduce the number of frivolous, inappropriate, or ill-supported waiver requests. Thus, EPA believes it will be able to respond in a reasonable period of time to a waiver request. If EPA requires a lengthy period to reach a decision on a waiver request which is denied, the Agency will generally consider time extensions to accommodate legitimate and reasonable registrant needs, whether to define acceptable protocols, evaluate alternative tests that might satisfy the Agency's requirements, or allow for consideration of laboratory capacity.

iod of time to a waiver request. If EPA requires a lengthy period to reach a decision on a waiver request which is denied, the Agency will generally consider time extensions to accommodate legitimate and reasonable registrant needs, whether to define acceptable protocols, evaluate alternative tests that might satisfy the Agency's requirements, or allow for consideration of laboratory capacity.

F. Minor Uses

Current § 158.60 outlines a number of non-regulatory policies EPA adopted to limit the economic impact of data requirements on minor use products while ensuring that the Agency had adequate data to assess the potential risks and benefits of these pesticides. Because minor use policies by themselves are somewhat fluid and subject to change periodically, EPA proposes to remove § 158.60. EPA, however, remains committed to the minor use program by imposing the mandates contained in FIFRA that relate to minor uses, such as extending exclusive use of minor use data, granting minor use waivers, and expediting minor use registrations. The Agency believes that tiered testing, outlined elsewhere in this proposal, coupled with its waiver policy in § 158.45 and priority review status, limit the economic burden for all pesticides by ensuring that registrants are required to develop only those studies that are essential for an appropriate safety evaluation.

VIII. How to Use the Data Tables (Subpart B)

EPA proposes to revise subpart B to update use patterns and clarify the steps needed to determine the appropriate data requirements from the tables in subparts, D, E, F, J, K, N, O, and U. Pesticide use patterns that are used to determine required testing have been revised for all of the data requirements tables to reflect the expanded use patterns contained in this proposal (see below).

A. Expanded Use Patterns

EPA proposes to subdivide the current 9 major use patterns listed in Appendix A of part 158 to 15 to more fully address nonagricultural uses

D, E, F, J, K, N, O, and U. Pesticide use patterns that are used to determine required testing have been revised for all of the data requirements tables to reflect the expanded use patterns contained in this proposal (see below).

A. Expanded Use Patterns

EPA proposes to subdivide the current 9 major use patterns listed in Appendix A of part 158 to 15 to more fully address nonagricultural uses. The revised use patterns would be terrestrial food crop, terrestrial feed crop, and terrestrial nonfood crop; aquatic food crop, aquatic nonfood crop, aquatic nonfood outdoor use and aquatic nonfood industrial use; greenhouse food crop and greenhouse nonfood crop; forestry; residential outdoor; indoor food; indoor nonfood; indoor medical; and indoor residential use. As mentioned above, the Agency proposes to remove the Pesticide Use Index (Appendix A) from the regulations because it is not a requirement. Instead, the Index will become a separate guidance document and placed on EPA's website and made available to the public. A guidance document would be easier to update and would provide the regulated community with the most current information.

B. Clarifying How to Use the Data Tables

Subpart B would contain a step-wise process to assist the applicant in determining the data needed to support its particular product. As with current practice, the actual data and studies required may be modified on an individual basis to fully characterize the use and properties of specific pesticide products under review. While EPA is attempting to assist the applicant in this subpart, 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/or FFDCA. Accordingly, applicants are encouraged to consult with the Agency on the appropriate data requirements as proposed here as they relate to their specific product prior to and during the registration process

e applicant in this subpart, 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/or FFDCA. Accordingly, applicants are encouraged to consult with the Agency on the appropriate data requirements as proposed here as they relate 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. Because of the variety of chemicals and use patterns, and because EPA must retain flexibility to tailor data requirements to its needs, it uses only qualitative descriptors in the tables. These 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 applicability of the data requirement.

The table descriptors NR (not required), R (required), and CR (conditionally required) can be viewed as markers along a spectrum of 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. The use of CR means a study is less likely to be required. Although only an approximation, if percentages were to be assigned, R could be viewed as representing the range of 50% to 100% and CR the range up to 50%. EPA welcomes comment on ways to characterize the data requirements that would better serve applicant needs.

EPA is continuing its longstanding system of identifying test substances in the tables. The standard descriptors of test substance are the following:

1. The technical grade of active ingredient (TGAI), used when evaluating the inherent toxicity or chemical characteristics of a pesticide.

2. The manufacturing use product (MP), used in certain product chemistry tests, usually for labeling purposes.

continuing its longstanding system of identifying test substances in the tables. The standard descriptors of test substance are the following:

1. The technical grade of active ingredient (TGAI), used when evaluating the inherent toxicity or chemical characteristics of a pesticide.

2. The manufacturing use product (MP), used in certain product chemistry tests, usually for labeling purposes.

3. The pure active ingredient (PAI), used in certain product chemistry tests requiring extremely basic chemical properties or manufacturing process information.

4. The pure active ingredient, radioactive (PAIRA), used primarily in residue chemistry studies when residues at very low levels (ppm) must be quantified in plant or animal tissue.

5. The end-use product (EP), used as the test substance when the Agency wants to refine its hazard or chemical profile based on actual concentrations, or needs to determine the impact of added inert ingredients on the hazard or chemical profile.

6. The typical end-use product (TEP), used as a representative product in tests that might otherwise require duplicative testing of a number of EPs.

Where changes in the test substance are proposed, such changes are described in the discussion of each proposed revision. EPA welcomes comment on its test substances and how the Agency uses them in a testing regimen. Such comments should be made in the context of the specific data requirement for which changes are proposed.

C. Identifying Data for Experimental Use Permits (EUPs)

Finally, the Agency is requesting comment on the best way to identify data requirements for EUPS. Some people believe that the brackets indicating what data requirements also apply to EUPs in the current data tables complicate the tables with extraneous symbols and codes. In an effort to make the data tables simpler and easier for an applicant to understand, one suggestion is to separate the EUP data requirements from the main data tables and make them a stand-alone table

equirements for EUPS. Some people believe that the brackets indicating what data requirements also apply to EUPs in the current data tables complicate the tables with extraneous symbols and codes. In an effort to make the data tables simpler and easier for an applicant to understand, one suggestion is to separate the EUP data requirements from the main data tables and make them a stand-alone table. Revised EUP data requirements could be housed in 40 CFR part 158 (data requirements) or in part 172 (EUP requirements). As part of this proposal, EUP data requirements for each discipline have been identified either in the regulatory text accompanying the data table or, as brackets, within the body of the table, itself. In general, the Agency proposes to retain the existing data requirements for EUPs with a few minor changes in the areas of environmental fate and ecological effects. The Agency is soliciting opinions on this approach or other approaches that may prove more efficient and useful to the applicant. If an alternative approach is accepted, the Agency may in the final rule, reformat the regulatory text or data tables.

D. Test Guidelines

The guidelines for the environmental fate series are currently being updated and where applicable, harmonized with the guidelines established by the OECD. Therefore, the Agency is showing the current guideline numbers in the preamble, regulatory text, and tables. If, before the final rule has been promulgated, these guidelines have been issued, EPA will insert the new guideline numbers in the Final Rule.

E. Purposes of the Registration Data Requirements

The Agency proposes to retain the material currently in § 158.202 Purposes of the registration data requirements in subpart D, Data Requirements Tables. Since a series of new subparts will replace subpart D, this material will be moved to subpart B.

IX. Product Chemistry Data Requirements (Subpart D)

w guideline numbers in the Final Rule.

E. Purposes of the Registration Data Requirements

IX. Product Chemistry Data Requirements (Subpart D)

A. General

The Agency uses product chemistry information to determine whether impurities of toxicological or environmental concern are present in pesticides and formulated products.

The Agency proposes to list entries in the data requirements table for product identification, composition, analysis, and certification of limits requirements. These requirements are currently contained in § § 158.155 through 158.180, and are proposed to be retained unchanged as new § § 158.320 through 158.355. Inclusion in the table for product chemistry is for the convenience of applicants--the requirements themselves are not affected by including them in the table. The test notes refer applicants to the subsequent section that discuss the requirements in detail.

The Agency's current policy as described in Pesticide Registration Notice 98-1 (January 12, 1998) allows applicants and registrants to submit a summary of the physical and chemical properties of non-integrated pesticide products, EPA Form 8570-36, rather than submit the studies upon which these data are based. The self-certification statement (EPA Form 8570-37) must be signed and dated by the applicant certifying that the submitted information was conducted in full compliance with the regulations (Attachment 2 to PR notice 98-1). The PR notice applies to applications for registration of manufacturing-use and end-use products of all pesticide products produced by a non-integrated formulation system.

B. Proposed Product Chemistry Data Requirements

1. Newly imposed data requirements . None.

2. Newly codified data requirements —i. UV/visible light absorption

pliance with the regulations (Attachment 2 to PR notice 98-1). The PR notice applies to applications for registration of manufacturing-use and end-use products of all pesticide products produced by a non-integrated formulation system.

B. Proposed Product Chemistry Data Requirements

1. Newly imposed data requirements . None.

2. Newly codified data requirements —i. UV/visible light absorption . The Agency proposes to add a requirement for data on the ultraviolet (UV)/visible light absorption in the 200-800 nanometers wavelength range (guideline 830.7050) as part of the basic data in the characterization and identification of a compound. This information will be used in conjunction with the photodegradation in water study (§ 158.1100) to determine if photodegradation is a possible route of dissipation in the environment. In order for a pesticide to undergo direct photolysis in the environment, it must absorb energy in the wavelength range emitted by sunlight. While the UV/visible light absorption spectrum will indicate whether or not the chemical absorbs in this range and hence may potentially photodegrade, it does not actually measure the photodegradation rate or identify photodegradates. Accordingly, test note 2 for the photodegradation study states that the photodegradation in water study will not be 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.

ii. Particle size, fiber length, and diameter distribution. The Agency proposes to add the conditional requirements for data on particle size, fiber length, and diameter distribution (guideline 830.7520). This study would be conditionally required for water insoluble test substances ( < 10 - 6 g/l) and fibrous test substances with diameter ≥ 0.1 μm. Data from this study are needed in the environmental fate assessment to estimate potential chemical drift to nontarget areas.

3. Revised data requirements —i

ents for data on particle size, fiber length, and diameter distribution (guideline 830.7520). This study would be conditionally required for water insoluble test substances ( < 10 - 6 g/l) and fibrous test substances with diameter ≥ 0.1 μm. Data from this study are needed in the environmental fate assessment to estimate potential chemical drift to nontarget areas.

3. Revised data requirements —i. Stability to temperatures, metals, and metal ions. The Agency proposes to change the requirement for stability data (guideline 830.6313) from “required” to “conditionally required.” Data on the stability to metals and metal ions is required only if the active ingredient is expected to come in contact with either material during storage. This proposed change does not alter the nature of the requirement.

ii. Explodability. The Agency proposes to change the requirement for explodability data (guideline 830.6316) from “required” to “conditionally required.” Since pesticides do not typically fall under this category, these data are only required for products that are potentially explosive. This proposed change does not alter the nature of the requirement.

iii. Partition coefficient (n-octanol/water). The Agency proposes to change the requirement from “conditionally required” to “required” (guidelines 830.7550, 830.7560, and 830.7570). The Agency is requiring this study because the majority of currently registered pesticides are organic non-ionic chemicals that are not expected to significantly hydrolyze or solubilize in water. In the event a chemical fully hydrolyzes or is completely soluble in water, this data requirement would be waived. This proposed change does not alter the nature of the requirement nor the conditions under which it is imposed.

iv. Density, dissociation constant, and vapor pressure

pesticides are organic non-ionic chemicals that are not expected to significantly hydrolyze or solubilize in water. In the event a chemical fully hydrolyzes or is completely soluble in water, this data requirement would be waived. This proposed change does not alter the nature of the requirement nor the conditions under which it is imposed.

iv. Density, dissociation constant, and vapor pressure. The Agency proposes to add test notes for the data requirements for density/relative density/bulk density (guideline 830.7300), dissociation constant (guideline 830.7370), and vapor pressure (guideline 830.7950) to better identify when these study requirements are applicable. These proposed minor changes do not expand the product chemistry requirement. Instead, they clarify the requirements by specifying which physical states or chemical forms the requirements apply.

X. Terrestrial and Aquatic Nontarget Organisms Data Requirements (Subpart E)

A. General

The Agency uses a tiered system of ecological effects testing to assess the potential risks of pesticides to aquatic and terrestrial vertebrates, invertebrates, and plants. These tests include studies arranged in a hierarchy from basic laboratory tests to applied field tests. The results of each tier are evaluated to determine the potential impacts on fish, wildlife and other nontarget organisms, and to indicate whether further laboratory and/or field studies are needed. These data requirements provide the Agency with ecological effects information, which, in turn, allows the Agency to determine if precautionary statements concerning toxicity or potential adverse effects to nontarget organisms are necessary.

nts concerning toxicity or potential adverse effects to nontarget organisms are necessary.

Higher tiered studies may be required when basic toxicity data and predicted exposure levels or environmental conditions suggest the potential for adverse effects. Field data are used to examine acute and chronic adverse effects on captive or monitored populations under natural or near-natural environments. Such studies are required only when the potential for adverse effects is high, based on the results of lower tier studies, or to confirm the need for mitigation measures. In some cases, the results of field studies may give rise to the need for further testing.

B. Proposed Requirements

The Agency is proposing two additional data requirements as well as other minor revisions that would clarify the existing data requirements. In some cases, the proposal is to change the

In addition, as discussed in more detail in this section, the Agency proposes to require an additional test species for the avian oral toxicity study, because current data requirements may not adequately characterize the risks that pesticides pose to songbirds. The Agency also proposes to conditionally require sediment testing to better assess the effects of sediment bound pesticide residues in aquatic environments. The Agency is proposing to require independent laboratory validation of environmental chemistry methods for terrestrial and aquatic field testing.

Finally, the Agency is proposing to eliminate the requirement for avian dietary testing for indoor and greenhouse uses, and to simplify the test notes for these requirements. The Agency invites comments on all aspects of these data requirements.

1. Newly imposed data requirements. None.

greenhouse uses, and to simplify the test notes for these requirements. The Agency invites comments on all aspects of these data requirements.

1. Newly imposed data requirements. None.

2. Newly codified data requirements. The Agency proposes to add testing of aquatic organisms exposed to treated sediment to better assess the effects of sediment bound pesticide residues in aquatic environments. Environmental risk estimates should be based on exposure data from the water column, sediment, and pore water (the water occupying space between sediment or soil particles), however, with the exception of field studies, the current data requirements are limited to water column exposures. 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. 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 organisms. The Agency does not believe these studies will be commonly required.

sediment bound compound and to characterize the possible impact to sediment dwelling organisms. The Agency does not believe these studies will be commonly required.

EPA's Contaminated Sediment Management Strategy (USEPA 1998) (Ref. 3) has been recently developed to provide a more unified approach to testing and risk assessment of aquatic species which inhabit and feed in the benthic environment. Testing would consist of whole sediment (spiked) tests; testing can also consist of chronic whole sediment toxicity tests and/or sampling for residues and biological monitoring of pesticides in the sediment after exposure. EPA has developed test protocols for chronic whole sediment tests of invertebrates. Test guidelines will be developed from these protocols. Protocols for further tests ( e.g. , acute pore water tests) and for vertebrate species are under consideration. Registrants are urged to meet with the Agency prior to development of their own protocols.

i. Whole sediment: acute toxicity to invertebrates, freshwater and marine. The Agency is proposing to conditionally require data for acute invertebrate sediment testing (guidelines 850.1735 and 850.1740) for terrestrial uses, aquatic food and nonfood outdoor uses, and forestry uses. This study would be required when the soil partition coefficient (K d ) is ≥ 50 mg/L, indicating the ability to absorb to sediment, and if the half-life of the pesticide in the sediment is ≤ 10 days in either the aerobic soil or aquatic metabolism studies. Registrants would need to consult with the Agency on appropriate test protocols.

ii. Whole sediment: chronic toxicity to invertebrates. The Agency proposes to conditionally require this study for the same use patterns as the above sediment toxicity tests

bsorb to sediment, and if the half-life of the pesticide in the sediment is ≤ 10 days in either the aerobic soil or aquatic metabolism studies. Registrants would need to consult with the Agency on appropriate test protocols.

ii. Whole sediment: chronic toxicity to invertebrates. The Agency proposes to conditionally require this study for the same use patterns as the above sediment toxicity tests. The study would be triggered when the estimated environmental concentration is greater than or equal to the acute sediment EC 50 /LC 50 or the soil partition coefficient (K d ) is ≥ 50 mg/L, indicating the ability to absorb to sediment; and if the half-life of the pesticide in the sediment is > 10 days in either the aerobic soil or aquatic metabolism studies. Registrants would need to consult with the Agency on appropriate test protocols.

3. Revised data requirements—Avian oral toxicity . The Agency proposes to require for certain uses, an additional test species for the acute avian oral toxicity study (guideline 850.2100), which currently recommends the use of mallard ducks or bobwhite quail. Testing on a passerine species ( i.e. , redwing blackbird) would be required for outdoor uses. The Agency is proposing to add this passerine species because of concern in the scientific community that data from tests with mallards or quail may not always adequately characterize the risks that pesticides pose to songbirds. Recent evaluation of the data collected over the past 10 years indicates passerines are more sensitive to pesticides than larger birds such as mallards and quail (which are currently the recommended test species) (Ref. 2) and in 1996, the SAP supported the need for testing on passerines

tests with mallards or quail may not always adequately characterize the risks that pesticides pose to songbirds. Recent evaluation of the data collected over the past 10 years indicates passerines are more sensitive to pesticides than larger birds such as mallards and quail (which are currently the recommended test species) (Ref. 2) and in 1996, the SAP supported the need for testing on passerines. In addition to comments on the proposed addition of a passerine species for the acute oral toxicity study, the Agency requests comments on whether this species should replace the existing bobwhite/mallard species or otherwise be conditional, and if so what criteria or triggers should be used to determine when the data should be required.

The Agency proposes to revise and simplify the test notes for the avian acute toxicity test. The single current footnote is structurally complex, so EPA has subdivided it into 4 test notes that are easier to understand and apply.

In addition, the Agency proposes to conditionally require testing of the typical end-use product (TEP) of granular and non-granular end-use products because the inherent toxicity of end-use products is better defined by testing the product. End-use products may contain chemicals that enhance efficacy by acting as solvents, stickers, and wetting agents. Although these chemicals are listed as inerts, their individual toxicity or combination with one another or the active ingredient (a.i.), may be more toxic than the technical grade of the active ingredient (TGAI).

i. Avian dietary toxicity. In the current regulation, the Agency requires the subacute avian dietary toxicity study (guideline 850.2200) for terrestrial and aquatic (food crop and nonfood), forestry, and domestic outdoor uses, and conditionally requires this study for indoor and greenhouse (food crop and nonfood) use sites, as part of a set of 4 basic avian (acute and dietary) and aquatic toxicity studies

dietary toxicity. In the current regulation, the Agency requires the subacute avian dietary toxicity study (guideline 850.2200) for terrestrial and aquatic (food crop and nonfood), forestry, and domestic outdoor uses, and conditionally requires this study for indoor and greenhouse (food crop and nonfood) use sites, as part of a set of 4 basic avian (acute and dietary) and aquatic toxicity studies. The results are used in decisions regarding environmental hazard statements on product labeling. Since the avian acute oral study more accurately reflects the inherent exposure to birds in this scenario, the Agency is proposing to no

This proposal would also add as a conditional requirement data on one avian species for aquatic nonfood residential uses if the acute avian oral LD 50 of the TGAI is less than or equal to 100 mg a.i./kg. Data would be required on a second species for this use if the avian dietary lethal concentration to cause mortality in 50% of the test animals (LC 50 ) in the first species tested is less than or equal to 500 ppm a.i. in the diet. The Agency is proposing to conditionally require the second species because the data will provide some assurance that EPA is not basing an assessment on a single species which might be highly sensitive (or the opposite) when compared to other birds. This particular use category (aquatic nonfood residential) is relatively small-scale, so the current regulations require testing on only one species. However, in the event that this test shows high toxicity, this concern is addressed by the conditional requirement for testing on a second species.

ressed by the conditional requirement for testing on a second species.

ii. Wild mammal toxicity . The Agency proposes to amend this conditional data requirement to eliminate the requirement for aquatic nonfood residential uses. In splitting the current aquatic use category, EPA is able to tailor the requirement to those use situations for which the data are needed (aquatic food and nonfood uses). The conditionality of the requirement would be unchanged, that is, required on a case-by-case basis depending on the results of lower toxicology tier studies, such as acute and subacute testing, intended use pattern, and environmental fate characteristics that indicate potential exposure.

iii. Avian reproduction. Because some pesticides are stable in the environment, or can be stored in plant tissues that may be used by birds as a food source, avian reproduction testing (guideline 850.2300) is conditionally required for pesticides to which birds are exposed repeatedly or continuously during or preceding the breeding season. In addition, research has shown that even short-term exposures to pesticides can lead to significant adverse reproductive effects. For example, several organophosphorus insecticides have been shown to significantly reduce egg production and lead to changes in eggshell quality within days of dietary exposure (Refs. 4, 5 and 6). Therefore, EPA proposes to require these studies for terrestrial (food crop, feed crop, and nonfood), aquatic food crop and nonfood outdoor, forestry, and residential outdoor uses.

orestry, and residential outdoor uses.

iv. Simulated or actual field testing for mammals and birds. Current part 158 conditionally requires field testing (guideline 850.2500) for terrestrial and aquatic (food crop and nonfood), forestry, and domestic outdoor uses. The Agency proposes to expand this conditional requirement to include terrestrial feed crop and aquatic nonfood outdoor uses, as well. The requirement would be based on the results of lower tiered studies such as acute and subacute bird and mammal testing, intended use pattern, and environmental fate characteristics that indicate potential exposure. Testing would be required only for those products that appear to pose significant risks to nontarget wildlife. The Agency is also proposing to require independent laboratory validation of the environmental chemistry methods used to generate data associated with this study.

v. Acute toxicity: freshwater fish. Currently part 158 requires the freshwater fish toxicity study (guideline 850.1075) for terrestrial and aquatic (food crop and nonfood), forestry, and domestic outdoor uses and conditionally requires these studies for greenhouse (food crop and nonfood) and indoor uses.

Although indoor and greenhouse uses usually require only one species of fish to be tested, in some instances a second fish species may be needed. For example, a chemical may be shown to be stable in the environment ( i.e. , hydrolysis study), have moderate toxicity (1 ppm LC 50 < 10 ppm) in the acute fish toxicity study, and may be released into the aquatic environment through effluent discharge. In such cases, the results of the two required acute aquatic toxicity studies (fish and invertebrates) may not be sufficient to rule out greater toxicity in a second species of fish. Testing on a second species will provide some assurance that EPA is not basing an assessment on a species that is highly sensitive (or the opposite) when compared with another species

nment through effluent discharge. In such cases, the results of the two required acute aquatic toxicity studies (fish and invertebrates) may not be sufficient to rule out greater toxicity in a second species of fish. Testing on a second species will provide some assurance that EPA is not basing an assessment on a species that is highly sensitive (or the opposite) when compared with another species. Therefore, in these cases, the Agency proposes to conditionally require a third acute study on a second species of fish to correlate with the results of the previous two acute aquatic studies and to ensure that the labeling is adequate to protect aquatic species. The additional study increases the likelihood that effluent criteria and product labeling reflect the pesticide's risk and inherent toxicity.

vi. Acute toxicity—estuarine and marine organisms. Acute data from estuarine testing enables the Agency to perform a risk assessment by comparing the toxic concentrations with the estimated or monitored levels in estuaries. The Agency proposes to change the conditional requirement for the acute LC 50 /EC 50 testing (guidelines 850.1025, 850.1035, 850.1045, 850.1055, and 850.1075) for terrestrial, aquatic (food crop and nonfood outdoor), residential outdoor, and forestry uses to required testing, and change the aquatic nonfood residential use to “not required.” Generally, three out of the five studies would be needed to satisfy the data requirement. Registrants may request a waiver of the study if the crop is never associated with coastal counties or there is a geographical restriction for a site that would normally be of concern.

phical restriction for a site that would normally be of concern.

vii. Chronic toxicity—fish early-life stage and aquatic invertebrate life-cycle. Currently, the Agency conditionally requires fish early-life stage and aquatic invertebrate life-cycle studies (guidelines 850.1300, 850.1350, and 850.1400) for terrestrial food and nonfood, aquatic food and nonfood, forestry, and domestic outdoor uses. These studies are not required for greenhouse food and nonfood, and indoor uses. The Agency is proposing several revisions that would clarify the applicability of the requirements. The first is to list the fish early-life stage and aquatic invertebrate life-cycle studies as separate requirements in the data table; then identify each test organism as a freshwater or saltwater species.

For the freshwater fish early-life stage and invertebrate life-cycle studies, the Agency proposes to change the conditional requirement for terrestrial and aquatic (food crop and nonfood) and forestry uses to required, and change the aquatic nonfood residential use to not required.

Currently, the freshwater invertebrate life cycle and fish early life stage tests are conditionally required for terrestrial, aquatic (food crop and nonfood), and forestry uses. When promulgated in 1984, one basis for the conditional nature of the requirements was that only one of the two tests was required, depending on whether fish or invertebrates were more sensitive in the acute studies. However, when a pesticide enters the aquatic environment, both groups of organisms will be exposed. Moreover, acute sensitivity is not a reliable indicator of chronic sensitivity, whether in the same or a different group of organisms, so that chronic data are needed regardless of the results of acute testing

ired, depending on whether fish or invertebrates were more sensitive in the acute studies. However, when a pesticide enters the aquatic environment, both groups of organisms will be exposed. Moreover, acute sensitivity is not a reliable indicator of chronic sensitivity, whether in the same or a different group of organisms, so that chronic data are needed regardless of the results of acute testing.

The proposed change to “not required” for aquatic nonfood residential use is due to the fact that the current “aquatic nonfood” use pattern is proposed to be split into aquatic

In addition, the Agency proposes to require both of these tests for all turf uses including residential, since exposure varies. This change is warranted because the relative sensitivity of fish and invertebrates can vary widely across chemicals. Currently, only the most sensitive of the two organisms, either fish or aquatic invertebrates, as determined by Tier I acute studies, is tested. However, since both organisms will be exposed when a pesticide enters an aquatic environment and the acute sensitivity of an invertebrate may not accurately predict the chronic sensitivity in fish and vice versa, the Agency believes that both species should be tested for chronic effects. The Agency cannot make the assumption that a chemical is not chronically toxic at much lower concentrations than some ratio of the LC 50 value would suggest.

viii. Aquatic organism bioavailability/biomagnification/toxicity tests. The Agency proposes to eliminate the requirement for these studies for aquatic nonfood residential or residential outdoor uses since exposure is expected to be minimal ( i.e. , insufficient quantities to accumulate in the tissues of aquatic organisms (guidelines 850.1710, 850.1730, and 850.1850).

ix. Simulated or actual field testing for aquatic organisms

ability/biomagnification/toxicity tests. The Agency proposes to eliminate the requirement for these studies for aquatic nonfood residential or residential outdoor uses since exposure is expected to be minimal ( i.e. , insufficient quantities to accumulate in the tissues of aquatic organisms (guidelines 850.1710, 850.1730, and 850.1850).

ix. Simulated or actual field testing for aquatic organisms. The Agency is clarifying that the conditional requirement (guideline 850.1950) applies to turf, however these studies would no longer be required for aquatic nonfood residential uses since exposure is expected to be minimal.

x. Honeybee acute contact toxicity. EPA is proposing to require this study (guideline 850.3020) for terrestrial (food crop, feed crop, and nonfood), aquatic food crop and nonfood (outdoor), forestry, and residential outdoor uses. This study is being added to the battery of studies required to support outdoor uses when honeybees are likely to be exposed to pesticides. Previously, the requirement was limited to outdoor use patterns when the crop may be in bloom and thereby be attractive to honey bees. The change from “conditionally required” to “ required” is to address those situations where blooming, pollen-shedding, or nectar-producing parts of nontarget plants adjacent to or within the treated area may be attractive to honey bees. Registrants may request a waiver of the study if use practices significantly restrict exposure of the pesticide to honey bees.

cide to honey bees.

xi. Honeybee-toxicity of residues on foliage. The current regulation conditionally requires honeybee toxicity of residues on foliage studies (guideline 850.3030) for terrestrial and aquatic (food crop and nonfood), forestry, and domestic outdoor uses. The study is required when the formulation contains one or more active ingredients having an acute LD 50 of less than 1 μg/bee. The Agency proposes to amend the requirement to require testing on the TEP when the formulation contains one or more active ingredients having an acute LD 50 of < 11 μg/bee, as determined in the acute contact study, and the use pattern indicates that honey bees may be exposed. The proposed data requirements rule (48 FR 53192) which was published in 1982, listed the correct value of < 11 μg/bee for the honeybee study.

xii. Field testing for pollinators. The Agency proposes to include terrestrial (feed crop) and aquatic nonfood (aquatic outdoor and residential) uses where honeybees are likely to be exposed to pesticides as a conditional requirement (guideline 850.3040).

C. Data Requirements Specific to Endangered Species Assessments and Determinations

Over the last several years, the Agency has been requiring, on a case-by-case basis for certain pesticides, data demonstrating specific geographic location(s) of threatened and endangered species (listed species), which can then be compared with areas of potential pesticide use. These data have been required when EPA determined that the estimated environmental concentration of the pesticide when applied according to the labeling appears to exceed the Agency's numeric concern levels for listed species. The specific species for which location information was needed, has been determined on a case-by-case basis based upon the use pattern of the pesticide and the sites on which it may be used

been required when EPA determined that the estimated environmental concentration of the pesticide when applied according to the labeling appears to exceed the Agency's numeric concern levels for listed species. The specific species for which location information was needed, has been determined on a case-by-case basis based upon the use pattern of the pesticide and the sites on which it may be used. These special data are currently not required by part 158, and have only been requested on a few occasions; however, the Agency anticipates that they may be requested in the future in connection with other registration and reregistration actions. In response to a Data Call-In notice for data on the location of all listed species, an industry task force is working to develop a database that may partly fulfill Agency needs, i.e. , geographic locations where potentially affected species are thought to occur. Access to the task force data by other registrants who may be required to provide such data in the future would be made available through appropriate data sharing mechanisms. Although the anticipated expanded burden on registrants is not large since it does not entail experimental or laboratory procedures, it is nevertheless not likely to be inconsequential. Consequently, the Agency is requesting comment on its utility and appropriateness.

In addition, through discussions about methods to evaluate the potential risks of pesticides to listed species, EPA and the Fish and Wildlife Service and the National Marine Fisheries Service (jointly referred to as the Services) identified several aspects of EPA's current approach for which there is some scientific uncertainty. While the Services agreed that EPA was using the best available scientific and commercial information to assess risks to listed species, the Services and EPA also agreed that where uncertainties existed, further research and investigation might help to develop improved risk assessment approaches

s) identified several aspects of EPA's current approach for which there is some scientific uncertainty. While the Services agreed that EPA was using the best available scientific and commercial information to assess risks to listed species, the Services and EPA also agreed that where uncertainties existed, further research and investigation might help to develop improved risk assessment approaches. The Agency recognizes that such research also could lead, in the long run, to additional data requirements for registration. Accordingly, the Agency seeks input on research areas that may be necessary to effectively characterize potential risks to listed endangered species from pesticide use. These include research to address the following types of uncertainties:

• Product use information by geographic location below the state and county levels

• Toxicity data and environmental fate measurements/exposure model predictions with end use products

• Toxicity data from surrogate species that quantify dose-response relationships for effects relevant to critical life stages of endangered species

• Measured or estimated values of physiological, biochemical, and morphological characteristics of endangered species and surrogate species to refine chemical-specific interspecies toxicity extrapolations

• Toxicity, exposure, uptake and elimination data to better determine any differences in interspecies sensitivity of non-target and endangered plant species exposed to herbicides

• Toxicity data to characterize potential effects to freshwater mussels

• Toxicity data to characterize potential effects to reptiles and amphibians.

The Agency seeks comment on:

1. The relative value of each of these research areas in better refining assessments of potential risks to listed species.

2. Input on specific research directions in these areas, including methodologies, protocols etc., that would be appropriate and useful in assessing the potential risks to listed species.

erize potential effects to reptiles and amphibians.

The Agency seeks comment on:

1. The relative value of each of these research areas in better refining assessments of potential risks to listed species.

2. Input on specific research directions in these areas, including methodologies, protocols etc., that would be appropriate and useful in assessing the potential risks to listed species.

3. Other types of research that would be of value in refining potential risks of a pesticide to a listed species.

4. The extent to which potential research areas reflect uncertainties that apply to pesticides generically; to chemical stressors generically, or to types of pesticides or chemicals stressors.

XI. Toxicology Data Requirements (Subpart F)

A. General

Toxicology studies are required by the Agency to assess the hazard of the pesticide to humans and domestic animals. These hazard data, when combined with exposure data, form the basis for the human risk assessment. Generally, using animals as a surrogate for humans, tests are carried out by the oral, dermal or inhalation route depending on the pesticide's pattern of use and physical form. The duration of the toxicity study approximates the estimated duration of human exposure, while considering species differences in maturational milestones and overall life span. Typical exposures may be “acute” (single dose), “subchronic” (intermediate), or “chronic” (long-term). If a pesticide is used on food and requires a tolerance, the dietary exposure may be over a lifetime, or a significant portion of a lifetime, and thus chronic/cancer and multi-generation reproductive studies would be required. Studies would be required to assess the hazard during a potentially susceptible stage of life, e.g. , prenatal developmental studies and developmental neurotoxicity studies, and to measure end points not always observed in the basic toxicity test battery, e.g. , acute and subchronic neurotoxicity studies

lifetime, and thus chronic/cancer and multi-generation reproductive studies would be required. Studies would be required to assess the hazard during a potentially susceptible stage of life, e.g. , prenatal developmental studies and developmental neurotoxicity studies, and to measure end points not always observed in the basic toxicity test battery, e.g. , acute and subchronic neurotoxicity studies.

In addition, EPA's Risk Assessment Guidelines set forth principles and procedures to guide EPA scientists in the conduct of Agency risk assessments, and to inform Agency decision makers and the public about these procedures. The guidelines emphasize that risk assessments will be conducted on a case-by-case basis, giving full consideration to all relevant scientific information. This case-by-case approach means that Agency experts review the scientific information on each agent and use the most scientifically appropriate interpretation to assess risk. The guidelines also stress that this information will be fully presented in Agency risk assessment documents, and that Agency scientists will identify the strengths and weaknesses of each assessment by describing uncertainties, assumptions, and limitations, as well as the scientific basis and rationale for each assessment.

This proposal includes the requirements for pesticides retained from the current 40 CFR 158.340 as well as proposed revisions that have been peer reviewed by the SAP. The basic data set proposed here includes toxicity studies needed to support high exposure pesticides, such as food use pesticides.

1. Acute studies (oral, dermal, and inhalation toxicity tests, eye and skin irritation tests and dermal sensitization)

2. Subchronic (90-day) feeding studies in rodents and nonrodents

3. Chronic feeding studies in rodents and nonrodents

4. Cancer studies in two species of rodents (rat and mouse preferred)

5. Prenatal developmental toxicity studies in rodents and nonrodents (rat and rabbit preferred)

es (oral, dermal, and inhalation toxicity tests, eye and skin irritation tests and dermal sensitization)

2. Subchronic (90-day) feeding studies in rodents and nonrodents

3. Chronic feeding studies in rodents and nonrodents

4. Cancer studies in two species of rodents (rat and mouse preferred)

5. Prenatal developmental toxicity studies in rodents and nonrodents (rat and rabbit preferred)

6. Two-generation reproduction study in rodents (rat preferred)

7. General metabolism study in rodents

8. Mutagenicity battery

9. Acute and subchronic neurotoxicity studies in rats

10. Immunotoxicity study in rodents

11. Developmental neurotoxicity study in rodents

B. Approach

1. Options for generating data. A required sequence of toxicological testing for new pesticides is not specified by the Agency. Rather, most decisions regarding the order of testing are left up to the individual registrant, based upon the understanding that there are many factors that could affect the testing progression. It is recommended, however, that the development of pharmacokinetic information, including data relevant to developing systems, be initiated early in the testing process in order to aid in the appropriate design of the studies and the interpretation of toxicological findings in adult and immature (developing) animals.

Generally, data requirements will proceed from single to multiple exposures, from shorter to longer duration, and from simpler to more complex. Different studies may be conducted simultaneously and various studies may be done in combination as well (an approach encouraged by the Agency to optimize resources and reduce the number of animals used in testing). Knowledge gained from results of earlier studies should be used to design subsequent study protocols in order to attain the greatest confidence in the results of the higher-order studies

fferent studies may be conducted simultaneously and various studies may be done in combination as well (an approach encouraged by the Agency to optimize resources and reduce the number of animals used in testing). Knowledge gained from results of earlier studies should be used to design subsequent study protocols in order to attain the greatest confidence in the results of the higher-order studies. For instance, conducting the subchronic (90-day) feeding study prior to the two-generation reproduction study would provide information on target organs that may be affected and that need to be specifically evaluated in the two-generation reproduction study.

2. Options for submitting nonfood use data. In proposed § 158.510 for nonfood uses of pesticides, EPA proposes to implement two approaches for complying with the toxicology data requirements. The first option, which parallels the testing scheme in the current regulations, would allow registrants and applicants to submit a set of acute, subchronic, chronic, and other toxicological studies on the active ingredient, with the specific makeup of the set of study requirements being based upon anticipated human exposure to the pesticide, as determined by the Agency. The makeup of the set of studies required for non-food use chemicals will be determined by the Agency based on the use pattern and expected exposure scenarios for the chemical. The following two examples illustrate the Agency's approaches:

i. A fairly volatile pesticide is used in the home where long-term exposure by both inhalation and dermal routes are expected. In this case, the toxicity studies required would be similar to that for a food-use chemical.

ii. In another example, a termite control pesticide is buried in the lawn near the house. There is very little exposure to anyone including the applicator. In this case, only Tier 1 data would be needed. In general, the level of toxicity studies will be determined by the magnitude, frequency and duration of the estimated human exposure

s required would be similar to that for a food-use chemical.

If hazards are identified based upon review of these studies, the Agency would decide what types of actual human exposure data ( i.e. , applicator and post-application studies) also would be required to evaluate risk. The second option would allow registrants and applicants of nonfood use pesticides to submit both toxicological studies and human exposure data simultaneously. For this option, toxicological data would be submitted under a tiered system. Agency review of the first-tier toxicological studies and the simultaneously submitted exposure data then would determine the need, for second- or third-tier toxicological studies. This option would permit flexibility in study requirements based on the identification and characterization of adverse treatment-

Under this second option, the required first-tier studies would consist of: Acute studies, a subchronic 90-day dermal study or a subchronic 90-day inhalation study, an acute and subchronic neurotoxicity screening battery in the rat, prenatal developmental toxicity studies in two species, two-generation reproduction study in rodents (rat preferred), immunotoxicity study in rodents, and a full initial battery of mutagenicity studies. The conditionally required second-tier studies would include both subchronic 90-day feeding studies, and sometimes a dermal penetration study. Depending on the results of completed studies, conditionally required third-tier studies would include both Chronic Feeding studies, both carcinogenicity studies, a reproduction study, and a metabolism study

d a full initial battery of mutagenicity studies. The conditionally required second-tier studies would include both subchronic 90-day feeding studies, and sometimes a dermal penetration study. Depending on the results of completed studies, conditionally required third-tier studies would include both Chronic Feeding studies, both carcinogenicity studies, a reproduction study, and a metabolism study. In addition, depending upon the results in the initial neurotoxicity and mutagenicity batteries, further neurotoxicity or mutagenicity testing may be required to address possible identified risk concerns.

C. Proposed Toxicology Data Requirements

EPA's proposed toxicology data requirements encompass studies expected to improve the Agency's understanding of the potential pesticide hazard to humans, including subpopulations such as infants and children. The proposed table in this subpart contains the toxicology data requirements EPA would rely on to identify potential hazards to humans and domestic animals for all conventional pesticides. These include acute, subchronic and chronic toxicity studies, as well as carcinogenicity, prenatal developmental toxicity, reproductive toxicity, mutagenicity, neurotoxicity and other specialized studies.

EPA recognizes that toxicology testing represents a large economic burden on registrants and incorporates the use of test animals. Consequently, the Agency works with industry, the scientific community, and advocates, to ensure that data requirements are imposed only when needed to make a sound scientific safety finding required under the law. Because of this concern, the Agency has adopted guidelines whereby several toxicological endpoints may be derived from one study and has instituted other avenues for combining studies. The Agency also recognizes that, in general, lower exposure uses often correlate with lower risk. Consequently, the Agency has adopted an approach that tends to levy more extensive data requirements on high exposure uses like food uses

ern, the Agency has adopted guidelines whereby several toxicological endpoints may be derived from one study and has instituted other avenues for combining studies. The Agency also recognizes that, in general, lower exposure uses often correlate with lower risk. Consequently, the Agency has adopted an approach that tends to levy more extensive data requirements on high exposure uses like food uses. It is also reflected in the tiering system for data submissions for nonfood uses and in the layout of the data tables.

1. Newly imposed data requirements—Immunotoxicity. The Agency proposes to require immunotoxicity testing for all pesticides. 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. In 1993, the National Research Council reviewed the technical literature and found that some pesticides are immunosuppressive (NRC, 1993). Because of the potential for pesticides to adversely impact the immune system, the EPA has developed a test guideline (870.7800) for immunotoxicity. The immunotoxicity test guideline was reviewed and endorsed by the FIFRA Science Advisory Panel and EPA's Science Advisory Board in 1996, and published in 1998 as part of the Office of Prevention, Pesticides and Toxic Substances' harmonized test guidelines.

Because the immune system is highly complex, studies not specifically conducted to assess immunotoxic endpoints 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 immunotoxicity (Refs. 7 and 8)

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 immunotoxicity (Refs. 7 and 8). Therefore, the Agency is proposing to require functional immunotoxicity testing along with the data from endpoints in other studies to predict the potential risk of pesticides on the immune system more accurately. The Agency invites public comment on all aspects of its proposed data requirement for functional immunotoxicity.

2. Newly codified data requirements— i. prenatal developmental toxicity . The Agency proposes to change the name of this requirement from “Teratogenicity” to “Prenatal Developmental Toxicity” to correspond with the name of the guideline (870.3700). An information based approach to testing is preferred which utilizes the best available knowledge on the chemical to develop a study protocol and testing strategy. Currently, both studies are required for food use pesticides, but for nonfood uses, only one prenatal developmental toxicity study is required, and the results of that study may trigger the conditional requirement for a second species. However, the response to developmental insult in one species is not necessarily the same in another species. The pharmaceutical thalidomide, which produces severe malformations in rabbits (and humans) but not rats following in utero exposure, is a classic example of this species-related difference in response. Additionally, the dose at which maternal or prenatal developmental toxicity is observed may not be the same across species, and the severity of the response in dams or fetuses may also differ

cies. The pharmaceutical thalidomide, which produces severe malformations in rabbits (and humans) but not rats following in utero exposure, is a classic example of this species-related difference in response. Additionally, the dose at which maternal or prenatal developmental toxicity is observed may not be the same across species, and the severity of the response in dams or fetuses may also differ. Consequently, there is a concern that the current testing paradigm for non-food use pesticides may not adequately characterize potential hazards to pregnant women and their fetuses. Given that the prenatal developmental toxicity study is used extensively to establish endpoints and doses for acute, short-term, and intermediate-term risk assessment, EPA believes it necessary to require studies in two species for all nonfood pesticides.

The Agency encourages registrants 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 (guideline 870.3800). This can be accomplished by utilizing a second mating of the parental animals of either generation. The dams would undergo cesarean section at one day prior to expected delivery and a separate evaluation would proceed as specified in guideline 870.3700. By combining protocols in this manner, a single study would 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 would not require the purchase of additional animals, and would increase the efficient utilization of the animals being studied. The second required prenatal developmental toxicity study would then be performed on the rabbit.

t of the combined study would be substantially less than that incurred by conducting the two studies separately. Moreover, a combined reproduction/developmental protocol would not require the purchase of additional animals, and would increase the efficient utilization of the animals being studied. The second required prenatal developmental toxicity study would then be performed on the rabbit.

ii. Neurotoxicity. Neurotoxicity studies evaluate the potential of a substance to adversely affect the structure and function of the adult

A new adult neurotoxicity test battery of seven studies would replace the current adult neurotoxicity test requirements. The current adult neurotoxicity test battery consists of three studies: acute delayed neurotoxicity (hen), 90-day neurotoxicity (hen), and 90-day neurotoxicity (mammal). In the current part 158, an adult acute neurotoxicity study in mammals is not listed. However, an adult subchronic neurotoxicity study is required if the acute oral, dermal, or inhalation toxicity studies show neurotoxicity or neuropathy. Currently, the neurotoxicity studies can be triggered either by statistically and/or biologically significant findings.

Under the proposal, some of these tests would be routinely required and others would be conditionally required. Two studies that would be required are an acute and a subchronic 90-day neurotoxicity study (guideline 870.6200) in rats. The acute study would be required to detect possible effects resulting from a single exposure. The subchronic study is intended to detect possible effects resulting from repeated or longer-term exposures. The requirement for a subchronic neurotoxicity study also may be satisfied by incorporating the required neurotoxicity testing into the standard 90-day subchronic feeding study in rats (guideline 870.3100)

study would be required to detect possible effects resulting from a single exposure. The subchronic study is intended to detect possible effects resulting from repeated or longer-term exposures. The requirement for a subchronic neurotoxicity study also may be satisfied by incorporating the required neurotoxicity testing into the standard 90-day subchronic feeding study in rats (guideline 870.3100). The acute and subchronic neurotoxicity studies in adult rats, in addition to providing data on the potential for neurotoxicity, also provide a basis for comparison of the potential for age-related differences in impacts on the nervous system with results from the developmental neurotoxicity study, if needed, for the same chemical.

A new, conditionally required, 28-day delayed neurotoxicity study in hens (guideline 870.6100) would be added. The 28-day delayed neurotoxicity test would be required if results of the acute neurotoxicity study (guideline 870.6100) indicate significant statistical or biological effects, or if other available data indicate the potential for this type of delayed neurotoxicity, as determined by the Agency. The Summary Report of the 1990 OECD Ad Hoc Meeting (Ref. 9) adds:

In the assessment and evaluation of the toxic characteristics of organophosphorus substances, the determination of the subchronic delayed neurotoxicity may be carried out, usually after initial information on delayed neurotoxicity has been obtained by acute testing or by the demonstration of inhibition and aging of neurotoxic esterase and acetylcholinesterase in hen neural tissue.

eurotoxic esterase and acetylcholinesterase in hen neural tissue.

The Agency believes that to evaluate the specific type of delayed neurotoxicity associated with some organophosphorus esters and related substances, a subchronic 28-day study in hens, rather than a 90-day study, would provide sufficient data. Thus, the duration of the subchronic hen study has been shortened from 90 days to 28 days. This is based on the finding that test chemicals reach equilibrium from both a pharmacokinetic and pharmacodynamic perpective; that is, the levels that cause effects, i.e. , LOAELs and NOELs, would be stable after 28 days of exposure. Another reason is that the 28-day study is able to identify effects as well as the 90-day study in that it includes a requirement for dosing 7 days a week, while the 90-day study only doses 5 days per week, allowing for some intermittent recovery. This change was recommended by a panel of experts at a 1990 OECD ad hoc meeting on various issues in neurotoxicity testing (Ref. 9). Hence, the 90-day study requirement has been deleted from the proposed table. The conditional testing requirement for the acute delayed neurotoxicity study in hens (guideline 870.6100) would be unchanged.

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