Pesticide programs: Conventional chemicals; registration data requirements,
[Federal Register: March 11, 2005 (Volume 70, Number 47)]
[Proposed Rules]
[Page 12276-12353]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr11mr05-29]
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Part II
Environmental Protection Agency
40 CFR Parts 152 and 158
Pesticides; Data Requirement for Conventional Chemicals; Proposed Rule
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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. 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. 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). 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:
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General Information
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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
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include pesticide manufacturers or formulators, importers of food, grower groups, or any person or company who seeks a tolerance. Potentially affected entities may include, but are not limited to:
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.
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What Should I Consider as I Prepare My Comments for EPA?
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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.
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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.
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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
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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. 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.
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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.
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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. 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.
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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
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pesticides were called in where gaps in the scientific data base occurred. The Agency has largely used its data call-in authority to require on a case-by-case basis the submission of most of the data requirements contained in this proposal.
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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.
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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.
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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.
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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.
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Linking FIFRA 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.
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Background
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Why does EPA Require Data for 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.
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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. 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
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as a public review and comment process.
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.
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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. 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.
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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. 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 .
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Why Have the Data Needs Changed Since 1984?
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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.
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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. 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.
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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.
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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.
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Purpose and Scope of this Proposal
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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.
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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.
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.
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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.
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.
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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.
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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. 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
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assessments for residential sites and for bystanders in other settings. This will benefit farmers and other workers by allowing EPA to make better informed regulatory decisions that are neither too stringent nor too lenient.
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. 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. 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.
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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.
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Overview of Proposed Changes
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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.
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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
Proposed Regulation and Current Regulation and Title
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
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Subpart D: 158.490 Wildlife and Aquatic Subpart E: 158.400 Organisms
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.
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``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. 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:
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EPA is proposing ``new requirements,'' never before imposed on any registrant.
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EPA is proposing ``newly codified requirements,'' which have been applied on a case-by-case basis, but are not in the CFR.
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EPA is proposing revisions to ``existing requirements.''
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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:
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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. 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.
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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.
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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.
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General Provisions of Part 158 (Subpart A)
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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.
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New material. New content has been added to subpart A. Specifically, EPA has added new Sec. 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.
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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 Sec. 158.1, Purpose and Scope. Paragraph (c) deleted.
158.25
Applicability of Deleted as redundant data
or unnecessary. requirements Applicability of this part to various regulatory actions is contained in proposed Sec. 158.5
158.30
Timing of the Deleted as imposition of unnecessary and not data
relevant. This requirements 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 Retained and revised. submissions. Discussed in Unit VII.B.
158.33
Procedures for Retained and revised. claims of
Discussed in Unit confidentiality VII.C. of data.
158.34
Flagging of
Retained. Criteria studies for
revised. potential adverse effects.
158.35
Flexibility of Deleted as redundant. the data
Mainly contains requirements cross-references to similar material elsewhere in part 158.
158.40
Consultation with Deleted. Consultation the Agency.
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 Information to be exemption
relocated to 40 CFR 152.85, which covers the formulator's exemption.
158.55
Agricultural vs. Deleted as Non-agricultural unnecessary. pesticides
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 Deleted. Material microbial
will be considered pesticides
for inclusion in future revisions of biochemical and microbial data requirements.
158.70
Acceptable
Revised. protocols
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158.75
Requirements for Paragraph (a) additional data retained. Paragraph (b) deleted as unnecessary. This material is covered by paragraph (a).
158.80
Acceptability of Paragraph (a) moved data
to Sec. 158.70(a) now refers to ``cited.'' Paragraph (b) deleted. Paragraph (c) retained. Paragraph (d) revised.
158.85
Revision of data Deleted as requirements and unnecessary. guidelines
Guideline references are contained in tables in each subpart.
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Format of Data Submissions
EPA proposes to reorganize for clarity the data submission requirements of Sec. 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.
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.
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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.
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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)). 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.
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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. 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
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and fate in the environment, and metabolism'' must be made available to the public. EPA considers metabolites to be a form of ``degradation product'' within the meaning of sec. 10(d)(1).
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).
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 Sec. 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 Sec. 158.33, and thus the first time that claims under sec. 10 (d)(1)(A), (B), or (C) were required to be identified.
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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. 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.
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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 Sec. 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 Sec. 174.9.
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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). 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
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pesticides on the environment submitted in connection with sec. 6(a)(2) of FIFRA (1-99), the rationale behind the class determinations applies to all data which meet the criteria quoted in this paragraph. In order to facilitate the timely release to the public of important safety and efficacy information beyond that contained in data reviews and 6(a)(2) notices, EPA is proposing to codify these determinations with respect to all information submitted in accordance with part 158.
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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.
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Flagging Criteria
EPA proposes to revise the flagging requirements of Sec. 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. Specifically, EPA proposes to:
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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.
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Combine reproductive, prenatal developmental toxicity and developmental neurotoxicity studies under one criterion to better focus on effects on children and infants.
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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.
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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.
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Waivers
EPA proposes to reformat its waiver process, currently contained in Sec. 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.
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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.
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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.
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Minor Uses
Current Sec. 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 Sec. 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 Sec. 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.
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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).
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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.
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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.
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:
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The technical grade of active ingredient (TGAI), used when evaluating the inherent toxicity or chemical characteristics of a pesticide.
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The manufacturing use product (MP), used in certain product chemistry tests, usually for labeling purposes.
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The pure active ingredient (PAI), used in certain product chemistry tests requiring extremely basic chemical properties or manufacturing process information.
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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.
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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.
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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.
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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. 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.
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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.
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Purposes of the Registration Data Requirements
The Agency proposes to retain the material currently in Sec. 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.
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Product Chemistry Data Requirements (Subpart D)
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General
The Agency uses product chemistry information to determine whether impurities of toxicological or environmental concern are present in pesticides and formulated products.
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Product chemistry data requirements are comprised of product identity and composition data along with the physical and chemical characteristics of a pesticides, plus any intentionally added ingredients and impurities in the final pesticide product. Included in this subpart are the specific, detailed requirements for product identity and chemical analysis. The Agency is proposing two additional data requirements and other minor revisions that would clarify the applicability of existing requirements. For example, the Agency proposes to revise the definition of an active ingredient and end-use product to include nitrogen stabilizers, which were added to the definition of ``pesticide'' in 1996.
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 Sec. Sec. 158.155 through 158.180, and are proposed to be retained unchanged as new Sec. Sec. 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.
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Proposed Product Chemistry Data Requirements
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Newly imposed data requirements. None.
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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 (Sec. 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 (-\6\ g/l) and fibrous test substances with diameter >=0.1 [mu]m. Data from this study are needed in the environmental fate assessment to estimate potential chemical drift to nontarget areas.
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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. 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.
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Terrestrial and Aquatic Nontarget Organisms Data Requirements (Subpart E)
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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.
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.
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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
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existing test requirement from ``conditionally required'' to ``required '' or ``not required.'' The data requirements for nontarget insects, formerly in Sec. 158.590, would be moved under this proposal to subpart E to consolidate the data requirements for nontarget organisms. Other changes include changes in test substance, conditions under which the test is required, and clarification of test notes.
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.
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Newly imposed data requirements. None.
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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.
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 (Kd) is >= 50 mg/L, indicating the ability to absorb to sediment, and if the half-life of the pesticide in the sediment is 50/LC50or the soil partition coefficient (Kd) 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.
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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. 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. 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
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longer require the avian dietary study for indoor and greenhouse uses.
This proposal would also add as a conditional requirement data on one avian species for aquatic nonfood residential uses if the acute avian oral LD50of 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 (LC50) 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.
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.
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 LC5050/EC50testing (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.
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.
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
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nonfood outdoor and aquatic nonfood residential. As the latter represents a much smaller use pattern, the Agency believes that data requirements can be reduced or eliminated for aquatic nonfood residential uses.
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 LC50value 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. 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.
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 LD50of less than 1 [mu]g/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 LD50of of 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:
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The relative value of each of these research areas in better refining assessments of potential risks to listed species.
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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.
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Other types of research that would be of value in refining potential risks of a pesticide to a listed species.
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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.
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Toxicology Data Requirements (Subpart F)
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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.
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.
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Acute studies (oral, dermal, and inhalation toxicity tests, eye and skin irritation tests and dermal sensitization)
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Subchronic (90-day) feeding studies in rodents and nonrodents
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Chronic feeding studies in rodents and nonrodents
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Cancer studies in two species of rodents (rat and mouse preferred)
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Prenatal developmental toxicity studies in rodents and nonrodents (rat and rabbit preferred)
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Two-generation reproduction study in rodents (rat preferred)
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General metabolism study in rodents
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Mutagenicity battery
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Acute and subchronic neurotoxicity studies in rats
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Immunotoxicity study in rodents
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Developmental neurotoxicity study in rodents
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Approach
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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. 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.
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Options for submitting nonfood use data. In proposed Sec. 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. 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-
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related toxicological effects and dose-response information, and estimates of potential human exposure. Additional second- or third-tier studies would be required on a case-by-case basis.
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. 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.
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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. It is also reflected in the tiering system for data submissions for nonfood uses and in the layout of the data tables.
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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). 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.
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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. 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.
ii. Neurotoxicity. Neurotoxicity studies evaluate the potential of a substance to adversely affect the structure and function of the adult
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nervous system. Since promulgation of the toxicology data requirements in 1984, there has been an increasing concern on the part of the scientific and public health communities that some pesticides may produce functional or structural effects on the nervous system that are not readily observed or adequately characterized in standard toxicological studies. The Agency believes that the current set of neurotoxicity studies are inadequate for some chemicals in their observation of behavioral effects and do not use optimal methods to evaluate the nervous tissue structure and function. To detect and characterize these potential effects more fully in certain chemicals, a battery of more sensitive testing would be required. Several neurotoxicity studies are proposed to be added to the already existing neurotoxicity study requirements for all conventional pesticide registrations. The objective of the new acute and subchronic battery is to evaluate the incidence and severity of the functional and/or behavioral effects, the level of motor activity, and the histopathology of the nervous system following exposure to a pesticide.
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). 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.
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.
The last three studies that comprise the neurotoxicity test battery are also new data requirements. The scheduled controlled operant behavior, peripheral nerve function, and sensory evoked potential neuropathology studies would be conditionally required if the results of the acute and/or the subchronic neurotoxicity studies show adverse effects on the central nervous system which affect learning, memory or performance, or adverse effects on visual, auditory, or somatosensory senses and/or concerns for peripheral neuropathy. The scheduled controlled operant behavior study (guideline 870.6500) evaluates substances that have been observed to produce neurotoxic signs in other studies (e.g., central nervous system depression or stimulation), as well as substances with a structural similarity to neurotoxicants which affect learning, memory, or performance. The peripheral nerve function study (guideline 870.6850) evaluates substances that have been shown to produce peripheral neuropathy or other neuropathological changes in other studies, as well as substances with a structural similarity to those causing such effects. The sensory evoked potential neurophysiology study (guideline 870.6855) evaluates substances that may affect the visual, auditory, or somatosensory (body sensation) senses. Substances tested include those expected to affect these senses or to detect changes based on data from other studies or based on their structural similarity to substances that do affect these senses. The scheduled controlled operant behavior, peripheral nerve function, and sensory evoked potential neurophysiology studies are being proposed at this time to be conditionally required, subject to the results of acute or subchronic neurotoxicity testing or for other reasons, such as structure activity considerations or to more fully characterize any neurotoxic effects seen in the acute and subchronic studies. The Agency believes that these three studies will be rarely required.
iii. Developmental neurotoxicity (DNT). The Agency is proposing that developmental neurotoxicity testing be conditionally required for conventional food use and nonfood use pesticides. In implementing this conditional requirement, registrants are encouraged to apply what is known about the chemical and its toxicity to develop a rational, science-based approach to this testing; this is discussed in more detail below. A DNT would be required (Ref. 10) using a weight-of-the- evidence approach when:
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The pesticide causes treatment-related neurological effects in adult animal studies, such as:
Clinical signs of neurotoxicity
Neuropathology
Functional or behavioral effects
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The pesticide causes treatment-related neurological effects in
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developing animals, following pre- and/or postnatal exposure such as:
Nervous system malformations or neuropathy
Brain weight changes in offspring
Functional or behavioral changes in the offspring
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The pesticide elicits a causative association between exposures and adverse neurological effects in human epidemiological studies
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The pesticide evokes a mechanism that is associated with adverse effects on the development of the nervous system, such as:
SAR relationship to known neurotoxicants
Altered neuroreceptor or neurotransmitter responses
In practice, EPA evaluates each pesticide using all available toxicological information that might indicate a need for a developmental neurotoxicity study. The developmental neurotoxicity study (guideline 870.6300) has been requested on a case-by-case basis for certain chemicals for food use and nonfood use registrations since the guideline was finalized in 1991. The Agency is proposing to conditionally require developmental neurotoxicity studies for all neurotoxic pesticides and/or when other criteria are met that indicated a potential for toxicity to the developing nervous system, based upon a weight-of-evidence evaluation of the toxicological database.
The criteria used in this evaluation were developed through extensive scientific peer review, including a 1999 FIFRA SAP expert review (and public comment) on the use of the FQPA 10X factor in pesticide risk assessment (Ref. 11). The Panel concluded that these criteria were reasonable and useful indicators which would increase concern for pre-/postnatal toxicity. EPA proposes the (conditional) addition of the developmental neurotoxicity study to the toxicology testing requirements since the two developmental toxicity studies do not include an in-depth assessment of the development of the nervous system. The SAP acknowledged that the criteria were not adequate for identifying every potential developmental neurotoxicant, supporting the Agency's concern about the criteria's limitations. Accordingly, the SAP agreed with the Agency's approach of calling in the full range of neurotoxicity studies, including developmental neurotoxicity, for existing conventional chemistry food-use pesticides that are known neurotoxicants, and for all new conventional food-use pesticides.
The prenatal developmental toxicity study (guideline 870.3700) and the two-generation reproduction study (guideline 870.3800), evaluate the potential for toxicity to offspring following pre- and/or postnatal exposure to a test substance. The prenatal developmental toxicity study, in which the maternal animals are exposed during pregnancy, is designed to assess fetal growth, viability, and the presence of structural alterations (i.e., variations and malformations that can be detected by careful external, visceral, and skeletal examinations of each fetus). The two-generation reproduction study evaluates fetal and pup growth and development, offspring survival, clinical observations, reproductive system maturation and function, and postmortem findings (i.e., organ weights, macro- and microscopic pathology). The developmental neurotoxicity study is designed to evaluate test animals for functional and behavioral deficiencies, as well as structural alterations to the nervous system, that may result from pesticide exposure that occurs in utero and/or during early postnatal life.
Currently, discussions on alternative testing paradigms are underway by the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) under the Agricultural Chemical Safety Assessment Technical Committee. The consensus of this effort to date (ILSI, 2001) (Ref. 12) is that toxicological testing should move away from a rigid guideline-based screening approach and towards a more knowledge-based approach such as is currently used for pharmaceutical testing (e.g., the International Committee on Harmonization, 1994). The Agency is in conceptual agreement with this philosophy and proposes to consider the basic precepts of such a toxicology testing paradigm in the application of the toxicology testing requirements that are used to support pesticide regulatory decisions (i.e., Sec. 158.500).
Under this paradigm, both the selection of studies that would be required, as well as the design of the tests themselves, could be influenced by other substantive and reliable information about the pesticide. Such information could include toxicity and dose-response data from other guideline or non-guideline studies, structure-activity relationships, data on the mechanism or mode of action of the chemical, pharmacokinetic data, studies that examine age-related sensitivity or susceptibility to chemical exposure, and information on potential or actual exposure to humans. These data could be used to inform a more targeted testing approach in the design of studies or to support a position that the requirement for specific toxicology tests listed in part 158 should be waived (under the authority described in Sec. 158.45). For example, on a chemical-by-chemical basis, the design of prenatal developmental toxicity and/or two-generation reproductive toxicity studies (both of which examine toxicological effects on immature animals) could be refined, or alternative tests that examine appropriate functional or structural endpoints would be considered. The proposed HESI approach to testing pesticides is anticipated to be published early summer 2005. Once published, the Agency would consider this approach and make appropriate recommendations following internal and external peer review.
In the case of the developmental neurotoxicity study, a thorough evaluation of all available information, including data on the pharmacokinetics and mode of action of the pesticide (if such data exist), could lead to different conclusions regarding the appropriate way to approach testing. For some chemicals, it might be concluded that adequate testing of the developing nervous system would be best accomplished with a standard developmental neurotoxicity study (guideline 870.6300). Refinements to the guideline study could include, for example, changes to the route and/or duration of exposure (e.g., initiation of dosing to maternal animals prior to gestation day 6, or direct gavage administration to pups during lactation), the evaluation of appropriate biomarkers of exposure or effect, the use of more targeted functional, behavioral, or cognitive testing in offspring, or the histopathological and/or morphometric evaluation of particular regions of the central or peripheral nervous system that are known to be affected by either the chemical or chemical class. For other chemicals, the information in the toxicological data base could lead to the conclusion that an alternative test should be performed instead of a guideline developmental neurotoxicity study, alternative chemical- specific methods could be identified as a preferred option.
In the case of organophosphorus and n-methyl carbamate pesticides whose primary mode of neurotoxic action is inhibition of acetyl cholinesterase, a comparative cholinesterase assay could be conducted in lieu of the DNT given that the inhibition of cholinesterase (ChEI) is the most sensitive effect for these classes of chemicals. Regulation on a threshold (or benchmark) dose for
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ChEI should be protective of neurotoxicity. Another example of such a testing scenario would be the use of a comprehensive screen of functional and structural thyroid perturbation (i.e., including T3, T4, and TSH levels) in adult and young animals, for a thyrotoxic chemical that has no other indications of direct nervous system toxicity. In such a case, it can be assumed that identification of maternal or offspring thyroid perturbations would signal any potential alterations in nervous system development, and that minimal effects on the thyroid would be detected at lower dose levels than would result in the types of frank functional, behavioral, or structural alterations that can be detected in the developmental neurotoxicity study. Therefore, it can be presumed that regulation of the chemical on the basis of threshold thyroid effects would be protective of any treatment-related alterations in neurological development that might potentially occur at higher doses. Alternatively, evaluation of the toxicology and exposure data bases for a pesticide may lead to the conclusion that there is no need to conduct a developmental neurotoxicity study, when there is reliable evidence demonstrating the lack of potential for neurotoxicity and/or for human exposure.
Whenever feasible, the Agency encourages registrants to conduct developmental neurotoxicity studies in combination with a two- generation reproduction study. In addition, if preliminary evidence indicates the need for evaluation of structural or functional toxicity of other organ systems in immature animals, these could also be examined within the context of the reproduction study. For developmental neurotoxicity assessment, this can be accomplished, for example, by utilizing the second generation (F2) offspring that are produced in the reproduction study to conduct the functional, behavioral, and neuropathological testing that is integral to the developmental neurotoxicity protocol. A combined reproduction/ developmental neurotoxicity protocol reduces the total number of animals assigned to testing (as compared to the number of animals required when the two studies are conducted independently), and results in a more efficient utilization of the animals already on test. Other benefits of using a combined study approach for any type of targeted functional testing in offspring would include the evaluation of a population of offspring with maximized exposure duration (i.e., that have been treated throughout pre- and postnatal life), greater assurance that steady state levels of test substance in the animals have been achieved prior to testing, and an evaluation of effects within the larger context of assessments of maternal and neonatal toxicity and offspring growth and development. Additionally, combined studies are likely to cost less and take less time, and reduce inter and intra-laboratory variability. The Agency invites public comment on all aspects of its proposed data requirements for developmental neurotoxicity.
iv. Mutagenicity. A battery of mutagenic tests is currently required to assess the potential of the test chemical to adversely affect the genetic material in the cell and subsequently serve as part of the Agency's weight-of-the-evidence approach for classifying potential human carcinogens. Mutagenicity data are also used to evaluate potential heritable effects in humans. The Agency is proposing to change the specific types of tests to be performed to satisfy the mutagenicity testing requirement (Refs. 13, 14 and 15). Mutagenicity testing would no longer be subdivided into the categories of gene mutation, structural chromosomal aberrations, and other genotoxic effects, with selection from a wide range of mutagenicity tests allowed to satisfy these categories. A more specific initial battery of mutagenicity tests and relevant information would be required to support the registration of each pesticide product. This initial battery would consist of a bacterial reverse mutation assay with Salmonella typhimurium and Escherichia coli (guideline 870.5100), an assay with mammalian cells in culture (guideline 870.5300), and an in vivo cytogenetics assay (guidelines 870.5385 or 870.5395).
The Agency has selected the bacterial assay because it is a primary test for detecting intrinsic mutagenicity of many classes of biologically active chemicals. The genetics of each test strain of Salmonella and select strains of E coli have been well-validated and the assay is easy to perform, is used routinely throughout the world, and has an extensive data base of tested chemicals. The mammalian cells in culture assay will detect a wider spectrum of possible genetic endpoints not assayed in the bacterial test. The in vivo cytogenetics assay provides an important examination of the potential effect a test compound may have on an intact mammalian system. Data from this study provides information on in vivo metabolism, repair capabilities, pharmacokinetic factors (e.g., biological half-life, absorption, distribution, excretion) and target organ/tissue effects.
Since there are many different mutagenicity tests available besides those in the initial battery, other types of testing by the registrant or other investigators may have been performed in the course of product research and development. In addition to the initial battery, data from such mutagenicity tests must be submitted to the Agency, along with a reference list of all studies and papers known to the applicant or registrant concerning the mutagenicity of the test chemical. Having this information at the beginning of a mutagenicity assessment will greatly facilitate EPA's effort to provide a more accurate assessment of the mutagenicity of the pesticide in question.
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Revised data requirements--i. Acute oral and dermal toxicity. In addition to performing studies using the TGAI, current requirements give the applicant a choice of performing these studies on the end-use product or a diluted end-use product. However, the Agency has determined that studies using the end-use product (EP) provide the most useful data and would only require additional testing on the diluted form if the product met the conditions for a restricted use classification under Sec. 152.170(b) or special review consideration under Sec. 154.7(a)(1). Hence the Agency proposes to change the test substance to support a registration for an end-use product for these two studies (guidelines 870.1100 and 870.1200) to read ``TGAI, EP, and possibly diluted EP.'' The Agency will notify the applicant when additional testing using the diluted product is required. The Agency invites public comment on all aspects of its proposal to modify the current use of the TGAI to include data from the same tests using the EP and possibly the diluted product.
ii. Primary eye irritation, primary dermal irritation, and dermal sensitization. EPA proposes to modify the existing data requirement for the EP to include testing with the TGAI. In order to more fully characterize the toxicity of the active ingredient of a pesticide, tests using the TGAI would now be required in addition to the test performed on the end-use product for these three studies (guidelines 870.2400, 870.2500 and 870.2600) to support the end-use product. Dermal and eye irritation and dermal sensitization testing of the TGAI have not previously been required in the toxicology data requirements table in Sec. 158.340 for the EP. These data, however, serve to identify hazards from exposure to the eyes, skin, and associated mucous membranes to the active ingredient. The
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Agency considers this information essential in accurately classifying the eye and skin irritation and the skin sensitization potential of the pesticide, and in determining whether any observed adverse effects are inherent to the active ingredient, or caused by the presence of other ingredients. The Agency invites public comment on all aspects of its proposal to modify the current use of the end-use product to include data from the same tests using the TGAI.
iii. 21-day dermal and 90-day dermal. For both food and nonfood uses, dermal testing may be needed on the end-use product if the product, or any component in it, could lead to potentially toxic effects or could possibly increase the dermal absorption of the active ingredient. The Agency proposes to require a 21- to 28-day subchronic dermal toxicity test (guideline 870.3200) for all food use pesticides. This test is being changed from conditionally required to routinely required since it is generally needed for worker risk assessments. Analyses of exposure information have shown that this duration of exposure is typical for agricultural workers in various components of their job. Since not all food use applications pose worker risk, the requirement will be tailored to the potential for worker exposure.
Dermal toxicity testing for nonfood uses would be required if the dermal route is the major route of exposure. In this latter case, a 90- day study (guideline 870.3250) is proposed to be required, in lieu of the shorter, subchronic study. This proposed conditional requirement is necessary in order to assess potential hazards associated with dermal exposure. If the major route of exposure for nonfood uses is the dermal route, the 21- to 28-day subchronic dermal toxicity test is insufficient to identify potential hazards.
iv. Carcinogenicity. The Agency proposes to change the name of the oncogenicity study to carcinogenicity (guideline 870.4200) to correspond with the name of the guideline. In addition, the Agency has determined that 90-day subchronic range-finding studies generally are needed to select appropriate doses for use in these carcinogenicity studies, since cancer studies with doses that are too low and do not cause any adverse effects can be rejected. These range-finding studies have been performed routinely by most investigators prior to the start of their cancer studies and have been submitted regularly to the Agency for review. Since the carcinogenicity study requires testing on rats and mice (which may differ in their response), the 90-day range-finding studies also need to include both species.
The Agency is proposing to formalize this routine practice by including these studies in the part 158 data requirements. The requirement for the 90-day oral study (guideline 870.3100) will be modified to include ``two rodent species- rat and mouse preferred''. Both rodent species would be required for food use pesticides and conditionally required for nonfood uses.
v. Reproduction. Under the current toxicology data requirements, a reproduction study (guideline 870.3800) is required for all food use pesticides, and conditionally required for nonfood use pesticides based on the anticipated level of exposure. The Agency proposes to amend the data table and require a reproduction study for nonfood uses, but qualify the requirement to emphasize that the requirement is based on potential exposure. Data on reproductive effects for a nonfood pesticide would be required unless there is no significant human exposure, as determined by the Agency, in terms of the frequency, magnitude, or duration of the exposure. For example, products such as pesticide treated fabric, diapers, or bedding; insect repellent lotions; or constant-release aerosols for indoor use would require reproductive data. This data requirement is still exposure-based and as such will not always be necessary.
This change is predicated on the fact that reproductive toxicity testing endpoints are not assessed in any of the other required studies for the nonfood uses, and that these other studies do not provide adequate triggers which would indicate the potential for reproductive adverse effects.Multi-generation reproductive studies provide critical scientific information needed to characterize potential hazard to the human population during a number of sensitive life stages, e.g., during in utero fetal development, perinatal life, adolescence, and adulthood. These studies can be used to select endpoints and doses for use in risk assessment and are considered a primary data source for reliable reference dose calculations (Ref. 16).
The need for a reproduction study in Tier 1 is bolstered by information developed by the Pest Management Regulatory Agency (PMRA) of Canada. (Ref. 17). In 1997, PMRA provided to the Agency the results of a preliminary study, which retrospectively evaluated reproduction studies as they affected risk assessment needs. The study was presented in the context of antimicrobial pesticides, for which a tiered toxicology testing scheme was being discussed. However, the results apply to similar tiered testing schemes across a broader spectrum of uses, such as what EPA is proposing for nonfood uses.
One aspect of the PMRA study looked to determine whether a reduced Tier 1 set of toxicology studies (consisting of acute toxicity, subchronic toxicity, developmental toxicity, and mutagenicity studies, but not a reproduction study) would adequately identify reproductive endpoints or concerns for risk assessment purposes. PMRA's results are telling with respect to reproductive effects:
For 67% of the evaluated chemicals (12/18) with reproductive endpoints of concern, the reduced Tier 1 data set would not have predicted reproductive effects identified in a reproduction study
Reproductive effects were not limited to a particular class of pesticide
Chemical structure was not useful as a predictive tool (of reproductive effects)
Mutagenicity studies were not helpful (in predicting reproductive effects)
EPA believes their results support the inclusion of reproduction studies in the Tier 1 nonfood testing regimen.
vi. Non-rodent chronic studies. The Agency is considering eliminating the requirement for a 1-year dog study. Under the current toxicology data requirements, a 1-year non-rodent (dog) study (guideline 83-1) is required for all food use pesticides or for nonfood uses if use of the pesticide product is likely to result in repeated human exposure over a significant portion of the human life-span. Evidence in the published literature suggests that the study may not be needed. (Ref. 18) The Agency's impression from its reviews is consistent with the conclusion reached in that study. However, the Agency possesses a large body of dog studies submitted over the last three decades, and believes it appropriate to conduct a comprehensive and systematic analysis of those studies. EPA is in the process of conducting such an analysis and expects to present its preliminary analysis to the SAP in the spring of 2005. At that time, the analysis and other supporting documents would be made available for public review and comment. If this review confirms that the study is no longer needed, the Agency would in the final rule eliminate the requirement for the 1-year dog study. EPA specifically seeks comment on the possibility of eliminating the 1-year dog study.
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Further Test Guideline Development
The data base to assess pre- and post-natal toxicity varies depending on the nature of the chemical. Some chemicals may need additional data in addition to the core data set for an adequate evaluation of potential hazards. The following studies may be required on a case-by-case basis to support the registration of particular pesticide products and the Agency has begun developing test guidelines for some of these studies. As the Agency's experience with these studies increases and if the studies are imposed more regularly, EPA may propose to include them in future revisions to part 158.
pharmacokinetics in fetuses and/or young animals
direct dosing of neonates prior to weaning for exposure through the maternal route
specialized developmental neurotoxicity of more sensitive sensory and/or cognitive functions
developmental immunotoxicity
developmental carcinogenesis
enhanced evaluation of potential endocrine disruption.
EPA solicits public comment on the Agency's possible request for such data, including the circumstances under which such data should be required.
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Nontarget Plant Protection Data Requirements (Subpart J)
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General
Plant protection studies are used by the Agency to evaluate the potential for adverse pesticidal effects to nontarget terrestrial and aquatic plant species. Nontarget plants include crop plants growing within the target or treated area (such as crop plants which are growing with weeds or plants which are hosts for insects and disease organisms), and those growing outside the target area (adjacent crop plants, endangered plants, and plants that are important to fish and wildlife for food and cover). Data from the plant protection studies will be used to determine if protective measures, such as precautionary labeling, are needed.
Data on plant protection include short-term acute greenhouse and simulated or full field studies arranged in a hierarchy from basic tests to applied field tests. The results of each tier of tests must be evaluated to determine the potential of the pesticide to cause adverse effects, and to determine whether further testing is required. Tier I and II studies are short-term and relatively inexpensive. They are required broadly to assess a pesticide's potential to harm plants in the early stages of plant growth (the first 14 to 21 days). The short- term acute greenhouse studies provide basic toxicity data which are used in a deterministic risk assessment screen. These data are used to establish acute toxicity levels of the pesticide to the test organisms; to compare toxicity information with measured or estimated pesticide residues in the environment in order to assess potential impacts on plants; and to indicate whether further greenhouse and/or field studies are needed.
If additional, more refined, information is needed, Tier III field studies would be triggered. Simulated field and full field studies may be required when basic data and environmental conditions suggest that the risk exceeds the Agency's level of concern for nontarget plants and the information sought is necessary to adequately refine the Agency's assessment of risk. Data from these studies are used to estimate the potential for adverse effects on plant reproduction and survival, taking into account the measured or estimated residues in the environment.
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Proposed Plant Protection Data Requirements
EPA is not proposing major changes to the plant protection data requirements from those currently listed in part 158. The proposed data requirements are being expanded to include use patterns where the potential for off-target exposure via surface run-off and spray drift are likely, or for uses that may result in discharges to the aquatic environment. The seed germination study would be eliminated.
In addition, the Agency is proposing to require independent laboratory validation of the environmental chemistry methods for terrestrial and aquatic field testing. Other changes include changes in test substance, conditions under which a test is required or in some cases, not required, and clarification of test notes. These changes are not expected to increase the burden of the existing data requirements.
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Newly imposed data requirements. None.
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Newly codified data requirements. None.
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Revised data requirements--i. Seed germination. The Agency proposes to eliminate the requirement for the seed germination study (guideline 850.4200). The information from this study would be obtained from the accompanying seedling emergence study (guideline 850.4100) which is currently required.
ii. Seedling emergence and vegetative vigor. Currently, Tier I seedling emergence (guideline 850.4100) and vegetative vigor (guideline 850.4150) studies are required for terrestrial and aquatic nonfood and forestry uses. Tier II tests (guidelines 850.4225 and 850.4250) are conditionally required for the same use patterns and are triggered by the results of the Tier I studies. Due to the potential for surface run-off or spray drift, EPA proposes to expand the seedling emergence and vegetative vigor data requirements to terrestrial food and feed crops, aquatic food crops, and residential outdoor uses. These studies would not be required for aquatic residential uses since limited exposure is expected from this use site.
The Agency also proposes that seedling emergence and vegetative vigor studies be conducted using the TEP instead of the currently required TGAI. The TEP that contains the highest percentage of active ingredient, and/or is the most commonly used, would be required. TEP testing eliminates the need for a separate solvent control because the solvent is already contained in the product formulation.
The Agency also proposes that vegetative vigor studies with granular or bait formulations not be required. Since the protocol for this study requires that the pesticide be applied directly to the plant surface, tests using granular or bait formulations would not be practical.
iii. Aquatic plant growth (algal and aquatic vascular plant toxicity). Currently the Agency requires Tier I aquatic plant growth studies for terrestrial and aquatic nonfood and forestry uses, and conditionally requires Tier II studies for these same use patterns using five aquatic plant species (Pseudokershneria subcapitata (green algae), Skeletonema costatum (marine diatom), Anabaena flos-aquae (blue-green cyanobacteria), Navicula sp. (freshwater diatom), and Lemna gibba (floating vascular macrophyte)) (guidelines 850.4400 and 850.5400). Again, due to the potential for off-target exposure via surface run-off and spray drift, the Agency proposes to extend this requirement to terrestrial food and feed crops, aquatic food crop, and residential outdoor uses. Tier II aquatic plant growth studies are proposed to be conditionally required for aquatic nonfood residential uses, using either the TGAI of TEP.
iv. Terrestrial field and aquatic field. The Agency is proposing to extend these Tier III conditional requirements (guideline 850.4300 and 850.4450, respectively) from terrestrial and aquatic nonfood and forestry uses to terrestrial food and feed crop, aquatic food crop, and residential outdoor uses when off-target movement appears likely (e.g., use
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patterns that readily release the pesticide into the environment). These phytotoxicity data are needed to evaluate the level of pesticide exposure to non-target terrestrial and aquatic plants and to assess the impact of pesticides on endangered and threatened plants. The Agency is also proposing to require independent laboratory validation of the environmental chemistry methods used to generate data associated with these studies. Independent laboratory validation is used to ensure the accuracy and reproducibility of the analytical methods that were used to conduct field studies. For example, independent laboratory validations have been required for food residue methods since 1989. EPA instituted this requirement because analytical protocols were often poorly written and incomplete in terms of the descriptions of all the necessary steps. The Agency scientists spent excessive amounts of time confirming that the methods worked properly and in some cases they could not duplicate the results of the studies. Since the independent laboratory validations have been required, a higher percentage of methods is successfully validated by EPA scientists and less time is required to do so. For laboratory tests, we rely on Good Laboratory Practice Standards (GLP) to assure the quality and integrity of the data submitted to the Agency. Ensuring reproducibility and quality of studies used in EPA's decision-making are also key components of EPA's Information Quality Guidelines.
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Post-application Exposure Data Requirements (Subpart K)
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General
While toxicology data depict the potential hazard of a pesticide, residue chemistry, applicator and post-application data serve to estimate the potential exposure to the chemical. Residue chemistry data (subpart O) provide EPA with dietary exposure information, applicator (subpart U) and post-application (subpart K) exposure data provide exposure data from other routes, such as dermal, inhalation, and oral.
The post-application data requirements are being revised because the existing data requirements no longer meet the needs of the Agency to protect human health from unreasonable adverse risks in all post- application settings. Data to determine post-application exposure are essential to assess the risk to people resulting from exposure to pesticides after they have been applied. Results from the post- application residue studies assess the presence of pesticide residues, while exposure monitoring data are used to determine the quantity of the pesticide and any of its potentially harmful degradates or metabolites to which people may be exposed. These data, in conjunction with appropriate toxicology information, are used to determine whether post-application risks are of concern at residential and occupational sites, and to develop, when appropriate, post-application restrictions.
The 1984 data requirements were developed to assess the risks to agricultural workers and others who must enter a treated field. The data were, and still are, required to protect these workers from exposures resulting from pesticide residues remaining on crops. Over the years, occupational safety concerns have led to the development of a number of state and federal programs for agricultural worker protection. More recently, the Agency has become increasingly concerned about post-application risks to persons in occupational settings other than conventional food, feed and fiber crop agriculture. Additional studies and information are needed to assess the risks to workers in nurseries and greenhouses, forests, golf courses, animal facilities, and other settings where a person may be exposed to pesticides. Depending on the setting and the type of application, exposure can result from residues on foliage (including turf grass), soil, or indoor surfaces.
The proposed data requirements also are being expanded to encompass potential risks from other settings where people may be exposed, such as golf courses, recreation areas, schools, and hospitals, regardless of whether they are on the job or are simple bystanders. The Agency has long been aware of the need for exposure data in this area. Under current practice, post-application exposure data are generally required for both occupational and residential settings. Currently, post- application exposure studies are required on a case-by-case basis when specific exposure and toxicity criteria triggers have been met. Moreover, FFDCA now mandates that EPA perform additional scientific analyses which have not been a routine part of the Agency's risk assessment process, such as the assessment of aggregate exposures from multiple pathways including dietary and non-dietary routes. Such exposures to pesticides have been associated with a significant proportion of reported incidents in the record.
Residential use sites, for data requirement purposes, encompass more than what would normally be considered homeowner use. A ``resident'' is a member of the general public, and ``exposure'' from a residential use site includes post-application exposure to anyone who, in the course of their daily activities, comes in contact with a pesticide after it has been applied. Post-application residential exposure to pesticides can occur in a variety of indoor and outdoor environments, and a vast number of different human activities can occur at these sites after the pesticides has been applied. Data reflecting new exposure patterns are required to determine whether a product may be used safely in and around homes, golf courses, parks, recreation areas, schools, hospitals, and public buildings. Numerous pesticides contribute to outdoor residential exposure including lawn chemicals, landscaping and garden products, rodent poison, and treated lumber. Indoor exposures can result from ant and roach killers, termite treatments, pet flea and tick products, and treated paint. While use of some products may result in intermittent exposures, use of others can result in people's exposure to the pesticide or its residues on a daily basis. In addition to acute or episodic exposures, chronic exposure to pesticides used in residential settings may be of concern.
EPA's current post-application exposure data base is not comprehensive, especially regarding exposures to pesticides in nonagricultural settings. The new data that would be collected under the approach outlined in this proposal would allow the Agency to conduct improved exposure assessments for residential and occupational sites. In addition, such post-application studies would allow the Agency to assess aggregated and cumulative risks to consumers, with special emphasis on children. The Agency invites public comment on all aspects of its proposed data requirements for post-application exposure.
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Criteria for Testing
EPA proposes to revise the toxicity and exposure criteria for post- application exposure studies. The Agency currently requires pesticide post-application exposure data when it determines that risks resulting from post-application exposures may be a concern in occupational or residential settings. The criteria for requiring post-application exposure monitoring data would be expanded to include a wider number of potential exposure scenarios in both occupational and non-occupational settings. The
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determination of whether or not a pesticide meets these criteria would be made by the Agency on a case-by-case basis.
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Toxicity criteria. In the 1984 regulations, EPA required post- application exposure data if the pesticide was classified as category I for acute dermal toxicity. EPA, however, is proposing to modify the toxicity criteria for requiring post-application exposure data. While the Agency remains concerned about pesticides that are highly toxic by the dermal route or that cause other significant effects by the dermal route, there is also strong concern about other types of toxic effects such as neurotoxicity, developmental effects and general systemic effects which are seen in oral studies, but would be relevant to any risk related to post-application exposure.
EPA is proposing that the toxicity criteria be based on all aspects of the toxicity of the active ingredient. Post-application exposure data would be required, as determined by the Agency, if the active ingredient meets any of the following including:
Evidence of potentially significant adverse effects have been observed in applicable toxicity studies,
Scientifically sound epidemiological or poisoning incident data indicate that adverse health effects may have resulted from post- application exposure to the pesticide.
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Exposure criteria. EPA proposes to expand the exposure criteria that would trigger post-application exposure studies to include residential settings and certain occupational settings both indoors and outdoors. Specifically, EPA is proposing the following exposure criteria. When there is potential exposure to humans from post- application pesticide residues from any media, typically, these exposures fall into the following areas.
i. For outdoor uses:
Occupational human post-application exposure to pesticide residues on plants or in soil could occur as the result of cultivation, pruning, harvesting, mowing or other work related activity. Such plants include agricultural food, feed, and fiber commodities, forest trees, horticultural plants in commercial greenhouses or nurseries, and turf grass,
Residential human post-application exposure to pesticide residues on plants or in soil could occur. Such plants include turf grass, fruits, vegetables, and ornamentals grown at sites, including, but not limited to, homes, parks, and recreation areas.
ii. For indoor uses:
Occupational human post-application exposure to pesticide residues could occur following the application of the pesticide to indoor spaces or surfaces at agricultural or commercial sites, such as, but not limited to, agricultural animal facilities and industrial or manufacturing facilities,
Residential human post-application exposure to pesticide residues could occur following the application of the pesticide to indoor spaces or surfaces at residential sites, such as, but not limited to, inside homes, daycare centers, hospitals, schools, and other public buildings.
The need for data from potential exposure resulting from situations not covered by these examples should be discussed with the Agency.
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Proposed Post-application Exposure Data Requirements
At a minimum, residue dissipation, exposure studies, and selected toxicity data are needed to assess post-application risk and determine, when appropriate, entry restrictions. Product use information, including registrant-generated or other surveys on actual use, and descriptions of human activity information are also used to define and refine post-application exposure and risk estimates.
The dissipation of pesticide residues may occur on foliage, soil, or indoor surfaces. To determine dissipation rate, the Agency uses, depending on the use of the pesticide, dislodgeable foliar residue dissipation data, turf grass transferable residue dissipation data, soil residue dissipation data, and/or indoor surface residue dissipation data. To determine the level of post-application human exposure, EPA may use dermal exposure, inhalation exposure, and/or nondietary ingestion studies. In some instances, such as exposure to swimmers, where passive dosimetry methods are not feasible, EPA may require a biological monitoring study. The Agency does not believe that this study will be commonly required. Certain toxicity data also are used in conjunction with the dissipation and exposure data. Typically, this information is obtained through existing toxicity data requirements (see Unit XI of this preamble and subpart F in the proposed regulatory text).
Post-application exposure monitoring data are proposed to be pesticide- or formulation-specific, however, surrogate exposure data may be submitted, if appropriate. In general, the studies required for estimating post-application exposure are dependent upon the pesticide site and use patterns, potentially exposed populations, significant exposure routes, and the time duration over which the exposure occurs. The employment of exposure mitigating measures, such as packaging or use restrictions, e.g., tamper-resistant bait stations, may alleviate the need for some or all of the data requirements in subpart K. Data would be required when any of the testing criteria is met. The Agency does not believe that ``full'' studies will be commonly required. Applicants are strongly encouraged to consult with the Agency to determine specific data requirements for their product.
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Newly imposed data requirements. None.
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Newly codified data requirements. EPA is proposing to base its data requirements for post-application exposure information on two distinct use patterns: occupational and residential. In doing so, the Agency proposes to expand the data requirements for post-application exposure data to include residential sites, nonagricultural sites, and agricultural sites other than conventional food, feed and fiber crop agriculture, which would include greenhouses, nurseries, forests, and animal facilities. New data requirements include indoor surface residue dissipation, biological monitoring data, product use and human activity information, nondietary ingestion exposure, and data reporting and calculation methodologies.
i. Indoor surface residue dissipation. The Agency proposes to add the Indoor Surface Residue Dissipation study (guideline 875.2300) as a new post-application exposure data requirement. These data characterize the pesticide residues found inside buildings on surfaces such as flooring, carpets, upholstery, counter tops, and other treated surfaces after the pesticide has been used. The measurement of indoor pesticide residues is particularly important for characterizing exposure to subpopulations that may spend a large portion of their time indoors, such as children or the elderly. Such data will be used to determine whether or not a pesticide could be safely used in an indoor residential or occupational setting.
ii. Biological monitoring. Biological monitoring data (guideline 875.2600) measure the amount of chemical to which a person has been internally exposed. This is done by measuring pesticide and/or metabolite compound concentrations in selected human tissues, fluids, or bodily wastes (feces and/or urine). EPA proposes to conditionally require biological
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monitoring studies as an alternative to passive dosimetry techniques. The Agency is providing this alternative because, typically, an exposure assessment will be performed relying on generic passive dosimetry data, which measures the potential dose or amount of the chemical on skin or in the air. However, passive dosimetry data usually overestimate exposure, because they only provide estimates of potential exposure, not measurements of absorbed dose. A biological monitoring study performed under the same label use conditions as the passive dosimetry study will provide data on the actual absorbed dose and will result in more accurate and refined risk assessments. Often, biological monitoring studies are voluntarily submitted by registrants. Again, both passive dosimetry studies and biological monitoring studies are always performed under real-world conditions and are representative of actual post application activities.
In addition, the Agency proposes to allow registrants to submit biological monitoring data in addition to, or in lieu of, dermal or inhalation passive dosimetry data provided adequate pharmacokinetic data are available and sufficiently understood to interpret the results.
iii. Product use information. EPA is proposing to require product use information (guideline 870.2700) for both the occupational and residential use patterns. Product use information will provide EPA with information about how the pesticide is actually used and applied. Data will include major use sites, typical application methods, ranges and typical values for application rates, timing and number of applications per season or per year, geographical distribution of use, use surveys, post-application entry restrictions, restricted-entry intervals, any available surveys that provide use information, and other use information relevant to potential exposure following a pesticide application. This use information will enable the Agency to conduct more accurate and realistic risk assessments, thus enabling the Agency to levy appropriate limitations on use to mitigate potential risks.
iv. Description of human activity. In addition to use information, the Agency proposes a new requirement describing the possible activities (guideline 875.2800) in which people may be engaged after a site has been treated. Human activities play a crucial role in the nature and magnitude of exposure to pesticides. These data are also useful for evaluating potential differences in exposures between different subpopulations (i.e., adults and children), and for determining how specific activity patterns affect exposure levels. Data would include information on types of human activities associated with use of the pesticide, principal source(s) of exposure, conditions (if any) mitigating exposure, expected frequency and duration of activities (including hours per day and days per year), description of exposed population, typical clothing worn and equipment used, any available surveys that provide human activity information, and other relevant use data.
In many cases, product use information coupled with the description of human activity information are used to help the Agency determine the most likely route(s) of exposure, whether through the skin, through the lungs, or through incidental ingestion.
v. Data reporting and calculations information. EPA proposes to require registrants to submit data reporting and calculation information whenever post-application exposure data are submitted. Data reporting and calculations information (guideline 875.2900) is an important component needed to assess the validity of the studies and the accuracy of the exposure calculations. Minimal information that must be submitted includes a description of the purpose of the study and what requirement(s) it is intended to satisfy, a summary of the study, a comprehensive section on materials, methods, and calculations, a section interpreting the scientific results of the study, a discussion of quality assurance, identification of the location of the raw data, and any relevant references, communications, and protocols.
vi. Nondietary ingestion exposure. The Agency proposes to conditionally require a nondietary ingestion exposure study (guideline 875.3000) to evaluate the potential oral exposures to humans, particularly children, from pesticide residues from sources other than food. Nondietary ingestion exposure would be expected in residential settings following applications such as:
(1) lawns (soil that contains pesticide residues);
(2) residential plantings (pesticide-treated foliage);
(3) outdoor surfaces (decks);
(4) indoor surfaces (pesticide-treated paint chips);
(5) residential fabrics (clothing, bedding, carpets);
(6) insect and rodent baits.
Nondietary ingestion may also occur through hand-to-mouth orobject- to-mouth transfer of pesticide residues during activities performedby children (e.g., crawling) that put them in close proximity with treatedsurfaces.
Studies would address such concerns as examining behavior patterns,monitoring the amount of soil or residue in the rinsate from hand-washing,and developing science-based models or formulas to estimate theinadvertent exposure. The results from these studies will be used toassess the risks associated with the incidental ingestion of pesticides bychildren following pesticide applications in residential settings. TheAgency is primarily concerned with nondietary exposures immediatelyfollowing application of the pesticide, therefore dissipation studiesalone would not provide the information needed to assess risks fromnondietary ingestion exposures. This study would not be required foroccupational uses.
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Revised data requirements. In addition to newly codified test requirements, EPA proposes to make significant changes to the existing post-application exposure data requirements. The use patterns requiring testing would be expanded from conventional food, feed, and fiber crop agricultural use sites to include other use sites as well. In some cases, the test requirement would change from ``conditionally required'' to ``required,'' and/or the test notes have been reworded to be clearer and easier to understand.
i. Dislodgeable foliar residue dissipation and turf transferable residues. The Dislodgeable Foliar Residue Dissipation study (guideline 875.2100) is currently conditionally required for evaluation of post- application conventional food, feed, and fiber crop agricultural exposure. The Agency proposes to expand this requirement to include testing for greenhouse, nursery, forest, and residential settings and change it from ``conditionally required'' to `` required'' for all use patterns. Applicants are encouraged to consult with the Agency to determine their applicable data needs. Like dislodgeable foliar residues, turf grass transferable residues are the amount of pesticide residues deposited onto the leaf surface that have not been absorbed into the leaf or dissipated from the surface, and that can be dislodged from the leaf surface. Turf grass transferable residues are pesticide residues on the surfaces of treated lawns, sod farms, golf courses, or other turf grass that are available for transfer to exposed humans (e.g., golf course workers and golfers, adults and children at residences, reentry workers on sod farms) when they contact the treated turf surfaces. These additional tests are necessary to evaluate dermal exposures
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resulting from contact with pesticide-treated plant surfaces, whether residential or occupational.
ii. Soil residue dissipation. The Agency proposes to also expand the Soil Residue Dissipation study (guideline 875.2200) to include broader agricultural (greenhouse, nursery, forest) and residential settings. This study would be required for occupational use sites and conditionally required for residential use sites. Soil residue dissipation data are used with toxicological endpoints of concern and concurrent human dermal exposure monitoring data to produce quantitative post-application risk assessments and to determine whether post-application risks from contact with treated soil are of concern at residential and occupational sites. TBTH and methyl parathion for use in nut tree plantations are examples of situations in which EPA found that these were exposures of concern. Without this data, the Agency would not be able to estimate exposure in these scenarios.
iii. Dermal and inhalation exposure. The Agency proposes to expand the data requirements for Dermal and Inhalation Exposure studies (guidelines 875.2400 and 875.2500) to include post-application exposure in occupational and residential (indoor and outdoor) settings. Both studies would be required instead of conditionally required for all use patterns. Currently, EPA requires dermal post-application exposure data when agricultural workers are expected to have contact with pesticide- treated food, feed, or fiber crops growing outdoors. The Agency proposes to expand the data requirements to include persons exposed to pesticide residues in residential settings and in other occupational settings, such as greenhouses, nurseries, forests, golf courses, and certain indoor environments. The Agency needs post-application dermal and inhalation data in order to perform the residential risk assessments needed to fulfill the requirements of the Food Quality Protection Act. In addition, the original requirements were not broad enough to assess risks to occupational workers in greenhouses, nurseries, forests, golf courses, and certain indoor environments, where post-application exposures may be a concern. The Agency has imposed two major DCI's for dermal and inhalation exposure data for agricultural chemicals (e.g., diazinon, iprodione, and chlorsulfuron) and for those applied to lawns (e.g., MCPA, triadimefon, trichlorfon, isofenphos, and cyfluthrin).
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Use of surrogate data. Surrogate data are data collected for another pesticide that may be applicable to the pesticide under review. Surrogate post-application exposure data are data generated using comparable methods and under similar conditions, and where contact with the treated surfaces is likewise similar. The assumption in the use of surrogate data is that in many post-application scenarios, the physical parameters of the contact with residues on varying surfaces (e.g., foliage, turf grass, soil, indoor surfaces), not the chemical properties of the pesticide itself, are most important in determining the level of residue transfer from treated surfaces to people.
At this time, EPA generally is not allowing the use of surrogate data for any of the post-application residue data (guidelines 875.2100, 875.2200, 875.2300, and 875.3000). EPA encourages applicants and registrants to generate needed exposure data using the pesticide product for which the registration is sought. Surrogate data are, however, accepted under certain circumstances for post-application exposure monitoring. The Agency recognizes the need to impose exposure data requirements judiciously to avoid unnecessary economic burdens on applicants. Surrogate exposure data estimations must have adequate information to address post- application exposure data requirements and must contain adequate replicates of acceptable quality data to reflect the exposure of concern, such as the type of plant or indoor surface and the post-application activity. When the data meet these criteria, the residue transfer coefficients derived from surrogate studies may be used to assess the occupational and residential post-application exposure to the pesticide. When surrogate data, however, prove inadequate for the Agency to estimate likely exposures, applicants and registrants will be required to submit the data required in subpart K.
Surrogate data may be obtained from several reliable sources. Some surrogate post-application data for workers in agricultural settings is available through the Agricultural Reentry Task Force. The task force has submitted to the Agency post-application exposure data. A database was developed that contains transfer coefficients for various agricultural work tasks and crops. Some surrogate post-application data for pesticide applications in residential settings is available through the Outdoor Residential Exposure Task Force. This task force submitted data to the Agency on post-application exposures following the use of different types of pesticide formulations typically found in outdoor residential settings.
In addition, the Agency may accept surrogate exposure data estimations from other agencies, such as the National Institute of Occupational Safety and Health (NIOSH), the Occupational Safety and Health Administration (OSHA), or the OECD to satisfy post-application exposure data requirements, if the data meet the basic quality assurance, quality control, good laboratory practice, and other scientific requirements set by EPA. Moreover, if EPA determines that industrial standards, such as the workplace standards set by OSHA, provide adequate protection for a particular pesticide use pattern exposure, data may not be required for that use pattern. The Agency invites public comment on all aspects of its proposal regarding the use of surrogate exposure data.
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Environmental Fate Data Requirements (Subpart N)
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General
Under current part 158, EPA requires a series of individual laboratory studies as well as field studies to assess the behavior and fate of a pesticide in the environment. Controlled environmental fate and transport laboratory studies are used to determine the persistence, mobility, and bioconcentration potential of a pesticide active ingredient and its major degradates. The studies offer information on how, or by what mechanism, the pesticide degrades or dissipates, the rate at which it degradates or dissipates, where it goes, and what transformation products are formed. Data from these studies are used as inputs to exposure models. These models estimate the expected environmental concentrations of the pesticide and its degradates under various environmental and use conditions. The laboratory studies also help to focus field study design by providing information on which transformation products are likely to be produced, and thus need to be tracked, and the environmental media (e.g., soil, sediment, water, air) that should be sampled, including the depth to which soil/sediment samples should be collected.
A conceptual model (hypothesis) is developed using assumptions derived from the laboratory data. Since the laboratory studies are controlled and evaluate specific fate and transport properties individually (i.e., degradation, metabolism, mobility, and bioconcentration), they allow for the development of a conceptual model that includes only those fate processes and degradates that are ``significant'' to the pesticide in question. Although
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laboratory data are the foundation for the hypothesis and the basis for the conceptual model approach, field studies provide the primary mechanism for testing and refining the hypothesis for the environmental fate and transport of a pesticide. Field studies give site-specific information on the fate and transport of a pesticide and its degradates under actual use conditions.
The field and laboratory data are integrated to characterize the persistence and transport of the pesticide and its degradates in the environment. From these data, quantitative environmental fate and drinking water exposure assessments are developed. Model-estimated environmental concentrations of the pesticide in different media under various pesticide application and site scenarios are calculated. These estimates of exposure are used in conjunction with toxicity data to assess whether a pesticide has the potential to cause adverse effects on human health and the environment, such as, wildlife, fish, and plants, including endangered species.
Persistence studies assess what happens to a pesticide when it interacts with water, soil, air, and sunlight. Mobility studies attempt to predict the potential of the pesticide to volatilize into the atmosphere, move into ground or surface waters, or bind to soil. Bioconcentration studies evaluate the potential to partition to aquatic biota and the degree to which bioconcentration can be reversed should external exposure to the active ingredient or degradates be reduced or eliminated. These studies are designed to help characterize how a pesticide active ingredient dissipates once it is released into the environment and to identify the major degradates that may result from these processes.
Degradation studies include hydrolysis, photodegradation in water, photodegradation in air, and photodegradation on soil. The hydrolysis study determines the potential of the pesticide to degrade from the influence of water alone. Photodegradation studies determine the potential to degrade in water, soil, or air when exposed to sunlight. During these studies, data are also collected concerning the identity, formation and persistence of major degradates.
Metabolism studies include aerobic soil metabolism, anaerobic soil metabolism, anaerobic aquatic metabolism, and aerobic aquatic metabolism. The soil microbial metabolism studies determine the persistence of the pesticide when it interacts with soil microorganisms under aerobic and anaerobic conditions. The aquatic metabolism studies produce similar data, but are generated by pesticide interaction with microorganisms in a water/sediment system. These studies also identify the significant degradates that result from biological degradation.
Mobility studies, which include leaching, adsorption/desorption, and volatility, provide information on the mode of transport and eventual destination of the pesticide in the environment. Scientists can predict the degree of pesticide mobility in soil from data generated from leaching and adsorption/desorption studies.
Bioconcentration studies in aquatic organisms are used to estimate the potential of a pesticide, under controlled laboratory conditions, to partition to the organisms from respiratory and dermal exposures. These studies also provide information on the degree to which bioconcentration of a pesticide or degradate can be reversed should pesticide levels in the surrounding aquatic environment be reduced.
Field studies which identify the environmental dissipation processes, assess the transformation, transport, and fate of a pesticide under actual use conditions with typically applied pesticide product at representative field sites. These studies characterize the relative importance of each route of dissipation of the pesticide and its major degradates. Data generated from field dissipation studies can provide more realistic estimates (albeit limited in time and space) of the persistence and transport of an active ingredient and its degradates when the pesticide product is applied under actual use conditions.
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Proposed Environmental Fate Data Requirements
The Agency is proposing to revise the environmental fate data requirements. The Agency is proposing to expand the applicable use pattern for the aerobic soil metabolism, terrestrial field dissipation, and aquatic field dissipation studies. The ground water monitoring study would be added as a separate requirement in the table.
The Agency is also proposing to require independent laboratory validation of the environmental chemistry methods used to generate data associated with the dissipation studies. Two residue studies, confined and field rotational crops, would be moved to the residue chemistry data requirements (subpart O). The long-term soil field dissipation study would be merged with the terrestrial field dissipation study. The accumulation study in irrigated crops would be eliminated. Other changes include conditions under which the tests are required or in some circumstances not required, and clarification of test notes.
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Newly imposed data requirements--aerobic soil metabolism. The Agency is proposing to conditionally require this test (guideline 835.4100) for aquatic food crop and aquatic nonfood uses in cases where the pesticide is applied to aquatic sites that are intermittently dry. Such sites include, but are not limited to cranberry bogs and rice paddies. EPA is proposing this change because pesticides which are applied to these sites are more likely to follow degradative pathways that resemble terrestrial rather than aquatic systems. This change was presented to the SAP in 1994, which endorsed the change.
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Newly codified data requirements--i.Terrestrial field dissipation. The Agency is clarifying that this requirement (guideline 835.6100) also applies to terrestrial feed crop uses, and is proposing to conditionally require this study for aquatic uses involving application to aquatic sites that are intermittently dry. Such sites include, but are not limited to cranberry bogs and rice paddies. This change was endorsed by the SAP in 1994. While the laboratory studies are designed to address one dissipation process at a time, terrestrial field dissipation studies address pesticide loss as a combined result of chemical and biological processes (e.g., hydrolysis, photolysis, microbial transformation) and physical migration (e.g., volatilization, leaching, plant uptake). Pesticide dissipation may proceed at different rates under field conditions and may result in formation of degradates at levels different from those observed in laboratory studies. Data from these studies can reduce potential overestimation of exposure and risk and can confirm assumptions of low levels of toxic degradates. Results can be used to propose scenario-specific effective risk mitigation. The Agency also proposes to merge this requirement with the long-term field dissipation study (formerly guideline 164-5). The current regulations specify that the long-term field dissipation study is required for pesticides that do not readily dissipate in soil. The field dissipation study would be extended in duration for pesticides that are persistent so that the decline curves for the parent chemical and important degradates can be fully characterized. Since the expanded applicability only applies to uses where the cultural practice of the crop includes periods where the soil is deliberately kept covered with water
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then dried, such as in rice or cranberries, the frequency of requesting this study will be quite low. The Agency is also proposing to require independent laboratory validation of environmental chemistry methods for this study to ensure the accuracy and reproducibility of the data, as previously discussed.
ii. Aquatic field dissipation. EPA proposes to conditionally require the aquatic field dissipation study (guideline 835.6200) for terrestrial food crop, feed crop, and nonfood uses. The conditions for requiring the study would be:
a. high persistence;
b. high mobility;
c. high potential to bioaccumulate;
d. high acute toxicity to aquatic organisms;
e. high potential for aquatic exposure. Factors such as environmental fate properties, target crops and application methods which are taken into account when determining if the potential for aquatic exposure is high. For example, a persistent and mobile pesticide that is aerially applied is more likely to runoff, drift, and persist in surface water compared to one that degrades rapidly by hydrolysis and is soil incorporated. Since the expanded applicability only applies to uses where the cultural practice of the crop includes periods where the soil is deliberately kept covered with water then dried, such as in rice or cranberries, the frequency of requesting this study will be quite low. The Agency also proposes to require independent laboratory validation for test methods used to generate data associated with this study to ensure the accuracy and reproducibility of the data, as previously discussed.
iii. Ground water monitoring. Ground water monitoring studies are designed to determine or confirm the potential of a pesticide or its degradates to reach ground water. The Agency proposes to add a ground water monitoring study (guideline 835.7100) as a conditional requirement for all of the terrestrial uses and for forestry uses. The requirement for ground water monitoring is conditional upon consideration of the toxicological characteristics of the pesticides and its potential to leach into ground water. This study would be triggered if the weight of the evidence of available data indicates that the pesticide and/or its degradates may leach into ground water. Ground water monitoring data may also be requested by the Agency if the existing data base is found to be inadequate to support decisions that are protective of ground water resources.
The likelihood of a pesticide to leach to ground water is initially evaluated by considering the persistence and mobility of the chemical indicated in environmental fate laboratory studies and the field dissipation study required under part 158, and through use of a screening-level simulation model. When the potential for environmental risk is indicated, or cannot be evaluated definitively by this screening assessment, monitoring is used to evaluate the potential of a pesticide to contaminate ground water resources. The results of prospective ground water monitoring studies can provide evidence not available from laboratory studies that natural factors cause a pesticide to degrade without contamination of water resources. Alternatively, they can provide evidence to indicate that ground water contamination could result from use according to the pesticide label, and they can help to quantify the levels at which that can occur.
In providing answers about the potential of a pesticide to leach into ground water and the magnitude of contamination under the most environmentally vulnerable and typical use conditions, ground water monitoring data give risk managers the information they need to make appropriate regulatory decisions. Measured concentrations of pesticides in ground water from prospective ground water monitoring studies are used as screening estimates of potential drinking water exposure for human dietary risk assessments. These studies are also often the best tool with which to estimate pesticide concentrations in drinking water drawn from shallow private wells. Monitoring of private drinking water wells is not required under the Safe Drinking Water Act, and data are therefore scarce for most pesticides.
Under certain circumstances, the Agency also requires ground water monitoring in specified use areas in order to investigate the extent of ground water contamination from previous pesticide use. The use- specific and soil-specific data from field scale monitoring studies also are intended to provide verification for estimates from modeling used to predict the impact of long-term pesticide use on water quality in other use areas. The results of prospective ground water monitoring studies have been and will be used to develop and improve models which allow the Agency to better evaluate the leaching potential of pesticides when data are scarce.
If a pesticide is determined to have a strong potential to leach into ground water and in doing so, poses a risk to human health or the environment, the Agency intends to work with industry to develop the appropriate risk reduction and mitigation measures. Thus, in some cases, ground water monitoring would be required to confirm the effectiveness of these mitigation actions or any other regulatory measures and to elicit appropriate regulatory responses that effectively prevent pollution of ground water resources. The Agency believes that this study will be rarely required.
The Agency is also proposing to require independent laboratory validation of the environmental chemistry methods used to generate data associated with this study. As previously discussed, this evaluation will be used by the Agency reviewers to verify the results of the data submitted.
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Revised data requirements--i. Hydrolysis. EPA proposes to clarify that the requirement for this study applies to terrestrial feed crop and aquatic residential uses. In addition, EPA would conditionally require hydrolysis testing for indoor food and nonfood uses. Hydrolysis testing (guideline 835.2120) may be required to support products for indoor food and nonfood uses for which environmental exposure is likely. Such use sites include, but are not limited to, agricultural premises, in or around farm buildings, barnyards, beehives, and fish or seafood processing premises. The proposed changes reflect concern about the potential movement of pesticides and their degradates into the environment.
ii. Photodegradation in water. The Agency is clarifying the applicability of the photodegradation in water study (guideline 835.2240) to reduce the frequency of the requirement, based upon the UV/visible absorption spectrum data submitted as part of the product chemistry data. (Sec. 158.310) The Agency proposes to indicate in a test note that data on photodegradation in water would not be required in cases where the electronic absorption spectra, measured at pHs 5, 7, and 9 of the chemical and its hydrolysis products, if any, do not show absorption or tailing between 290 and 800 nanometers. These testing parameters were announced in an Environmental Fate and Effects Division Policy Note in March 1992, as well as the 1993 Pesticide Reregistration Rejection Rate Analysis - Environmental Fate (EPA 738-R-93-010).
iii. Photodegradation on soil. Currently, photodegradation on soil studies (guideline 835.2410) are conditionally required for terrestrial food crop and forestry uses, with the test note indicating that studies are not required if the use involves application to soils solely by injection of the product into the soil or by incorporation
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of the product into the soil upon application. The Agency is proposing to change the designation of the requirement for this study from conditionally required for terrestrial food crop and forestry uses to required, expand the use patterns to include terrestrial nonfood uses, and retain the test note indicating when the studies will not be required. This change represents current practice and is in accord with international harmonization efforts under NAFTA.
iv. Photodegradation in air. Data from photodegradation in air studies (guideline 835.2370) provide information about the potential of the pesticide to degrade in air when it interacts with sunlight. Because of the potential for exposure to highly volatile pesticides in greenhouses, residential, and certain outdoor settings, EPA is proposing to expand the requirement from terrestrial food crop to terrestrial feed crop and nonfood, greenhouse food crop and nonfood, forestry, and residential outdoor uses on a conditional basis. This requirement is based on use patterns and other pertinent factors including but not limited to Henry's law constant (the solubility of a gas is directly proportional to the partial pressure exerted by the gas). In combination with volatility studies, this information is needed to develop a profile of the pesticide in the atmosphere. In view of methodological difficulties with the study, including, but not limited to, wall effects, the test note has been amended to recommend consultation with the Agency before tests are performed.
v. Anaerobic aquatic metabolism. EPA proposes to require this study (guideline 835.4400) for terrestrial food crop, feed crop, and terrestrial nonfood uses where the pesticide is likely to move from the site of application to nearby aquatic systems. Anaerobic aquatic metabolism studies measure the formation of pesticide residues in water and hydrosoil under anaerobic or oxygen-poor conditions. Since the degradation or dissipation rates and pathways of pesticides in aquatic systems can be different from those of terrestrial systems, soil metabolism studies alone may not be adequate to cover these use patterns.
vi. Aerobic aquatic metabolism. The Agency is clarifying that this requirement (guideline 835.4300) applies to aquatic residential uses, and is proposing to expand this requirement to include terrestrial food crop, feed crop, and nonfood, and forestry uses. Aerobic aquatic metabolism studies measure the formation of pesticide residues under aerobic or oxygen-rich conditions in water or sediment while the pesticide is dispersed in aquatic environments. Since the degradation or dissipation rates and pathways of pesticides in aquatic systems can be different from those of terrestrial systems, soil metabolism studies alone may not be adequate to cover these use patterns.
Note also that the Agency is reasserting that Anaerobic Soil Metabolism studies (guideline 835.4200) are required for terrestrial food crop, feed crop, and terrestrial nonfood uses. Due to a printing error, this data requirement was inadvertently omitted from the data tables in 1991 and subsequent publications of the CFR. This action would restore the data requirement in the table. The scope and nature of the requirement would not change.
vii. Forestry field dissipation. EPA is proposing to change the status of the forestry dissipation study (guideline 835.6300) from required to conditionally required. Forestry use patterns are broad in scope, range from the application of pesticides to individual trees, to aerial applications covering very large areas, and may apply to tree farms or reforestation efforts. As a result, it is difficult to extrapolate data from tests in particular forestry systems to other forests of regulatory interest. Therefore, this study would need to be tailored to address exposures of concern for particular uses. When the Agency determines that a study is needed, a suggested protocol would need to be submitted and approved by the Agency prior to initiation of the study. The Agency believes that this study will be rarely required. The Agency also proposes to require independent laboratory validation for test methods used to generate data associated with this study to ensure the accuracy and reproducibility of the data, as previously discussed.
viii. Accumulation in fish. EPA is proposing minor clarifications to this study requirement (guideline 850.1730). As such, the revised data tables would indicate that this conditional requirement applies to terrestrial feed crop and aquatic residential uses. Further, the Agency proposes to indicate in the test note that studies are required unless:
a. The octanol/water partition coefficients of the pesticide/major degradates are less than 1,000 (indicative of a relatively low potential for accumulation in fish),
b. There are no potential exposures to fish and other nontarget aquatic organisms, or
c. The hydrolytic half-life is less than 5 days at pH 5, 7, and 9.
ix. Accumulation in aquatic nontarget organisms. EPA is proposing to expand the conditional requirement for a nontarget aquatic organism accumulation study to terrestrial food crop, feed crop, and nonfood uses; and aquatic food and aquatic nonfood residential uses (guideline 850.1950). The study would be triggered if significant concentrations of the active ingredient and/or its principal degradation products are likely to occur in aquatic environments and may potentially accumulate in aquatic organisms. The Agency proposes to require this study in situations involving direct application of the pesticide to aquatic systems, from various terrestrial sites where run-off or other movement of the pesticide into nearby aquatic systems is likely, or in intercropping situations involving aquatic animal species and traditional aquatic plant crops, e.g., crayfish and rice. The Agency believes that this study will be rarely required.
x. Confined and field rotational crops. Because the presence of residues in rotational crops is primarily a dietary risk concern, the Agency proposes to move the data requirements for confined and field rotational crops (guidelines 860.1850 and 860.1900) from environmental fate data requirements to residue chemistry data requirements (subpart O).
xi. Accumulation studies in irrigated crops. The Agency proposes to eliminate the environmental fate requirement for the accumulation studies in irrigated crops (formerly guideline 165- 3). Pesticide residue data and information to address the potential for pesticides to be present in crops irrigated with treated water may be obtained from the Magnitude of the Residue in Irrigated Crops study (guideline 860.1540) in subpart O.
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Residue Chemistry Data Requirements (Subpart O)
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General
Residue chemistry data are used by the Agency to estimate people's dietary exposure to pesticide residues from food. The residue chemistry data base is designed to determine the composition of the pesticide residue and how much of that residue is present in the food people eat. Residue chemistry studies include those which define the nature of the residue, i.e., metabolism studies, and those which measure how much of
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the residue of concern is present in food, feed, and water, i.e., magnitude of the residue studies. Most food use pesticides require both types of studies. Both plant and livestock metabolism studies are needed to determine the breakdown of the pesticide in a living system, that is, whether the parent compound stays intact or is converted into metabolites. Occasionally, the metabolites are toxic and, as such, are included in the analyses as a residue of concern. Magnitude of the residue studies, also called residue field trials, are done for all foods, such as, fruit and vegetable crops, processed foods, meat and poultry products (including milk and eggs), potable water, fish, and other instances where food may be exposed to pesticide treatment.
In addition to dietary risk assessments, residue chemistry data are used to establish pesticide tolerances which, in turn, are used for enforcement purposes (see Unit XV.B. below). Therefore, methods for detecting the presence and amount of the residue are needed. Detection methods are used by EPA for study validation purposes, and by FDA, USDA, and the states for food inspection purposes.
EPA is proposing changes to the residue chemistry data requirements to better estimate dietary exposure to pesticide residues in or on food or feed, to more accurately assess and reassess tolerances and tolerance exemptions, and to provide additional tools for the enforcement of pesticide residue tolerances to ensure that food entering the commercial market meets the ``reasonable certainty of no harm'' standard under FFDCA. The Agency is proposing to codify data needs that have evolved since the 1984 regulations were issued, and clarify and simplify existing data requirements.
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Tolerances
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Residue chemistry data. Residue chemistry data are used to assess human dietary exposure and establish tolerances (or tolerance exemptions) for pesticide residues present in food and feed. Pesticide tolerances are listed in 40 CFR part 180. Tolerances are used primarily for enforcement purposes and represent the maximum legal amount of pesticide residue allowed in or on food or animal feed in interstate commerce. Results from data generated from crop field trials are used to set the tolerance for that particular crop. A tolerance or exemption from tolerance must be established for a pesticide to be registered under FIFRA for uses on the food or feed, and for food or feed bearing pesticide residues to be imported into the United States. Wherever possible, EPA tries to harmonize its tolerances with Maximum Residue Levels (MRLs) established by other countries.
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Import tolerances. In cases where a pesticide is not registered in the United States, interested persons may submit a petition requesting that EPA establish a tolerance or tolerance exemption for residues of a pesticide in or on a commodity to allow that treated commodity to be legally imported. These tolerances, called import tolerances, can be established for any food or feed commodity, but are usually established for foods grown outside the United States and its territories, such as bananas or coffee. For new tolerances with no accompanying U.S. registration, part 158 will require that tolerance petitioners provide the information and/or data necessary to make the required safety finding under FFDCA. While there is generally no distinction in data requirements between an import tolerance and any other tolerance issued by EPA, some important differences occur in the way data is generated. This usually includes residue data representative of the pesticide's use in the exporting country. EPA issued proposed guidance for registrants of import tolerances in June 2000 (65 FR 35069). EPA expects to issue its final guidance on import tolerances in the near future.
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Proposed Residue Chemistry Data Requirements
The residue chemistry data table has been modified to include general use patterns that include food uses, plus the residential outdoor use pattern. EPA is not proposing significant changes to the residue chemistry data requirements from those currently listed in part 158. Two data requirements would be added as separate requirements in the data table. These data (storage stability and multiresidue methods) have been imposed by the Agency on a case-by-case basis. The Reduction In Residue study is now called ``anticipated residues;'' a longstanding independent method validation is being proposed; and two residue studies, confined and field rotational crops, which were formerly environmental fate data requirements, would be moved to the residue chemistry data requirements. Other changes include changes in test substance, conditions under which the test is required, and clarification of test notes. These are not expected to substantively increase the nature or burden of the existing data requirement.
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Newly imposed data requirements. None.
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Newly codified data requirements--i. Storage stability. The Agency proposes to add a storage stability study (guideline 860.1380) as an explicit requirement to validate the Magnitude of the Residue studies. Magnitude of the residue studies address how levels of pesticide residues in samples of human foods and livestock feeds are determined. These samples are often stored for extended periods of time prior to analysis. Since tolerances are based on residues at the time of harvest (or sample collection) and the residues may be lost by processes such as degradation and volatilization during storage prior to analysis, storage stability data depicting the presence of residues during this period are critical to validation of the results of the field trial studies. Such data have been required previously as a part of the magnitude of the residue studies, but will now be codified as a separate requirement in the data tables.
ii. Multiresidue methods. The Agency also proposes to codify a multiresidue methods study (guideline 860.1360) as a separate requirement. Multiresidue methodology data are currently part of the residue analytical method requirement. These data are important in designing pesticide monitoring and enforcement programs, and as such, multiresidue methodology data is being proposed as a separate requirement. In food monitoring programs, it is not practical or feasible to test for individual pesticides. Since the residue analytical method requirement is intended to refer to a method that is specific for one pesticide (sometimes called a ``single residue method'') and the multiresidue procedures currently used are designed to measure as many pesticides as possible, it is clearer to list these as two separate data requirements. The Agency will amend the test note to stress that any analytical methodology must be evaluated for its ability to detect metabolites included in the tolerance expression.
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Revised data requirements--i. Nature of the residue in livestock. Also called an animal metabolism study, EPA is proposing several small changes to the Nature of the Residue in Livestock Study (guideline 860.1300). First, the Agency proposes to require livestock metabolism studies whenever a pesticide is applied to crops used for livestock feed and would indicate this change in the test note for this study. In 1984, livestock metabolism studies were conditionally required and were triggered by the presence of residues in the livestock feed. The Agency changed its policy in July 1989 and now proposes to incorporate it by regulation. The data provides essential information
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on the potential transfer and bioconcentration of residues in meat and milk for all pesticides applied to feed items. Therefore, in cases where pesticide misuse results in residues on feed items not expected to have residues from approved uses, the Agency will have data from which to estimate the potential residues in the affected animal commodities.
The Agency is also proposing to change the test substance for this study from the pure active ingredient, radio-labeled (PAIRA) ``and plant metabolites'' to the PAIRA ``or plant metabolite.'' The test substance ``metabolites'' will be changed to ``metabolite'' to prevent dosing with more than one compound in any one study. This is needed because in studies involving simultaneous dosing with both the active ingredient and plant metabolites, it is impossible to determine the amount of metabolite due to active metabolism from that introduced through dosing. Simultaneous dosing with the active ingredient and any metabolites may not produce useful results, because the active ingredient and metabolites may have different metabolic pathways that cannot be differentiated. In most cases dosing with only the parent compound is necessary. However, in cases where plant and animal metabolites are found to differ, a separate study in which livestock are dosed with a unique plant metabolite may also be required.
The livestock metabolism study would be required when a pesticide is applied to livestock premises or is used in livestock drinking water. Such applications may result in both oral and dermal exposure of animals to the pesticide and, depending on the results, may precipitate magnitude of the residue studies to quantify the residues in meat, milk, poultry, and eggs. Finally, the Agency proposes to delete the conditional requirement for the nature of the residue in livestock study for residential outdoor uses since livestock are not found in this use pattern.
ii. Residue analytical methods. Residue analytical methods are used to validate the residue field trial studies in plant and animal commodities and as a means of enforcement of established tolerances. The Agency proposes to change the test substance for residue analytical methods (guideline 860.1340) from the ``TGAI and metabolites'' to the ``residue of concern.'' This will focus the study on only those chemicals with potential toxicity, typically the pure active ingredient and other compounds of concern (i.e., metabolites and degradates), and not on the other components of the TGAI.
As part of this data requirement, the Agency is also proposing to require an independent laboratory validation of residue analytical methods to ensure the accuracy and reproducibility of data used for tolerance enforcement purposes. As previously discussed, this policy has been in place since 1988.
iii. Magnitude of the residue in processed food and feed. The Agency proposes to change the test substance for processing studies (guideline 860.1520) from an end-use product (EP) to a ``typical'' end- use product (TEP). A processing study is needed for only one representative end-use product proposed for use on a given commodity or site. For a given active ingredient, the Agency believes that, in general, variations of the formulation will not affect the behavior of the active ingredient with respect to processing a raw agricultural commodity bearing residues of that chemical. This change would codify a longstanding practice in EPA.
iv. Magnitude of the residue in meat, milk, poultry, and eggs. In line with the livestock metabolism study, the Agency proposes to change the test substance for the meat/milk/poultry/egg study (guideline 860.1480). Due to the difficulties in interpreting results of studies in which a mixture is fed, the Agency is currently discouraging the feeding of mixtures and is instead requesting the feeding of isolated compounds in livestock studies. Hence, the test substance will be changed to read a single plant metabolite instead of metabolites in the plural. Provided that plant and animal metabolites are the same, the parent compound must be the test substance in livestock feeding studies. If any plant metabolite exists that is not also an animal metabolite, a separate feeding study may be required involving dosing with that unique plant metabolite. The Agency will inform the applicant when this additional testing is required. It is rare that this study is requested.
Unlike the livestock metabolism studies, however, livestock feeding studies are generally not required when residues are not demonstrated to be present in the feed. The Agency proposes to clarify that data generally are not required when:
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Residues are not found on feed items or
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Livestock metabolism studies indicate minimal transfer of the pesticide residue to tissues, milk or eggs. For those pesticides which leave non-detectable or low residues in feed items and for which the livestock metabolism study shows little transfer of radioactivity to tissues, the Agency may be able to conclude that data on the level of residues in livestock and their byproducts are not necessary.
v. Magnitude of the residue in potable water, fish, and irrigated crops. Like the study for processed food and feed commodities, the Agency proposes to change the test substance from an EP to a TEP to determine pesticide residues in potable water, fish, and irrigated crops (guideline 860.1400). Residue data are needed for only one representative end-use product of each formulation type proposed for use on a given commodity or site. For each formulation type for a given active ingredient, the Agency believes that, in general, variations of the formulation will not affect the behavior of the active ingredient.
vi. Anticipated residues. The Agency proposes to change the title of the Reduction of Residue study to Anticipated Residues. The new title emphasizes the Agency's intent to use, where appropriate and feasible, data showing the actual residues in food as consumed, as opposed to residues in crops at harvest. For example, market basket surveys can be one way of generating better dietary exposure estimates. The Agency also proposes to indicate in the test note that alternative data, such as market basket surveys, may be required.
The Agency also proposes to add a test note to this study to address the need for residue data on acutely toxic pesticides in single servings of raw agricultural commodities. Most residue data provided to the Agency are based on composited samples. For example, 20 apples collected from different trees may be blended together prior to determining the pesticide residues. This procedure is adequate for estimating dietary risk from pesticides whose toxic effects arise from exposure over a long time period; however, data on composited samples may not be adequate for assessing acute risk from ingestion of single servings of a raw agricultural commodity bearing pesticide residues (e.g., one apple). This proposed analysis of single serving sizes will allow the Agency to more accurately assess acute dietary risks. This additional study would be required only where commodities are consumed in single serving amounts. Historically, the Agency has only asked for this study once. EPA expects that the utility of this study would be for old chemicals with risk concerns. However, for newer chemicals (e.g., reduced risk chemicals) which are the focus of these data requirements, this requirement would rarely be invoked.
vii. Confined and field rotational crops. Because the presence of residues
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in rotational crops is primarily a dietary risk concern, the Agency proposes to move the data requirements for confined and field rotational crops (guidelines 860.1850 and 860.1900) from an environmental fate requirement (subpart N) to subpart O. The Agency also proposes to revise the test note addressing the requirement for the Field Rotational Crop study. Currently, a Field Rotational Crop study is required when significant pesticide residues are found in the soil at the time of planting. The use of soil residues alone to predict crop residues does not take into account the metabolites of chemicals in the soil and the differing abilities of plants to take up such residues. Since the confined study involves the actual measurement of residues in rotational crops under worst-case conditions, the Agency believes that it is more appropriate to use the results of the Confined Rotational Crop study as a screen for potential residues in crops grown under field conditions and the footnote for the field study will be revised to reflect this approach.
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Applicator Exposure Data Requirements (Subpart U)
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General
Individuals who handle pesticides are subject to potential risks stemming from pesticide exposure. Because of this, exposure data tailored specifically to address pesticide handlers are crucial. Pesticide handlers (i.e., applicators) are persons who mix, load, apply, or otherwise come into contact with pesticides during the application process. An applicator can be a professional or a homeowner. The risks to applicators is evaluated based upon the results of the toxicity and human exposure studies. Monitoring data are used to quantify the exposure. The proposed data requirements for applicator exposure would allow the Agency to conduct improved exposure assessments for those who handle pesticides.
The current data requirements in part 158 do not contain studies to determine applicator exposure from pesticide use. The Agency, however, has long been aware of the necessity for applicator data to assess the risks from handling pesticides and has frequently asked for such data. In 1987, the Agency published guidelines for such studies. Since that time, applicator exposure studies have been requested when specific exposure and toxicity criteria triggers were met. Since EPA believes these data are essential for fulfilling its mandate to protect human health from pesticide risk, including aggregated and cumulative risks, it is proposing to make the applicator exposure studies a standard part of its regulatory data requirements.
EPA proposes to codify requirements for application exposure data in part 158 as a new subpart U. The purpose of codifying these data requirements is to assist pesticide registrants and others in determining which studies are required, and aid them in designing and conducting field studies that measure potential dermal and respiratory exposure to pesticides during handling activities. These test requirements cover exposure monitoring studies for people involved in mixing, loading, and applying pesticides; flagging during aerial applications; and other tasks, such as cleaning of equipment and spill cleanup that result in direct contact with pesticides. The requirements cover not only agricultural applicators, but other occupational applicators and residential applicators as well.
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Criteria for Testing
The Agency proposes to establish toxicity and exposure criteria for applicator exposure studies. These criteria are based on the toxicity of the active ingredient and the proposed exposure pattern of the product.
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Toxicity criteria. EPA proposes that applicator exposure data be required for occupational and residential exposures for pesticide active ingredients that indicate potential adverse effects from toxicity studies, such as developmental toxicity, carcinogenicity, neurotoxicity, reproductive toxicity, immunotoxicity, 90-day oral toxicity, 21-day dermal toxicity, 90-day inhalation toxicity, and chronic feeding.
Specifically, EPA is proposing that the toxicity criteria be based on the toxicity of the active ingredient. Applicator exposure monitoring data would be required, as determined by the Agency, if the active ingredient meets any of the following criteria:
i. Evidence of potentially significant adverse effects have been observed in applicable toxicity studies. For example, toxicity studies may indicate that the active ingredient is a possible or likely human carcinogen and that carcinogenic risk can be assessed using a linear extrapolation approach with a Q1*. Or, toxicity studies may indicate that the active ingredient may cause developmental, neurotoxic, reproductive, or immunotoxic effects or may inhibit cholinesterase and establish a toxicological endpoint of concern that can be used to assess risks to applicators and other handlers.
ii. Scientifically sound epidemiological or poisoning incident data indicate that adverse health effects may have resulted from handling of the pesticide. For example, EPA reviews data in the:
a. Office of Pesticide Programs Incident Data System reports of incidents from various sources, including registrants, other federal and state health and environmental agencies and individual consumers);
b. Toxic Exposure Surveillance System (a national data collection system of Poison Control Center data);
c. National Pesticide Information Center database (NPIC is a toll- free information service supported by the Office of Pesticide Programs that fields calls about human and animal incidents); and
d. California Department of Pesticide Regulation exposure incident database. California physicians are required, by statute, to report to their local health officer all occurrences of illness suspected of being related to exposure to pesticides. The majority of the incidents involve workers. CDPR has collected uniform data on suspected pesticide poisonings since 1982.
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Exposure criteria. EPA proposes to establish exposure criteria that would trigger applicator exposure studies. In determining what studies are required, EPA considers the product's use patterns, use surveys, application methods, whether the product is for indoor or outdoor use, whether the exposure is expected to be occupational or residential, the duration of the exposure (i.e., short-term, intermediate-term, or long-term), whether sensitive subpopulations might be exposed, and other criteria. Applicator exposure monitoring studies would be required if either dermal or respiratory exposure is likely to occur during the prescribed use. Applicants are strongly encouraged to consult with the Agency to determine applicable data needs.
Specifically, EPA is proposing the following exposure criteria. Data would be required, as determined by the Agency, if either of the following conditions is met:
i. Dermal exposure is likely to occur when used as directed on the label,
ii. Respiratory exposure is likely to occur when used as directed on the label.
Because these exposure scenarios are covered under the broad categories of occupational and residential, the table in Sec. 158.1520 lists only these two use patterns.
The Agency may also require data when exposure is likely, when the pesticide is used in a commonly recognized and widespread manner. Thus, if the Agency knows that a
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particular product or class of products is frequently used in a manner that isn't directed on the label, the Agency can still require data.
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Proposed Applicator Exposure Data Requirements
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Newly imposed data requirements. None.
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Newly codified data requirements. EPA is proposing seven separate data elements for applicator exposure data.
i. Dermal exposure studies. The Agency proposes to add data requirements for both outdoor and indoor dermal exposure studies (guidelines 875.1100 and 875.1200) in order to estimate the dermal exposure to persons directly handling pesticides. Dermal exposures can and do occur at levels that can cause adverse effects. Dermal applicator exposure studies employ passive dosimetry techniques which estimate the amount of a chemical impinging on the surface of the skin. The amount of pesticide potentially available for absorption through the skin can be estimated by trapping the material before it contacts the skin or by removing the material that has contacted the skin before it has been absorbed.
ii Inhalation exposure studies. To estimate occupational and residential human post-application inhalation exposure to pesticide residues, the Agency proposes to add data requirements for both outdoor and indoor inhalation exposure studies (guidelines 875.1300 and 875.1400). Inhalation exposures can and do occur at levels that can cause adverse effects. Protocols must be submitted for approval prior to initiation of the study. Details for developing protocols are available from the Agency.
iii. Biological monitoring. Data from biological monitoring studies (guideline 875.1500) provide the Agency with estimates of the internal dose or amount of a pesticide in the body. EPA proposes to allow the submission of biological monitoring data in addition to, or in lieu of, dermal or inhalation exposure data provided the human pharmacokinetics of the pesticide residue is sufficiently understood to permit the back calculation to determine the total internal dose. Biological monitoring offers the advantage of assessing the internal dose, as opposed to the exposure or amount of chemical coming in contact with the surface of the skin or available for inhalation in the lungs as measured using passive dosimetry techniques. Biological monitoring is being proposed as a conditional requirement.
iv. Data reporting and calculations information. EPA proposes to require registrants to submit data reporting and calculation information (guideline 875.1600) whenever handler exposure data are submitted. Data reporting and calculations information is important because it allows EPA to assess the quality of an applicator exposure study and the accuracy of the exposure calculations derived from the study. Information that must be submitted includes a description of the purpose of the study and what requirement(s) it is intended to satisfy, a summary of the study, a comprehensive section on materials, methods, and calculations, a section interpreting the scientific results of the study, a discussion of quality assurance, identification of the location of the raw data, and any references, communications, and protocols relevant to the conduct of the study.
v. Product use information. EPA is proposing to require product use information (guideline 875.1700) for both the occupational and residential use patterns. Product use information assists EPA to more accurately assess pesticide exposure to applicators by describing how the pesticide is actually used and applied in occupational and residential settings. EPA requires this information because differences in use can translate to significant differences in exposure, and thus risk. The required information is to encompass a description of the application of the pesticide and include the range and typical values for: Application rates; amount of formulated product or active ingredient handled per day and per year or season; acreage or area treated per day and per year or season; timing of and number of treatments per year or season for private and commercial handlers; exposure time per activity; types of handling equipment used, geographical distribution of usage; any available surveys that provide use information, and other relevant use data.
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Use of surrogate data. To support the registration of a pesticide product, EPA encourages applicants and registrants to generate needed exposure data with the particular pesticide product. However, the Agency recognizes the need to impose exposure data requirements judiciously to minimize the economic burdens on applicants, and at the same time, obtain sufficient data and information for exposure and risk assessments. Therefore, whenever possible, surrogate data will be used to assess the occupational and residential exposure to pesticides. Because the Agency does not commonly require these studies and because surrogate data is often available, the Agency does not expect that ``full'' studies will often be needed. However, when surrogate data prove inadequate for the Agency to estimate likely exposures, applicants and registrants would be required to submit the additional data proposed in subpart U.
Surrogate applicator exposure data may adequately satisfy these data requirements under certain circumstances. Surrogate applicator data must be generated using comparable methods and under similar usage conditions as the product under review. Surrogate exposure data estimations must have adequate information to address handler exposure data requirements and must contain adequate replicates of acceptable quality data to reflect the specific use prescribed by the label, including formulation type, application equipment, methods and rates, personal protective equipment, engineering controls and other pertinent use directions or restrictions.
Surrogate data may be obtained from several reliable sources. For many years, the Agency has been expanding its Pesticide Handlers Exposure Database (PHED) which provides surrogate data for a wide variety of handler exposure scenarios. PHED is a generic database containing measured exposure data for persons involved in the handling or application of pesticides in the field and contains data for over 2000 monitored exposure events. Users can select data from each major PHED file (e.g., mixer/loader, applicator, flagger, or mixer/loader/ applicator) and construct exposure scenarios that are representative of the use of the chemical. Although the PHED database was originally developed for the agricultural workplace, it now contains information that is applicable to other pesticide use scenarios, including residential settings. In general, PHED is not appropriate for assessing highly volatile or gaseous pesticides (e.g., fumigants). EPA, Health Canada, pesticide registrants, and other interested entities are participating in a task force to update, refine, and expand the handler exposure database.
Some surrogate data for outdoor pesticide applications in residential settings (occupational and residential handlers) also is available through the Outdoor Residential Exposure Task Force. The Task Force has submitted data to the Agency on mixer, loader, and applicator exposures during use of several types of equipment typically found in residential settings. The Agency may accept surrogate exposure data estimations from NIOSH, OSHA,
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and OECD to satisfy handler exposure data requirements, if the data meet the basic quality assurance, quality control, good laboratory practice, and other scientific requirements set by EPA. Moreover, if EPA determines that industrial standards, such as the workplace standards set by OSHA, provide adequate protection under the standard set by FIFRA for a particular pesticide use pattern, applicator exposure data may not be required for that use pattern.
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Data Requirements Not Affected by this Proposal
EPA is proposing today a major restructuring of current part 158 for clarity and comprehensibility, but is not proposing substantive revisions to all portions of current part 158. Several specific sections of part 158 may be revised in the future, including the following:
Section 158.440 Spray drift data requirements
Section 158.640 Product performance data requirements
Section 158.690 Biochemical pesticide data requirements
Section 158.740 Microbial pesticide data requirements
In addition, the Agency intends later to propose other changes to current part 158, including the creation of separate subparts to address data requirements for the registration of antimicrobial pesticide products and biochemical and microbial pesticide products.
In order to accommodate the restructuring of part 158 without creating confusion for readers of this proposal, EPA proposes to revise the Table of Contents for part 158 to include the future subpart designations for these sections, and to add and reserve the appropriate subparts in the revised part 158. The regulatory text of the sections for which no change is proposed is not reprinted in this proposal, and EPA is not requesting comment on any aspect of those unchanged data requirements.
If EPA does not issue these other proposals before this proposal is issued in final form, EPA will transfer the contents of the current part 158 that are not specifically addressed in this proposal into their new subparts, essentially unchanged. This step will be necessary because at that time subpart D which currently contains the sections will be redesignated to contain only product chemistry data requirements.
At the same time, EPA expects to make needed technical revisions to accommodate the new structure of part 158, without changing the substance of the data requirements. For example, section numbers will be assigned within the new subpart; cross-references will be updated; and footnotes will be restructured as test notes and given Arabic numerals, e.g., footnote (iv) would become test note (4). EPA believes these minor technical revisions can be accommodated within the final rule without specific proposal at this time.
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Peer Review
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National Research Council Recommendations
In 1988, Congress directed the National Academy of Sciences to study the vulnerability of infants and children to dietary pesticides. The National Research Council was charged with ``examining scientific and policy issues faced by government agencies, particularly EPA, in regulating pesticide residues in foods consumed by infants and children.'' In so doing, the NRC was asked to:
Examine the adequacy of current risk assessment policies and methods;
Assess information on the dietary intakes of infants and children;
Evaluate data on pesticide residues in the food supply;
Identify toxicological issues; and
Develop relevant research priorities.
The Council reviewed current EPA practices and data requirements related to dietary risk assessment as well as testing modifications planned by the Agency. In 1993, the NRC issued a report (Ref. 1) entitled, ``Pesticides in the Diets of Infants and Children.'' The panel of experts concluded that, at that time, EPA approaches to data requirements and risk assessments emphasized the evaluation of the effects of pesticides in mature animals and, in general, there was a lack of data on pesticide toxicity in developing organisms.
The Council was not specifically charged with evaluating the data requirements as proposed today. Nonetheless, the Council made recommendations with respect to regulatory needs for data development that EPA is today proposing:
The report stated the need to investigate the effects of pesticide exposure on immunotoxic responses in infants and children. ``Analysis of the impact or toxicity of agricultural chemicals on the immune system is essential. Regulatory development of a battery of consensus tests is critical to protect the developing immune system.'' (Ref. 1, p. 110).
The report supported the Agency's proposed requirement for acute and subchronic neurotoxicity testing for pesticides and ``encourages the agency to make this a general requirement for all food-use pesticides.'' (Ref. 1, p. 156).
The report strongly encouraged further work in the area of developmental neurotoxicity. ``Neurodevelopmental effects must be part of the battery of end points evaluated for toxicants.... Regulatory development of a battery of consensus tests will be .... necessary to ensure public confidence.'' (Ref. 1, p. 110).
The report suggested that the Agency impose a requirement for developmental toxicity for all classes of pesticides registered for food uses. ``A modified reproductive/developmental toxicity study in the rat is suggested for registration of all food-use pesticides.... the committee recommends that this study be made a requirement for registration for all food-use pesticides.'' (Ref. 1, p. 155)
Other recommendations by the Council included an in utero chronic toxicity/carcinogenicity test and the inclusion of thyroid function into existing tests. The Council also recommended a conditional requirement for visual system toxicity testing, especially for cholinesterase-inhibiting compounds. These recommendations were brought to the SAP and are discussed in Unit XVIII.B. Other recommendations arising from the NRC report are still being considered for use on a case-by-case basis, as summarized in the list of potential data requirements in Unit XI.D.
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FIFRA Science Advisory Panel
In 1994, EPA held a 2-day meeting of the SAP to review the Agency's proposed amendments to the data requirements for pesticide registrations contained in 40 CFR part 158. The SAP was asked to comment on each data requirement and identify, in their opinion, which ones were necessary to fully and thoroughly evaluate the potential hazard of a chemical compound and which ones were not intrinsically useful in providing practical scientific information. The revisions presented to the Panel, i.e., the changes to the data requirements presented in this notice, were generally endorsed. Data requirements, as they related to the application of the newly mandated FFDCA safety factor, were also presented to the SAP in 1998 and 1999. No new issues of a scientific nature have surfaced since these meetings that would warrant SAP review. Copies of documents prepared for the SAP and the final reports from each of the meetings can be found on EPA's web site at http://www.epa.gov/scipoly/sap. A copy of the 1994 final report also
can be found in the public
[[Page 12311]]
docket for this rulemaking. The Panel's comments and conclusions are summarized below.
-
Terrestrial and aquatic nontarget organisms. In 1994, EPA requested comment from the SAP on the merits of requiring sediment and pore water toxicity testing to its data requirements for pesticides and whether the Agency's proposed tiered approach is appropriate. The Agency also requested comment on proposals to add additional testing requirements. The Panel believed that the addition of sediment and pore water testing would provide additional useful information and the proposed tiered approach appeared to provide a reasonable sequence of tests. Further, the Panel supported the requirement of both fish early lifestage and invertebrate life-cycle tests for certain aquatic and terrestrial uses and the addition of granular and other typical end-use products in avian oral testing. The SAP agreed that the avian reproduction test be expanded to include all outdoor uses, but the test protocol should be flexible in order to reflect more accurately the environmental fate of the chemical.
-
Toxicology. At the 1994 meeting, EPA put forth the revisions to part 158 that included acute and subchronic neurotoxicity studies, as well as immunotoxicity studies in adults as first tier tests. The Agency also included in its presentation several studies recommend by the NRC in their 1993 report. In its final report the SAP offered comments and cited some specific recommendations for improvement.
For the few studies the SAP did not endorse, the Panel could not find a significant scientific justification for the routine use of the data. For example, due to increased concerns about the potential effects of pesticides on the visual system, special visual system testing was suggested by the NRC as a data requirement. The Panel, however, concluded that there was insufficient scientific evidence to require special visual system testing. After reviewing its toxicology data base, at that time, for visual effects, i.e., pathological damage to the eye, EPA found that only five organophosphates and one carbamate exhibited visual effects. Cholinesterase-inhibition was considered the more sensitive endpoint and using this as an endpoint would be protective of the supposed visual system effects. Therefore, since the Agency already was regulating these pesticides at much lower doses than those expected to produce adverse effects on visual systems, it concluded that there was already adequate protection from any possible visual effects.
Similarly, the SAP did not recommend additional testing on in utero exposure in carcinogenicity studies, a 90-day drinking water study, nor testing for thyroid function or other endocrine effects in routine chronic studies. Regarding the need to examine the potential perinatal or postnatal toxicity from pesticide residues in the diets of children, the Panel did not believe a special new study was warranted. In each of these instances the SAP thought it was premature to include a data requirement in part 158 until methods have been scientifically validated and guidelines developed, and the data could be scientifically evaluated to yield meaningful results.
In 1998, EPA presented the SAP an issues paper on the use of the FQPA safety factor to address the special sensitivity of infants and children to pesticides. Here the Agency presented the Panel another, and more detailed, discussion of the toxicology data base, especially in regard to developmental neurotoxicity testing criteria and requirements. The developmental neurotoxicity study specifically was put in the context of the appropriateness of a possible additional safety factor. At that time, the SAP did not reach a consensus on whether this study should be routinely or conditionally required. The issue of what is a complete and reliable data set was brought before the SAP again in May 1999. The majority of the Panel supported the Agency's approach to applying data requirements but advised the Agency to revisit the first tier toxicology data base every few years to update data requirements as needed. The Panel also agreed with the Agency in the need to require the neurotoxicity battery of studies, including developmental neurotoxicity testing, for new conventional high exposure, i.e., food use, pesticide registrations.
-
Nontarget plant protection. In 1994, EPA presented the SAP with its plant protection data requirements. The SAP was asked to provide specific information or guidance on a number of issues. The SAP supported the elimination of the seed germination test. In addition, the Panel recommended changing the test substance from the technical grade active ingredient to the typical end-use product for terrestrial plant studies and eliminating Tier I testing of phytotoxins on terrestrial plants.
-
Occupational and residential exposure. Data requirements for exposure assessment for both applicators and those exposed to pesticides post-application were presented to the SAP in 1994. The Agency did not present any specific questions on exposure assessment for application or post-application exposure, and, by comparison to other subparts addressed in the response, the SAP had relatively few comments on data revisions for exposure monitoring and assessment. Several areas of clarification were advised, especially with regard to what data would be needed for what use patterns. It was also suggested that the Agency work with representatives from industry to develop a clear set of guidelines for both residential and occupational settings.
Working in collaboration with Health Canada, and OECD, EPA drafted guidelines for post-application exposures studies. They were peer- reviewed by EPA's Office of Research and Development, the California Department of Pesticide Regulation, representatives from academia, and the American Crop Protection Association. The Agency presented its post-application exposure guidelines and standard operating procedures to the SAP in 1998 and again in 1999. In 1999, the SAP approved and commended the Agency for making significant strides toward developing scenario-based residential and non-occupational exposure assessments that are sufficiently conservative as to not underestimate exposures. (Ref. 11)
-
Environmental fate. Three of the significant changes that the Agency is proposing for the environmental fate data requirements, i.e., conditionally requiring aerobic soil metabolism and terrestrial field dissipation for aquatic uses involving sites that are intermittently dry, and conditionally requiring ground water monitoring for terrestrial and forestry use, were presented to the SAP at the 1994 meeting. The SAP endorsed these changes as well as the independent laboratory validation of analytical methods.
-
Residue chemistry. In 1994, EPA presented the SAP with its residue chemistry data requirements. While no specific questions were directly posed to the Panel, the SAP made a few comments. The SAP endorsed the independent laboratory validation of analytical methods, the establishment of a separate data requirement for multiresidue methodology, and a requirement for storage stability data. In addition, the Panel supported the Agency's efforts to identify the circumstances under which single serving analyses would be needed for acutely toxic pesticides.
[[Page 12312]]
-
-
-
International Harmonization of Data Requirements
EPA is working closely with other countries toward greater uniformity in testing, reviewing and evaluating pesticides. The benefits of international regulatory cooperation on pesticides are potentially great: improved science through greater information exchange, and reduced regulatory and resource burdens on national governments and regulated parties through harmonized pesticide registration review. Over the last several years, substantial progress has been made toward international cooperation on pesticide regulatory review. Member countries of the OECD, including the United States, have agreed upon harmonized guidance for the formats of industry data submissions (dossiers) and country data review reports (monographs). Countries now frequently exchange pesticide reviews or consult with one another on key technical aspects of a review. EPA has worked jointly with Canada, dividing up detailed evaluation work on a number of pesticides. The Agency has entered into information exchange and comparative review arrangements on a pilot basis with other countries, as well. The objective of these work sharing arrangements has been to pool scientific knowledge and to use resources in the most efficient way possible.
As the international regulatory community works toward greater harmonization on pesticide review, attention has turned to data requirements, how they compare from one country to another and what can or should be done to establish common requirements. To the extent that data requirements for pesticide registration are similar, sharing reviews and comparing evaluations is easier and more meaningful. Establishing similar requirements also can reduce the resources that must be spent to conduct testing. Requirements that differ considerably from one country to another can mean that registrants who are looking to register a pesticide in more than one country must conduct many different studies to satisfy all the various national requirements.
The United States and Canada have worked together to harmonize data requirements across all disciplines. Data requirements and protocols for the two countries have been carefully compared. The data requirements proposed in this document represent U.S. national requirements but they reflect extensive consultation with Canada and are harmonized with Canada's requirements to a high degree. The two countries plan to continue to work together to keep data requirements for all disciplines as similar as possible.
OECD Member countries have had discussions about harmonizing data requirements within the OECD community. The pesticide industry took on the complex task of looking at data requirement differences among Member countries to identify areas that might benefit from harmonization. They presented their preliminary findings to the OECD Working Group on Pesticides meeting in June 2001. They reported, consistent with the positions of scientific reviewers in OECD Member countries, that toxicology data requirements are quite similar across countries. Issues can arise sometimes, however, because study protocols or guidelines used to generate the studies to meet the requirements are not always harmonized. In other words, a particular study requirement might be the same from one country to the next, but the study submitted to meet the requirement can run into problems if done according to a protocol that is acceptable in one country but not another. Overall, however, it appears that reasonable harmonization has been achieved for toxicology studies done according to OECD Guidelines revised since 1997. This does not mean that there is no room for additional harmonization work on toxicology data requirements and study guidelines, but rather that there are other testing areas where there is much less consistency on data requirements and study protocols across countries.
Ecotoxicological and environmental fate studies present a particular challenge for harmonization. Data requirements in these areas can differ considerably from one country to another depending upon how countries' tiered approaches to data requirements are applied. National data requirements have to be tied to national use patterns and environmental and ecological conditions. A reliable environmental hazard assessment, for example, must be based on studies that accurately reflect the climate, soil types and agricultural practices of the country doing the assessment. Because ecological and environmental studies must be representative of national conditions to adequately support national risk assessments, harmonization of data requirements and study protocols for these types of studies can be difficult. Harmonization can require extensive dialogue between scientists to determine which data requirements can act as common requirements. Harmonization can also involve protocol/guideline development or revisions in order for the studies produced to meet common data requirements to be widely accepted.
-
Research Involving Human Subjects
In the United States, all research with human subjects conducted or supported by the Federal government is governed by a set of regulations referred to as the Common Rule. The Common Rule contains requirements designed to protect human subjects of research and to ensure that they are treated ethically. EPA, along with 16 other federal departments and agencies, promulgated the Common Rule in 1991. See 40 CFR part 26 (EPA's Common Rule). In all of the scientific research with human subjects conducted or supported by EPA, the Agency has been and remains committed to full compliance with the Common Rule
Both the current version of part 158 and the version of part 158 being proposed contain requirements for the conduct of studies that involve testing with human participants. These studies include: metabolism and pharmacokinetic studies, biological monitoring studies, human exposure studies, and insect repellent efficacy studies. It should be noted that neither the current nor proposed version of the part 158 contains a provision that requires testing of human participants in a study designed to identify or quantify a toxic endpoint. If studies required under part 158 were conducted or supported by EPA (or another Federal agency), they would be subject to the Common Rule. Although the Common Rule applies only to research conducted or supported by Federal agencies, EPA recognizes that many public and private research and academic institutions and private companies, both in the United States and in other countries, including non-federal U.S. and non-U.S. governmental organizations, have their own specific policies related to the protection of human participants in research.
EPA has been considering its policies and rules regarding the conduct of studies involving human participants by organizations that are not part of the Federal government and that do not receive support from a Federal agency. (These are referred to as ``third party'' researchers). On February 8, 2005 (70 FR 6661)(FRL-7695-4), EPA issued a Federal Register Notice announcing that it plans to conduct rulemaking to make the provisions of the Common Rule, 40 CFR part 26, applicable to certain newly conducted third-party human studies. The Notice also indicated that EPA may propose to adopt some or all of the Department of Health and Human
[[Page 12313]]
Services' (DHHS) protections for research with vulnerable populations. The DHHS rules are contained in 45 CFR part 46, subparts B (pregnant women, human fetuses, and neonates), C (prisoners), and D (children) and apply when members of these groups are being considered as potential participants in covered research.
-
ILSI Work on New Toxicity Paradigm
The Health and Environmental Sciences Institute (HESI)/ International Life Sciences Institute initiated a project in 2001 titled ``Developing Strategies for Agricultural Safety Evaluation.'' The purpose of this project was to bring together scientific experts from government, academia and industry, including the international community to determine whether the current testing paradigm for pesticide chemicals could be made more efficient and accurate. Agency scientists from EPA's Office of Pesticide Programs and Office of Research and Development are involved in this project. The HESI technical work groups have developed a tiered approach that takes into account the toxicological properties and the use pattern of the chemicals, and attempts to minimize the number of animals necessary to produce a thorough health assessment of the chemicals of interest. The HESI reports are anticipated to be submitted for publication in the Journal Critical Reviews and Toxicology, April 2005. The draft HESI papers can currently be viewed in PDF format at http://hesi.ilsi.org/publications/pubslist.cfm?publicationid=578. Once the reports are
published (anticipated for summer 2005), the Agency will consider the HESI tier approach, as well as other available proposals on toxicology testing including the ongoing National Academy of Sciences project on the future of toxicology testing, to determine what revisions to current testing guidelines and data requirements may be appropriate. Before considering regulatory approaches, the Agency will need to develop scientific position papers concerning the new approach for Agency internal and external review (including review by the FIFRA Science Advisory Panel), and public comment. Regulatory changes will be made, as needed, to keep the data requirements current, as stated in proposed Sec. 158.30(b).
Information on the HESI project can be found at the following website: http://hesi.ilsi.org/index.cfm?pubentityid=55 Information on the NAS project can be found at the following website: http://www4.nas.edu/webcr.nsf/5c50571a75df494485256a95007. a091e/
f6b42dd0563b352e85256e5d0007281e.
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Animal Welfare Concerns
The Agency is committed to the development and use of alternative approaches to animal testing. The Agency understands many people's concern about the use of animals for research and data development purposes. EPA has received comments concerning the use of new and revised test methods which would reduce the number of test animals in studies, or refine procedures to make them less stressful to animals. Where testing is needed to develop scientifically adequate data, the Agency is committed to reducing or replacing, wherever possible, the number of animals used for testing by incorporating in vitro (non- animal) test methods or other alternative approaches that have been scientifically validated and have received regulatory acceptance. EPA considers these goals and commitments to be important considerations in developing health effects data, consistent with the essential need to conduct scientifically sound chemical hazard/risk assessments in support of the Agency's mission.
Taking into consideration principles of sound science and the requirements of FIFRA to protect humans (including sensitive subpopulations) and the environment from unreasonable uncertainty of no harm from pesticide exposure, the Agency is committed to avoiding unnecessary or duplicative animal testing. For example, currently EPA accepts data on the pH of a chemical as a screen to judge whether the chemical may be corrosive to the eye or skin. Making this determination avoids actual testing on animals. Many long-term studies can be combined so that several toxicological end-points can be discerned from fewer studies. The Agency already has bridging and batching policies in place to allow the use of acute toxicity, sensitization, or irritation test data on products to be used to support other products. At EPA's initiative, these policies have been incorporated into the new Globally Harmonized System for Classification and Labeling.
The Agency plays an important role in the Federal Interagency Committee for the Validation of Alternative Methods (ICCVAM) (http://iccvam.niehs.nih.gov/home.htm ). ICCVAM, a standing committee made up of
15 federal agencies and established through the National Institute of Environmental Health Sciences, which works to:
-
Encourage the reduction of the number of animals used in testing.
-
Seek opportunities to replace test methods requiring animals with alternative test methods when acceptable alternative methods are available.
-
Refine existing test methods to optimize animal use when there is no substitute for animal testing. ICCVAM convenes independent peer review panels to evaluate specific proposed test methods and has developed consensus criteria for judging the validation status of test methods.
Guideline 870.1100 references the use of appropriate alternative test protocols as a means of reducing the number of animals used to evaluate acute effects of chemical exposure. Yet the Agency and the scientific community also recognize that test guidelines are designed to be updated and supplemented frequently. As new tests and test batteries are validated, the Agency presents them to the SAP. The Agency considers the SAP's determination of the reliability of the test guidelines and their applicability to meeting its regulatory needs under FIFRA. After SAP review, the Agency is planning to incorporate validated in vitro screening data for skin corrosion to its test guidelines. As other appropriate alternative or in vitro methods become available, they will continue to be added to the test guidelines.
-
-
Summary of Changes Being Proposed
Table 3 contains a line-by-line listing of every data requirement contained in current part 158, as well as new requirements proposed today, organized in the order of the proposed new subparts D through U. Columns 1 and 2 contain Pesticide Assessment Guideline numbers and current titles, respectively. Columns 3 and 4 contain OPPTS Harmonized Guidelines numbers and proposed titles, respectively. Column 5 contains an explanation of the changes proposed for each requirement, or that no change is proposed.
[[Page 12314]]
Table 3.--Part 158: Proposed Changes to Data Requirements\1\
Proposed Guideline No.
Current requirement Guideline No. requirement
Change
Subpart D--Product Chemistry and Guideline No.
Product Identity and Composition................................................................................
61-1
Product composition
830.1550 Product identity No changes. and composition
61-2
Description of
830.1600 Description of No changes. materials used to
materials used to produce the product
produce the product
61-2
Description of
830.1620 Description of No changes. production process
production process
61-2
Description of
830.1650 Description of No changes. formulation process
formulation process
61-2
Discussion of
830.1670 Discussion of No changes. formulation of
formulation of impurities
impurities
62-1
Preliminary analysis
830.1700 Preliminary
No changes. analysis
62-2
Certified limits
830.1750 Certified limits No changes.
62-3
Enforcement
830.1800 Enforcement
No changes. analytical method
analytical method
64-1
Submittal of samples
830.1900 Submittal of
No changes. samples
Physical and Chemical Properties................................................................................
63-2
Color
830.6302 Color
No changes.
63-3
Physical state
830.6303 Physical state No changes.
63-4
Odor
830.6304 Odor
No changes.
63-5
Melting point
830.7200 Melting point/ No changes. melting range
63-6
Boiling point
830.7220 Boiling point/ No changes. boiling range
63-7
Density, bulk
830.7300 Density/relative Clarified test note density, or specific
density/bulk
to better identify gravity
density
when this test requirement is applicable. 63-8
Solubility
830.7840 Water solubility No changes. 830.7860
63-9
Vapor pressure
830.7950 Vapor pressure Clarified test note to better identify when this test requirement is applicable.
63-10
Dissociation constant
830.7370 Dissociation
Clarified test note constants in
to better identify water
when this test requirement is applicable.
63-11
Octanol/water
830.7550 Partition
Changed from partition
830.7560 coefficient (n- ``conditionally coefficient
830.7570 octanol/water) required'' to ``required.''
63-12
pH
830.7000 pH
No changes.
63-13
Stability
830.6313 Stability to
Changed from normal and
``required'' to elevated
``conditionally temperatures, required.'' metals, and metal ions
63-14
Oxidizing or reducing
830.6314 Oxidation/
No changes. action
reduction: chemical incompatability
63-15
Flammability
830.6315 Flammability
No changes.
63-16
Explodability
830.6316 Explodability Changed from ``required'' to ``conditionally required.''
[[Page 12315]]
63-17
Storage stability
830.6317 Storage stability No changes.
63-18
Viscosity
830.7100 Viscosity
No changes.
63-19
Miscibility
830.6319 Miscibility
No changes.
63-20
Corrosion
830.6320 Corrosion
No changes. characteristics
characteristics
63-21
Dielectric breakdown
830.6321 Dielectric
No changes. voltage
breakdown voltage
None
830.7050 UV/visible light Proposed absorption
requirement.
None
830.7520 Particle size, Proposed conditional fiber length, and requirement. diameter distribution
Subpart E--Nontarget Organisms Data Requirements
Avian and Mammalian Testing.....................................................................................
71-1
Avian oral LD50
850.2100 Avian oral
Added testing on a toxicity
second species (passerine) for some uses. Expanded requirement to include testing with the TEP. Clarified test note to better identify when this test requirement is applicable.
71-2
Avian dietary LC50
850.2200 Avian dietary Changed from toxicity
``conditionally required'' to ``not required'' for greenhouse and indoor uses. Added a conditional requirement for testing one avian species for aquatic nonfood residential uses. Data on a second avian species may also be required.
71-3
Wild mammal toxicity
850.2400 Wild mammal
Clarified test note toxicity
to better identify when this test is applicable.
71-4
Avian reproduction
850.2300 Avian reproduction Changed from ''conditionally required'' to ``required'' for terrestrial, aquatic food, aquatic nonfood outdoor, forestry, and residential outdoor uses.
71-5
Simulated or actual
850.2500 Simulated or
Expanded conditional field testing-
actual field
requirement to mammals and birds
testing
terrestrial feed and aquatic nonfood outdoor uses. Added independent laboratory validation of methods.
Sediment Testing................................................................................................
None
850.1735 Whole sediment-- Proposed conditional 850.1740 acute
requirement. invertebrates (freshwater and marine)
None
None Whole sediment-- Proposed conditional chronic
requirement. invertebrates (freshwater and marine)
Nontarget Insect Testing.......................................................................................
141-1
Honey bee acute
850.3020 Honey bee acute Changed from contact LD50
contact toxicity ``conditionally required'' to ``required'' for all terrestrial, aquatic food, aquatic nonfood outdoor, forestry, and residential outdoor uses.
141-2
Honey bee--toxicity
850.3030 Honey bee--
Clarified test note. of residues on
toxicity of foliage
residues on foliage
141-4
Honey bee subacute
141-4 Honey bee subacute Eliminated feeding study
feeding study requirement.
[[Page 12316]]
141-5
Field testing for
850.3040 Field testing for Expanded conditional pollinators
pollinators
requirement to terrestrial feed and aquatic nonfood (outdoor and residential) uses.
142-1
Acute toxicity to
142-1 Acute toxicity to No changes. aquatic insect
aquatic insect
142-1
Aquatic insect life-
142-1 Aquatic insect No changes. cycle study
life-cycle study
142-3
Simulated or actual
142-3 Simulated or
No changes. field testing for
actual field aquatic insects
testing for aquatic insects
143-1
Nontarget insect
143-1 Nontarget insect No changes. 143-2........................ testing--predators
143-2 testing--predator 143-3........................ and parasites
143-3 s and parasites
Aquatic Organism Testing.......................................................................................
72-1
Freshwater fish LC50
850.1075 Freshwater fish Added conditional toxicity
requirement for a second species of fish for greenhouse and indoor uses. Added testing requirement using the TEP.
72-2
Acute LC50 freshwater
850.1010 Acute toxicity No changes invertebrates
freshwater invertebrates
72-3
Acute LC50 estuarine
850.1025 Acute toxicity Changed from and marine organisms
850.1035 estuarine and ``conditionally 850.1045 marine organisms required'' to 850.1055
``required'' for 850.1075
terrestrial, aquatic (food and nonfood outdoor), residential outdoor, and forestry uses; changed the aquatic nonfood residential use to ``not required.''
72-4
Fish early-life stage
850.1300 Aquatic
Changed from and Aquatic
invertebrate life- ``conditionally invertebrate life-
cycle
required'' to cycle
(freshwater)
``required'' for terrestrial, aquatic (food and nonfood outdoor), and forestry uses. Changed the aquatic nonfood residential use to ``not required.''
72-4
None
850.1350 Aquatic
Expanded the invertebrate life- conditional cycle (saltwater) requirement to include terrestrial feed and aquatic nonfood outdoor uses. Changed the aquatic nonfood residential use to ``not required.''
72-4
None
850.1400 Fish early-life Changed from stage
``conditionally (freshwater)
required'' to ``required'' for terrestrial, aquatic (food and nonfood outdoor), and forestry uses. Changed the aquatic nonfood residential use to ``not required.''
72-4
None
850.1400 Fish early-life Expanded the stage (saltwater) conditional requirement to include terrestrial feed and aquatic nonfood outdoor uses. Changed the aquatic nonfood residential use to ``not required.''
72-5
Fish life-cycle
850.1500 Fish life-cycle No changes.
72-6
Aquatic organism
850.1710 Aquatic organisms Changed from accumulation
850.1730 bioavailability/ ``conditionally 850.1850 biomagnification/ required'' to ``not toxicity tests required'' for aquatic nonfood residential and residential outdoor uses.
72-7
Simulated or actual
850.1950 Simulated or
Changed from field testing--
actual field
``conditionally aquatic organisms
testing--aquatic required'' to ``not organisms
required'' for aquatic nonfood residential uses. Clarified that the conditional requirement applies to turf use.
[[Page 12317]]
Subpart F--Toxicology Data Requirements
Acute Testing..................................................................................................
81-1
Acute oral toxicity--
870.1100 Acute oral
Modified test rat
toxicity--rat substance.
81-2
Acute dermal toxicity
870.1200 Acute dermal
Modified test toxicity
substance.
81-3
Acute inhalation
870.1300 Acute inhalation No changes. toxicity--rat
toxicity--rat
81-4
Primary eye
870.2400 Primary eye
Added testing using irritation--rabbit
irritation--rabbi the TGAI to support t
end-use products.
81-5
Primary dermal
870.2500 Primary dermal Added testing using irritation
irritation
the TGAI to support end-use products.
81-6
Dermal sensitization
870.2600 Dermal
Added testing using sensitization the TGAI to support end-use products.
81-7
Acute delayed
870.6100 Delayed
No changes. neurotoxicity--hen
neurotoxicity (acute)--hen
None
870.6200 Acute
Replaces current neurotoxicity--ra neurotoxicity t
battery.
Subchronic Testing.............................................................................................
82-1
90-day Feeding--
870.3100 90-day Feeding-- Requirement modified rodent
rodent
to include 2 rodent species.
82-1
90-day Feeding--non-
870.3150 90-day Feeding-- No changes. rodent
non-rodent
82-2
21-day Dermal
870.3200 21-day Dermal Changed from ``conditionally required'' to ``required'' for all food uses. Not required for nonfood uses.
82-3
90-day Dermal
870.3250 90-day Dermal Changed from ``conditionally required'' to ``required'' for all nonfood uses.
82-4
90-day Inhalation--
870.3465 90-day inhalation-- No changes. rat
rat
82-5
90-day Neurotoxicity-- 870.6200 90-day
Changed from mammal
Neurotoxicity--ra ``conditionally t
required'' to ``required.''
82-5
90-day Neurotoxicity-- 870.6100 28-day
Proposed conditional hen
Neurotoxicity--he requirement. n
Replaces 90-day neurotoxicity hen study.
Chronic Testing................................................................................................
83-1
Chronic feeding--
870.4100 Chronic feeding-- No changes. rodent and non-
rodent and non- rodent
rodent
83-2
Oncogenicity--rat and
870.4200 Carcinogenicity--r Changed name. mouse, preferred
at and mouse, Proposed requirement preferred
to perform range finding studies.
Developmental Toxicity and Reproduction........................................................................
83-3
Teratogenicity--2
870.3700 Prenatal
Changed name. species
developmental Testing required on toxicity--rat and a 2nd species for rabbit, preferred food and nonfood uses.
83-4
Reproduction--2
870.3800 Reproduction
Changed from generation
``conditionally required'' to ``required'' for nonfood uses based on potential exposure.
[[Page 12318]]
None
870.6300 Developmental Proposed conditional neurotoxicity requirement. To conduct developmental neurotoxicity testing utilizing information about the chemical and its toxicity to develop a science-- based approach to testing.
Mutagenicity Testing...........................................................................................
84-2
Gene mutation
870.5100 Bacterial reverse Replaces current mutation assay mutagenicity battery.
84-2
Structural chromosome
870.5300 In vitro mammalian Replaces current aberration
870.5375 cell assay
mutagenicity battery.
84-4
Other genotoxic
870.5385 In vivo
Replaces current effects
870.5395 cytogenetics
mutagenicity battery.
Other mutagenicity No changes. studies
Special Testing................................................................................................
85-1
General metabolism
870.7485 General metabolism No changes.
85-2
Dermal penetration
870.7600 Dermal penetration No changes.
86-1
Domestic animal
870.7200 Companion animal No changes. safety
safety
None
870.6500 Scheduled
Replaces current controlled
neurotoxicity operant behavior battery.
None
870.6850 Peripheral nerve Replaces current function
neurotoxicity battery.
None
870.6855 Neurophysiology: Replaces current sensory evoked neurotoxicity potentials
battery.
None
870.7800 Immunotoxicity New requirement. Required for food uses and nonfood uses. Subpart J--Nontarget Plant Protection
121-1
Target area
850.4025 Target area
No changes. phytotoxicity
phytotoxicity
Nontarget area phytotoxicity--Tier I...........................................................................
122-1
Seed germination/
850.4200 Seed germination Eliminated seedling emergence
requirement.
122-1
Seed germination/
850.4100 Seedling emergence Expanded requirement Seedling emergence
to include terrestrial food and feed, aquatic food, and residential outdoor uses. Changed test substance from TGAI to TEP.
122-1
Vegetative vigor
850.4150 Vegetative vigor Expanded requirement to include terrestrial food and feed, aquatic food, and residential outdoor uses. Changed test substance from TGAI to TEP. Eliminated requirement for data on granular and bait formulations.
122-2
Aquatic plant growth
850.4400 Aquatic plant Expanded requirement 850.5400 growth
to include terrestrial food and feed, aquatic food, and residential outdoor uses.
Nontarget area phytotoxicity--Tier II..........................................................................
123-1
Seed germination
850.4200 Seed germination Eliminated requirement.
[[Page 12319]]
123-1
Seedling emergence
850.4225 Seedling emergence Expanded conditional requirement to include terrestrial food and feed, aquatic food, and residential outdoor uses. Changed test substance from TGAI to TEP.
123-1
Vegetative vigor
850.4250 Vegetative vigor Expanded conditional requirement to include terrestrial food and feed, aquatic food, and residential outdoor uses. Changed test substance from TGAI to TEP. Eliminated requirement for data on granular and bait formulations.
123-2
Aquatic plant growth
850.4400 Aquatic plant Expanded conditional 850.5400 growth
requirement to include terrestrial food and feed, aquatic food, residential outdoor, aquatic nonfood residential, and indoor uses.
Nontarget area phytotoxicity - Tier III
124-1
Terrestrial field
850.4300 Terrestrial field Expanded conditional requirement to include terrestrial food and feed, aquatic food, and residential outdoor uses. Added requirement for independent method validation.
124-2
Aquatic field
850.4450 Aquatic field Expanded conditional requirement to include terrestrial food and feed, aquatic food, and residential outdoor uses. Added requirement for independent method validation.
Subpart K--Post-application Exposure
132-1
Foliar dissipation
875.2100 Dislodgeable
Revised testing foliar residue criteria. Expanded dissipation and use sites to turf transferable include testing for residues
greenhouses, nurseries, forests, residential settings, and turf grass. Changed from ``conditionally required'' to ``required''.
132-2
Soil dissipation
875.2200 Soil residue
Revised testing dissipation
criteria. Expanded use sites to include testing for greenhouses, nurseries, forests, and residential (conditionally required) settings.
None
875.2300 Indoor surface Proposed residue
requirement. dissipation
Subject to revised testing criteria.
133-3
Dermal exposure
875.2400 Dermal exposure Revised testing criteria. Expanded use sites to include testing for greenhouses, nurseries, forests, residential settings, and turf grass. Changed from ``conditionally required'' to ``required''.
133-4
Inhalation exposure
875.2500 Inhalation
Revised testing exposure
criteria. Expanded use sites to include testing for greenhouses, nurseries, forests, residential settings, golf courses, and certain indoor environments. Changed from ``conditionally required'' to ``required.''
[[Page 12320]]
None
875.2600 Biological
Proposed conditional monitoring
requirement. Subject to revised testing criteria
None
875.2700 Product use
Proposed information
requirement. Subject to revised testing criteria.
None
875.2800 Description of Proposed human activity requirement. Subject to revised testing criteria.
None
875.2900 Data reporting and Proposed calculations
requirement. Subject to revised testing criteria.
None
875.3000 Nondietary
Proposed requirement ingestion
for residential exposure
uses. Not required for occupational uses. Subject to revised testing criteria
Subpart N-Environmental Fate
Degradation Testing............................................................................................
161-1
Hydrolysis
835.2120 Hydrolysis
Expanded conditional requirement to include indoor food and nonfood, and residential indoor uses.
161-2
Photo degradation in
835.2240 Photodegradation Clarified conditions water
in water
for when study is required.
161-3
Photodegradation on
835.2410 Photodegradation Changed from soil
on soil
``conditionally required'' to ``required'' for terrestrial food and forestry uses. Expanded requirement to include terrestrial nonfood uses.
161-4
Photodegradation in
835.2370 Photodegradation Expanded conditional air
in air
requirement to include all terrestrial, greenhouse, forestry, and residential outdoor uses.
Metabolism Testing
162-1
Aerobic soil
835.4100 Aerobic soil
New expanded metabolism
metabolism
conditional requirement to include aquatic uses where the pesticide is applied to aquatic sites that are intermittently dry.
162-2
Anaerobic soil
835.4200 Anaerobic soil Reinserted. metabolism
metabolism
Erroneously omitted from published CFR.
162-4
Aerobic aquatic
835.4300 Aerobic aquatic Expanded requirement metabolism
metabolism
to include all terrestrial and forestry uses.
162-3
Anaerobic aquatic
835.4400 Anaerobic aquatic Expanded requirement metabolism
metabolism
to include all terrestrial uses.
Mobility Testing................................................................................................
163-1
Leaching and
835.1230 Leaching and
No changes. adsorption/
835.1240 adsorption/ desorption
desorption
163-2
Volatility (Lab)
835.1410 Laboratory
No changes. volatility
163-3
Volatility (Field)
835.8100 Field volatility No changes.
Dissipation Testing.............................................................................................
[[Page 12321]]
164-1
Soil
835.6100 Terrestrial field Expanded conditional dissipation
requirement to include aquatic uses involving application to aquatic sites that are intermittently dry. Merged with the long-term field dissipation study. Added independent laboratory validation of methods.
164-2
Aquatic (sediment)
835.6200 Aquatic field Expanded conditional dissipation
requirement to include all terrestrial uses. Clarified conditions for when study is required. Added independent laboratory validation of methods.
164-3
Forestry
835.6300 Forestry
Changed from dissipation
``required'' to ``conditionally required.'' Added independent laboratory validation of methods.
164-4
Combination and tank
835.6400 Combination and No changes. mixes
tank mixes
164-5
Soil, long term
None
Merged with the terrestrial field dissipation study.
Accumulation Testing............................................................................................
165-1
Confined rotational
None
Moved to Subpart O-- crops
Residue Chemistry.
165-2
Field rotational
None
Moved to Subpart O-- crops
Residue Chemistry.
165-3
Accumulation in
None
Eliminated irrigated crops
requirement.
165-4
Accumulation in fish
850.1730 Accumulation in Clarified conditions fish
for when study is required.
165-5
Accumulation in
850.1950 Accumulation in Expanded conditional aquatic nontarget
aquatic nontarget requirement to organisms
organisms
include all terrestrial uses.
None
835.7100 Ground water
Proposed conditional monitoring
requirement. Added independent laboratory validation of methods.
Subpart O--Residue Chemistry
Supporting Information
171-2
Chemical identity
860.1100 Chemical identity No changes.
171-3
Directions for use
860.1200 Directions for use No changes.
171-6
Proposed tolerance
860.1550 Proposed tolerance No changes.
171-7
Reasonable grounds in
860.1560 Reasonable grounds No changes. support of the
in support of the petition
petition
171-13
Submittal of
860.1650 Submittal of
No changes. analytical reference
analytical standards
reference standards
Nature of the Residue...........................................................................................
171-4
Nature of the residue
860.1300 Nature of the No changes. in plants
residue in plants
[[Page 12322]]
171-4
Nature of the residue
860.1300 Nature of the Clarified test in animals
residue in
substance. animals
Expanded requirement to include: 1. Testing whenever treated crops used for feed. 2. Cases when a pesticide is applied to livestock premises or is used in livestock drinking water. Eliminated requirement for residential outdoor use.
Analytical Methods..............................................................................................
171-4
Residue analytical
860.1340 Residue analytical Clarified test method
method
substance. Added independent laboratory validation requirement.
None
860.1360 Multiresidue
Previously part of method
the residue analytical method study.
Magnitude of the Residue Testing................................................................................
None
860.1380 Storage stability Previously part of data
the magnitude of the residue studies.
171-4
Crop field trials
860.1500 Crop field trials No changes.
171-4
Processed food/feed
860.1520 Processed food/ Clarified test feed
substance.
171-4
Meat/milk/poultry/
860.1480 Meat/milk/poultry/ Clarified test eggs
eggs
substance. Clarified conditions for when study is required.
171-4
Potable water
860.1400 Potable water Clarified test substance.
171-4
Fish
860.1400 Fish
Clarified test substance.
171-4
Irrigated crops
860.1400 Irrigated crops Clarified test 165-3........................
substance.
171-4
Food handling
860.1460 Food handling No changes.
171-5
Reduction in Residues
Anticipated
Name change. residues
Expanded requirement to include testing on a single serving.
165-1
Confined rotational
860.1850 Confined
Moved from crops
rotational crops Environmental Fate data requirements.
165-2
Field rotational
860.1900 Field rotational Moved from crops
crops
Environmental Fate data requirements. Modified conditions for when study is required.
Subpart U--Applicator Exposure
None
875.1100 Dermal outdoor Proposed 875.1600 exposure
requirement. Subject to new testing criteria.
None
875.1200 Dermal indoor Proposed 875.1600 exposure
requirement. Subject to new testing criteria.
None
875.1300 Inhalation outdoor Proposed 875.1600 exposure
requirement. Subject to new testing criteria.
None
875.1400 Inhalation indoor Proposed 875.1600 exposure
requirement. Subject to new testing criteria.
[[Page 12323]]
None
875.1500 Biological
Proposed conditional 875.1600 monitoring
requirement. Subject to new testing criteria.
None
875.1600 Data reporting and Proposed calculations
requirement. Subject to new testing criteria.
None
875.1700 Product use
Proposed information
requirement. Subject to new testing criteria.
\1\ If the study requirement is not identified as a ``new requirement,'' then the change has been required on a case-by-case basis.
-
Public Comments Sought
EPA invites you to provide your views on the various options as proposed, other approaches, the potential impacts of the various options (including possible unintended consequences), and any data or information that you would like the Agency to consider during the development of the final rule. In addition, the Agency welcomes specific comments on the following topics of particular interest to the Agency:
-
Ensuring high quality data to meet EPA's mandates. These proposed revisions to the pesticide data requirements in part 158 are intended to ensure that the Agency has the data required to support a determination of ``reasonable certainty of no harm'' under FFDCA and are an integral part of the data needed for an ``unreasonable adverse effects'' determination under FIFRA. In developing this proposed rule, EPA has evaluated its data needs to conduct the significantly expanded risk assessments required by new statutory mandates. EPA believes that this proposal describes the data needed (and only the data needed) for this purpose. The Agency welcomes your specific comments on the need for, value of, and any alternatives to, the data requirements described in this document to meet its mandates.
-
Ensuring a sound scientific basis that is consistent with advances in scientific understanding. These proposed revisions are intended to ensure that the data requirements in part 158 reflect current scientific understanding and scientific advances since they were issued in 1984. As discussed throughout this document, and summarized in Unit XVIII, many of these proposed revisions have been presented to, and reflect the advice and recommendations of the NRC or SAP. Issues and related materials that are brought by EPA to the SAP undergo a public review and comment opportunity before the SAP issues its report with recommendations to the Agency. The Agency welcomes your comments on the scientific basis of this proposed rule.
-
Improving the transparency and usefulness of part 158. Many of the revisions proposed in this document are intended to improve the usefulness of part 158 in identifying the specific data requirements that could apply to a particular pesticide application. As with the original design of part 158 in 1984, given the variety in pesticide chemistry, exposure, and hazard, these revisions are intended to retain a fair amount of flexibility in their application, while improving clarity and transparency to the regulated community. In future efforts to improve clarity and usefulness, EPA intends to issue separate revisions addressing antimicrobial pesticides, biochemical and microbial pesticides, which will highlight data requirements that apply to those pesticides. The Agency welcomes your specific comments on the Agency's efforts in this respect as described in this document and your specific suggestions for further improvements. In particular, the Agency welcomes public comment on the clarity of the proposed data requirements and the relationship between the proposed data requirements and EPA's statutory determinations.
-
Estimating costs and benefits. As summarized in Unit XXVII.A., the Agency has prepared a qualitative assessment of the benefits of the proposed rule, and estimates the potential annual costs to the regulated community of approximately $50 million more than current data requirements as described in part 158. The Agency believes that the costs of the rule are justified by the benefits from enhanced protection of human health and the environment. The Agency welcomes comments on its economic analysis of the proposed rule, as well as on its underlying assumptions and economic data. 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. As indicated in Unit V.B.1, EPA's underlying principle in developing the proposed revisions has been to strike an appropriate balance between the need for adequate data to make the statutorily mandated determinations and informed risk management decisions, while minimizing data collection burdens on pesticide applicants. The Agency welcomes your specific comments on the Agency's efforts described in this document and your specific suggestions for further improvements.
-
Enhancing international harmonization. EPA is active in a number of scientific harmonization and regulatory coordination efforts through international and regional organizations, and directly with other countries, in order to develop common or compatible international approaches to pesticide review and registration. In addition, EPA has encouraged registrants to coordinate data submissions in the three NAFTA countries to facilitate joint reviews. The Agency believes that these proposed revisions reflect these efforts, and welcomes your comments on this specific point.
-
Reducing, replacing and refining the use of animals in generating required data. As discussed in Unit XXII, where testing is needed to develop scientifically adequate data, the Agency is committed to reducing or replacing, wherever possible, the number of animals used for testing by incorporating in vitro (non-animal) test methods or other alternative approaches that have been scientifically validated and have received regulatory acceptance. The Agency understands that many people remain concerned about the use of animals for research and data development purposes, and has received several requests for more expeditious adoption of alternate methods. The Agency plays an important role in the Federal interagency efforts to encourage the
[[Page 12324]]
reduction of the number of animals used in testing; seek opportunities to replace test methods requiring animals with alternative test methods when acceptable alternative methods are available; and refine existing test methods to optimize animal use when there is no substitute for animal testing. Recognizing the different roles of data requirements and test guidelines, the Agency welcomes your specific comments on its efforts to ensure that the data requirements continue to provide sufficient flexibility to allow for the use of alternative approaches that have been scientifically validated and have received regulatory acceptance. The Agency welcomes specific recommendations on ways to reduce the number of animals tested while still allowing the Agency to meet its statutory obligations.
-
-
References
The Agency has established an official docket for this rulemaking under Docket ID No. OPP-2004-0387. All of the documents that have been included in that docket are listed in the ``EDOCKET'' index available at http://www.epa.gov/edocket. Select ``Quick Search'' and then use the
Docket ID No. to access the index. The following is a listing of the documents that are specifically referenced in this proposed rule. These documents, and other supporting materials, are included in the docket index. Please note that the official docket includes the documents located in the docket as well as the documents that are referenced in those documents. As indicated previously, not all docket materials are available electronically, but all publicly available docket materials are available through the Docket facility as described under ADDRESSES.
-
National Research Council, ``Pesticides in the Diets of Infants and Children,'' National Academy Press, Washington, D.C., 1993.
-
Mineau et al., 2001. Pesticide Acute Toxicity Reference Values for Birds, Review of Environmental Contamination and Toxicology, 170: 13-74.
-
U.S. Environmental Protection Agency. 1998. EPA's Contaminated Sediment Management Strategy. EPA-823-R-98-001. Office of Water, 4305, Washington, D.C. http://www.epa.gov/ waterscience/cs/stratndx.html.
-
Bennett et al., Overview of Methods for Evaluating Effects of Pesticides on Reproduction in Birds., U.S. EPA, Environmental Research Laboratory, Corvalis, OR., EPA 600/3-91/048.
-
Bennet et al., 1990. Effects on the Duration and Timing of Dietary Methyl Parathion Exposure on Bobwhite Reproduction, Environmental Toxicology and Chemistry, 9: 1473-1480.
-
Bennett et al., 1991. Effects of Dietary Exposure to Methyl Parathion on Egg-laying and Incubation in Mallards, Environmental Toxicology and Chemistry, 10: 501-507.
-
Luster et al., 1992. Risk Assessment in Immunotoxicology I. Sensitivity and Predictability of Immune tests, Fundam. Appl. Toxicol, 18: 200-210.
-
Luster et al., 1993. Risk Assessment in Immunotoxicology II. Relationships Between Immune and Host Resistance Tests, Fundamental amd Applied Toxicology, 21: 71-82.
-
USEPA (1990) 1990 OECD Ad Hoc Meeting on Neurotoxicity Testing. Summary Report. September 1990. Eastern Research Group, MA.
-
Determination of the Appropriate FQPA Safety Factor(s) in Tolerance Assessment. Office of Pesticide Programs, U.S. Environmental Protection Agency, Washington D.C, February, 2002.
-
FIFRA Scientific Advisory Panel. SAP Report No. 99-03, May 25, 1999 FIFRA Scientific Advisory Panel Meeting, May 25-27, 1999, held at the Sheraton Crystal City Hotel, Arlington, Virginia.
-
ILSI (2001) Developing strategies for agricultural chemical safety evaluation, a report from an April 22-23, 2001 workshop. ILSI Health and Environmental Sciences Institute. http://hesi.ilsi.org/activities/ actslist.cfm?pubentityid =8&pubactivityid=261 2001 draft).
-
USEPA (U.S. Environmental Protection Agency), Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Animals, Series 84, Mutagenicity, Addendum 9, Office of Pesticides and Toxic Substances, EPA-540/09-91-122, NTIS Publication No. PB91-158394, Washington, DC, 1991.
-
K. Dearfield, A. Auletta, M. Cimino and M. Moore, Considerations in the U.S. Environmental Protection Agency's testing approach for mutagenicity, Mutation Research 258 (1991) 259-283.
-
USEPA (U.S. Environmental Protection Agency), Guidelines for mutagenicity risk assessment, 51 FR 34006-34012 (1986).
-
Dourson, M.L., Knauf, L.A., and Swartout, J.C. (1972). On Reference Dose (RfD) and its underlying toxicity data base. Toxicology and Industrial Health 8:171-189.
-
Health Canada, Pesticide Management Regulatory Agency (1997) Reproductive Toxicity Testing in Proposed 40 CFR part 158, Subdivision W - Data Requirements for Antimicrobial Pesticides. November 1997 draft. Attachment to memorandum from Don Grant (PMRA) to Norm Cook/Tim McMahon/Sue Makris (USEPA/OPP), December 1, 1997.
-
Spielmann, H., and Gerbracht, U. (2001). The use of dogs as second species in regulatory testing of pesticides. Part II: subacute, subchronic and chronic studies in the dog. Archives of Toxicology 75(1): 1-21.
-
U. S. EPA, 2004. ``Economic Analysis of the Proposed Rule Changing Data Requirements for Conventional Pesticides,'' BEAD/OPP/ USEPA, Washington, DC. Document ID No. 2004-0387-00.
-
-
FIFRA Review Requirements
In accordance with FIFRA sec. 25(a), this proposal was submitted to the FIFRA SAP, the Secretary of Agriculture, and appropriate Congressional Committees. The SAP has waived its review of this proposal, and no comments were received from any of the Congressional Committees. USDA participated fully in the OMB interagency review process, and where warranted, changes were made to the proposal based upon its comments.
-
Statutory and Executive Order Reviews
-
Executive Order 12866
Under Executive Order 12866, entitled Regulatory Planning and Review (58 FR 51735, October 4, 1993), the Office of Management and Budget (OMB) determined that this proposed rule is a ``significant regulatory action'' under sec. 3(f) of the Executive Order because this action might raise novel legal or policy issues or otherwise have a potentially significant impact on pesticide producers or registrants of pesticide products. As a result of this OMB determination, EPA submitted this proposed rulemaking to OMB for review under Executive Order 12866 and any changes made in response to OMB comments have been documented in the public docket for this rulemaking as required by sec. 6(a)(3)(E) of the Executive Order.
EPA has prepared an economic analysis of the potential costs associated with this proposed action, which is contained in a document entitled ``Economic Analysis of the Proposed Rule Changing Data Requirements for Conventional Pesticides'' (Ref. 19). A copy of this Economic Analysis is available in the public docket for this action, and is briefly summarized here.
The cost of the proposed rule is calculated as the estimated costs for the
[[Page 12325]]
proposed changes to the existing data requirements as currently codified in 40 CFR part 158. Since most of the data requirements contained in this proposal have been applied on a case-by-case basis over the years to reflect the evolution of scientific understanding and concerns, the Agency further categorizes the proposed revisions that are not currently codified as either newly codified (i.e., data requirements that are not currently in part 158, but are, in practice, required on a case-by-case basis) or expanded existing requirements (i.e., change in frequency with which a currently codified data requirement would be imposed. For example, a change from conditionally- required to required, or visa versa. Another example is a change in use pattern for an existing requirement) or newly imposed (i.e., data requirement have not been previously imposed).
Using the currently codified requirements as the baseline for the impact analysis, the total annual impact to the pesticide industry is estimated to be about $51 million. Of this estimated total annual impact, about $28.9 million per year represents the cost of new data requirements that were imposed over the years but were not specified in the existing part 158, and about $21.6 million represents the cost of modified or expanded existing data requirements (i.e., data requirements for certain tests and use patterns in the CFR that are changing from conditionally required (CR) to required (R)). As they have been applied to an increasing number of registrations, these data requirements have become more regularly required and are now being proposed. Included in the $51 million is about $1.9 million that is attributable to newly imposed requirements. The costs of the newly imposed requirements represents the increase costs over current practices, and therefore provide the estimated practical impact of this proposed rule to the pesticide industry.
To calculate the potential costs associated with this proposal, EPA first identified the test necessary to generate the data required, and then gathered information on the price that laboratories might charge a firm to conduct that test for the firm. We assumed that the data required would always need to be generated, but often the data are already available because the firm generated it for their own use. In such cases, the firm would simply need to submit those data to EPA, which involves less burden and cost than generating it. Some firms may have surrogate data that could be used, while others may qualify for a waiver. Both of which also involve less costs than generating the data anew. For each test identified, we averaged the low and high cost estimates provided by the various laboratories. Variations can be related to differences in the assumptions about the test performed (e.g., protocol, species used), or it could simply be a difference in the price charged by the laboratory.
EPA then used historical data on pesticide registration actions that occurred over a 7 year period (1996-2002) to identify the entities that sought pesticide registration actions in the past. The data required for each registration action depends on several factors, including the type of registration action (e.g., registration of a new active ingredient food use, registration of a new active ingredient non-food use, registration and amendments to registrations involving a major new use); data category or discipline (e.g., toxicology, residue chemistry, human exposure), and use pattern (how the product will be used). To estimate the average incremental cost of each type of registration action, the percentage of time a particular test was required was estimated by EPA scientists, based on their past experience in the program and their involvement in developing the new data requirements.
The Agency prepared an industry profile using the same historical data on pesticide registration actions to identify the companies involved in those actions, and based it on public information gathered about those companies. EPA also used this industry profile to analyze the potential impacts of the proposed rule on small businesses, the results of which are summarized in Unit XXVII.C. The incremental costs, and a more detailed discussion of the estimating methodology employed in the analysis are presented in the economic impact analysis prepared for this proposed rule (Ref. 19).
Since the likely overall impact of this proposal on businesses is small, the Agency believes that a deleterious effect on the availability of pesticides to users is unlikely. On balance, the Agency believes that the costs of the rule are justified by the benefits from enhanced protection of human health and the environment.
The data requirements in part 158 potentially apply to new pesticides submitted for registration, to new uses of currently registered pesticides, and to existing chemicals whose databases are subject to Agency review to determine if they continue to meet registration standards. For these existing chemicals, part 158 data requirements are potentially relevant to three review programs.
Reregistration (mandated in 1988) and tolerance reassessment (mandated in 1996) are well underway. Data requirements under those programs have largely been imposed on registrants of existing chemicals, and the data have been submitted. EPA anticipates that by the time this proposed rule is promulgated, few of the data requirements will remain to be imposed for existing chemicals. Only those that are ``new'' or ``newly codified '' (e.g., developmental neurotoxicity, immunotoxicity, sediment testing) have not been broadly required and may be imposed in the future under the reregistration or tolerance reassessment programs. Continued data needs for existing chemicals must be imposed under the Agency's Data Call-In (DCI) program.
Should such data be needed for reregistration or tolerance reassessment after promulgation of this rule, EPA anticipates that it will articulate the specific burden and costs associated with each DCI pursuant to the appropriate Information Collection Request (ICR) approvals under the Paperwork Reduction Act (PRA). Since the approval process for the PRA requires that EPA characterize the information collection burdens and costs incurred by registrants to comply with a DCI, a complete estimate of the burden and costs for the DCIs will be provided at that time. EPA believes that the public process associated with the PRA approval for the DCI related ICRs is a reasonable way to account for the data costs without double counting the burden. Accordingly, in this proposal EPA has not evaluated the potential burden of the proposed data requirements on registrants of existing chemicals.
A third program, registration review, mandated in 1996, requires that EPA establish a program for the periodic review of existing chemicals (goal is every 15 years). Any data requirements to be levied under that program will also be imposed under a DCI. At this time, EPA is developing a proposed rule to establish procedures for this program. An Advance Notice of Proposed Rulemaking was published in the Federal Register on April 26, 2000 (65 FR 24585)(FRL-6488-9).
The data requirements in this proposed rule are expected to apply to all chemicals subject to registration review (i.e., all existing chemicals), depending on the conditions expressed in both final rules (this part 158 and the future registration review rule). At this time EPA has not determined how the
[[Page 12326]]
registration review program will function. Until the registration review program is better defined, any estimates of burden/cost will be unreliable and highly speculative. Moreover, since the requirements will also be imposed via DCIs, such burdens will also be characterized under PRA procedures described earlier.
Accordingly, EPA intends to describe generally the burden and costs of potential data requirements at the time the registration review rule is proposed, and ultimately, to more accurately and fully characterize the individual DCI burden and costs during the public process associated with PRA approval.
-
Paperwork Reduction Act (PRA)
Pursuant to the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq., an agency may not conduct or sponsor, and a person is not required to respond to an information collection request unless it displays a currently valid OMB control number. The OMB control numbers for EPA's regulations, after appearing in the preamble of the final rule, are listed in 40 CFR part 9 and 48 CFR chapter 15, and included on the related collection instrument (e.g., form or survey). Under the PRA, ``burden'' means the total time, effort, or financial resources expended by persons to generate, maintain, retain, or disclose or provide information to or for a Federal agency. This includes the time needed to review instructions; develop, acquire, install, and utilize technology and systems for the purposes of collecting, validating, and verifying information, processing and maintaining information, and disclosing and providing information; adjust the existing ways to comply with any previously applicable instructions and requirements; train personnel to be able to respond to a collection of information; search data sources; complete and review the collection of information; and transmit or otherwise disclose the information.
EPA has determined that this proposed rule imposes no significant additional information collection and paperwork burden. The information collection activity contained in this proposed rule, i.e., the paperwork collection activities related to the submission of data to EPA in order to register a conventional pesticide product, are already approved by OMB under several existing ICRs. Specifically, the program activities which would generate a paperwork burden under this proposal are covered by the following ICRs:
-
The activities associated with the establishment of a tolerance are currently approved under OMB Control No. 2070-0024 (EPA ICR No. 0597);
-
The activities associated with the application for a new or amended registration of a pesticide are currently approved under OMB Control No. 2070-0060 (EPA ICR No. 0277);
-
The activities associated with the generation of data for reregistration are currently approved under OMB Control No. 2070-0107 (EPA ICR No. 1504); and
-
The activities associated with the generation of data for special review are currently approved under OMB Control No. 2070-0057 (EPA ICR No. 0922).
These existing ICRs cover the paperwork activities contained in this proposal because these activities already occur as part of the Agency's existing program activities. These program activities are an integral part of the Agency pesticide program and the corresponding ICRs will continue to be regularly renewed pursuant to the PRA. The approved burden in these ICRs were already increased in 1996 to accommodate the potential increased burden related to the implementation of the new safety standard imposed in 1996 by FQPA.
The total estimated average annual public reporting burden currently approved by OMB for these various activities ranges from 8 hours to approximately 3,000 hours per respondent, depending on the activity and other factors surrounding the particular pesticide product. Additional information about this estimate is provided in the Economic Analysis for this rulemaking.
Comments are requested on the Agency's need for this information, the accuracy of the burden estimates, and any suggested methods for minimizing respondent burden, including through the use of automated collection techniques. The Agency is particularly interested in receiving comment on the estimated testing costs and burdens that are presented in the Economic Analysis, as well as suggestions for how the Agency might best be able to provide updated and more detailed estimates in the context of the individual ICRs during the regular renewals of those ICRs every 3 years. Send comments to EPA as part of your overall comments on this proposed action in the manner specified in Unit I.C. In the final rule, the Agency will address any comments received regarding the information collection requirements contained in this proposal.
-
-
Regulatory Flexibility Act
Pursuant to sec. 605(b) of the Regulatory Flexibility Act (RFA), 5 U.S.C. 601 et seq., the Agency hereby certifies that this proposal will not have a significant adverse economic impact on a substantial number of small entities. This determination is based on the Agency's economic analysis performed for this rulemaking, which is summarized in Unit XXVII.A., and a copy of which is available in the public docket for this rulemaking. The following is a brief summary of the factual basis for this certification.
As part of the economic analysis prepared for this rulemaking, EPA used historical data to prepare an industry profile of potentially impacted entities prepared for the economic analysis for this rulemaking, EPA determined that this proposed rule is not expected to impact any small not-for-profit organizations or small governmental jurisdictions. As such, the small entity impact analysis prepared as part of the economic analysis evaluated potentially impacted businesses that could be considered small businesses as defined by the Small Business Administration, which uses the maximum number of employees or sales for businesses in each industry sector, as that sector is defined by NAICS. For example, entities defined as Pesticide and Other Agricultural Chemical Manufacturing (325320) are considered to be a small business if they employ 500 or fewer people.
Although, as illustrated by the industry profile, the conventional pesticide industry is primarily composed of large, multi-national corporations, EPA used historical data to evaluate potential impacts on small firms that could be subject to the proposed requirements.
To determine the universe of small entities that could be subject to the proposed requirements, the Agency used workforce data to determine the size for 565 firms for which financial data had been gathered for the economic analysis. Based on that data, EPA determined that 449 qualified as small businesses using the SBA definition. Using the resulting ratio of 79%, the Agency estimated that out of the total 1804 firms in the pesticide industry, approximately 1434 firms might qualify as small and could make up the universe of small entities that could be subject to the proposed requirements.
EPA then used historical data to estimate the number of small entities potentially impacted, and the extent of that potential impact. EPA used workforce data gathered on 120 firms identified as impacted by the proposal using historical data to determine the size of 97 firms. Based on that data, we determined that 49 firms of the 97 firms (51%) qualified as small businesses.
[[Page 12327]]
Data was unavailable for 23 firms, but using the same ratio (51%), EPA estimated that a total of 61 small firms could be potentially impacted by the proposal. Out of the universe of 1434 small firms that could be subject to the proposed requirements, or out of the 61 small firms potentially impacted, only 35 small firms are expected to experience a cost increase representing 1% or more of gross sales, of which only 23 small firms are expected to experience a cost increase representing 3% or more of gross sales. Given these estimated impacts on small businesses, EPA has concluded that the proposed revisions will not have a significant adverse economic impact on a substantial number of small entities.
EPA is particularly interested in receiving comment from small businesses as to the benefits, costs and impacts of this proposed rule. Any comments regarding the estimated potential small entity economic impacts that this proposed regulatory action may impose on small entities should be submitted to the Agency in the manner specified in Unit I.
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Unfunded Mandates Reform Act
Under Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4), EPA has determined that this action does not contain a Federal mandate that may result in expenditures of $100 million or more for State, local, and tribal governments, in the aggregate, or the private sector in any one year. As described in Unit XXVII.A., the annual costs associated with this action are estimated to total $51 million. This cost represents the incremental cost to applicant and registrants attributed to the additional or modified data requirements contained in this proposal. In addition, since State, local, and tribal governments are rarely a pesticide applicant or registrant, the proposed rule is not expected to significantly or uniquely affect small governments. Accordingly, this action is not subject to the requirements of secs. 202 and 205 of UMRA.
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Executive Order 13132
Pursuant to Executive Order 13132, entitled Federalism (64 FR 43255, August 10, 1999), EPA has determined that this proposed rule does not have ``federalism implications,'' because it will not have substantial direct effects on the states, on the relationship between the national government and the states, or on the distribution of power and responsibilities among the various levels of government, as specified in the Order. As indicated above, instances where a state is a registrant are extremely rare. Therefore, this proposed rule may seldom affect a state government. Thus, Executive Order 13132 does not apply to this proposed rule. In the spirit of the Order, and consistent with EPA policy to promote communications between the Agency and State and local governments, EPA specifically solicits comment on this proposed rule from State and local officials.
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Executive Order 13175
As required by Executive Order 13175, entitled Consultation and Coordination with Indian Tribal Governments (65 FR 67249, November 6, 2000), EPA has determined that this proposed rule does not have tribal implications because it will not have substantial direct effects on tribal governments, on the relationship between the Federal government and the Indian tribes, or on the distribution of power and responsibilities between the Federal government and Indian tribes, as specified in the Order. As indicated above, at present, no tribal governments hold, or have applied for, a pesticide registration. Thus, Executive Order 13175 does not apply to this proposed rule. In the spirit of the Order, and consistent with EPA policy to promote communications between the Agency and State and local governments, EPA specifically solicits comment on this proposed rule from tribal officials.
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Executive Order 13045
Executive Order 13045, entitled Protection of Children from Environmental Health Risks and Safety Risks (62 FR 19885, April 23, 1997) does not apply to this proposed rule because this action is not designated as an ``economically significant'' regulatory action as defined by Executive Order 12866 (see Unit XXVII.A.). Further, this proposal does not establish an environmental standard that is intended to have a negatively disproportionate effect on children. To the contrary, this action will provide added protection for children from pesticide risk. The proposed data requirements are intended to address risks that, if not addressed, could have a disproportionate negative impact on children. EPA will use the data and information obtained by this proposed rule to carry out its mandate under FFDCA to give special attention to the risks of pesticides to sensitive subpopulations, especially infants and children.
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Executive Order 13211
This rule is not subject to Executive Order 13211, entitled Actions concerning Regulations that Significantly Affect Energy Supply, Distribution, or Use (66 FR 28355, May 22, 2001) because it is not likely to have any significant adverse effect on the supply, distribution, or use of energy.
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National Technology Transfer and Advancement Act
Section 12(d) of the National Technology Transfer and Advancement Act of 1995 (NTTAA), 15 U.S.C. 272 note) directs EPA to use voluntary consensus standards in its regulatory activities unless to do so would be inconsistent with applicable law or impractical. Voluntary consensus standards are technical standards (e.g., materials specifications, test methods, sampling procedures, etc.) that are developed or adopted by voluntary consensus standards bodies. NTTAA directs EPA to provide Congress, through OMB, explanations when the Agency decides not to use available and applicable voluntary consensus standards. This regulation proposes the types of data to be required to support conventional pesticide registration but does not propose to require specific methods or standards to generate those data. Therefore, this proposed regulation does not impose any technical standards that would require Agency consideration of voluntary consensus standards. The Agency invites comment on its conclusion regarding the applicability of voluntary consensus standards to this rulemaking.
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Executive Order 12898
This proposed rule does not have an adverse impact on the environmental and health conditions in low-income and minority communities. Therefore, under Executive Order 12898, entitled Federal Actions to Address Environmental Justice in Minority Populations and Low-Income Populations (59 FR 7629, February 16, 1994), the Agency has not considered environmental justice-related issues. Although not directly impacting environmental justice-related concerns, the collection of the information contained in this proposed rule will enable the Agency to protect human health and the environment by being better able to prioritize chemical substances of concern.
List of Subjects in 40 CFR Parts 152 and 158
Administrative practice and procedure, Agricultural commodities,
[[Page 12328]]
Pesticides and pests, Reporting and recordkeeping requirements.
Dated: February 28, 2005. Stephen L. Johnson, Acting Administrator.
Therefore, it is proposed that chapter I of title 40 of the Code of Federal Regulations be amended as follows:
PART 152--[AMENDED]
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In part 152:
a. The authority citation continues to read as follows:
Authority: 7 U.S.C. 136-136y. Subpart U is also issued under 31 U.S.C. 9701.
b. In Sec. 152.50, by amending paragraph (f)(1) by revising the reference ``FIFRA sec. 3(c)(1)(D)'' to read ``FIFRA sec. 3(c)(1)(F),'' and by revising paragraph (f)(2) to read as follows:
Sec. 152.50 Contents of application.
* * * * *
(f) * * *
(2) An applicant must furnish any data specified in part 158 of this chapter that are required by the Agency to determine that the product meets the registration standard of FIFRA sec. 3(c)(5) or 3(c)(7), as applicable, and FIFRA sec. 10. An applicant may request a waiver of any data requirement by following the procedures in Sec. 158.45 of this chapter. Each study must comply with:
(i) Section 158.32 of this chapter, with respect to format of submission.
(ii) Section 158.33 of this chapter, with respect to studies for which a claim of trade secret or confidential business information is made.
(iii) Section 158.34 of this chapter, with respect to flagging for potential adverse effects.
(iv) Section 160.12 of this chapter, with respect to a statement whether studies were conducted in accordance with Good Laboratory Practices of part 160. * * * * *
PART 158--[AMENDED]
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In part 158:
a. By revising the authority citation to read as follows:
Authority: 7 U.S.C. 136-136y; 21 U.S.C. 346a.
b. By revising the table of contents for part 158 to read as follows: Subpart A--General Provisions Sec. 158.1 Purpose and scope. 158.3 Definitions. 158.5 Applicability. 158.30 Flexibility. 158.32 Format of data submissions. 158.33 Confidential data. 158.34 Flagging of studies for potential adverse effects. 158.45 Waivers. 158.70 Satisfying data requirements. 158.75 Requirements for additional data. 158.80 Use of other data. Subpart B--How to Use Data Tables 158.100 Pesticide use categories. 158.110 Required and conditionally required data. 158.120 Determining data requirements. 158.130 Purposes of the registration data requirements. Subpart C [Reserved] Subpart D--Product Chemistry 158.300 Definitions. 158.310 Product chemistry data requirements table. 158.320 Product identity and composition. 158.325 Description of materials used to produce the product. 158.330 Description of production process. 158.335 Description of formulation process. 158.340 Discussion of formation of impurities. 158.345 Preliminary analysis. 158.350 Certified limits. 158.355 Enforcement analytical method. Subpart E--Terrestrial and Aquatic Nontarget Organisms 158.400 Terrestrial and aquatic nontarget organisms data requirements table. Subpart F--Toxicology 158.500 Toxicology data requirements table. 158.510 Tiered testing options for nonfood pesticides. Subpart G--Product Performance 158.610 Product performance data requirements. Subparts H-I [Reserved] Subpart J--Nontarget Plant Protection 158.700 Nontarget plant protection data requirements table. Subpart K--Post-application Exposure 158.800 General requirements. 158.810 Criteria for testing. 158.820 Post-application exposure data requirements table. Subpart L--Biochemical Pesticides 158.910 Biochemical pesticide data requirements. Subpart M--Microbial Pesticides 158.1010 Microbial pesticide data requirements. Subpart N--Environmental Fate 158.1100 Environmental fate data requirements table. Subpart O--Residue Chemistry 158.1200 Definitions. 158.1210 Residue chemistry data requirements table. Subpart P--Pesticide Management and Disposal 158.1300 [Reserved] Subpart R--Spray Drift 158.1410 Spray drift data requirements. Subpart U--Applicator Exposure 158.1500 General requirements. 158.1510 Criteria for testing. 158.1520 Applicator exposure data requirements table. Subpart V--Inert Ingredients 158.1600 [Reserved] Subpart W--Antimicrobial Pesticides 158.1700 [Reserved]
c. By revising subpart A to read as follows:
Subpart A--General Provisions
Sec. 158.1 Purpose and scope.
(a)Purpose. The purpose of this part is to specify the kinds of data and information EPA requires in order to make regulatory judgements under FIFRA secs. 3, 4, and 5 about the risks and benefits of pesticide products. Further, this part specifies the data and information needed to determine the safety of pesticide chemical residues under FFDCA sec. 408.
(b) Scope. (1) This part describes the minimum data and information EPA typically requires to support an application for pesticide registration or amendment; support the reregistration of a pesticide product; or establish or maintain a tolerance or exemption from the requirement of a tolerance for a pesticide chemical residue.
(2) This part establishes general policies and procedures associated with the submission of data in support of a pesticide regulatory action.
(3) This part does not include study protocols, methodology, or standards for conducting or reporting test results; nor does this part describe how the Agency uses or evaluates the data and information in its risk assessment and risk management decisions, or the regulatory determinations that may be based upon the data.
Sec. 158.3 Definitions.
All terms defined in sec. 2 of the Federal Insecticide, Fungicide, and Rodenticide Act apply to this part and are used with the meaning given in the Act. Applicable terms from the Federal Food, Drug, and Cosmetic Act also apply to this part. Individual subparts may contain definitions that pertain solely to that subpart. The following additional terms apply to this part:
Applicant means any person or entity that applies to the Agency for:
(1) An application for registration, amended registration, or reregistration
[[Page 12329]]
of a pesticide product under FIFRA secs. 3, 4 or 24(c).
(2) An application for an experimental use permit under FIFRA sec. 5.
(3) An application for an exemption under FIFRA sec. 18.
(4) A petition or other request for establishment or modification of a tolerance, for an exemption for the need for a tolerance, or for other clearance under FFDCA sec. 408.
(5) A submission of data in response to a notice issued by EPA under FIFRA sec. 3(c)(2)(B).
(6) Any other application, petition, or submission sent to EPA intended to persuade EPA to grant, modify, or leave unmodified a registration or other approval required as a condition of sale or distribution of a pesticide.
(7) For the purposes of this part, an applicant includes a registrant.
Registration includes a new registration, amended registration and reregistration, unless stated otherwise.
Sec. 158.5 Applicability.
(a) This subpart describes the data that are required to support the registration of each pesticide product. The information specified in this part must be submitted with each application for new or amended registration or for reregistration, if it has not been submitted previously or if the previously submitted information is not complete and accurate.
(b) The requirements of this part apply to the following applicants:
(1) Any person who submits an application for a new or amended registration in accordance with FIFRA sec. 3.
(2) Any person who submits an application for an experimental use permit in accordance with FIFRA sec. 5.
(3) Any person who petitions the Agency to establish, modify, or revoke a tolerance or exemption from a tolerance in accordance with FFDCA sec. 408.
(4) Any person who submits data or information to support the continuation of a registration in accordance with FIFRA sec. 3 or 4.
Sec. 158.30 Flexibility.
(a) FIFRA provides EPA flexibility to require, or not require, data and information for the purposes of making regulatory judgements for pesticide products. EPA maintains its authority to tailor data needs to individual pesticide chemicals. The actual data required may be modified on an individual basis to fully characterize the use and properties, characteristics, or effects of specific pesticide products under review. The Agency encourages each applicant to consult with EPA to discuss the data requirements particular to its product prior to and during the registration process.
(b) The Agency cautions applicants that the data routinely required in this part may not be sufficient to permit EPA to evaluate the potential of the product to cause unreasonable adverse effects to man or the environment. EPA may require the submission of additional data or information beyond that specified in this part if such data or information are needed to appropriately evaluate a pesticide product.
(c) This part will be updated as needed to reflect evolving program needs and advances in science.
Sec. 158.32 Format of data submissions.
(a) General. (1) The requirements of this section apply to any data submitted or cited to EPA in support of any new, pending, or existing regulatory action under FIFRA or FFDCA, including, but not limited to:
(i) Registration, amended registration or reregistration.
(ii) Experimental use permit.
(iii) Data Call-in.
(iv) Establishment, modification or revocation of a tolerance or exemption.
(v) Submission of adverse effects information under FIFRA sec. 6(a)(2).
(2) The requirements of this section do not apply to administrative materials accompanying a data submission, including forms, labeling, and correspondence.
(b) Transmittal document. Each submission in support of a regulatory action must be accompanied by a transmittal document, which includes:
(1) Identity of the submitter.
(2) The transmittal date.
(3) Identification of the regulatory action with which the submission is associated, e.g., the registration or petition number.
(4) A list of the individual documents included in the submission.
(c) Individual documents. Unless otherwise specified by the Agency, each submission must be in the form of individual documents or studies. Previously submitted documents should not be resubmitted unless specifically requested by the Agency, but should be cited with adequate information to identify the previously submitted document. Each study or document should include the following:
(1) A title page including the following information:
(i) The title of the study, including identification of the substance(s) tested and the test name or data requirement addressed.
(ii) The author(s) of the study.
(iii) The date the study was completed.
(iv) If the study was performed in a laboratory, the name and address of the laboratory, project numbers or other identifying codes.
(v) If the study is a commentary on or supplement to another previously submitted study, full identification of the other study with which it should be associated in review.
(vi) If the study is a reprint of a published document, all relevant facts of publication, such as the journal title, volume, issue, inclusive page numbers, and date of publication.
(2) The appropriate statement(s) regarding any data confidentiality claims as described in Sec. 158.33.
(3) A statement of compliance or non-compliance with respect to Good Laboratory Practice Standards as required by 40 CFR 160.12, if applicable.
(4) A complete and accurate English translation must be included for any information that is not in English.
(5) A flagging statement as prescribed by Sec. 158.34, if applicable.
Sec. 158.33 Confidential data.
(a) Definitions. For the purposes of this section:
(1) Registered or previously registered pesticide means any pesticide containing an active ingredient contained in a product that is, or has ever been, an active ingredient in a product registered under sec. 3 of FIFRA. A registered pesticide that is the subject of an application for a new use falls within the category of ``registered or previously registered pesticide.''
(2) Safety and efficacy information means 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 and fate in the environment, and metabolism.
(b) Applicability. (1) This section applies to information submitted pursuant to this part. It supplements the general confidentiality procedures in 40 CFR part 2, subpart B, including FIFRA confidentiality procedures at 40 CFR 2.307. To the extent that provisions in this section conflict with those in 40 CFR part 2, subpart B, the provisions in
[[Page 12330]]
this section take precedence. The provisions of 40 CFR 2.308 do not apply to information to which this section applies. In addition to complying with the requirements of this section, 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 Sec. 174.9 of this chapter.
(2) FFDCA sec. 408(i) protects confidential information submitted in connection with an application for a tolerance or exemption to the same extent as FIFRA sec. 10. References in this section to FIFRA sec. 10 are deemed to apply equally to information submitted pursuant to FFDCA sec. 408, pursuant to the authority in sec. 408(i).
(c) Method of asserting business confidentiality claims--(1) Claim required. Information to which this section applies (and which is submitted on or after the effective date of this regulation) will be deemed as not subject to a confidentiality claim unless a claim for that information is made in accordance with the procedures specified in this paragraph. Information not subject to a confidentiality claim may be made available to the public without further notice, subject to the requirements of FIFRA sec. 10(g).
(2) Statement required. Upon submission to EPA, each document must be accompanied by a signed and dated document containing one of the following statements:
(i) Statement 1.
No claim of confidentiality, on any basis whatsoever, is made for any information contained in this document. I acknowledge that information not designated as within the scope of FIFRA sec. 10(d)(1)(A), (B), or (C)and which pertains to a registered or previously registered pesticide is not entitled to confidential treatment and may be released to the public, subject to the provisions regarding disclosure to multinational entities under FIFRAsec. 10(g).
(ii) Statement 2.
Information claimed as confidential has been removed to aconfidential attachment.
No claims or markings on the document or any attachments, other than these statements and attachments submitted per in accordance with paragraph (c)(3) of this section, will be recognized as asserting a claim of confidentiality. The format of data submissions is set forth in Sec. 158.32.
(3) Confidential attachment. (i) All information claimed as confidential must be submitted in a separate confidential attachment to the document and cross referenced to the specific location in the document from which it was removed. The confidential attachment must have its own title page and be paginated separately from the non- confidential document.
(ii) All information in the confidential attachment that consists of (or whose disclosure would in turn disclose) manufacturing or quality control processes must be individually identified in the confidential attachment as a claim for information within the scope of FIFRA sec. 10(d)(1)(A).
(iii) All information in the confidential attachment that consists of (or whose disclosure would in turn disclose) the details of any methods for testing, detecting, or measuring the quantity of any deliberately added inert ingredient of a pesticide, must be individually identified in the confidential attachment as a claim for information within the scope of FIFRA sec. 10(d)(1)(B).
(iv) All information in the confidential attachment that consists of (or whose disclosure would in turn disclose) the identity or percentage quantity of any deliberately added inert ingredient of a pesticide must be individually identified in the confidential attachment as a claim for information within the scope of FIFRA sec. 10(d)(1)(C).
(v) Information in the confidential attachment that is designated in accordance with paragraphs (c)(3)(ii) - (iv) of this section must be on a separate page from information that is not so designated.
(4) Voluntary release of information to States and foreign governments. Submitters are encouraged to include with the statement required under paragraph (c)(2) of this section the following additional statement to allow EPA to share information with State and foreign governments:
I authorize the Environmental Protection Agency to release any information contained in this document to State or foreign governments, without relinquishing proprietary rights or any confidentiality claims asserted above.
EPA will not consider such a statement to be a waiver of confidentiality or proprietary claims for the information.
(d) Release of information. (1) Safety and efficacy information that was submitted to EPA on or after May 4, 1988 and that has not been designated by the submitter as FIFRA sec. 10(d)(1)(A), (B), or (C) information in accordance with the applicable requirements of this section is not entitled to confidential treatment and may be disclosed to the public without further notice to the submitter, in accordance with paragraph (d)(2) of this section. Safety and efficacy information which has been designated by the submitter as FIFRA sec. 10(d)(1) (A), (B), or (C) information is entitled to confidential treatment only to the extent provided by FIFRA sec. 10(b), this section, and 40 CFR 2.208.
(2) Information that is not entitled to be protected as confidential in accordance with FIFRA sec. 10(b), this section and with EPA confidentiality regulations at 40 CFR part 2, subpart B, may be released to the public without the affirmation of non-multinational status provided under FIFRA sec. 10(g), provided that the information does not contain or consist of any complete unpublished report submitted to EPA, or 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.
(3) Information designated as releasable to state or foreign governments in accordance with paragraph (c)(4) of this section may be released to such a government without further notice to the submitter. EPA will inform the State or foreign government of any of the confidentiality claims associated with the information.
Sec. 158.34 Flagging of studies for potential adverse effects.
(a) Any applicant who submits a study of a type listed in paragraph (b) of this section must submit with the study a statement in accordance with paragraph (c) of this section.
(b) The following table indicates the study types and the criteria to be applied to each. Column 1 lists the study types by name. Column 2 lists the associated Pesticide Assessment Guideline number. Column 3 lists the criteria applicable to each type of study. Column 4 lists the reporting code to be included in the statement specified in paragraph (c) of this section when any criterion is met or exceeded.
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Table--Flagging Criteria
Criteria: Treated animals show Criteria Study Type(s)
Guideline No.
any of the following:
No.
Carcinogenicity or combined carcinogenicity/
870.4200, An incidence of neoplasms in
1 chronic feeding study
870.3100, males or females which increases 870.3150 with dose (positive trend p-\6\ g/l) and fibrous test substances with diameter >=0.1 [mu]m.
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Required for all organic chemicals unless they dissociate in water or are partially or completely soluble in water.
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Not required for salts.
Sec. 158.320 Product identity and composition.
Information on the composition of the pesticide product must be furnished. The information required by paragraphs (a), (b), and (f) of this section must be provided for each product. In addition, if the product contains is produced by an integrated system, the information on impurities required by paragraphs (c) and (d) of this section must be provided.
(a) Active ingredient. The following information is required for each active ingredient in the product:
(1) If the source of any active ingredient in the product is an EPA-registered product:
(i) The chemical and common name (if any) of the active ingredient, as listed on the source product.
(ii) The nominal concentration of the active ingredient in the product, based upon the nominal concentration of active ingredient in the source product.
(iii) Upper and lower certified limits of the active ingredient in the product, in accordance with Sec. 158.350.
(2) If the source of any active ingredient in the product is not an EPA-registered product:
(i) The chemical name according to Chemical Abstracts Society (CAS) nomenclature, the CAS Registry Number, and any common names.
(ii) The molecular, structural, and empirical formulae and the molecular weight or weight range.
(iii) The nominal concentration.
(iv) Upper and lower certified limits of the active ingredient in accordance with Sec. 158.350.
(v) The purpose of the ingredient in the formulation.
(b) Inert ingredients. The following information is required for each inert ingredient (if any) in the product:
(1) The chemical name of the ingredient according to Chemical Abstracts Society nomenclature, the CAS Registry Number, and any common names (if known). If the chemical identity or chemical composition of an ingredient is not known to the applicant because it is proprietary or trade secret information, the applicant must ensure that the supplier or producer of the ingredient submits to the Agency (or has on file with the Agency) information on the identity or chemical composition of the ingredient. Generally, it is not required that an applicant know the identity of each ingredient in a mixture that he uses in his product. However, in certain circumstances, the Agency may require that the applicant know the identity of a specific ingredient in such a mixture. If the Agency requires specific knowledge of an ingredient, it will notify the applicant in writing.
(2) The nominal concentration in the product.
(3) Upper and lower certified limits in accordance with Sec. 158.350.
(4) The purpose of the ingredient in the formulation.
(c) Impurities of toxicological significance associated with the active ingredient. For each impurity associated with the active ingredient that is determined by EPA to be toxicologically significant, the following information is required:
(1) Identification of the ingredient as an impurity.
(2) The chemical name of the impurity.
(3) The nominal concentration of the impurity in the product.
(4) A certified upper limit, in accordance with Sec. 158.350.
(d) Other impurities associated with the active ingredient. For each other impurity associated with an active ingredient that was found to be present in any sample at a level >=0.1 percent by
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weight of the technical grade active ingredient the following information is required:
(1) Identification of the ingredient as an impurity.
(2) The chemical name of the impurity.
(3) The nominal concentration of the impurity in the final product.
(e) Impurities associated with an inert ingredient. [Reserved]
(f) Ingredients that cannot be characterized. If the identity of any ingredient or impurity cannot be specified as a discrete chemical substance (such as mixtures that cannot be characterized or isomer mixtures), the applicant must provide sufficient information to enable EPA to identify its source and qualitative composition.
Sec. 158.325 Description of materials used to produce the product.
The following information must be submitted on the materials used to produce the product:
(a) Products not produced by an integrated system. (1) For each active ingredient that is derived from an EPA-registered product:
(i) The name of the EPA-registered product.
(ii) The EPA registration number of that product.
(2) For each inert ingredient:
(i) Each brand name, trade name, common name, or other commercial designation of the ingredient.
(ii) All information that the applicant knows (or that is reasonably available to him) concerning the composition (and, if requested by the Agency, chemical and physical properties) of the ingredient, including a copy of technical specifications, data sheets, or other documents describing the ingredient.
(iii) If requested by the Agency, the name and address of the producer of the ingredient or, if that information is not known to the applicant, the name and address of the supplier of the ingredient.
(b) Products produced by an integrated system. (1) The information required by paragraph (a)(1) of this section concerning each active ingredient that is derived from an EPA-registered product (if any).
(2) The following information concerning each active ingredient that is not derived from an EPA-registered product:
(i) The name and address of the producer of the ingredient (if different from the applicant).
(ii) Information about each starting material used to produce the active ingredient, as follows:
(A) Each brand name, trade name, or other commercial designation of the starting material.
(B) The name and address of the person who produces the starting material or, if that information is not known to the applicant, the name and address of each person who supplies the starting material.
(C) All information that the applicant knows (or that is reasonably available to him), concerning the composition (and if requested by the Agency, chemical or physical properties) of the starting material, including a copy of all technical specifications, data sheets, or other documents describing it.
(3) The information required by paragraph (a)(2) of this section concerning each inert ingredient.
(c) Additional information. On a case-by-case basis, the Agency may require additional information on substances used in the production of the product.
Sec. 158.330 Description of production process.
If the product is produced by an integrated system, the applicant must submit information on the production (reaction) processes used to produce the active ingredients in the product. The applicant must also submit information about the formulation process, in accordance with Sec. 158.335.
(a) Information must be submitted for the current production process for each active ingredient that is not derived from an EPA- registered product. If the production process is not continuous (a single reaction process form starting materials to active ingredient), but is accomplished in stages or by different producers, the information must be provided for each such production process.
(b) The following information must be provided for each process resulting in a separately isolated substance:
(1) The name and address of the producer who uses the process, if not the same as the applicant.
(2) A general characterization of the process (e.g., whether it is a batch or continuous process).
(3) A flow chart of the chemical equations of each intended reaction occurring at each step of the process, and of the duration of each step and of the entire process.
(4) The identity of the materials used to produce the product, their relative amounts, and the order in which they are added.
(5) A description of the equipment used that may influence the composition of the substance produced.
(6) A description of the conditions (e.g., temperature, pressure, pH, humidity) that are controlled during each step of the process to affect the composition of the substance produced, and the limits that are maintained.
(7) A description of any purification procedures (including procedures to recover or recycle starting materials, intermediates or the substance produced).
(8) A description of the procedures used to assure consistent composition of the substance produced, e.g., calibration of equipment, sampling regimens, analytical methods, and other quality control methods.
Sec. 158.335 Description of formulation process.
The applicant must provide information on the formulation process of the product (unless the product consists solely of a technical grade of active ingredient) as required by the following sections:
(a) Section 158.330(b)(2), pertaining to characterization of the process.
(b) Section 158.330(b)(4), pertaining to ingredients used in the process.
(c) Section 158.330(b)(5), pertaining to process equipment.
(d) Section 158.330(b)(6), pertaining to the conditions of the process.
(e) Section 158.330(b)(8), pertaining to quality control measures.
Sec. 158.340 Discussion of formation of impurities.
The applicant must provide a discussion of the impurities that may be present in the product, and why they may be present. The discussion should be based on established chemical theory and on what the applicant knows about the starting materials, technical grade of active ingredient, inert ingredients, and production or formulation process. If the applicant has reason to believe that an impurity that EPA would consider toxicologically significant may be present, the discussion must include an expanded discussion of the possible formation of the impurity and the amounts at which it might be present. The impurities which must also be discussed are the following, as applicable:
(a) Technical grade active ingredients and products produced by an integrated system. (1) Each impurity associated with the active ingredient which was found to be present in any analysis of the product conducted by or for the applicant.
(2) Each other impurity which the registrant or applicant has reason to believe may be present in his product at any time before use at a level >=0.1 percent (1,000 ppm) by weight of the technical grade of the active ingredient, based on what he knows about the following:
(i) The composition (or composition range) of each starting material used to produce his product.
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(ii) The impurities which the applicant knows are present (or believes are likely to be present) in the starting materials, and the known or presumed level (or range of levels) of these impurities.
(iii) The intended reactions and side reactions which may occur in the production of the product, and the relative amounts of byproduct impurities produced by such reactions.
(iv) The possible degradation of the ingredients in the product after its production but prior to its use.
(v) Post-production reactions between the ingredients in the product.
(vi) The possible migration of components of packaging materials into the pesticide.
(vii) The possible carryover of contaminants from use of production equipment previously used to produce other products or substances.
(viii) The process control, purification and quality control measures used to produce the product.
(b) Products not produced by an integrated system. Each impurity associated with the active ingredient which the applicant has reason to believe may be present in the product at any time before use at a level >=0.1 percent (1,000 ppm) by weight of the product based on what he knows about the following:
(1) The possible carryover of impurities present in any registered product which serves as the source of any of the product's active ingredients. The identity and level of impurities in the registered source need not be discussed or quantified unless known to the formulator.
(2) The possible carryover of impurities present in the inert ingredients in the product.
(3) Possible reactions occurring during the formulation of the product between any of its active ingredients, between the active ingredients and inert ingredients, or between the active ingredient and the production equipment.
(4) Post-production reactions between any of the product's active ingredients and any other component of the product or its packaging.
(5) Possible migration of packaging materials into the product.
(6) Possible contaminants resulting from earlier use of equipment to produce other products.
(c) Expanded discussion. On a case-by-case basis, the Agency may require an expanded discussion of information of impurities:
(1) From other possible chemical reactions.
(2) Involving other ingredients.
(3) At additional points in the production or formulation process.
Sec. 158.345 Preliminary analysis.
(a) If the product is produced by an integrated system, the applicant must provide a preliminary analysis of each technical grade of active ingredient contained in the product to identify all impurities present at 0. 1 percent or greater of the technical grade of the active ingredient. The preliminary analysis should be conducted at the point in the production process after which no further chemical reactions designed to produce or purify the substances are intended.
(b) Based on the preliminary analysis, a statement of the composition of the technical grade of the active ingredient must be provided. If the technical grade of the active ingredient cannot be isolated, a statement of the composition of the practical equivalent of the technical grade of the active ingredient must be submitted.
Sec. 158.350 Certified limits.
The applicant must propose certified limits for the ingredients in the product. Certified limits become legally binding limits upon approval of the application. Certified limits will apply to the product from the date of production to date of use, unless the product label bears a statement prohibiting use after a certain date, in which case the certified limits will apply only until that date.
(a) Ingredients for which certified limits are required. Certified limits are required on the following ingredients of a pesticide product:
(1) An upper and lower limit for each active ingredient.
(2) An upper and lower limit for each inert ingredient.
(3) If the product is a technical grade of active ingredient or is produced by an integrated system, an upper limit for each impurity of toxicological significance associated with the active ingredient and found to be present in any sample of the product.
(4) On a case-by-case basis, certified limits for other ingredients or impurities as specified by EPA.
(b) EPA determination of standard certified limits for active and inert ingredients. (1) Unless the applicant proposes different limits as provided in paragraph (c) of this section, the upper and lower certified limits for active and inert ingredients will be determined by EPA. EPA will calculate the certified limits on the basis of the nominal concentration of the ingredient in the product, according to the table in paragraph (b)(2) of this section.
(2) Table of standard certified limits.
Standard Certified Limits
If the nominal concentration (N) The certified limits for that for the ingredient and
ingredient will be as follows: percentage by weight for the --------------------------------------- ingredient is:
Upper Limit
Lower Limit
N 50, two avian dietary LC50, two avian reproduction studies, two freshwater fish LC50, one freshwater invertebrate EC50, one honeybee acute contact LD50, one freshwater fish early-life stage, one freshwater invertebrate life- cycle, and three estuarine acute LC50/EC50 studies - fish, oyster, and mysid. All other outdoor residential uses, i.e., gardens and ornamental will not usually require the freshwater fish early-life stage, the freshwater invertebrate life-cycle, and the acute estuarine tests.
(c) Key: R=Required; CR=Conditionally required; NR=Not required; [ ]=Required or conditionally required for an experimental use permit; TGAI=Technical grade of the active ingredient; TEP=Typical end-use product; PAI=Pure active ingredient; Commas between the test substances (i.e., TGAI, TEP) indicate that data may be required on the TGAI or the TEP depending on the conditions set forth in the test note.
(d) Table. The following table shows the data requirements for nontarget terrestrial and aquatic organism. The table notes are shown in paragraph (e) of this section.
Terrestrial and Aquatic Nontarget Organism Data Requirements
Use Pattern
Aquatic Guideline Number
Data Requirement
------------------------------------------------------
Test substance Test Note No. Terrestrial
Nonfood
Forestry
Residential Greenhouse
Indoor Food ------------------------------------
Outdoor Outdoor
Residential
Avian and Mammalian Testing
850.2100
Avian oral
[R]
[R]
[R]
R
[R]
[R]
CR
CR
TGAI, TEP
1, 2, 3, 4 toxicity
850.2200
Avian dietary [R]
[R]
[R]
CR
[R]
[R]
NR
NR
TGAI
1, 3, 5, 6 toxicity
850.2400
Wild mammal CR
CR
CR
NR
CR
CR
NR
NR
TGAI
7 toxicity
850.2300
Avian
R
R
R
NR
R
R
NR
NR
TGAI
1, 5 reproduction
850.2500
Simulated or CR
CR
CR
NR
CR
CR
NR
NR
TEP
8, 9 actual field testing
Aquatic Organisms Testing
[[Page 12341]]
850.1075
Freshwater fish [R]
[R]
[R]
R
[R]
R
CR
CR
TGAI, TEP
1, 2, 10, 11 toxicity
850.1010
Acute toxicity [R]
[R]
[R]
R
[R]
R
CR
CR
TGAI, TEP
1, 2, 11, 12 freshwater invertebrates
850.1025
Acute toxicity R
R
R
NR
R
R
NR
NR
TGAI, TEP
1, 11, 13, 14 850.1035.................... estuarine and 850.1045.................... marine 850.1055.................... organisms 850.1075....................
850.1300
Aquatic
R
[R]
[R]
NR
[R]
CR
NR
NR
TGAI
1, 12, 14 invertebrate life-cycle (freshwater)
850.1350
Aquatic
CR
CR
CR
NR
CR
CR
NR
NR
TGAI
14, 16, 17 invertebrate life-cycle (saltwater)
850.1400
Fish early-life R
[R]
[R]
NR
[R]
CR
NR
NR
TGAI
1, 14, 15 stage (freshwater)
850.1400
Fish early-life CR
CR
CR
NR
CR
CR
NR
NR
TGAI
14, 17, 18 stage (saltwater)
850.1500
Fish life-cycle CR
CR
CR
NR
CR
CR
NR
NR
TGAI
19, 20
850.1710
Aquatic
CR
CR
CR
NR
CR
NR
NR
NR
TGAI, PAI,
21 850.1730.................... organisms
degradate 850.1850.................... bioavailability , biomagnificatio n, toxicity
850.1950
Simulated or CR
CR
CR
NR
CR
CR
NR
NR
TEP
9, 22 actual field testing for aquatic organisms
Sediment Testing
850.1735
Whole sediment: CR
CR
CR
NR
CR
NR
NR
NR
TGAI
23 acute freshwater invertebrates
850.1740
Whole sediment: CR
CR
CR
NR
CR
NR
NR
NR
TGAI
23 acute marine invertebrates
--
Whole sediment: CR
CR
CR
NR
CR
NR
NR
NR
TGAI
24 chronic invertebrates freshwater and marine
Insect Pollinator Testing
850.3020
Honey bee acute [R]
[R]
[R]
NR
[R]
R
NR
NR
TGAI
1 contact toxicity
850.3030
Honey bee
CR
CR
CR
NR
CR
CR
NR
NR
TEP
25 toxicity of residues on foliage
850.3040
Field testing CR
CR
CR
CR
CR
CR
NR
NR
TEP
26 for pollinators
[[Page 12342]]
Nontarget Insect Testing
142-1
Acute toxicity --
--
--
--
--
--
--
--
TGAI
27 to aquatic insects
142-1
Aquatic insect --
--
--
--
--
--
--
--
TEP
27 life-cycle
142-3
Simulated or --
--
--
--
--
--
--
--
TEP
27 actual field testing for aquatic insects
143-1
Predators and --
--
--
--
--
--
--
--
TEP
27 143-2....................... parasites 143-3.......................
(e) Test notes. The following test notes apply to terrestrial and aquatic nontarget organisms data requirements in the table to paragraph (d) of this section:
-
Data using the TGAI are required to support all outdoor end- use product uses including, but not limited to turf. Data are generally not required to support end-use products in the form of a gas, a highly volatile liquid, a highly reactive solid, or a highly corrosive material.
-
For greenhouse and indoor end-use products, data using the TGAI are required to support manufacturing-use products to be reformulated into these same end-use products or to support end-use products when there is no registered manufacturing-use product. Avian acute oral not required for liquid formulations for greenhouse and indoor uses. Study not required if there is no potential for environmental exposure.
-
Data using the TEP are conditionally required based on the results of the avian acute oral (TGAI) and avian subacute dietary tests, intended use pattern, and environmental fate characteristics that indicate potential exposure.
-
Data are preferred on redwing blackbird (Agelaius phoneiceus) and either mallard or bobwhite quail for terrestrial, aquatic, forestry, and residential outdoor uses. Data are preferred on mallard or bobwhite quail for indoor and greenhouse uses.
-
Data are preferred on mallard and bobwhite quail.
-
For aquatic nonfood residential uses, data are required to support liquid and solid formulated products on one species if the avian oral LD50of the TGAI is less than or equal to 100 mg a.i./kg. Data on a second species are required if the avian dietary LC50in the first species tested is less than or equal to 500 ppm a.i. in the diet.
-
Tests are required based on the results of lower tier toxicology studies, such as the acute and subacute testing, intended use pattern, and environmental fate characteristics that indicate potential exposure.
-
Tests are required based on the results of lower tier studies such as acute, subacute or reproduction bird and mammal testing, intended use pattern, and environmental fate characteristics that indicate potential exposure.
-
Environmental chemistry methods used to generate data associated with this study must include results of a successful confirmatory method trial by an independent laboratory. Test standards and procedures for independent laboratory validation are available as addenda to the guideline for this test requirement.
-
Data are preferred on rainbow trout and bluegill for terrestrial, aquatic, forestry, and residential outdoor uses. For indoor and greenhouse uses, testing with only one of either fish species is required. Generally, a second species will not be required for indoor and greenhouse use if the selected species LC50is 1 ppm or less. However, if the TGAI is stable in the hydrolysis study, and the LC50value of the first fish tested is between 1 ppm and 10 ppm, then testing with both species is required.
-
Freshwater fish LC50(the most sensitive of the species tested) using the TGAI, freshwater invertebrate EC50(preferably Daphnia), and acute LC50/ EC50estuarine and marine organisms studies using the EP or TEP are required for any product which meets any of the following conditions:
i. The end-use pesticide will be introduced directly into an aquatic environment (e.g., aquatic herbicides and mosquito larvicides) when used as directed.
ii. The maximum expected environmental concentration (MEEC) or the estimated environmental concentration in the aquatic environment is equal to or greater than one-half the LC50or EC50of the TGAI when the EP is used as directed.
iii. An ingredient in the end-use formulation other than the active ingredient is expected to enhance the toxicity of the active ingredient or to cause toxicity to aquatic organisms.
-
Data are preferred on Daphnia magna.
-
Data are preferred on eastern oyster (Crassostrea virginica) and oppossum shrimp (America mysis) formerly (Mysidopsis bahia) and silver side (Menidia sp. )
-
Data are generally not required for other, non-turf, outdoor residential uses, i.e., gardens and ornamentals.
-
Data are preferred on rainbow trout. If fathead minnow (Pimephales promelus) is used, a 96 hour LC50on that species must also be provided.
-
Data are preferred on oppossum shrimp (America mysis) formerly (Mysidopsis bahia).
-
Data are required on estuarine species if the product is:
i. Intended for direct application to the estuarine or marine environment.
ii. Expected to enter this environment in significant concentrations because of its expected use or mobility patterns.
iii. If the acute LC50or EC5050or LC50and any of the following conditions exist:
-
-
Studies of other organisms indicate the reproductive physiology of fish and/or invertebrates may be affected.
-
Physicochemical properties indicate bioaccumulation of the pesticide.
-
The pesticide is persistent in water (e.g., half-life in water greater than 4 days).
-
Data are preferred on sheepshead minnow (Cypinodon variegatus).
-
Data are required on estuarine species if the product is intended for direct application to the estuarine or marine environment, or the product is expected to enter this environment in significant concentrations because of its expected use or mobility patterns.
-
Data are required if the end-use product is intended to be applied directly to water, or is expected to be transported to water from the intended use site, and when any of the following conditions apply:
[[Page 12343]]
i. If the estimated environmental concentration [See Hazard Evaluation Division Standard Evaluation Procedure Ecological Risk Assessment (EPA-540/09-86-167)] is greater than or equal to 0.1 of the no-observed-effect level in the fish early life-stage or invertebrate life-cycle test;
ii. If studies of other organisms indicate that the reproductive physiology of fish may be affected.
-
Required based on the results of fish or aquatic nontarget organism accumulation studies (guidelines 850.1730 and 850.1950).
-
Tests are required based on the results of lower tier studies such as acute and chronic aquatic organism testing, intended use pattern, and environmental fate characteristics that indicate significant potential exposure.
-
Testing is required if the soil partition coefficient (Kd) is equal to or greater than 50 and the half-life of the pesticide in the sediment is equal to or less than 10 days in either the aerobic soil or aquatic metabolism studies. Registrants should consult with the Agency on appropriate test protocols.
-
Testing is required if:
i. The estimated environmental concentration is equal to or greater than the acute sediment EC50/LC50.
ii. The soil partition coefficient (Kd) is equal to or greater than 50.
(iii) The half-life of the pesticide in the sediment is greater than 10 days in either the aerobic soil or aquatic metabolism studies. Registrants should consult with the Agency on appropriate test protocols.
-
Data required only when the formulation contains one or more active ingredients having an acute LD50of
-
-
