[Federal Register Volume 70, Number 47 (Friday, March 11, 2005)]
[Proposed Rules]
[Pages 12277-12353]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-4466]
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Part II
Environmental Protection Agency
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40 CFR Parts 152 and 158
Pesticides; Data Requirement for Conventional Chemicals; Proposed Rule
Federal Register / Vol. 70, No. 47 / Friday, March 11, 2005 /
Proposed Rules
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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.
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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. [email protected].
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: [email protected].
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be affected by this action if you are a producer or
registrant of a pesticide product, including agricultural, residential,
and industrial pesticides, but not including antimicrobial, biochemical
or microbial pesticides, or inert ingredients in pesticide products.
This proposal also may affect any person or company who might petition
the Agency for new tolerances, hold a pesticide registration with
existing tolerances, or any person or company who is interested in
obtaining or retaining a tolerance in the absence of a registration,
that is, an import tolerance. This latter group may
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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.
B. What Should I Consider as I Prepare My Comments for EPA?
1. Submitting CBI. Do not submit this information to EPA through
EDOCKET, regulations.gov or e-mail. Clearly mark the part or all of the
information that you claim to be CBI. For CBI information in a disk or
CD ROM that you mail to EPA, mark the outside of the disk or CD ROM as
CBI and then identify electronically within the disk or CD ROM the
specific information that is claimed as CBI. In addition to one
complete version of the comment that includes information claimed as
CBI, a copy of the comment that does not contain the information
claimed as CBI must be submitted for inclusion in the public docket.
Information so marked will not be disclosed except in accordance with
procedures set forth in 40 CFR part 2.
2. Tips for Preparing Your Comments. When submitting comments,
remember to:
Identify the rulemaking by docket number and other
identifying information (subject heading, Federal Register date and
page number).
Follow directions - The agency may ask you to respond to
specific questions or organize comments by referencing a Code of
Federal Regulations (CFR) part or section number.
Explain why you agree or disagree; suggest alternatives
and substitute language for your requested changes.
Describe any assumptions and provide any technical
information and/or data that you used.
If you estimate potential costs or burdens, explain how
you arrived at your estimate in sufficient detail to allow for it to be
reproduced.
Provide specific examples to illustrate your concerns, and
suggest alternatives.
Explain your views as clearly as possible, avoiding the
use of profanity or personal threats.
Make sure to submit your comments by the comment period
deadline identified.
II. Organization of Preamble
This preamble is organized according to the outline in this unit.
I. General Information
II. Organization of Preamble
III. Statutory Authorities and Regulatory Framework
IV. Background
V. Purpose and Scope of this Proposal
VI. Overview of Proposed Changes
VII. General Provisions of Part 158 (subpart A)
VIII. How to Use the Data Tables (subpart B)
IX. Product Chemistry Data Requirements (subpart D)
X. Terrestrial and Aquatic Nontarget Organisms Data Requirements
(subpart E)
XI. Toxicology Data Requirements (subpart F)
XII. Nontarget Plant Protection Data Requirements (subpart J)
XIII. Post-Application Exposure Data Requirements (subpart K)
XIV. Environmental Fate Data Requirements (subpart N)
XV. Residue Chemistry Data Requirements (subpart O)
XVI. Applicator Exposure Data Requirements (subpart U)
XVII. Data Requirements Not Affected by this Proposal
XVIII. Peer Review
XIX. International Harmonization of Data Requirements
XX. Research Involving Human Subjects
XXI. ILSI Work on New Toxicity Paradigm
XXII. Animal Welfare Concerns
XXIII. Summary of Changes Being Proposed
XXIV. Public Comments Sought
XXV. References
XXVI. FIFRA Review Requirements
XXVII. Statutory and Executive Order Reviews
III. Statutory Authorities and Regulatory Framework
EPA is authorized to regulate pesticides under two federal
statutes. The Federal Insecticide, Fungicide and Rodenticide Act
(FIFRA) regulates the sale, distribution, and use of pesticide products
through a licensing (registration) scheme. The Federal Food, Drug and
Cosmetic Act (FFDCA), among other things, regulates the safety of
pesticide residues in food and feed. Both FIFRA and FFDCA were amended
in 1996 by the Food Quality Protection Act (FQPA) to strengthen the
protections offered, with particular emphasis on protection of
children.
This action is issued under the authority of secs. 3, 4, 5, 10, 12,
and 25 of FIFRA (7 U.S.C. 136-136y) and sec. 408 of FFDCA (21 U.S.C.
346a). The data required for a registration, reregistration,
experimental use permit, or tolerance are listed in 40 CFR part 158.
A. FIFRA
Under FIFRA, every pesticide product must be registered (or
specifically exempted from registration under FIFRA sec. 25(b)) with
EPA before it may be sold or distributed in the United States. To
obtain a registration, an applicant or registrant must demonstrate to
the Agency's satisfaction that, among other things, the pesticide
product, when used in accordance with widespread and commonly
recognized practice, will not cause ``unreasonable adverse effects'' to
humans or the environment. This safety determination, as defined in the
statute, requires the Agency to consider the risk of the use of the
pesticide and weigh this against its benefit. EPA must determine that
the safety standard contained in FIFRA is met before granting a federal
pesticide registration.
1. Registration. Section 3 of FIFRA contains the requirements for
registration. Specifically, FIFRA sec. 3(c)(2) provides EPA broad
authority, before and after registration, to require scientific testing
and submission of the resulting data to the Agency by registrants and
applicants of pesticide products. An applicant for registration must
furnish EPA with substantial amounts of data on the pesticide, its
composition, toxicity, potential human exposure, environmental
properties and ecological effects, as well as information on its
efficacy in certain cases. Although the data requirements are imposed
primarily as a part of initial registration, EPA is authorized under
FIFRA sec. 3(c)(2)(B) to require a registrant to develop and submit
additional data to maintain a registration. This post registration data
call-in authority recognizes that the scientific underpinnings of risk
assessment change, and is another means by which EPA may keep data for
use in risk assessment current with evolving science.
2. Reregistration. FIFRA sec. 4 requires that EPA reregister each
pesticide product first registered before November 1984. This date was
chosen based upon the fact that pesticides registered since 1984 were
subject to the part 158 requirements of the 1984 regulation. Additional
data for older
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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.
3. Experimental use permits. Subject to some exceptions, FIFRA sec.
5 requires persons seeking experimental use of pesticides under field
conditions to obtain an experimental use permit (EUP). An EUP allows
limited use of a pesticide for specified experimental and data
collection purposes intended to support future registration of the
pesticide. Because an EUP is for limited use under controlled
conditions, the data needed to support issuance of the permit are
correspondingly less than those required for full registration. For
example, when performing crop field trials, a registrant may opt to
destroy the treated crop rather than generate the needed residue
chemistry data to establish a temporary tolerance. The regulations
governing the issuance of EUPs are found in 40 CFR part 172.
B. FFDCA
FFDCA mandates EPA to determine that the level of pesticide
chemical residues in food and feed will be safe for human consumption.
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.
1. Establishing tolerances. Under FFDCA sec. 408, EPA is authorized
to establish tolerances for pesticide residues in food and feed, or to
exempt a pesticide from the requirement of a tolerance, if warranted.
In this preamble, references to tolerances include exemptions from
tolerance since the standards and procedures for both are the same. As
previously mentioned, in 1996, FQPA modified FFDCA to establish a
single health-based standard for tolerance-setting and enhanced the
risk assessment process to more clearly focus on pesticide risks to
children. The new safety standard applies to tolerances in a number of
regulatory situations, including:
Permanent tolerances that support registration under
FIFRA;
Tolerances for imported products which are established to
allow importation of pesticide-treated commodities, but for which no
U.S. registration is sought;
Time-limited tolerances which are established for FIFRA
sec. 18 emergency exemptions; and
Temporary tolerances established for experimental use
permits under FIFRA sec. 5.
2. Reassessing tolerances. Under FFDCA sec. 408(q), EPA must
reassess each tolerance established before August 3, 1996, on a
prescribed 10-year schedule. The Agency has reassessed many tolerances
under its reregistration program. Numerous regulatory decisions have
been made based upon available data and information required by the
existing data requirements, and supplemented by additional data
provided by registrants through data call-ins or voluntary submissions.
C. Linking FIFRA and FFDCA Safety Standards
Unless EPA is able to establish or maintain a needed tolerance or
exemption under FFDCA, a pesticide cannot be registered under FIFRA for
a food/feed use. FQPA created a specific linkage (FIFRA sec. 2(bb))
between the ``unreasonable adverse effects'' finding under FIFRA and
the determination of pesticide residue safety of ``reasonable certainty
of no harm'' under FFDCA. In essence, a pesticide that is inconsistent
with, or does not meet, the FFDCA sec. 408 safety standard poses an
unreasonable adverse effect that precludes new or continued
registration. Thus, both FIFRA and FFDCA standards must be met for
pesticides intended to be registered in the United States for food or
feed uses.
Given this linkage between registration and tolerances, it makes
sense for EPA to define data requirements for both purposes: the data
required to support a determination of ``reasonable certainty of no
harm'' under FFDCA are an integral part of the data needed for an
``unreasonable adverse effects'' determination under FIFRA.
Consequently, when promulgated, these proposed data requirements would
encompass the basic data requirements for both registration and
tolerance-setting determinations. EPA will retain its authority to
require additional data on a case-by-case basis.
IV. Background
A. Why does EPA Require Data for Pesticide Registrations?
Under the FFDCA and the FIFRA, anyone seeking to register a
pesticide product is required to provide information to EPA that
demonstrates their products can be used without posing unreasonable
risk to human health and the environment, and for food uses, that there
is a reasonable certainty that no harm will result from exposures to
the residues of their pesticide product. As appropriate for the
particular pesticide product, EPA uses the information provided to
evaluate the pesticide for a wide range of adverse human health
effects, from eye and skin irritation to cancer and birth defects, and
to assess how the pesticide affects animal and plant species, non-
target insect species, and what happens to the pesticide in soil,
water, and air.
B. What are the Data Requirements?
First promulgated in 1984, the data requirements in 40 CFR part 158
outline the kinds of data and related information typically needed to
register a pesticide. The data requirements are organized by major
pesticide type (e.g., conventional, antimicrobial, biochemical/
microbial, etc.), scientific discipline (e.g., toxicology, etc.), and
major use site (e.g., outdoor vs. indoor). Part 158 also outlines the
associated procedures for submitting the data, requesting a waiver from
a requirements, and other associated procedures. Since there is much
variety in pesticide chemistry, exposure, and hazard, part 158 is
designed to be flexible. Table notes to each data requirement explain
under what conditions data are typically needed. The Agency also
recognizes, however, that due to the particular nature and risk of some
pesticides, registrants may seek to obtain data waivers or may suggest
alternative approaches to satisfying requirements. Over the years since
1984, other data requirements have been implemented on a case-by-case
basis. 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.
1. The establishment of standardized data requirements. Until 1984,
data requirements were based on longstanding requirements initially put
in place when pesticides were regulated by the U.S. Department of
Agriculture (USDA) and the Food and Drug Administration (FDA). However,
because virtually all of EPA's decisions relating to the registration
of pesticides or the establishment of tolerances depend on Agency
evaluation of scientific studies, EPA has throughout the years
developed standardized data requirements and test guidelines, and
established evaluation procedures and peer review processes to ensure
the quality and consistency of scientific studies.
The current provisions in part 158 were originally promulgated in
October, 1984. Prior to this, data requirements for the registration of
pesticides were contained in a variety of guidance documents, not in
regulatory form. Part 158 was intended to be a concise presentation of
what data were required and under what circumstances. Once codified,
part 158 specified standard hazard and exposure studies required for
registration and tolerance setting and also identified conditions under
which more specialized studies might be required. Guidelines, i.e.,
instructions and test methods on how to perform a study, had meanwhile
been issued as a series of Pesticide Assessment Guidelines. These
documents, updated in 1996, describe acceptable protocols, test
conditions, and data reporting guidelines to ensure that EPA's
regulatory decisions are based on sound scientific data.
2. Relationship between the harmonized test guidelines and part 158
requirements. EPA has established a unified library for test guidelines
issued by the Office of Prevention, Pesticides and Toxic Substances
(OPPTS) for use in testing chemical substances to develop data for
submission to EPA under the Toxic Substances Control Act (TSCA), FFDCA
or FIFRA. This unified library of test guidelines represents an Agency
effort that began in 1991 to harmonize the test guidelines within
OPPTS, as well as to harmonize the OPPTS test guidelines with those of
the Organization for Economic Cooperation and Development (OECD) of the
European Community. 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.
C. Why Have the Data Needs Changed Since 1984?
1. 1988 FIFRA amendments. In 1988, FIFRA was amended to ensure that
older pesticides met the scientific standards of the day. Among other
things, the amendments provided for the acceleration of the
reregistration program by establishing statutory deadlines and new
procedures. The 1988 changes to FIFRA are important because it was
during this effort that EPA recognized that some of the 1984 data
requirements were becoming out of date. The Agency then used the
reregistration process to focus on needed changes.
2. The National Academy of Sciences 1993 Report. With increasing
emphasis on protecting children's health, EPA began to examine its data
requirements relative to evaluating the potential risks from pesticides
to sensitive subpopulations. The Agency sought the advice of the
National Academy of Sciences' National Research Council (NRC) to assess
its risk assessment methodologies and to provide additional information
on the extent to which children may be at risk given emerging
scientific information and technologies. In their 1993 report entitled,
``Pesticides in the Diets of Infants and Children,'' (Ref. 1) NRC
offered recommendations for further protecting infants and children
from pesticides in their diet. The NRC called for the Agency to require
more data and adopt better risk assessment methodologies. For example,
the Council called for increased testing in the area of immune
function, neurodevelopmental and reproductive testing, and
neurotoxicity testing. NRC also suggested adding a thyroid screen to
existing subchronic and chronic toxicity tests and additional tests on
age-related physiological changes and pharmacokinetics in immature
animals.
At the time the 1993 report was released, EPA had already begun
work on many of the recommendations to improve the quality of its risk
assessments. New testing guidelines and protocols were developed. Since
then, many of the testing requirements recommended by the NRC have been
incorporated into the Agency's standard evaluation requirements and
practices. In addition, in line with the Council's recommendations and
the FIFRA Scientific Advisory Panel's (SAP) advice, EPA recently
expanded its neurotoxicity and developmental neurotoxicity study
requirements. These updated requirements are contained in this
proposal.
3. The Food Quality Protection Act of 1996 (FQPA). Passage of FQPA
in 1996 reformed our nation's pesticide and food safety laws, resulting
in changes in EPA's approach to protecting human health from risks
associated with pesticide use. As mentioned, FQPA modified both FIFRA
and FFDCA and established a single health-based standard for food-use
pesticides and added protections for infants and children.
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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.
V. Purpose and Scope of this Proposal
A. What is the Scope of this Proposal?
This proposal applies only to conventional pesticides. In general,
a conventional pesticide is considered as a synthetic chemical or a
natural substance with a toxic mode of action. It is applicable to both
manufacturing-use and end-use products. It does not include data
requirements for antimicrobial, biochemical or microbial pesticides;
inert ingredients; or changes to existing spray drift or product
performance (efficacy) data requirements for conventional chemicals.
B. Why is EPA Proposing these Revisions?
EPA has a number of objectives in proposing this regulation to
update and revise the data requirements in 40 CFR part 158. First, this
proposal will update the requirements in part 158 to reflect changes
that have occurred over time and which are generally applied already.
Second, this proposal will provide clarity on the data requirements
themselves, with data requirements reformatted to promote efficiency in
registration decision processes. Third, information developed in
fulfilling these data requirements will improve the scientific basis
supporting increasingly complex risk management decisions.
1. Updating the 1984 requirements. Although most of the specific
requirements in part 158 have not changed since the data requirements
were first published in 1984, there is information that is out-of date
or may be unclear. The underlying science has advanced (e.g., NAS in
1993 suggested changes to better protect children). The Agency's
legislative mandate has been broadened to address new concerns. For
example, given the stricter mandates imposed by the 1988 FIFRA
amendments (emphasis on exposure to population subgroups) and the 1996
FQPA amendments to FIFRA and FFDCA, EPA finds that it is more
frequently requesting certain data, and the Agency believes it should
detail more specifically the conditions under which these tests will be
required. Thus the proposed change entails both new tests and broadened
requirements for some current tests.
This regulation will reflect the changes in data requirement
practices that have evolved through practice since the 1984 data
requirement rule was promulgated and address data needed to meet
requirements created by statutory amendments to FIFRA and FFDCA. In
addition, the rule will eliminate redundant data submission
requirements.
EPA's underlying principle in development of this regulation is to
strike an appropriate balance between the need for adequate data to
make informed risk management decisions while minimizing the data
collection burden.
Until this proposal is promulgated, the Agency will continue to use
existing authority in 40 CFR part 158, to obtain these data on a case-
by-case basis should they be necessary to support a registration.
2. Reorganizing part 158 to improve usability. EPA proposes to
reorganize and reformat part 158 subpart A (General Provisions), and
subpart B (How to Use Data Tables), and reorganize and renumber subpart
D (Data Requirement Tables) into several individual subparts (see Table
1 in Unit VI). Each subpart would contain the data requirement tables
for an individual scientific discipline and references to correlate
with the Pesticide Assessment Guidelines. The Agency also proposes to
remove from the regulations the current Appendix A, (a compendium of
pesticide use sites and use categories), and create a separate
Pesticide Use Index Guidance Document. Since the information contained
in Appendix A only serves as reference material and is not being stated
as a requirement, EPA believes that a guidance document format is
easier to keep current and therefore better serves the regulated
community. The information will be placed on EPA's website and made
available to the public.
3. Improving the scientific basis for pesticide registration
decisions. 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
[[Page 12282]]
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.
C. How Will this Proposal Affect Existing Registrations?
This proposal concerns prospective data requirements for future
registrations of pesticides. That is, these proposed data requirements
would apply to all new registrations of pesticides after the rule is
finalized. The Agency does not intend to apply these requirements
retrospectively to all existing pesticide registrations. While the
intended future applicability of this proposed rule is to new
applications, the Agency may find it necessary to call-in some data on
certain existing registrations, as warranted by emerging risks of
concern on particular pesticides or as a result of possible future
programmatic changes and priorities on existing pesticides.
VI. Overview of Proposed Changes
A. Phased approach
This proposal is the first in a series of revisions aimed at
comprehensively updating EPA's pesticide data requirements. The data
requirements discussed in this proposal pertain to conventional
pesticides. Future proposals will address data requirements for
antimicrobial pesticides, biochemical and microbial pesticides, inert
ingredients in pesticide products, and product performance data
requirements.
B. Organizational changes
Part 158 is currently divided into four subparts:
Subpart A, General Provisions
Subpart B, How to Use Data Tables
Subpart C, Product Chemistry Data Requirements
Subpart D, Data Requirements Tables
EPA proposes to reorganize part 158 to more closely correspond with
the Office of Prevention, Pesticides, and Toxic Substances (OPPTS)
Harmonized Guidelines, primarily by creating a series of new subparts
to replace subpart D. Each subpart will address an individual
scientific discipline or data type. In this preamble, EPA will refer to
the proposed new subpart and section designations when discussing the
data requirements. Table 1 below provides a cross-reference between the
current and proposed new subparts. Future new subparts are included for
information.
Table 1.--Part 158: Proposed Change to Subpart Designations
------------------------------------------------------------------------
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
-------------------------------------------
[[Page 12283]]
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.
C. ``New Requirement'' Vs.``Newly Codified Requirement.''
FIFRA is a licensing statute, under which regulatory decisions on
the registrability of an individual product is based upon data specific
to the product and its uses. EPA is authorized to require the
submission of data that it needs to make the registration decision in
the context of any individual application for registration, amended
registration or reregistration. EPA may also impose a data requirement
after registration in order to maintain the registration, using
specific Data Call-In (DCI) authority of FIFRA sec. 3(c)(2)(B).
Since 1984, when part 158 was first promulgated, EPA's data
requirements have evolved as the general scientific understanding of
the potential hazards posed by pesticides has grown. Most of the data
requirements contained in this new proposal have been applied on a
case-by-case basis to support individual applications, or imposed via a
DCI on all registrants of similar products. Thus EPA's actual data
requirements have progressed as scientific understanding and concerns
have evolved, but part 158 data requirements have not been updated to
keep pace.
The result of this regulatory lag is that EPA regards many data
requirements in today's proposal to be ``newly codified requirements,''
routinely applied in practice on a case-by-case basis but simply not
codified in the CFR. However, because they have not been codified, they
are considered to be ``new requirements'' never before imposed on the
regulated industry. For the purposes of this proposal, EPA has
evaluated the costs and burdens of all proposed requirements, whether
``new'' or ``newly codified '' against the data requirements as
originally promulgated in 1984, termed `` existing requirements.'' Many
of these studies can be categorized as rarely to infrequently required.
In this preamble, EPA is proposing new and revised data
requirements that encompass all three categories of requirements:
1. EPA is proposing ``new requirements,'' never before imposed on
any registrant.
2. EPA is proposing ``newly codified requirements,'' which have
been applied on a case-by-case basis, but are not in the CFR.
3. EPA is proposing revisions to ``existing requirements.''
D. Types of Revisions Being Proposed
Part 158 is a massive and complex set of tables that describe
pesticide data requirements. Each data requirement is currently
established and its scope and applicability defined according to a
number of parameters. Having comprehensively evaluated its data
requirement parameters, EPA is proposing changes in all areas of data
requirements. Some of these changes are clarifications or housekeeping
changes without cost or burden, others have the effect of increasing or
decreasing the burden of the data requirement. The types of changes may
be broadly categorized as follows:
1. Substantive changes--i. Addition of a requirement. This
encompasses both ``new requirements'' and ``newly codified
requirements.'' For example, EPA is proposing a ``new requirement'' for
immunotoxicity testing. On the other hand, data requirements for
applicator exposure (subpart U) are entirely ``newly codified.``
ii. Elimination of a requirement, sometimes with substitution of a
new requirement. For example, EPA is wholly eliminating the requirement
for seed germination testing. By contrast, the existing requirement for
a battery of mutagenicity studies is being eliminated in favor of a
specific set of mutagenicity studies.
iii. A change to the number or type of species that must be tested.
For example, EPA proposes to require acute avian toxicity testing on an
additional passerine species in some instances. EPA also proposes to
require that certain toxicity studies be conducted routinely with two
species instead of one.
iv. A change in the conditionality of the test requirement. For
example, EPA is proposing to change a number of requirements from
conditionally required to fully required, or vice versa. In some cases,
this change is a minor change in the actual frequency (and burden) of
the requirement. In other cases, the change may represent a substantive
increase in frequency of requirement.
v. A change to the use patterns to which a data requirement
applies. As described elsewhere, EPA proposed to increase the number of
use pattern descriptors from 9 to 15. In some cases, EPA proposes to
extend requirements currently limited to food uses to nonfood uses,
e.g., prenatal developmental toxicity studies. A second example would
be a proposed expansion of certain studies into greenhouse and indoor
use patterns, for example, avian oral toxicity requirements.
vi. A change to the test substance to be used. Typical test
substances include the technical grade of active ingredient (TGAI), the
manufacturing-use product, the end-use product, and a ``typical
product.'' For example, EPA proposes to require primary eye and primary
dermal irritation, and dermal sensitization testing using the TGAI in
addition to the end-use product.
vii. A clarification in the notes describing the test. For example,
EPA is proposing in a test note that analytical methods for residue
chemistry and environmental fate be validated by an independent
laboratory.
2. Technical changes having no substantive effect--i. Relocation of
a requirement. For example, EPA proposes to move the magnitude of
residues in rotational crops data requirement from environmental fate
requirements to residue chemistry requirements.
[[Page 12284]]
ii. A change to the title of a data requirement. For example, EPA
proposes to rename the ``teratogenicity'' data requirement to
``prenatal developmental toxicity'' to more accurately reflect the
nature of the study.
iii. Subdividing an existing requirement to create two separate
entries. For example, EPA proposes to separately list the storage
stability requirement for residue samples. This requirement is
currently included in the plant and animal metabolism data requirement.
A change of this nature is intended to highlight an aspect of a test
requirement for the regulated community.
iv. Merging two data requirements into a single requirement. For
example, EPA proposes to merge the terrestrial field dissipation study
with the long-term field dissipation study because both studies provide
similar information.
Each data requirement for which a revision is proposed is discussed
in detail in subsequent units of this preamble. Readers are referred to
the table in Unit XXIII. for a line-by-line listing of every current
and proposed data requirement and the types of changes proposed. If no
change is proposed, the table contains a notation to that effect.
VII. General Provisions of Part 158 (Subpart A)
A. General
Subpart A serves as an introduction to the data requirements in
part 158. As proposed, current material has been substantially revised
to be more concise and easier to understand. EPA has eliminated much of
the redundancy in current subpart A and streamlined the remaining
material. Unless otherwise superseded by part 174, the regulations of
this part apply to plant-incorporated protectants.
1. New material. New content has been added to subpart A.
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.
2. Disposition of current subpart A material. The following
sections of current subpart A are proposed to be deleted or
substantially revised. The following Table 2 explains each section.
Table 2.--Disposition of Current Subpart A Material
------------------------------------------------------------------------
Section Title Disposition
------------------------------------------------------------------------
158.20 Overview Paragraph (a) deleted
Paragraph (b).
Content contained in
proposed 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
-------------------------------
[[Page 12285]]
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.
------------------------------------------------------------------------
B. 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.
C. Confidential Business Information
EPA proposes to clarify its policies on confidentiality claims
asserted by submitters and on the release of information by the Agency.
Section 158.33 discusses information that may be claimed as
confidential and the procedures for asserting such a claim. It also
discusses information that may be released by EPA, and circumstances
under which such information can be released. Any release of
information by EPA would be in accordance with FIFRA sec. 10, FFDCA
sec. 408, and EPA regulations under the Freedom of Information Act (5
U.S.C. 552) found in 40 CFR part 2. The revisions to procedures for
asserting confidentiality claims would not apply to data submitted to
the Agency before the date of promulgation of this rule. Further
regulatory provisions regarding confidentiality can be found at 40 CFR
part 2.
1. Confidentiality of 408 information. EPA also proposes to
implement the revised confidentiality provisions in FFDCA sec. 408(i).
Prior to the changes made in FFDCA by FQPA in 1996, confidentiality of
information submitted in support of a tolerance or exemption was
governed by old sec. 408(f), which made all such information
confidential until publication of a regulation establishing a tolerance
or exemption (unless the submitter explicitly waived confidential
protection). This section was replaced in 1996 by current sec. 408(i),
which provides in part, ``Data and information that are or have been
submitted to the Administrator under this section or sec. 348 of this
title in support of a tolerance or an exemption from a tolerance shall
be entitled to confidential treatment for reasons of business
confidentiality and to exclusive use and data compensation to the same
extent provided by secs 3 and 10 of the Federal Insecticide, Fungicide,
and Rodenticide Act.'' EPA has never formally interpreted the meaning
of sec. 408(i) with respect to confidential information.
The likely intent of Congress was to accord information submitted
in support of a tolerance or exemption the same confidentiality
protections that apply to data submitted under FIFRA, especially
considering the extent to which FIFRA and FFDCA were intertwined more
closely by FQPA. Treating information submitted under the two statutes
identically means that they are subject to the same protections (e.g.,
restrictions on disclosure of entire studies to multinational
corporations in accordance with FIFRA sec. 10(g)) and the same
disclosure requirements (e.g., mandatory public availability of safety
and efficacy information in accordance with FIFRA 10(d)(1)). In fact,
this discussion may be largely academic, because EPA expects that
nearly all data submitted under part 158 in support of a tolerance or
exemption will also be information submitted under FIFRA. The only
exception would pertain to import tolerances or exemptions for
pesticides that are not used in the United States, submissions which
are uncommon. All references in this preamble to FIFRA sec. 10 are
therefore intended to apply equally to information submitted pursuant
to FFDCA 408.
2. Safety and efficacy information. Information pertaining to the
safety and efficacy of registered pesticides must in most cases be made
available to the public. The existing provisions in 40 CFR 158.33
regarding the confidentiality of safety and efficacy information have
in some cases been unclear to registrants and applicants, resulting in
confusion regarding what information is claimed as confidential. EPA
seeks to clarify these provisions, and to clear up some long-standing
misconceptions as to the eligibility of inert ingredient and process
information for confidential treatment.
FIFRA sec. 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
[[Page 12286]]
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.
3. Information pertaining to unregistered pesticides. Although
safety and efficacy information (which by definition pertains only to
registered or previously registered pesticides) is made publicly
available by statute, if the information pertains to unregistered
pesticides (including both applications for new active ingredients and
import tolerances for pesticides used only outside the United States)
it is not subject to the same mandatory disclosure requirement. Such
information may be entitled to confidential treatment if it meets the
requirements of sec. 10(b). In practice, EPA believes that information
relating to the effects of unregistered pesticides that is not within
one of the exceptions in FIFRA sec. 10(d)(1)(A), (B), or (C) will
seldom meet this test. Much of the information in studies is valuable
only to the extent that it can be used for registration/tolerance
purposes, and protection from unauthorized submission or citation of a
study by persons other than the submitter is provided by the FIFRA and
FFDCA data compensation provisions and by FIFRA sec. 10(g). Moreover,
because such information becomes publicly available once the pesticide
is registered, competitors will eventually be able to get access to the
information. Thus, confidentiality should normally be appropriate only
when disclosure of the information prior to registration would give
competitors an advance look at information that they could use to their
advantage.
At the same time, the period prior to registration is of special
importance for public participation in the registration process. Under
FIFRA sec. 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.
4. Confidentiality claims for plant-incorporated protectant
information. Part 174 was incorporated into 40 CFR effective September
17, 2001. The regulations in part 158 apply to plant-incorporated
protectants unless otherwise superseded by part 174. In addition to
complying with the requirements of 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.
5. Disclosure of data to multinational entities. Also included is a
proposed provision governing the release of data to foreign or
multinational pesticide companies. Under sec. 10(g) of FIFRA, EPA
requires that any person requesting information from the Agency affirm
that he or she is not an ``entity engaged in the production, sale, or
distribution of pesticides in countries other than the United States or
in addition to the United States'' and that the information will not be
disclosed to such an entity. The requirement for such an affirmation
applies to all data received by the Agency under FIFRA (and FFDCA) and
is not limited to confidential business information.
In Class Determinations 3-85 (50 FR 48833, November 27, 1985) and
1-99 (64 FR 70019, December 15, 1999) EPA elucidated the criteria for
determining whether information and documents derived from studies or
reports submitted to the agency are subject to the restrictions of
FIFRA sec. 10(g). In order to be outside the scope of sec. 10(g),
documents must not (1) ``contain or consist of any complete unpublished
report submitted to EPA '' or (2) ``contain or consist of excerpts or
restatements of any such report which reveal the full methodology and
complete results of the study, test, or experiment, and all explanatory
information necessary to understand the methodology or interpret the
results.'' (50 FR 48834). 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
[[Page 12287]]
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.
6. Release to state and foreign governments with consent. EPA also
is including in this proposal a provision to facilitate the release and
exchange of information with State and foreign regulatory agencies. In
an effort to promote harmonization and to conserve resources through
work share programs, the exchange of data often is beneficial and
desirable. Applicants would have the option of signing a statement
authorizing the Agency to release information contained in their
documents for such purposes. Although most governments provide
protection for confidential information, EPA cannot guarantee how a
particular government would treat specific information disclosed to it.
Consequently, the submitter should be aware of any risk involved before
granting consent to disclosure. However, EPA would not view disclosure
to a government that protected confidential information as otherwise
waiving confidential treatment for the information.
D. Flagging Criteria
EPA proposes to revise the flagging requirements of 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:
1. Reduce the number of study criteria from 11 to 7 by combining
certain studies under one criterion. The new criteria would eliminate
distinctions between subchronic and chronic studies in most cases.
2. Combine reproductive, prenatal developmental toxicity and
developmental neurotoxicity studies under one criterion to better focus
on effects on children and infants.
3. Consolidate the criteria that address the No-Observed-Adverse-
Effect Levels (NOAEL) into a single criterion covering all studies from
which NOAELs are derived. In so doing, EPA would change references to
cholinesterase inhibition to ``acute toxicity.'' This change
acknowledges that NOAELs are now derived for a number of acute toxicity
effects, not just cholinesterase inhibition. In a similar vein, EPA
would eliminate the specific ``less than 10X'' and ``less than 100X''
triggers for NOAEL study flagging in favor of a more general
description of ``less than the current NOAEL.'' Both of these changes
could result in more studies being flagged.
4. Update the guidelines references, and terminology, e.g.,
teratogenicity studies are now called prenatal developmental toxicity
studies; the ADI is now referred to as the RfD. EPA believes that these
revisions to the criteria will simplify the application of the criteria
by submitters, even though additional studies may be required to be
flagged.
E. Waivers
EPA proposes to reformat its waiver process, currently contained in
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.
1. Waiver requests submitted as part of an application for
registration. Waiver requests submitted in conjunction with an
application for registration, amended registration, experimental use
permit, or petition for tolerance are considered in the context, and in
the same time frame, as the application is considered, based upon the
application review period in FIFRA sec. 33. The review periods
currently range from 90 days for minor amendments to as much as 3 years
for new chemical applications. Consideration of waiver requests (and
there may be multiple requests in a single application) is done by
Agency scientists when the application is reviewed scientifically.
2. Waiver requests submitted in response to Data Call-Ins for
studies that are required in part 158. 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.
F. 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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VIII. How to Use the Data Tables (Subpart B)
EPA proposes to revise subpart B to update use patterns and clarify
the steps needed to determine the appropriate data requirements from
the tables in subparts, D, E, F, J, K, N, O, and U. Pesticide use
patterns that are used to determine required testing have been revised
for all of the data requirements tables to reflect the expanded use
patterns contained in this proposal (see below).
A. Expanded Use Patterns
EPA proposes to subdivide the current 9 major use patterns listed
in Appendix A of part 158 to 15 to more fully address nonagricultural
uses. The revised use patterns would be terrestrial food crop,
terrestrial feed crop, and terrestrial nonfood crop; aquatic food crop,
aquatic nonfood crop, aquatic nonfood outdoor use and aquatic nonfood
industrial use; greenhouse food crop and greenhouse nonfood crop;
forestry; residential outdoor; indoor food; indoor nonfood; indoor
medical; and indoor residential use. As mentioned above, the Agency
proposes to remove the Pesticide Use Index (Appendix A) from the
regulations because it is not a requirement. Instead, the Index will
become a separate guidance document and placed on EPA's website and
made available to the public. A guidance document would be easier to
update and would provide the regulated community with the most current
information.
B. Clarifying How to Use the Data Tables
Subpart B would contain a step-wise process to assist the applicant
in determining the data needed to support its particular product. As
with current practice, the actual data and studies required may be
modified on an individual basis to fully characterize the use and
properties of specific pesticide products under review. While EPA is
attempting to assist the applicant in this subpart, it is important to
emphasize that it is the applicant's obligation under FIFRA to
demonstrate that an individual product meets the standard under FIFRA
and/or FFDCA. Accordingly, applicants are encouraged to consult with
the Agency on the appropriate data requirements as proposed here as
they relate to their specific product prior to and during the
registration process.
EPA is continuing its current system of identifying the
applicability of data requirements in the data tables. Because of the
variety of chemicals and use patterns, and because EPA must retain
flexibility to tailor data requirements to its needs, it uses only
qualitative descriptors in the tables. These are used for convenience
to make the table format feasible, but serve only as a general
indication of the applicability of a data requirement. In all cases,
the test notes referred to in the table must be consulted to determine
the actual applicability of the data requirement.
The table descriptors NR (not required), R (required), and CR
(conditionally required) can be viewed as markers along a spectrum of
the likelihood that the data requirement applies. The use of R does not
necessarily indicate that a study is always required, but that it is
more likely to be required than not. The use of CR means a study is
less likely to be required. Although only an approximation, if
percentages were to be assigned, R could be viewed as representing the
range of 50% to 100% and CR the range up to 50%. EPA welcomes comment
on ways to characterize the data requirements that would better serve
applicant needs.
EPA is continuing its longstanding system of identifying test
substances in the tables. The standard descriptors of test substance
are the following:
1. The technical grade of active ingredient (TGAI), used when
evaluating the inherent toxicity or chemical characteristics of a
pesticide.
2. The manufacturing use product (MP), used in certain product
chemistry tests, usually for labeling purposes.
3. The pure active ingredient (PAI), used in certain product
chemistry tests requiring extremely basic chemical properties or
manufacturing process information.
4. The pure active ingredient, radioactive (PAIRA), used primarily
in residue chemistry studies when residues at very low levels (ppm)
must be quantified in plant or animal tissue.
5. The end-use product (EP), used as the test substance when the
Agency wants to refine its hazard or chemical profile based on actual
concentrations, or needs to determine the impact of added inert
ingredients on the hazard or chemical profile.
6. The typical end-use product (TEP), used as a representative
product in tests that might otherwise require duplicative testing of a
number of EPs.
Where changes in the test substance are proposed, such changes are
described in the discussion of each proposed revision. EPA welcomes
comment on its test substances and how the Agency uses them in a
testing regimen. Such comments should be made in the context of the
specific data requirement for which changes are proposed.
C. Identifying Data for Experimental Use Permits (EUPs)
Finally, the Agency is requesting comment on the best way to
identify data requirements for EUPS. Some people believe that the
brackets indicating what data requirements also apply to EUPs in the
current data tables complicate the tables with extraneous symbols and
codes. In an effort to make the data tables simpler and easier for an
applicant to understand, one suggestion is to separate the EUP data
requirements from the main data tables and make them a stand-alone
table. Revised EUP data requirements could be housed in 40 CFR part 158
(data requirements) or in part 172 (EUP requirements). As part of this
proposal, EUP data requirements for each discipline have been
identified either in the regulatory text accompanying the data table
or, as brackets, within the body of the table, itself. In general, the
Agency proposes to retain the existing data requirements for EUPs with
a few minor changes in the areas of environmental fate and ecological
effects. The Agency is soliciting opinions on this approach or other
approaches that may prove more efficient and useful to the applicant.
If an alternative approach is accepted, the Agency may in the final
rule, reformat the regulatory text or data tables.
D. Test Guidelines
The guidelines for the environmental fate series are currently
being updated and where applicable, harmonized with the guidelines
established by the OECD. Therefore, the Agency is showing the current
guideline numbers in the preamble, regulatory text, and tables. If,
before the final rule has been promulgated, these guidelines have been
issued, EPA will insert the new guideline numbers in the Final Rule.
E. Purposes of the Registration Data Requirements
The Agency proposes to retain the material currently in 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.
IX. Product Chemistry Data Requirements (Subpart D)
A. General
The Agency uses product chemistry information to determine whether
impurities of toxicological or environmental concern are present in
pesticides and formulated products.
[[Page 12289]]
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.
B. Proposed Product Chemistry Data Requirements
1. Newly imposed data requirements. None.
2. Newly codified data requirements--i. UV/visible light
absorption. The Agency proposes to add a requirement for data on the
ultraviolet (UV)/visible light absorption in the 200-800 nanometers
wavelength range (guideline 830.7050) as part of the basic data in the
characterization and identification of a compound. This information
will be used in conjunction with the photodegradation in water study
(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 (<10-\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.
3. Revised data requirements--i. Stability to temperatures, metals,
and metal ions. The Agency proposes to change the requirement for
stability data (guideline 830.6313) from ``required'' to
``conditionally required.''Data on the stability to metals and metal
ions is required only if the active ingredient is expected to come in
contact with either material during storage. This proposed change does
not alter the nature of the requirement.
ii. Explodability. The Agency proposes to change the requirement
for explodability data (guideline 830.6316) from ``required'' to
``conditionally required.'' Since pesticides do not typically fall
under this category, these data are only required for products that are
potentially explosive. This proposed change does not alter the nature
of the requirement.
iii. Partition coefficient (n-octanol/water). The Agency proposes
to change the requirement from ``conditionally required'' to
``required'' (guidelines 830.7550, 830.7560, and 830.7570). The Agency
is requiring this study because the majority of currently registered
pesticides are organic non-ionic chemicals that are not expected to
significantly hydrolyze or solubilize in water. In the event a chemical
fully hydrolyzes or is completely soluble in water, this data
requirement would be waived. This proposed change does not alter the
nature of the requirement nor the conditions under which it is imposed.
iv. Density, dissociation constant, and vapor pressure. The Agency
proposes to add test notes for the data requirements for density/
relative density/bulk density (guideline 830.7300), dissociation
constant (guideline 830.7370), and vapor pressure (guideline 830.7950)
to better identify when these study requirements are applicable. These
proposed minor changes do not expand the product chemistry requirement.
Instead, they clarify the requirements by specifying which physical
states or chemical forms the requirements apply.
X. Terrestrial and Aquatic Nontarget Organisms Data Requirements
(Subpart E)
A. General
The Agency uses a tiered system of ecological effects testing to
assess the potential risks of pesticides to aquatic and terrestrial
vertebrates, invertebrates, and plants. These tests include studies
arranged in a hierarchy from basic laboratory tests to applied field
tests. The results of each tier are evaluated to determine the
potential impacts on fish, wildlife and other nontarget organisms, and
to indicate whether further laboratory and/or field studies are needed.
These data requirements provide the Agency with ecological effects
information, which, in turn, allows the Agency to determine if
precautionary statements concerning toxicity or potential adverse
effects to nontarget organisms are necessary.
Higher tiered studies may be required when basic toxicity data and
predicted exposure levels or environmental conditions suggest the
potential for adverse effects. Field data are used to examine acute and
chronic adverse effects on captive or monitored populations under
natural or near-natural environments. Such studies are required only
when the potential for adverse effects is high, based on the results of
lower tier studies, or to confirm the need for mitigation measures. In
some cases, the results of field studies may give rise to the need for
further testing.
B. Proposed Requirements
The Agency is proposing two additional data requirements as well as
other minor revisions that would clarify the existing data
requirements. In some cases, the proposal is to change the
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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.
1. Newly imposed data requirements. None.
2. Newly codified data requirements. The Agency proposes to add
testing of aquatic organisms exposed to treated sediment to better
assess the effects of sediment bound pesticide residues in aquatic
environments. Environmental risk estimates should be based on exposure
data from the water column, sediment, and pore water (the water
occupying space between sediment or soil particles), however, with the
exception of field studies, the current data requirements are limited
to water column exposures. The effects of sediment bound pesticides (or
their degradates) on aquatic environments cannot be accurately assessed
from bioassays on compounds suspended in the water column alone. For
example, lipophilic or hydrophobic chemicals can dissipate from the
water column, but may remain in the aquatic environment adsorbed to
sediment. Sediment bound pesticides may differ significantly from
pesticides in solution, showing different physical, chemical, and
biological properties, chemical partitioning, bioavailability,
concentrations in interstitial or pore water, exposure from sediment
ingestion and possible manifestations of food chain effects. By serving
as a potential pesticide sink, exposure to these compounds may lead to
significant environmental risk to a wide variety of fish and aquatic
invertebrates which live and feed at the bottom of a lake or stream.
Sediment toxicity testing is needed to assess the bioavailability of a
sediment bound compound and to characterize the possible impact to
sediment dwelling organisms. The Agency does not believe these studies
will be commonly required.
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 <=
10 days in either the aerobic soil or aquatic metabolism studies.
Registrants would need to consult with the Agency on appropriate test
protocols.
ii. Whole sediment: chronic toxicity to invertebrates. The Agency
proposes to conditionally require this study for the same use patterns
as the above sediment toxicity tests. The study would be triggered when
the estimated environmental concentration is greater than or equal to
the acute sediment EC50/LC50 or 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.
3. Revised data requirements--Avian oral toxicity. The Agency
proposes to require for certain uses, an additional test species for
the acute avian oral toxicity study (guideline 850.2100), which
currently recommends the use of mallard ducks or bobwhite quail.
Testing on a passerine species (i.e., redwing blackbird) would be
required for outdoor uses. The Agency is proposing to add this
passerine species because of concern in the scientific community that
data from tests with mallards or quail may not always adequately
characterize the risks that pesticides pose to songbirds. Recent
evaluation of the data collected over the past 10 years indicates
passerines are more sensitive to pesticides than larger birds such as
mallards and quail (which are currently the recommended test species)
(Ref. 2) and in 1996, the SAP supported the need for testing on
passerines. 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
[[Page 12291]]
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 LD50 of the TGAI is less than or equal to 100 mg
a.i./kg. Data would be required on a second species for this use if the
avian dietary lethal concentration to cause mortality in 50% of the
test animals (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
LC50 < 10 ppm) in the acute fish toxicity study, and may be
released into the aquatic environment through effluent discharge. In
such cases, the results of the two required acute aquatic toxicity
studies (fish and invertebrates) may not be sufficient to rule out
greater toxicity in a second species of fish. Testing on a second
species will provide some assurance that EPA is not basing an
assessment on a species that is highly sensitive (or the opposite) when
compared with another species. Therefore, in these cases, the Agency
proposes to conditionally require a third acute study on a second
species of fish to correlate with the results of the previous two acute
aquatic studies and to ensure that the labeling is adequate to protect
aquatic species. The additional study increases the likelihood that
effluent criteria and product labeling reflect the pesticide's risk and
inherent toxicity.
vi. Acute toxicity--estuarine and marine organisms. Acute data from
estuarine testing enables the Agency to perform a risk assessment by
comparing the toxic concentrations with the estimated or monitored
levels in estuaries. The Agency proposes to change the conditional
requirement for the acute LC50/EC50 testing
(guidelines 850.1025, 850.1035, 850.1045, 850.1055, and 850.1075) for
terrestrial, aquatic (food crop and nonfood outdoor), residential
outdoor, and forestry uses to required testing, and change the aquatic
nonfood residential use to ``not required.'' Generally, three out of
the five studies would be needed to satisfy the data requirement.
Registrants may request a waiver of the study if the crop is never
associated with coastal counties or there is a geographical restriction
for a site that would normally be of concern.
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 LC50 value would
suggest.
viii. Aquatic organism bioavailability/biomagnification/toxicity
tests. The Agency proposes to eliminate the requirement for these
studies for aquatic nonfood residential or residential outdoor uses
since exposure is expected to be minimal (i.e., insufficient quantities
to accumulate in the tissues of aquatic organisms (guidelines 850.1710,
850.1730, and 850.1850).
ix. Simulated or actual field testing for aquatic organisms. 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 LD50 of 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
LD50 of <11 [mu]g/bee, as determined in the acute contact
study, and the use pattern indicates that honey bees may be exposed.
The proposed data requirements rule (48 FR 53192) which was published
in 1982, listed the correct value of <11 [mu]g/bee for the
honeybee study.
xii. Field testing for pollinators. The Agency proposes to include
terrestrial (feed crop) and aquatic nonfood (aquatic outdoor and
residential) uses where honeybees are likely to be exposed to
pesticides as a conditional requirement (guideline 850.3040).
C. Data Requirements Specific to Endangered Species Assessments and
Determinations
Over the last several years, the Agency has been requiring, on a
case-by-case basis for certain pesticides, data demonstrating specific
geographic location(s) of threatened and endangered species (listed
species), which can then be compared with areas of potential pesticide
use. These data have been required when EPA determined that the
estimated environmental concentration of the pesticide when applied
according to the labeling appears to exceed the Agency's numeric
concern levels for listed species. The specific species for which
location information was needed, has been determined on a case-by-case
basis based upon the use pattern of the pesticide and the sites on
which it may be used. These special data are currently not required by
part 158, and have only been requested on a few occasions; however, the
Agency anticipates that they may be requested in the future in
connection with other registration and reregistration actions. In
response to a Data Call-In notice for data on the location of all
listed species, an industry task force is working to develop a database
that may partly fulfill Agency needs, i.e., geographic locations where
potentially affected species are thought to occur. Access to the task
force data by other registrants who may be required to provide such
data in the future would be made available through appropriate data
sharing mechanisms. Although the anticipated expanded burden on
registrants is not large since it does not entail experimental or
laboratory procedures, it is nevertheless not likely to be
inconsequential. Consequently, the Agency is requesting comment on its
utility and appropriateness.
In addition, through discussions about methods to evaluate the
potential risks of pesticides to listed species, EPA and the Fish and
Wildlife Service and the National Marine Fisheries Service (jointly
referred to as the Services) identified several aspects of EPA's
current approach for which there is some scientific uncertainty. While
the Services agreed that EPA was using the best available scientific
and commercial information to assess risks to listed species, the
Services and EPA also agreed that where uncertainties existed, further
research and investigation might help to develop improved risk
assessment approaches. The Agency recognizes that such research also
could lead, in the long run, to additional data requirements for
registration. Accordingly, the Agency seeks input on research areas
that may be necessary to effectively characterize potential risks to
listed endangered species from pesticide use. These include research to
address the following types of uncertainties:
Product use information by geographic location below the
state and county levels
Toxicity data and environmental fate measurements/exposure
model predictions with end use products
Toxicity data from surrogate species that quantify dose-
response relationships for effects relevant to critical life stages of
endangered species
Measured or estimated values of physiological,
biochemical, and morphological characteristics of endangered species
and surrogate species to refine chemical-specific interspecies toxicity
extrapolations
Toxicity, exposure, uptake and elimination data to better
determine any differences in interspecies sensitivity of non-target and
endangered plant species exposed to herbicides
Toxicity data to characterize potential effects to
freshwater mussels
Toxicity data to characterize potential effects to
reptiles and amphibians.
The Agency seeks comment on:
1. The relative value of each of these research areas in better
refining assessments of potential risks to listed species.
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2. Input on specific research directions in these areas, including
methodologies, protocols etc., that would be appropriate and useful in
assessing the potential risks to listed species.
3. Other types of research that would be of value in refining
potential risks of a pesticide to a listed species.
4. The extent to which potential research areas reflect
uncertainties that apply to pesticides generically; to chemical
stressors generically, or to types of pesticides or chemicals
stressors.
XI. Toxicology Data Requirements (Subpart F)
A. General
Toxicology studies are required by the Agency to assess the hazard
of the pesticide to humans and domestic animals. These hazard data,
when combined with exposure data, form the basis for the human risk
assessment. Generally, using animals as a surrogate for humans, tests
are carried out by the oral, dermal or inhalation route depending on
the pesticide's pattern of use and physical form. The duration of the
toxicity study approximates the estimated duration of human exposure,
while considering species differences in maturational milestones and
overall life span. Typical exposures may be ``acute'' (single dose),
``subchronic'' (intermediate), or ``chronic'' (long-term). If a
pesticide is used on food and requires a tolerance, the dietary
exposure may be over a lifetime, or a significant portion of a
lifetime, and thus chronic/cancer and multi-generation reproductive
studies would be required. Studies would be required to assess the
hazard during a potentially susceptible stage of life, e.g., prenatal
developmental studies and developmental neurotoxicity studies, and to
measure end points not always observed in the basic toxicity test
battery, e.g., acute and subchronic neurotoxicity studies.
In addition, EPA's Risk Assessment Guidelines set forth principles
and procedures to guide EPA scientists in the conduct of Agency risk
assessments, and to inform Agency decision makers and the public about
these procedures. The guidelines emphasize that risk assessments will
be conducted on a case-by-case basis, giving full consideration to all
relevant scientific information. This case-by-case approach means that
Agency experts review the scientific information on each agent and use
the most scientifically appropriate interpretation to assess risk. The
guidelines also stress that this information will be fully presented in
Agency risk assessment documents, and that Agency scientists will
identify the strengths and weaknesses of each assessment by describing
uncertainties, assumptions, and limitations, as well as the scientific
basis and rationale for each assessment.
This proposal includes the requirements for pesticides retained
from the current 40 CFR 158.340 as well as proposed revisions that have
been peer reviewed by the SAP. The basic data set proposed here
includes toxicity studies needed to support high exposure pesticides,
such as food use pesticides.
1. Acute studies (oral, dermal, and inhalation toxicity tests, eye
and skin irritation tests and dermal sensitization)
2. Subchronic (90-day) feeding studies in rodents and nonrodents
3. Chronic feeding studies in rodents and nonrodents
4. Cancer studies in two species of rodents (rat and mouse
preferred)
5. Prenatal developmental toxicity studies in rodents and
nonrodents (rat and rabbit preferred)
6. Two-generation reproduction study in rodents (rat preferred)
7. General metabolism study in rodents
8. Mutagenicity battery
9. Acute and subchronic neurotoxicity studies in rats
10. Immunotoxicity study in rodents
11. Developmental neurotoxicity study in rodents
B. Approach
1. Options for generating data. A required sequence of
toxicological testing for new pesticides is not specified by the
Agency. Rather, most decisions regarding the order of testing are left
up to the individual registrant, based upon the understanding that
there are many factors that could affect the testing progression. It is
recommended, however, that the development of pharmacokinetic
information, including data relevant to developing systems, be
initiated early in the testing process in order to aid in the
appropriate design of the studies and the interpretation of
toxicological findings in adult and immature (developing) animals.
Generally, data requirements will proceed from single to multiple
exposures, from shorter to longer duration, and from simpler to more
complex. Different studies may be conducted simultaneously and various
studies may be done in combination as well (an approach encouraged by
the Agency to optimize resources and reduce the number of animals used
in testing). Knowledge gained from results of earlier studies should be
used to design subsequent study protocols in order to attain the
greatest confidence in the results of the higher-order studies. For
instance, conducting the subchronic (90-day) feeding study prior to the
two-generation reproduction study would provide information on target
organs that may be affected and that need to be specifically evaluated
in the two-generation reproduction study.
2. Options for submitting nonfood use data. In proposed 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.
C. Proposed Toxicology Data Requirements
EPA's proposed toxicology data requirements encompass studies
expected to improve the Agency's understanding of the potential
pesticide hazard to humans, including subpopulations such as infants
and children. The proposed table in this subpart contains the
toxicology data requirements EPA would rely on to identify potential
hazards to humans and domestic animals for all conventional pesticides.
These include acute, subchronic and chronic toxicity studies, as well
as carcinogenicity, prenatal developmental toxicity, reproductive
toxicity, mutagenicity, neurotoxicity and other specialized studies.
EPA recognizes that toxicology testing represents a large economic
burden on registrants and incorporates the use of test animals.
Consequently, the Agency works with industry, the scientific community,
and advocates, to ensure that data requirements are imposed only when
needed to make a sound scientific safety finding required under the
law. Because of this concern, the Agency has adopted guidelines whereby
several toxicological endpoints may be derived from one study and has
instituted other avenues for combining studies. The Agency also
recognizes that, in general, lower exposure uses often correlate with
lower risk. Consequently, the Agency has adopted an approach that tends
to levy more extensive data requirements on high exposure uses like
food uses. It is also reflected in the tiering system for data
submissions for nonfood uses and in the layout of the data tables.
1. Newly imposed data requirements--Immunotoxicity. The Agency
proposes to require immunotoxicity testing for all pesticides.
Immunotoxicity testing is necessary to evaluate the potential of a
chemical to produce adverse effects on the immune system. Immune system
suppression has been associated with increased incidences of infections
and neoplasia. In 1993, the National Research Council reviewed the
technical literature and found that some pesticides are
immunosuppressive (NRC, 1993). Because of the potential for pesticides
to adversely impact the immune system, the EPA has developed a test
guideline (870.7800) for immunotoxicity. The immunotoxicity test
guideline was reviewed and endorsed by the FIFRA Science Advisory Panel
and EPA's Science Advisory Board in 1996, and published in 1998 as part
of the Office of Prevention, Pesticides and Toxic Substances'
harmonized test guidelines.
Because the immune system is highly complex, studies not
specifically conducted to assess immunotoxic endpoints are inadequate
to characterize a pesticide's potential immunotoxicity, even if some
tissues subject to immunotoxic insult are examined. While data from
hematology, lymphoid organ weights, and histopathology of routine
chronic or subchronic toxicity studies may offer useful information on
potential immunotoxic effects, these endpoints alone are insufficient
to predict immunotoxicity (Refs. 7 and 8). Therefore, the Agency is
proposing to require functional immunotoxicity testing along with the
data from endpoints in other studies to predict the potential risk of
pesticides on the immune system more accurately. The Agency invites
public comment on all aspects of its proposed data requirement for
functional immunotoxicity.
2. Newly codified data requirements-- i. prenatal developmental
toxicity. The Agency proposes to change the name of this requirement
from ``Teratogenicity'' to ``Prenatal Developmental Toxicity'' to
correspond with the name of the guideline (870.3700). An information
based approach to testing is preferred which utilizes the best
available knowledge on the chemical to develop a study protocol and
testing strategy. Currently, both studies are required for food use
pesticides, but for nonfood uses, only one prenatal developmental
toxicity study is required, and the results of that study may trigger
the conditional requirement for a second species. However, the response
to developmental insult in one species is not necessarily the same in
another species. The pharmaceutical thalidomide, which produces severe
malformations in rabbits (and humans) but not rats following in utero
exposure, is a classic example of this species-related difference in
response. Additionally, the dose at which maternal or prenatal
developmental toxicity is observed may not be the same across species,
and the severity of the response in dams or fetuses may also differ.
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:
1. The pesticide causes treatment-related neurological effects in
adult animal studies, such as:
Clinical signs of neurotoxicity
Neuropathology
Functional or behavioral effects
2. 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
3. The pesticide elicits a causative association between exposures
and adverse neurological effects in human epidemiological studies
4. 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
[[Page 12297]]
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.
3. 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
[[Page 12298]]
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.
[[Page 12299]]
D. 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.
XII. Nontarget Plant Protection Data Requirements (Subpart J)
A. 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.
B. 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.
1. Newly imposed data requirements. None.
2. Newly codified data requirements. None.
3. 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
[[Page 12300]]
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.
XIII. Post-application Exposure Data Requirements (Subpart K)
A. 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.
B. 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
[[Page 12301]]
determination of whether or not a pesticide meets these criteria would
be made by the Agency on a case-by-case basis.
1. 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.
2. 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.
C. 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.
1. Newly imposed data requirements. None.
2. 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
[[Page 12302]]
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.
3. 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
[[Page 12303]]
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).
4. 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.
XIV. Environmental Fate Data Requirements (Subpart N)
A. 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
[[Page 12304]]
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.
B. 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.
1. 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.
2. 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
[[Page 12305]]
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.
3. 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
[[Page 12306]]
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.
XV. Residue Chemistry Data Requirements (Subpart O)
A. 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
[[Page 12307]]
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.
B. Tolerances
1. 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.
2. 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.
C. 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.
1. Newly imposed data requirements. None.
2. 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.
3. 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
[[Page 12308]]
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:
1. Residues are not found on feed items or
2. Livestock metabolism studies indicate minimal transfer of the
pesticide residue to tissues, milk or eggs. For those pesticides which
leave non-detectable or low residues in feed items and for which the
livestock metabolism study shows little transfer of radioactivity to
tissues, the Agency may be able to conclude that data on the level of
residues in livestock and their byproducts are not necessary.
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
[[Page 12309]]
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.
XVI. Applicator Exposure Data Requirements (Subpart U)
A. 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.
B. 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.
1. 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.
2. 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
[[Page 12309]]
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.
C. Proposed Applicator Exposure Data Requirements
1. Newly imposed data requirements. None.
2. 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.
3. 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,
[[Page 12310]]
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.
XVII. 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.
XVIII. Peer Review
A. 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.
B. 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.
1. 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.
2. 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.
3. 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.
4. 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)
5. 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.
6. 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]]
XIX. 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.
XX. 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.
XXI. 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.
XXII. 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:
1. Encourage the reduction of the number of animals used in
testing.
2. Seek opportunities to replace test methods requiring animals
with alternative test methods when acceptable alternative methods are
available.
3. 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.
XXIII. 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.
XXIV. 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:
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
XXV. 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.
1. National Research Council, ``Pesticides in the Diets of Infants
and Children,'' National Academy Press, Washington, D.C., 1993.
2. Mineau et al., 2001. Pesticide Acute Toxicity Reference Values
for Birds, Review of Environmental Contamination and Toxicology, 170:
13-74.
3. 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.
4. 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.
5. 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.
6. 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.
7. Luster et al., 1992. Risk Assessment in Immunotoxicology I.
Sensitivity and Predictability of Immune tests, Fundam. Appl. Toxicol,
18: 200-210.
8. Luster et al., 1993. Risk Assessment in Immunotoxicology II.
Relationships Between Immune and Host Resistance Tests, Fundamental amd
Applied Toxicology, 21: 71-82.
9. USEPA (1990) 1990 OECD Ad Hoc Meeting on Neurotoxicity Testing.
Summary Report. September 1990. Eastern Research Group, MA.
10. 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.
11. 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.
12. 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).
13. 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.
14. 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.
15. USEPA (U.S. Environmental Protection Agency), Guidelines for
mutagenicity risk assessment, 51 FR 34006-34012 (1986).
16. 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.
17. 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.
18. 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.
19. 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.
XXVI. 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.
XXVII. Statutory and Executive Order Reviews
A. 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.
B. 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:
1. The activities associated with the establishment of a tolerance
are currently approved under OMB Control No. 2070-0024 (EPA ICR No.
0597);
2. 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);
3. The activities associated with the generation of data for
reregistration are currently approved under OMB Control No. 2070-0107
(EPA ICR No. 1504); and
4. The 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.
C. 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.
D. Unfunded Mandates Reform Act
Under Title II of the Unfunded Mandates Reform Act of 1995 (UMRA)
(Public Law 104-4), EPA has determined that this action does not
contain a Federal mandate that may result in expenditures of $100
million or more for State, local, and tribal governments, in the
aggregate, or the private sector in any one year. As described in 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.
E. Executive Order 13132
Pursuant to Executive Order 13132, entitled Federalism (64 FR
43255, August 10, 1999), EPA has determined that this proposed rule
does not have ``federalism implications,'' because it will not have
substantial direct effects on the states, on the relationship between
the national government and the states, or on the distribution of power
and responsibilities among the various levels of government, as
specified in the Order. As indicated above, instances where a state is
a registrant are extremely rare. Therefore, this proposed rule may
seldom affect a state government. Thus, Executive Order 13132 does not
apply to this proposed rule. In the spirit of the Order, and consistent
with EPA policy to promote communications between the Agency and State
and local governments, EPA specifically solicits comment on this
proposed rule from State and local officials.
F. Executive Order 13175
As required by Executive Order 13175, entitled Consultation and
Coordination with Indian Tribal Governments (65 FR 67249, November 6,
2000), EPA has determined that this proposed rule does not have tribal
implications because it will not have substantial direct effects on
tribal governments, on the relationship between the Federal government
and the Indian tribes, or on the distribution of power and
responsibilities between the Federal government and Indian tribes, as
specified in the Order. As indicated above, at present, no tribal
governments hold, or have applied for, a pesticide registration. Thus,
Executive Order 13175 does not apply to this proposed rule. In the
spirit of the Order, and consistent with EPA policy to promote
communications between the Agency and State and local governments, EPA
specifically solicits comment on this proposed rule from tribal
officials.
G. Executive Order 13045
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.
H. 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.
I. National Technology Transfer and Advancement Act
Section 12(d) of the National Technology Transfer and Advancement
Act of 1995 (NTTAA), 15 U.S.C. 272 note) directs EPA to use voluntary
consensus standards in its regulatory activities unless to do so would
be inconsistent with applicable law or impractical. Voluntary consensus
standards are technical standards (e.g., materials specifications, test
methods, sampling procedures, etc.) that are developed or adopted by
voluntary consensus standards bodies. NTTAA directs EPA to provide
Congress, through OMB, explanations when the Agency decides not to use
available and applicable voluntary consensus standards. This regulation
proposes the types of data to be required to support 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.
J. 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]
1. 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]
2. 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.
[[Page 12331]]
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<=
0.05); or
A statistically significant 2
(pairwise p<= 0.05) increase of
any type of neoplasm in any test
group, males or females at any
dose level, compared to
concurrent control animals of
the same sex; or
An increase in any type of 3
uncommon or rare neoplasms in
any test group, males or females
animals at any dose level,
compared to concurrent controls
of the same sex; or
A decrease in the time to 4
development of any type of
neoplasms in any test group,
males or females at any dose
level, compared to concurrent
controls of the same sex.
------------------------------------------------
Prenatal developmental toxicity 870.3700 When compared to concurrent 5
Reproduction and fertility..................... 870.3800 controls, treated offspring show
Developmental neurotoxicity.................... 870.6300 a dose-related increase in
malformations, pre- or post-
natal deaths, or persistent
functional or behavioral changes
on a litter basis in the absence
of significant maternal toxicity
at the same dose level.
------------------------------------------------
Neurotoxicity 870.6100 When compared to concurrent 6
870.6200 controls, treated animals show a
statistically or biologically
significant increase in
neuropathological lesions or
persistent functional or
behavioral changes.
------------------------------------------------
Chronic feeding 870.4100 The no observed adverse effect 7
Carcinogenicity................................ 870.4200 level (NOAEL) from one of these
Reproduction and fertility..................... 870.3800 studies is less than the NOAEL
Prenatal developmental toxicity................ 870.3700 currently used by the Agency as
Developmental neurotoxicity.................... 870.6300 the basis for either the acute
Acute or 90-day neurotoxicity.................. 870.6200 or chronic reference dose.
----------------------------------------------------------------------------------------------------------------
(c) Identification of studies. For each study of a type identified
in paragraph (b) of this section, the applicant (or registrant in the
case of information submitted under FIFRA sec. 3(c)(2)(B)) shall
include the appropriate one of the following two statements, together
with the signature of the authorized representative of the company, and
the date of signature:
1. Statement 1.
I have applied the criteria of 40 CFR 158.34 for flagging
studies for potential adverse effects to the results of the attached
study. This study neither meets nor exceeds any of the applicable
criteria.``
2. Statement 2.
I have applied the criteria of 40 CFR 158.34 for flagging
studies for potential adverse effects to the results of the attached
study. This study meets or exceeds the criteria numbered [insert all
applicable reporting codes].
Sec. 158.45 Waivers.
(a) The data requirements specified in this part as applicable to a
category of products will not always be appropriate for every product
in that category. Some products may have unusual physical, chemical, or
biological properties or atypical use patterns which would make
particular data requirements inappropriate, either because it would not
be possible to generate the required data or because the data would not
be useful in the Agency's evaluation of the risks or benefits of the
product. The Agency will waive data requirements it finds are
inappropriate, but will ensure that sufficient data are available to
make the determinations required by the applicable statutory standards.
(b)(1) Applicants are encouraged to discuss the request with the
Agency before developing and submitting supporting data, information,
or other materials.
(2) All waiver requests must be submitted to the Agency in writing.
The request must clearly identify the data requirement(s) for which a
waiver is sought along with an explanation and supporting rationale why
the applicant believes the data requirement should be waived. In
addition, the applicant must describe any unsuccessful attempts to
generate the required data, furnish any other information which the
applicant(s) believes would support the request, and when appropriate,
suggest alternative means of obtaining data to address the concern
which underlies the data requirement.
(c) The Agency will review each waiver request and subsequently
inform the applicant in writing of its decision. If the decision could
apply to more than the requested product, the Agency, in its
discretion, may choose to send a notice to all registrants or publish a
notice in the Federal Register announcing the decision. An Agency
decision denying a written request to waive a data requirement is a
final Agency action.
Sec. 158.70 Satisfying data requirements.
(a) General policy. The Agency will determine whether the data
submitted or cited to fulfill the data requirements specified in this
part are acceptable. This determination will be based on the design and
conduct of the experiment from which the data were derived, and an
evaluation of whether the data fulfill the purpose(s) of the data
requirement. In evaluating experimental design, the Agency will
consider whether generally accepted methods were used, sufficient
numbers of measurements were made to achieve statistical reliability,
and sufficient controls were built into all phases of the experiment.
The Agency will evaluate the conduct of each experiment in terms of
whether the study was conducted in conformance
[[Page 12332]]
with the design, good laboratory practices were observed, and results
were reproducible. The Agency will not reject data merely because they
were derived from studies which, when initiated were in accordance with
an Agency-recommended protocol, even if the Agency subsequently
recommends a different protocol, as long as the data fulfill the
purposes of the requirements as described in this paragraph.
(b) Good laboratory practices. Applicants must adhere to the good
laboratory practice (GLP) standards described in 40 CFR part 160 when
conducting studies to support the registration, amended registration or
reregistration of a pesticide product. Applicants must also adhere to
GLP standards when conducting a study in support of a waiver request of
any data requirement which is within the scope of the GLP requirements.
(c) Agency guidelines. EPA has published Pesticide Assessment
Guidelines that contain standards for conducting acceptable tests,
guidance on the evaluation and reporting of data, definition of terms,
and suggested study protocols. Copies of the Pesticide Assessment
Guidelines may be obtained through the National Service Center for
Environmental Publications (NSCEP), or by visiting the agency's website
at www.epa.gov/pesticides. EPA publications can be ordered online
(www.epa.gov/ncepihom/nepishom), or by telephone at 1-800-490-9198.
(d) Study protocols--(1) General. Any appropriate protocol may be
used to generate the data required by this part, provided that it meets
the purpose of the test standards specified in the pesticide assessment
guidelines, and provides data of suitable quality and completeness as
typified by the protocols cited in the guidelines. Applicants should
use the test procedure which is most suitable for evaluation of the
particular ingredient, mixture, or product. Accordingly, failure to
follow a suggested protocol will not invalidate a test if another
appropriate methodology is used.
(2) Organization for Economic Cooperation and Development (OECD)
protocols. Tests conducted in accordance with the requirements and
recommendations of the applicable OECD protocols can be used to develop
data necessary to meet the requirements specified in this part.
Applicants should note, however, that certain of the OECD recommended
test standards, such as test duration and selection of test species,
are less restrictive than those recommended by EPA. Therefore, when
using OECD protocols, care should be taken to observe the test
standards in a manner such that the data generated by the study will
satisfy the requirements of this part.
(e) Combining studies. Certain toxicology studies may be combined
to satisfy data requirements. For example, carcinogenicity studies in
rats may be combined with the rat chronic toxicity study. Combining
appropriate studies may be expected to reduce usage of test animals as
well as reduce the cost of studies. EPA encourages this practice by
including standards for acceptable combined tests in the Pesticide
Assessment Guidelines. Registrants and applicants are encouraged to
consider combining other tests when practical and likely to produce
scientifically acceptable results. Registrants and applicants, however,
must consult with the EPA before initiating combined studies.
Sec. 158.75 Requirements for additional data.
The data routinely required by this part may not be sufficient to
permit EPA to evaluate every pesticide product. If the information
required under this part is not sufficient to evaluate the potential of
the product to cause unreasonable adverse effects on man or the
environment, additional data requirements will be imposed. However, EPA
expects that the information required by this part will be adequate in
most cases for an assessment of the properties of the pesticide.
Sec. 158.80 Use of other data.
(a) Data developed in foreign countries. With certain exceptions,
laboratory and field study data developed outside the United States may
be submitted in support of a pesticide registration. Data generated in
a foreign country which the Agency will not consider include, but are
not limited to, data from tests which involved field test sites or a
test material, such as a native soil, plant, or animal, that is not
characteristic of the United States. Applicants submitting foreign data
must take steps to assure that U.S. materials are used, or be prepared
to supply data or information to demonstrate the lack of substantial or
relevant differences between the selected material or test site and the
U.S. material or test site. Once submitted, the Agency will determine
whether or not the data meet the data requirements.
(b) Data generated for other purposes. Data developed for purposes
other than satisfaction of FIFRA data requirements, such as monitoring
studies, may also satisfy data requirements in this part. Consultation
with the Agency should be arranged if applicants are unsure about
suitability of such data.
d. By revising subpart B to read as follows:
Subpart B--How to Use the Data Tables
Sec. 158.100 Pesticide use categories.
(a) General use categories. There are six broad use categories used
in the data tables. The six broad categories include terrestrial
outdoor uses, aquatic outdoor uses, greenhouse uses, forestry uses,
residential outdoor uses, and indoor uses of all types. The 6 broad use
categories are further subdivided into 15 general use categories which
are the basis for data requirements established by use pattern. Within
the data tables, general use categories have been combined into single
columns when the data requirements are the same for the combined uses.
If there are no data requirements for a specific use, the column for
that use is not included in the table. The 15 general use pattern
groups used in the data table in this part are:
(1) Terrestrial food crop use.
(2) Terrestrial feed crop use.
(3) Terrestrial nonfood crop use.
(4) Aquatic food crop use.
(5) Aquatic nonfood residential use.
(6) Aquatic nonfood outdoor use.
(7) Aquatic nonfood industrial use.
(8) Greenhouse food crop use.
(9) Greenhouse nonfood crop use.
(10) Forestry use.
(11) Residential outdoor use.
(12) Residential indoor use.
(13) Indoor food use.
(14) Indoor nonfood use.
(15) Indoor medical use.
(b) Use pattern index. The Use Pattern Index is a comprehensive
list of specific pesticide use patterns. The use index is alphabetized
separately by site for all agricultural and all nonagricultural uses.
The Use Pattern Index associates each pesticide use pattern with one or
more of the 15 general use categories. It should be used in conjunction
with the data tables to determine the applicability of data
requirements to specific uses. The Pesticide Use Pattern Index, which
will be updated periodically, is available from the Agency or may be
obtained from the Agency's website at http://www.epa.gov/pesticides.
(c) Applicants unsure of the correct use category for their
particular product should consult the Agency.
Sec. 158.110 Required and conditionally required data.
Some data and information specified in this part are required (R)
for the evaluation of some or all types of products. However, other
data and
[[Page 12333]]
information specified as conditionally required (CR) are required only
if the product's pattern of use, results of other tests, or other
pertinent factors meet the criteria specified in those sections.
(a) Data designated as ``required'' (R) for products with a given
use pattern are required by EPA to evaluate the risks or benefits of a
product having that use pattern. Further clarification of the
applicability of the data requirement often is located in the test
notes accompanying the table.
(b) Data designated as ``conditionally required'' (CR) for products
with a given use pattern are required by EPA to evaluate the risks or
benefits of a product having that use pattern if the product meets the
conditions specified in the notes accompanying the requirement. The
determination of whether the data must be submitted is based on the
product's use pattern, physical or chemical properties, expected
exposure of nontarget organisms, and/or results of previous testing
(for example, tier testing). Applicants must evaluate each applicable
test note for the conditions and criteria to be considered in
determining whether conditionally required data must be submitted.
Sec. 158.120 Determining data requirements.
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 set forth here as
they relate to their specific product prior to and during the
registration process.
(a) Finding the appropriate data table. (1) Pesticide data
requirements for conventional chemical active ingredients and related
substances are presented in subparts D, E, F, G, J, K, N, O, and U of
this part in the form of a series of data tables, each addressing a
particular scientific discipline or data topic. Data requirements for
biochemical and microbial pest control agents are contained and are
described separately within subparts L and M of this part,
respectively.
(2) Key to table notations. R = required data; CR = conditionally
required data; NR = Not required; MP = manufacturing-use product; EP =
end-use product; TEP = typical end-use product; TGAI = technical grade
of the active ingredient; PAI = ``pure'' active ingredient; PAIRA =
``pure'' active ingredient, radiolabeled; Choice = choice of several
test substances depending on studies required. Brackets indicate which
data requirements also apply to experimental use permits (EUPS).
(b) Identifying required studies. To determine the specific kinds
of data needed to support the registration use of each pesticide
product, the applicant should:
(1) Refer to the applicable subpart(s) of this part. These subparts
describe the data requirements including data tables for each subject
area.
(2) Select the general use pattern(s) that best covers the use
pattern(s) specified on the pesticide product label as explained in
Sec. 158.100. All applicable use patterns must be included.
(3) Proceed down the appropriate general use pattern column in the
table and note which tests are required (R), conditionally required
(CR), or not required (NR). Required and conditionally required studies
are described in Sec. 158.110.
(4) Review the notes for each requirement to determine its
applicability to the specific product proposed for registration.
(5)(i) Proceed down the Test substance columns and determine the
appropriate test substance needed for that study. For toxicology
studies, if the data are intended to support a manufacturing-use
product, use the first column. If the data are intended to support an
end-use product, use the information listed in the second column.
(ii) The test substances columns specify which substance is to be
subjected to testing. Applicants should note that the substance that
should be used when performing the study may or may not be the product
itself. For example, the data from a certain study may be required to
support the registration of an end-use product, but the test substance
column may state that the particular test shall be performed using the
technical grade of the active ingredient(s) in the end-use product.
(iii) Manufacturing-use products (MP) and end-use products (EP)
containing a single active ingredient and no intentionally added inert
ingredients are considered identical in composition to each other, and
to the technical grade of the active ingredient (TGAI) from which they
were derived. Therefore, the data from a test conducted using any one
of these as the test substance is also suitable to meet the requirement
(if any) for the same test to be conducted using either of the other
substances.
(6) Refer to the Pesticide Assessment Guideline reference number
for each study located in the last column. See Sec. 158.70(c) for
information pertaining to the guidelines and how to obtain copies.
Sec. 158.130 Purposes of the registration data requirements.
(a) General. The data requirements for registration are intended to
generate data and information necessary to address concerns pertaining
to the identity, composition, potential adverse effects and
environmental fate of each pesticide.
(b) [Reserved].
(c) Residue chemistry. (1) Residue chemistry data are used by the
Agency to estimate the exposure of the general population to pesticide
residues in food and for setting and enforcing tolerances for pesticide
residues in food or feed.
(2) Information on the chemical identity and composition of the
pesticide product, the amounts, frequency and time of the pesticide
application, and results of test on the amount of residues remaining on
or in the treated food or feed, are needed to support a finding as to
the magnitude and identity of residues which result in food or animal
feed as a consequence of a proposed pesticide usage.
(3) Residue chemistry data are also needed to support the adequacy
of one or more methods for the enforcement of the tolerance, and to
support practicable methods for removing residues that exceed any
proposed tolerance.
(d) Environmental fate--(1) General. The data generated by
environmental fate studies are used to: assess the toxicity to man
through exposure of humans to pesticide residues remaining after
application, either upon reentering treated areas or from consuming
inadvertantly-contaminated food; assess the presence of widely
distributed and persistent pesticides in the environment which may
result in loss of usable land, surface water, ground water, and
wildlife resources; and, assess the potential environmental exposure of
other nontarget organisms, such as fish and wildlife, to pesticides.
Another specific purpose of the environmental fate data requirements is
to help applicants and the Agency estimate expected environmental
concentrations of pesticides in specific habitats where threatened or
endangered species or other wildlife populations at risk are found.
(2) Degradation studies. The data from hydrolysis and photolysis
studies are used to determine the rate of pesticide degradation and to
identify pesticides
[[Page 12334]]
that may adversely affect nontarget organisms.
(3) Metabolism studies. Data generated from aerobic and anaerobic
metabolism studies are used to determine the nature and availability of
pesticides to rotational crops and to aid in the evaluation of the
persistence of a pesticide.
(4) Mobility studies. These data requirements pertain to leaching,
adsorption/desorption, and volatility of pesticides. They provide
information on the mode of transport and eventual destination of the
pesticide in the environment. This information is used to assess
potential environmental hazards related to: contamination of human and
animal food; loss of usable land and water resources to man through
contamination of water (including ground water); and habitat loss of
wildlife resulting from pesticide residue movement or transport in the
environment.
(5) Dissipation studies. The data generated from dissipation
studies are used to assess potential environmental hazards (under
actual field use conditions) related to: reentry into treated areas;
hazards from residues in rotational crops and other food sources; and
the loss of land as well as surface and ground water resources.
(6) Accumulation studies. Accumulation studies indicate pesticide
residue levels in food supplies that originate from wild sources or
from rotational crops. Rotational crop studies are necessary to
establish realistic crop rotation restrictions and to determine if
tolerances may be needed for residues on rotational crops. Data from
irrigated crop studies are used to determine the amount of pesticide
residues that could be taken up by representative crops irrigated with
water containing pesticide residues. These studies allow the Agency to
establish label restrictions regarding application of pesticides on
sites where the residues can be taken up by irrigated crops. These data
also provide information that aids the Agency in establishing any
corresponding tolerances that would be needed for residues on such
crops. Data from pesticides accumulation studies in fish are used to
establish label restrictions to prevent applications in certain sites
so that there will be minimal residues entering edible fish or shell
fish. These residue data are also used to determine if a tolerance or
action level is needed for residues in aquatic animals eaten by humans.
(e) Hazards to humans and domestic animals. Data required to assess
hazards to humans and domestic animals are derived from a variety of
acute, subchronic and chronic toxicity tests, and tests to assess
mutagenicity and pesticide metabolism.
(1) Acute studies. Determination of acute oral, dermal and
inhalation toxicity is usually the initial step in the assessment and
evaluation of the toxic characteristics of a pesticide. These data
provide information on health hazards likely to arise soon after, and
as a result of, short-term exposure. Data from acute studies serve as a
basis for classification and precautionary labeling. For example, acute
toxicity data are used to calculate farmworker reentry intervals and to
develop precautionary label statements pertaining to protective
clothing requirements for applicators. They also provide information
used in establishing the appropriate dose levels in subchronic and
other studies; provide initial information on the mode of toxic
action(s) of a substance; and determine the need for child resistant
packaging. Information derived from primary eye and primary dermal
irritation studies serves to identify possible hazards from exposure of
the eyes, associated mucous membranes and skin.
(2) Subchronic studies. Subchronic tests provide information on
health hazards that may arise from repeated exposures over a limited
period of time. They provide information on target organs and
accumulation potential. The resulting data are also useful in selecting
dose levels for chronic studies and for establishing safety criteria
for human exposure. These tests are not capable of detecting those
effects that have a long latency period for expression (e.g.,
carcinogenicity).
(3) Chronic studies. Chronic toxicity (usually conducted by feeding
the test substance to the test species) studies are intended to
determine the effects of a substance in a mammalian species following
prolonged and repeated exposure. Under the conditions of this test,
effects which have a long latency period or are cumulative should be
detected. The purpose of long-term oncogenicity studies is to observe
test animals over most of their life span for the development of
neoplastic lesions during or after exposure to various doses of a test
substance by an appropriate route of administration.
(4) Developmental toxicity and reproduction studies. The
developmental toxicity study is designed to determine the potential of
the test substance to induce structural and/or other abnormalities to
the fetus as the result of exposure of the mother during pregnancy.
Two-generation reproduction testing is designed to provide information
concerning the general effects of a test substance on gonadal function,
estrus cycles, mating behavior, conception, parturition, lactation,
weaning, and the growth and development of the offspring. The study may
also provide information about the effects of the test substance on
neonatal morbidity, mortality, and preliminary data on teratogenesis
and serve as a guide for subsequent tests.
(5) Mutagenicity studies. For each test substance a battery of
tests are required to assess potential to affect the mammalian cell's
genetic components. The objectives underlying the selection of a
battery of tests for mutagenicity assessment are:
(i) To detect, with sensitive assay methods, the capacity of a
chemical to alter genetic material in cells.
(ii) To determine the relevance of these mutagenic changes to
mammals.
(iii) When mutagenic potential is demonstrated, to incorporate
these findings in the assessment of heritable effects, oncogenicity,
and possibly, other health effects.
(6) Metabolism studies. Data from studies on the absorption,
distribution, excretion, and metabolism of a pesticide aid in the
valuation of test results from other toxicity studies and in the
extrapolation of data from animals to man. The main purpose of
metabolism studies is to produce data which increase the Agency's
understanding of the behavior of the chemical in its consideration of
the human exposure anticipated from intended uses of the pesticide.
(f) Applicator and post-application exposure. Data are used to
evaluate exposures to persons in occupational and non-occupational
settings, including agricultural, residential, commercial,
institutional and recreational sites. Data include oral, dermal and
inhalation exposure data, post-application residue data, post-
application monitoring data, use information, and human activity
information. These data, together with toxicology data, are used to
determine whether application or post-application risks are of concern,
and, where appropriate, to develop post-application restrictions such
as reentry restrictions.
(g) Pesticide spray drift evaluation. Data required to evaluate
pesticide spray drift are derived from studies of droplet size spectrum
and spray drift field evaluations. These data contribute to the
development of the overall exposure estimate and, along with data on
toxicity for humans, fish and wildlife, or plants, are used to assess
the potential hazard of pesticides to these organisms. A purpose common
to all these tests is to provide data which will be used to determine
the need for (and
[[Page 12335]]
appropriate wording for) precautionary labeling to minimize the
potential adverse effect to nontarget organisms.
(h) Hazards to nontarget organisms--(1) General. The information
required to assess hazards to nontarget organisms are derived from
tests to determine pesticidal effects on birds, mammals, fish,
terrestrial and aquatic invertebrates and plants. These tests include
short-term acute, subacute, reproduction, simulated field, and full
field studies arranged in a hierarchial or tier system which progresses
from the basic laboratory tests to the applied field tests. The results
of each tier of test must be evaluated to determine the potential of
the pesticide to cause adverse effects, and to determine whether
further testing is required. A purpose common to all data requirements
is to provide data which determines the need for (and appropriate
wording for) precautionary label statements to minimize the potential
adverse effects to nontarget organisms.
(2) Short-term studies. The short-term acute and subchronic
laboratory studies provide basic toxicity information which serves as a
starting point for the hazard assessment. These data are used: to
establish acute toxicity levels of the active ingredient to the test
organisms; to compare toxicity information with measured or estimated
pesticide residues in the environment in order to assess potential
impacts on fish, wildlife and other nontarget organisms; and to
indicate whether further laboratory and/or field studies are needed.
(3) Long-term and field studies. Additional studies (i.e., avian,
fish, and invertebrate reproduction, lifecycle studies and plant field
studies) may be required when basic data and environmental conditions
suggest possible problems. Data from these studies are used to:
estimate the potential for chronic effects, taking into account the
measured or estimated residues in the environment; and to determine if
additional field or laboratory data are necessary to further evaluate
hazards. Simulated field and/or field data are used to examine acute
and chronic adverse effects on captive or monitored fish and wildlife
populations under natural or near-natural environments. Such studies
are required only when predictions as to possible adverse effects in
less extensive studies cannot be made, or when the potential for
adverse effects is high.
(i) Product performance. Requirements to develop data on product
performance provide a mechanism to ensure that pesticide products will
control the pests listed on the label and that unnecessary pesticide
exposure to the environment will not occur as a result of the use of
ineffective products. Specific performance standards are used to
validate the efficacy data in the public health areas, including
disinfectants used to control microorganisms infectious to man in any
area of the inanimate environment and those pesticides used to control
vertebrates (such as rodents, birds, bats and skunks) that may directly
or indirectly transmit diseases to humans.
Subpart C [Removed and Reserved]
e. By removing and reserving subpart C.
f. By revising subpart D to read as follows:
Subpart D--Product Chemistry
Sec. 158.300 Definitions.
The following terms are defined for the purposes of this subpart:
Active ingredient means any substance (or group of structurally
similar substances, if specified by the Agency) that will prevent,
destroy, repel or mitigate any pest, or that functions as a plant
regulator, desiccant, defoliant, or nitrogen stabilizer, within the
meaning of FIFRA sec. 2(b).
End-use product means a pesticide product whose labeling: (1)
Includes directions for use of the product (as distributed or sold, or
after combination by the user with other substances) for controlling
pests or defoliating, desiccating or regulating growth of plants, or as
a nitrogen stabilizer, and (2) does not state that the product may be
used to manufacture or formulate other pesticide products.
Formulation means: (1) The process of mixing, blending, or dilution
of one or more active ingredients with one or more other active or
inert ingredients, without an intended chemical reaction, to obtain a
manufacturing-use product or an end-use product, or (2) the repackaging
of any registered product.
Impurity means any substance (or group of structurally similar
substances if specified by the Agency), in a pesticide product other
than an active ingredient or an inert ingredient, including unreacted
starting materials, side reaction products, contaminants, and
degradation products.
Impurity associated with an active ingredient means: (1) Any
impurity present in the technical grade of active ingredient; and (2)
any impurity which forms in the pesticide product through reactions
between the active ingredient and any other component of the product or
packaging of the product.
Inert ingredient means any substance (or group of structurally
similar substances if designated by the Agency), other than the active
ingredient, which is intentionally included in a pesticide product.
Integrated system means a process for producing a pesticide product
that: (1) Contains any active ingredient derived from a source that is
not an EPA-registered product; or (2) contains any active ingredient
that was produced or acquired in a manner that does not permit its
inspection by the Agency under FIFRA sec. 9(a) prior to its use in the
process.
Manufacturing-use product means any pesticide product other than an
end-use product. A product may consist of the technical grade of active
ingredient only, or may contain inert ingredients, such as stabilizers
or solvents.
Nominal concentration means the amount of an ingredient which is
expected to be present in a typical sample of a pesticide product at
the time the product is produced, expressed as a percentage by weight.
Starting material means a substance used to synthesize or purify a
technical grade of active ingredient (or the practical equivalent of
the technical grade ingredient if the technical grade cannot be
isolated) by chemical reaction.
Technical grade of active ingredient means a material containing an
active ingredient: (1) Which contains no inert ingredient, other than
one used for purification of the active ingredient; and (2) which is
produced on a commercial or pilot plant production scale (whether or
not it is ever held for sale).
Sec. 158.310 Product chemistry data requirements table.
(a) General. (1) Sections 158.100 through 158.130 describe how to
use this table to determine the product chemistry data requirements for
a particular pesticide product. Notes that apply to an individual test
and include specific conditions, qualifications, or exceptions to the
designated test are listed in paragraph (f) of the section.
(2) Depending on the results of the required product chemistry
studies, appropriate use restrictions, labeling requirements, or
special packaging requirements may be imposed.
(3) All product chemistry data, as described in this section, are
required to be submitted to support a request for an experimental use
permit.
(b) Use patterns. Product chemistry data are required for all
pesticide products and are not use specific.
(c) Test substance. Data requirements that list only the
manufacturing-use product as the test substance apply to
[[Page 12336]]
products containing solely the technical grade of the active ingredient
and manufacturing-use products to which other ingredients have been
intentionally added.
(d) Key. R=Required; CR=Conditionally required; MP=Manufacturing-
use product; NR=Not required; EP=End-use product; TGAI=Technical grade
of the active ingredient; PAI=Pure active ingredient.
(e) Table. The following table shows the data requirements for
product chemistry. The table notes are shown in paragraph (f) of this
section.
Product Chemistry Data Requirements
----------------------------------------------------------------------------------------------------------------
Use Pattern Test substance to support
Guideline Number Data Requirement -------------------------------------------------- Test Note
All MP EP No.
----------------------------------------------------------------------------------------------------------------
Product Identity and Composition................................................................................
----------------------------------------------------------------------------------------------------------------
830.1550 Product identity R MP EP 1
and composition
-------------------------------
830.1600 Description of R MP EP 2
materials used
to produce the
product
-------------------------------
830.1620 Description of R MP EP 3
production
process
-------------------------------
830.1650 Description of R MP EP 4
formulation
process
-------------------------------
830.1670 Discussion of R MP, and possibly EP, and possibly 5
formulation of TGAI TGAI
impurities
-------------------------------
830.1700 Preliminary CR MP, and possibly EP, and possibly 6, 9, 10
analysis TGAI TGAI
-------------------------------
830.1750 Certified limits R MP EP 7
-------------------------------
830.1800 Enforcement R MP EP 8
analytical
method
-------------------------------
830.1900 Submittal of CR MP, PAI and TGAI EP, PAI, TGAI 9, 11
samples
-------------------------------
Physical and Chemical Properties..................................................................
---------------------------------------------------------------------------------------------------
830.6302 Color R MP and TGAI TGAI 9
-------------------------------
830.6303 Physical state R MP and TGAI EP and TGAI 9
-------------------------------
830.6304 Odor R MP and TGAI TGAI 9
-------------------------------
830.6313 Stability to R TGAI TGAI 9, 12
normal and
elevated
temperatures,
metals, and
metal ions
-------------------------------
830.6314 Oxidation/ CR MP EP 13
reduction:
chemical
incompatability
-------------------------------
830.6315 Flammability CR MP EP 14
-------------------------------
830.6316 Explodability CR MP EP 15
-------------------------------
830.6317 Storage R MP EP
stability
-------------------------------
830.6319 Miscibility CR MP EP 16
-------------------------------
830.6320 Corrosion R MP EP
characteristics
-------------------------------
830.6321 Dielectric CR NR EP 17
breakdown
voltage
-------------------------------
830.7000 pH CR MP and TGAI EP and TGAI 9, 18
-------------------------------
830.7050 UV/visible light R TGAI TGAI
absorption
-------------------------------
830.7100 Viscosity CR MP EP 19
-------------------------------
830.7200 Melting point/ R TGAI or PAI TGAI or PAI 9, 20
melting range
-------------------------------
830.7220 Boiling point/ R TGAI or PAI TGAI or PA 9, 21
boiling range
-------------------------------
830.7300 Density/relative R MP and TGAI EP and TGAI 9, 22
density/bulk
density
-------------------------------
830.7370 Dissociation R TGAI or PAI TGAI or PAI 9, 23
constants in
water
-------------------------------
830.7520 Particle size, CR TGAI or PAI TGAI or PAI 24
fiber length,
and diameter
distribution
-------------------------------
[[Page 12337]]
830.7550 Partition CR TGAI or PAI TGAI or PAI 25
830.7560.................... coefficient (n-
830.7570.................... octanol/water)
-------------------------------
830.7840 Water solubility R TGAI or PAI TGAI or PAI 9
830.7860....................
-------------------------------
830.7950 Vapor pressure R TGAI or PAI TGAI or PAI 9, 26
----------------------------------------------------------------------------------------------------------------
(f) Test notes. The following test notes are applicable to the
product chemistry data requirements in the table to paragrpah (e) of
this section:
1. Data must be provided in accordance with Sec. 158.320.
2. Data must be provided in accordance with Sec. 158.325.
3. Data must be provided in accordance with Sec. 158.330.
4. Data must be provided in accordance with Sec. 158.335.
5. Data must be provided in accordance with Sec. 158.340.
6. Data must be provided in accordance with Sec. 158.345.
7. Data must be provided in accordance with Sec. 158.350.
8. Data must be provided in accordance with Sec. 158.355.
9. If the TGAI cannot be isolated, data are required on the
practical equivalent of the TGAI.
10. Data are required if the product is produced by an
integrated system.
11. Basic manufacturers are required to provide the Agency with
a sample of each TGAI used to formulate a product produced by an
integrated system when the new TGAI is first used as a formulating
ingredient in products registered under FIFRA. A sample of the
active ingredient (PAI) suitable for use as an analytical standard
is also required at this time. Samples of end-use products produced
by an integrated system must be submitted on a case-by-case basis.
12. 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.
13. Required when the product contains an oxidizing or reducing
agent.
14. Required when the product contains combustible liquids.
15. Required when the product is potentially explosive.
16. Required when the product is an emulsifiable liquid and is
to be diluted with petroleum solvent.
17. Required when the EP is a liquid and is to be used around
electrical equipment.
18. Required when the test substance is soluble or dispersible
in water.
19. Required when the product is a liquid.
20. Required when the TGAI is solid at room temperature.
21. Required when the TGAI is liquid at room temperature.
22. True density or specific density are required for all test
substances. Data on bulk density is required for MPs that are solid
at room temperature.
23. Required when the test substance contains an acid or base
functionality (organic or inorganic) or an alcoholic functionality
(organic).
24. Required for water insoluble test substances
(<10-\6\ g/l) and fibrous test substances with diameter
>=0.1 [mu]m.
25. Required for all organic chemicals unless they dissociate in
water or are partially or completely soluble in water.
26. 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
[[Page 12338]]
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.
[[Page 12339]]
(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 <=1.0% N + 10%N N - 10%N
---------------------------------
1.0% <=N <=20.0% N + 5%N N - 5%N
---------------------------------
20.0%<=N<=100.0% N + 3%N N - 3%N
------------------------------------------------------------------------
(c) Applicant proposed limits. (1) The applicant may propose a
certified limit for an active or inert ingredient that differs from the
standard certified limit calculated according to paragraph (b)(2) of
this section.
(2) If certified limits are required for impurities, the applicants
must propose a certified limit. The standard certified limits may not
be used for such substances.
(3) Certified limits should:
(i) Be based on a consideration of the variability of the
concentration of the ingredient in the product when good manufacturing
practices and normal quality control procedures are used.
(ii) Allow for all sources of variability likely to be encountered
in the production process.
(iii) Take into account the stability of the ingredient in the
product and the possible formation of impurities between production and
sale or distribution.
[[Page 12340]]
(4) The applicant may include an explanation of the basis of his
proposed certified limits, including how the certified limits were
arrived at (e.g., sample analysis, quantitative estimate based on
production process), and its accuracy and precision. This will be
particularly useful if the range of the certified limit for an active
or inert ingredient is greater than the standard certified limits.
(d) Special cases. If the Agency finds unacceptable any certified
limit (either standard, or applicant proposed), the Agency will inform
the registrant or applicant of its determination and will provide
supporting reasons. The Agency may also recommend alternative limits to
the applicant. The Agency may require, on a case-by-case basis, any or
all of the following:
(1) More precise limits.
(2) More thorough explanation of how the certified limits were
determined.
(3) A narrower range between the upper and lower certified limits
than that proposed.
(e) Certification statement. The applicant must certify the
accuracy of the information presented, and that the certified limits of
the ingredients will be maintained. The following statement, signed by
the authorized representative of the company, is acceptable:
I hereby certify that, for purposes of FIFRA sec. 12(a)(1)(C),
the description of the composition of [insert product name], EPA
Reg. No. [insert registration number], refers to the composition set
forth on the Statement of Formula and supporting materials. This
description includes the representations that: (1) No ingredient
will be present in the product in an amount greater than the upper
certified limit or in an amount less than the lower certified limit
(if required) specified for that ingredient in a currently approved
Statement of Formula (or as calculated by the Agency); and (2) If
the Agency requires that the source of supply of an ingredient be
specified, that all quantities of such ingredient will be obtained
from the source specified in the Statement of Formula.
Sec. 158.355 Enforcement analytical method.
An analytical method suitable for enforcement purposes must be
provided for each active ingredient in the product and for each other
ingredient or impurity that the Agency determines to be toxicologically
significant.
g. By adding subpart E to read as follows:
Subpart E--Terrestrial and Aquatic Nontarget Organisms
Sec. 158.400 Terrestrial and aquatic nontarget organisms data
requirements table.
(a) General. Sections 158.100 through 158.130 describe how to use
this table to determine the terrestrial and aquatic nontarget data
requirements for a particular pesticide product. Notes that apply to an
individual test including specific conditions, qualifications, or
exceptions to the designated test are listed in paragraph (e) of this
section.
(b) Use patterns. (1) The terrestrial use pattern includes products
classified under the general use patterns of terrestrial food crop,
terrestrial feed crop, and terrestrial nonfood crop. The greenhouse use
pattern includes products classified under the general use patterns of
greenhouse food crop and greenhouse nonfood crop. The indoor use
pattern includes products classified under the general use patterns of
indoor food, and indoor nonfood use.
(2) Data are also required for the general use patterns of aquatic
food crop, aquatic nonfood residential, aquatic nonfood outdoor,
forestry and residential outdoor use.
(3) In general, for all outdoor end-use products including turf,
the following studies are required: two avian oral LD50, 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:
1. 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.
2. 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.
3. 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.
4. 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.
5. Data are preferred on mallard and bobwhite quail.
6. For aquatic nonfood residential uses, data are required to
support liquid and solid formulated products on one species if the
avian oral LD50 of the TGAI is less than or equal to 100
mg a.i./kg. Data on a second species are required if the avian
dietary LC50 in the first species tested is less than or
equal to 500 ppm a.i. in the diet.
7. 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.
8. 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.
9. 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.
10. 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
LC50 is 1 ppm or less. However, if the TGAI is stable in
the hydrolysis study, and the LC50 value of the first
fish tested is between 1 ppm and 10 ppm, then testing with both
species is required.
11. Freshwater fish LC50 (the most sensitive of the
species tested) using the TGAI, freshwater invertebrate
EC50 (preferably Daphnia), and acute LC50/
EC50 estuarine 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 LC50 or
EC50 of 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.
12. Data are preferred on Daphnia magna.
13. Data are preferred on eastern oyster (Crassostrea virginica)
and oppossum shrimp (America mysis) formerly (Mysidopsis bahia) and
silver side (Menidia sp. )
14. Data are generally not required for other, non-turf, outdoor
residential uses, i.e., gardens and ornamentals.
15. Data are preferred on rainbow trout. If fathead minnow
(Pimephales promelus) is used, a 96 hour LC50 on that
species must also be provided.
16. Data are preferred on oppossum shrimp (America mysis)
formerly (Mysidopsis bahia).
17. 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 LC50 or EC50< 1 mg/l.
iv. If the estimated environmental concentration in water is
equal to or greater than 0.01 of the acute EC50 or
LC50 and any of the following conditions exist:
A. Studies of other organisms indicate the reproductive
physiology of fish and/or invertebrates may be affected.
B. Physicochemical properties indicate bioaccumulation of the
pesticide.
C. The pesticide is persistent in water (e.g., half-life in
water greater than 4 days).
18. Data are preferred on sheepshead minnow (Cypinodon
variegatus).
19. 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.
20. 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.
21. Required based on the results of fish or aquatic nontarget
organism accumulation studies (guidelines 850.1730 and 850.1950).
22. 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.
23. 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.
24. 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.
25. Data required only when the formulation contains one or more
active ingredients having an acute LD50 of <11 [mu]g/bee
as determined in the honey bee acute contact study (guideline
850.3020) and the use pattern(s) indicate(s) that honey bees may be
exposed to the pesticide.
26. Required if any of the following conditions are met:
i. Data from other sources (Experimental Use Permit program,
university research, registrant submittals, etc.) indicate potential
adverse effects on colonies, especially effects other than acute
mortality (reproductive, behavioral, etc.);
ii. Data from residual toxicity studies indicate extended
residual toxicity.
iii. Data derived from studies with arthropods other than bees
that indicate potential chronic, reproductive, or behavioral
effects.
27. This requirement is reserved pending further evaluation by
EPA to determine what and when data should be required, and to
develop appropriate test methods.
h. By adding subpart F to read as follows:
Subpart F--Toxicology
Sec. 158.500 Toxicology data requirements table.
(a) General. Sections 158.100 through 158.130 describe how to use
this table to determine the toxicology data requirements for a
particular pesticide product. Notes that apply to an individual test
and include specific conditions, qualifications, or exceptions to the
designated test are listed in paragraph (e) of this section.
(b) Use patterns. (1) Food use patterns include products classified
under the general use patterns of terrestrial food crop use,
terrestrial feed crop use, aquatic food crop use, greenhouse food crop
use, and indoor food use.
(2) Nonfood use patterns include products classified under the
general use patterns of terrestrial nonfood crop use, aquatic nonfood
crop use, aquatic nonfood outdoor use, greenhouse nonfood crop use,
forestry use, residential outdoor use, indoor nonfood use, and indoor
residential use.
(c) Key. R=Required; CR=Conditionally required; NR=Not required; [
]=Required or conditionally required for an experimental use permit;
MP=Manufacturing-use product; EP=End-use product; TGAI=Technical grade
of the active ingredient; PAI=Pure active ingredient; PAIRA=Pure active
ingredient radio-labeled; Choice=Choice of several test substances
depending on study required.
(d) Table.The following table shows the toxicology data
requirements. The table notes are shown in paragraph (e) of this
section.
Table--Toxicology Data Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
Use Pattern Test substance to support
Guideline Number Data Requirements -------------------------------------------------------------------------------- Test Note No.
Food Nonfood MP EP
--------------------------------------------------------------------------------------------------------------------------------------------------------
Acute Testing
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.1100 Acute oral [R] [R] MP and TGAI TGAI, EP, and 1, 2
toxicity--rat possibly diluted
EP
---------------------------------
870.1200 Acute dermal [R] [R] MP and TGAI TGAI, EP, and 1, 2, 3
toxicity possibly diluted
EP
---------------------------------
870.1300 Acute inhalation [R] [R] MP and TGAI TGAI and EP 4
toxicity - rat
---------------------------------
870.2400 Primary eye [R] [R] MP TGAI and EP 3
irritation -
rabbit
---------------------------------
870.2500 Primary dermal [R] [R] MP TGAI and EP 1, 3
irritation
---------------------------------
870.2600 Dermal [R] [R] MP TGAI and EP 3, 5
sensitization
---------------------------------
870.6100 Delayed [CR] [CR] TGAI TGAI 6
neurotoxicity
(acute) - hen
---------------------------------
870.6200 Acute R R TGAI TGAI 7
neurotoxicity -
rat
---------------------------------
Subchronic Testing
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.3100 90-day Oral - [R] CR TGAI TGAI 8, 9
rodent
---------------------------------
[[Page 12344]]
870.3150 90-day Oral - non- [R] CR TGAI TGAI 8
rodent
---------------------------------
870.3200 21/28-day Dermal R NR TGAI TGAI and EP 10, 11
---------------------------------
870.3250 90-day Dermal CR R TGAI TGAI and EP 11, 12
---------------------------------
870.3465 90-day Inhalation - CR CR TGAI TGAI 13, 14
rat
---------------------------------
870.6100 28-day Delayed CR CR TGAI TGAI 15
neurotoxicity-hen
---------------------------------
870.6200 90-day R R TGAI TGAI 7, 16
Neurotoxicity -
rat
---------------------------------
Chronic Testing
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.4100 Chronic oral - [R] CR TGAI TGAI 17, 18, 19
rodent and non-
rodent
---------------------------------
870.4200 Carcinogenicity - R CR TGAI TGAI 9, 17, 18, 19, 20,
two rodent 21
species - rat and
mouse preferred
---------------------------------
Developmental Toxicity and Reproduction
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.3700 Prenatal [R] R TGAI TGAI 22, 23, 24, 25, 26
Developmental
toxicity - rat
and rabbit,
preferred
---------------------------------
870.3800 Reproduction [R] R TGAI TGAI 26, 27, 28
---------------------------------
870.6300 Developmental CR CR TGAI TGAI 26, 27, 28
neurotoxicity
---------------------------------
Mutagenicity Testing....................................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.5100 Bacterial reverse [R] R TGAI TGAI 29
mutation assay
870.5300 In vitro mammalian [R] R TGAI TGAI 29, 30
870.5375........................ cell assay
---------------------------------
870.5385 In vivo [R] R TGAI TGAI 29, 31
870.5395........................ cytogenetics
---------------------------------
Special Testing
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.7485 Metabolism and R CR PAI or PAIRA PAI or PAIRA 32
pharmacokinetics
---------------------------------
870.7200 Companion animal CR CR -- Choice 33
safety
---------------------------------
870.7600 Dermal penetration CR CR Choice Choice 34
---------------------------------
870.6500 Scheduled CR CR TGAI TGAI 35
controlled
operant behavior
---------------------------------
870.6850 Peripheral nerve CR CR TGAI TGAI 35
function
---------------------------------
870.6855 Neurophysiology: CR CR TGAI TGAI 35
sensory evoked
potentials
---------------------------------
870.7800 Immunotoxicity R R TGAI TGAI
--------------------------------------------------------------------------------------------------------------------------------------------------------
(e) Test notes. The following test notes are applicable to
toxicological data requirements in paragraph (d) of this section:
1. Not required if test material is a gas or a highly volatile
liquid.
2. Diluted EP testing is required to support the end product
registration if results using the EP meet the criteria for
restricted use classification under Sec. 152.170(b) or special
review consideration under Sec. 154.7(a)(1).
3. Not required if test material is corrosive to skin or has a
pH of less than 2 or greater than 11.5.
4. Required if the product consists of, or under conditions of
use will result in, a respirable material (e.g., gas, vapor,
aerosol, or particulate).
5. Required if repeated dermal exposure is likely to occur under
conditions of use.
6. Required if the test material is an organophosphorus
substance, which includes uncharged organophosphorus esters,
thioesters, or anhydrides of organophosphoric, organophosphonic, or
organophosphoramidic acids, or of related phosphorothioic,
phosponothioic, or phosphorothioamidic acids, or is structurally
related to other substances that may cause the delayed neurotoxicity
sometimes seen in this class of chemicals.
7. Additional measurements such as cholinesterase activity for
certain pesticides, e.g., organophosphates and some carbamates, will
also be required. The route of exposure must correspond with the
primary route of exposure.
[[Page 12345]]
8. Required in rat for nonfood use pesticides if oral exposure
could occur, such as through drinking water.
9. A 90-day range-finding study in both rats and mice is
required to determine dose levels if carcinogenicity studies are
required. If the mouse carcinogenicity study is not required, the
90-day mouse subchronic study is likewise not required.
10. Required for agricultural uses or if repeated human dermal
exposure may occur. Not required if an acceptable 90-day dermal
toxicity study is performed and submitted.
11. EP testing is required if the product, or any component of
it, may increase dermal absorption of the active ingredient(s) as
determined by testing using the TGAI, or increase toxic or
pharmacologic effects.
12. Required for food uses if either of the following criteria
is met:
i. The use pattern is such that the dermal route would be the
primary route of exposure.
ii. The active ingredient is known or expected to be metabolized
differently by the dermal route of exposure than by the oral route,
and a metabolite is the toxic moiety.
13. Required if there is the likelihood of significant repeated
inhalation exposure to the pesticide as a gas, vapor, or aerosol.
14. Based on estimates of the magnitude and duration of human
exposure, studies of shorter duration, e.g., 21- or 28-days, may be
sufficient to satisfy this requirement. Registrants should consult
with the Agency to determine whether studies of shorter duration
would meet this requirement.
15. Required if results of 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.
16. All 90-day subchronic studies in rats can be designed to
simultaneously fulfill the requirements of the 90-day neurotoxicity
study using separate groups of animals for testing. Although the
subchronic guidelines include the measurement of neurological
endpoints, they do not meet the requirement of the 90-day
neurotoxicity study (guideline 870.6200).
17. Required if either of the following are met:
i. The use of the pesticide is likely to result in repeated
human exposure over a considerable portion of the human lifespan, as
determined by the Agency.
ii. The use requires a tolerance or an exemption from the
requirement of a tolerance be established.
18. Based on the results of the acute and subchronic
neurotoxicity studies, or other available data, a combined chronic
toxicity and neurotoxicity study may be required.
19. Studies which are designed to simultaneously fulfill the
requirements of both the chronic oral and carcinogenicity studies
(i.e., a combined study under guideline 870.4300) may be conducted.
Minimum acceptable study durations are:
i. Chronic rodent feeding study (food use) - 24 months.
ii. Chronic rodent feeding study (nonfood use) - 12 months.
iii. Chronic nonrodent feeding study - 12 months.
iv. Mouse carcinogenicity study - 18 months.
v. Rat carcinogenicity study - 24 months.
20. Required if any of the following, as determined by the
Agency, are met:
i. The use of the pesticide is likely to result in significant
human exposure over a considerable portion of the human life span
which is significant in terms of either time, duration, or magnitude
of exposure.
ii. The use requires a tolerance or an exemption from the
requirement of a tolerance be established.
iii. The active ingredient, metabolite, degradate, or impurity
(A) is structurally related to a recognized carcinogen, (B) causes
mutagenic effects as demonstrated by in vitro or in vivo testing, or
(C) produces a morphologic effect in any organ (e.g., hyperplasia,
metaplasia) in subchronic studies that may lead to a neoplastic
change.
21. If this study is modified or waived, a subchronic 90-day
oral study (guideline 870.3100) conducted in the same species may be
required.
22. Testing in two species is required for all uses.
23. Unless the chemical or physical properties of the test
substance, or the pattern of exposure, suggest a more appropriate
route of exposure, the oral route, by oral intubation, is preferred.
24. Additional testing by other routes may be required if the
pesticide is determined to be a prenatal developmental toxicant
after oral dosing.
25. May be combined with the two-generation reproduction study
in rodents (870.3800) by utilizing a second mating of the parental
animals in either generation. The dams are to undergo a cesarean
section at one day prior to expected delivery date and evaluated
separately as specified in guideline 870.3700.
26. An information-based approach to testing is preferred, which
utilizes the best available knowledge on the chemical (hazard,
pharmacokinetic, or mechanistic data) to determine whether a
standard guideline study, an enhanced guideline study, or an
alternative study should be conducted to assess potential hazard to
the developing animal, or in some cases to support a waiver for such
testing. Registrants should submit any alternative proposed testing
protocols and supporting scientific rationale to the Agency prior to
study initiation.
27. A DNT would be required using a weight-of-the-evidence
approach when:
i. The pesticide causes treatment-related neurological effects
in adult animal studies (i.e, clinical signs of neurotoxicity,
neuropathology, functional or behavioral effects).
ii. The pesticide causes treatment-related neurological effects
in developing animals, following pre- and/or postnatal exposure
(i.e., nervous system malformations or neuropathy, brain weight
changes in offspring, functional or behavioral changes in the
offspring).
iii. The pesticide elicits a causative association between
exposures and adverse neurological effects in human epidemiological
studies.
iv. The pesticide evokes a mechanism that is associated with
adverse effects on the development of the nervous system (i.e., SAR
relationship to known neurotoxicants, altered neuroreceptor or
neurotransmitter responses).
28. The use of a combined study that utilizes the two-generation
reproduction study in rodents (870.3800) as a basic protocol for the
addition of other endpoints or functional assessments in the
immature animal is encouraged.
29. At a minimum, an initial battery of mutagenicity tests with
possible confirmatory testing is required. Other relevant
mutagenicity tests that may have been performed, plus a complete
reference list must also be submitted.
30. Choice of assay using either:
i. Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene
locus, maximizing assay conditions for small colony expression or
detection.
ii. Chinese hamster ovary (CHO) or Chinese hamster lung
fibroblast (V79) cells, hypoxanthine-guanine phosphoribosyl
transferase (hgprt) gene locus, accompanied by an appropriate in
vitro test for clastogenicity.
ii.) CHO cells strains AS52, xanthine-guanine phosphoribosyl
transferase (xprt) gene locus.
31. Choice of assays. Assays using rodent bone marrow, using
either metaphase analysis (aberrations), or micronucleus assay are
preferred.
32. Required when chronic or carcinogenicity studies are
required. May be required if significant adverse effects are seen in
available toxicology studies and these effects can be further
elucidated by metabolism studies.
33. May be required if the product's use will result in exposure
to domestic animals through, but not limited to, direct application
or consumption of treated feed.
34. Required if toxic effects are identified in the oral or
inhalation study. A risk assessment assuming that dermal absorption
is equal to oral absorption must be performed to determine if the
study is required, and to identify the doses and duration of
exposure for which dermal absorption is to be quantified.
35. May be required based on adverse effects seen in the acute
or subchronic neurotoxicity screening studies, or other studies, or
if the test substance is structurally related to a chemical known to
cause effects best assessed by these studies.
Sec. 158.510 Tiered testing options for nonfood pesticides.
For nonfood use pesticides only, applicants have two options for
generating and submitting required toxicology (Sec. 158.500) and human
exposure (Sec. 158.820, Sec. 158.1110, and Sec. 158.1420) studies.
The options in this paragraph do not apply to pesticides used in or on
food. Applicants are to select one of the following:
(a) Acute, subchronic, chronic, and other toxicological studies on
the active ingredient must be submitted together. The specific makeup
of the set of toxicology study requirements is based
[[Page 12346]]
on the anticipated exposure to the pesticide as determined by the
Agency. If hazards are identified based upon review of these studies,
specific exposure data will be required to evaluate risk.
(b) Certain toxicological and exposure studies must be submitted
simultaneously with the toxicology data submitted in a tiered system.
Exposure data must be submitted along with first tier toxicology data.
The requirement for additional second and third level toxicology
testing will be determined by the Agency based on the results of the
first tiered studies.
(1) The required first-tier toxicology studies consist of:
(i) Battery of acute studies (guidelines 870.1100 - 870.2600)
(ii) A subchronic 90-day dermal study (guideline 870.3250) or a
subchronic 90-day inhalation study (guideline 870.3465)
(iii) An acute and subchronic neurotoxicity screening battery in
the rat (guidelines 870.6100 and 870.6200); a developmental
neurotoxicity study in the rat (guideline 870.6300)
(iv) Prenatal developmental toxicity studies in both the rat and
rabbit (guideline 870.3700).
(v) Reproduction and fertility studies in rats (guideline 870.3800)
(vi) Battery of mutagenicity studies (guideline 870.5100 -
870.5395)
(vii) Immunotoxicity study (guideline 870.7800)
(2) The conditionally required second-tier studies include:
(i) Subchronic 90-day feeding studies in both the rodent and
nonrodent (guidelines 870.3100 and 870.3150)
(ii) Dermal penetration study (guideline 870.7600)
(3) The conditionally required third-tier studies include:
(i) Chronic feeding studies in both the rodent and nonrodent
(guideline 870.4100)
(ii) Carcinogenicity (guidelines 870.4200)
(iii) Metabolism study (guideline 870.7485)
(iv) Additional mutagenicity testing (no guideline number)
Subpart G--Product Performance
i. By adding subpart G entitled ``Product Performance''.
Sec. 158.610 [Redesignated from Sec. 158.640]
j. By redesignating Sec. 158.640 as Sec. 158.610 and adding
redesignated Sec. 158.610 to subpart G.
Subparts H-I [Reserved]
k. By adding and reserving subparts H and I.
l. By adding subpart J to read as follows:
Subpart J--Nontarget Plant Protection
Sec. 158.700 Nontarget plant protection data requirements Table.
(a) General. Sections 158.100 through 158.130 describe how to use
this table to determine the nontarget plant data requirements for a
particular pesticide product. Notes that apply to an individual test
include specific conditions, qualifications, or exceptions to the
designated test are listed in paragraph (e) of this section.
(b) Use patterns. (1) The terrestrial use pattern includes products
classified under the general use patterns of terrestrial food crop,
terrestrial feed crop, and terrestrial nonfood. The aquatic use pattern
includes the general use patterns of aquatic food crop, aquatic nonfood
residential, and aquatic nonfood outdoors.
(2) Data are also required for the general use patterns of forestry
use and residential outdoor use.
(c) Key. R=Required; CR=Conditionally required; NR=Not required;
TGAI=Technical grade of the active ingredient; TEP=Typical end-use
product.
(d) Table. The following table shows the nontarget plant protection
data requirements. The table notes are shown in paragraph (e) of this
section.
Table--Nontarget Plant Protection Data Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
Use Pattern
------------------------------------------------------------
Guideline Number Data Requirement Forestry and Test substance Test Note No.
Terrestrial Aquatic Residential
Outdoor
--------------------------------------------------------------------------------------------------------------------------------------------------------
Nontarget Area Phytotoxicity - Tier I
--------------------------------------------------------------------------------------------------------------------------------------------------------
850.4100 Seedling emergence R R R TEP 1, 2, 3
---------------------------------
850.4150 Vegetative vigor R R R TEP 1, 2
---------------------------------
850.4400 Aquatic plant R R R TEP or TGAI 1, 2
850.5400...................... growth (algal and
aquatic vascular
plant toxicity)
---------------------------------
Nontarget Area Phytotoxicity - Tier II
--------------------------------------------------------------------------------------------------------------------------------------------------------
850.4225 Seedling emergence CR CR CR TEP 1, 3, 4, 5
---------------------------------
850.4250 Vegetative vigor CR CR CR TEP 1, 4, 5
---------------------------------
850.4400 Aquatic plant CR CR CR TEP or TGAI 1, 4, 6
850.5400...................... growth (algal and
aquatic vascular
plant toxicity)
---------------------------------
Nontarget Area Phytotoxicity - Tier III
--------------------------------------------------------------------------------------------------------------------------------------------------------
850.4300 Terrestrial field CR CR CR TEP 1, 7, 8
---------------------------------
850.4450 Aquatic field CR CR CR TEP 1, 8
---------------------------------
Target Area Phytotoxicity
--------------------------------------------------------------------------------------------------------------------------------------------------------
850.4025 Target area CR CR CR TEP 1, 7, 9
phytotoxicity
--------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 12347]]
(e) Test notes. The following test notes apply to the table in
paragraph (d) of this section.
1. Not required for contained pesticide treatments such as bait
boxes and pheromone traps unless adverse effects reports are
received by the Agency.
2. Required for all outdoor pesticide uses except for known
phytotoxicants (such as herbicides, desiccants, defoliants).
3. Generally not required for granular formulations. May be
requested on a case-by-case basis.
4. Required for known phytotoxicants such as herbicides,
desiccants, defoliants, and plant growth regulators.
5. Required if a terrestrial species exhibits a 25 percent or
greater detrimental effect in Tier I.
6. Required if an aquatic species exhibits a 50 percent or
greater detrimental effect in Tier I.
7. Not required for aquatic residential uses.
8. Environmental chemistry methods used to generate data must
include results of a successful confirmatory method trial by an
independent laboratory.
9. Tests are required based on the results of lower tier
phytotoxicity studies, adverse incident reports, intended use
pattern, and environmental fate characteristics that indicate
potential exposure.
m. By adding subpart K to read as follows:
Subpart K--Post-application Exposure
Sec. 158.800 General requirements.
(a) Certain measures taken to reduce or mitigate exposure may
affect the need for data. Where label, formulation, or packaging and
use restrictions, e.g., child-resistant bait stations, are expected to
significantly decrease or eliminate exposure, these data requirements
may not be required.
(b) If EPA determines that industrial standards, such as the
workplace standards set by Occupational Safety and Health
Administration, provide adequate protection for a particular pesticide
use pattern, post-application exposure data may not be required for
that use pattern. Applicants should consult with the Agency on
appropriate testing before the initiation of studies.
(c) The Agency may accept surrogate exposure data from other
sources to satisfy post-application exposure data requirements if the
data meet the basic quality assurance, quality control, good laboratory
practice, and other scientific needs of EPA. In order to be acceptable,
among other things, the Agency must find that the surrogate exposure
data have adequate information to address post-application exposure
data requirements and contain adequate replicates of acceptable quality
data to reflect the specific use prescribed on the label and the post-
application activity of concern, including formulation type,
application methods and rates, type of activity, and other pertinent
information. The Agency will consider using such surrogate data for
evaluating human exposure on a case-by-case basis.
Sec. 158.810 Criteria for testing
Exposure data described in Sec. 158.820(d) are required based upon
toxicity and exposure criteria. Data are required if a product meets,
as determined by the Agency, either or both of the toxicity criteria in
paragraph (a) of this section and either or both of the exposure
criteria in paragraph (b) of this section.
(a) Toxicity criteria. (1) Evidence of potentially significant
adverse health effects have been observed in any applicable toxicity
studies.
(2) Scientifically sound epidemiological or poisoning incident data
indicate that adverse health effects may have resulted from post-
application exposure to the pesticide.
(b) 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.
(1) For outdoor uses. (i) 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, ornamental plants, and turf grass.
(ii) Residential human post-application exposure to pesticide
residues on plants or in soil could occur. Such plants may include turf
grass, fruits, vegetables, and ornamentals grown at sites, including,
but not limited to, homes, parks, and recreation areas.
(2) For indoor uses. (i) 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.
(ii) 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.
Sec. 158.820 Post-application exposure data requirements table
(a) General. Sections 158.100 through 158.130 describe how to use
this table to determine the post-application data requirements for a
particular pesticide product. Notes that apply to an individual test
and include specific conditions, qualifications, or exceptions to the
designated test are listed in paragraph (e) of this section.
(b) Use patterns. (1) Occupational use patterns include products
classified under the general use patterns of terrestrial food crop,
terrestrial feed crop, terrestrial nonfood use, aquatic food crop,
aquatic nonfood use, aquatic nonfood outdoor, aquatic nonfood
industrial, forestry, greenhouse food, greenhouse nonfood, indoor food,
and indoor nonfood. Occupational use patterns also include commercial
(``for hire'') applications to residential outdoor and indoor sites.
(2) Residential use patterns include residential outdoor use and
indoor residential use. These use patterns are limited to
nonoccupational,i.e., nonprofessional, pesticide applications.
(c) Key. R=Required; CR=Conditionally required; NR=Not required;
TEP=Typical End-use product.
(d) Table. The data requirements listed in the following table
pertain to pesticide products that meet the testing criteria outlined
in Sec. 158.810. The table notes are shown in paragraph (e) of this
section.
Post-Application Exposure Data Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
Use Pattern
Guideline Number Data Requirement ----------------------------------------------- Test Substance Test Note No.
Occupational Residential
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.2100 Dislodgeable foliar R R TEP 1, 2, 3, 4, 5
residue and turf
transferable residues
------------------------------------
[[Page 12348]]
875.2200 Soil residue R CR TEP 1, 2, 6, 7
dissipation
------------------------------------
875.2300 Indoor surface residue R R TEP 1, 2, 8, 9
dissipation
------------------------------------
875.2400 Dermal exposure R R TEP 1, 2, 10, 11, 12
------------------------------------
875.2500 Inhalation exposure R R TEP 1, 10, 11, 12
------------------------------------
875.2600 Biological monitoring CR CR TEP 1, 12, 13
------------------------------------
875.2700 Product use R R TEP --
information
------------------------------------
875.2800 Description of human R R TEP --
activity
------------------------------------
875.2900 Data reporting and R R TEP 14
calculations
------------------------------------
875.3000 Nondietary ingestion NR R TEP 1, 11, 15
exposure
--------------------------------------------------------------------------------------------------------------------------------------------------------
(e) Test notes. The following test notes apply to the data
requirements in the table to paragraph (d) of this section:
1. Protocols must be submitted for approval prior to the
initiation of the study. Details for developing protocols are
available from the Agency.
2. Bridging applicable residue dissipation data to dermal
exposure data is required.
3. Turf grass transferable residue dissipation data are required
when pesticides are applied to turf grass. Dislodgeable foliar
residue dissipation data are required when pesticides are applied to
the foliage of plants other than turf grass.
4. Data are required for occupational sites, if (i) there are
uses on turf grass or other plant foliage, and (ii) the human
activity data indicate that workers are likely to have post-
application dermal contact with treated foliage while participating
in typical activities.
5. Data are required for residential sites if there are uses on
turf grass or other plant foliage.
6. Data are required for occupational sites, if (i) there are
outdoor or greenhouse uses to or around soil or other planting
media, and (ii) the human activity data indicate that workers are
likely to have post-application dermal contact with treated soil or
planting media while participating in typical activities.
7. Data are required for residential sites if the pesticide is
applied to or around soil or other planting media both outdoors and
indoors, e.g., residential greenhouse or houseplant uses.
8. Data are required for occupational sites if the pesticide is
applied to or around on non-plant surfaces, e.g., flooring or
countertops, and if the human activity data indicate that workers
are likely to have post-application dermal contact with treated
indoor surfaces while participating in typical activities.
9. Data are required for residential sites if the pesticide is
applied to or around non-plant surfaces, e.g., flooring and
countertops.
10. Data are required for occupational sites if the human
activity data indicate that workers are likely to have post-
application exposures while participating in typical activities.
11. Data are required for residential sites if post-application
exposures are likely.
12. Biological monitoring data may be submitted in addition to,
or in lieu of, dermal and inhalation exposure data provided the
human pharmocokinetics of the pesticide and/or metabolite/analog
compounds (i.e., whichever method is selected as an indicator of
body burden or internal dose) allow for a back-calculation to the
total internal dose.
13. Data are required when passive dosimetry techniques are not
applicable for a particular exposure scenario, such as a swimmer
exposure to pesticides.
14. Data reporting and calculations are required when any post-
application exposure monitoring data are submitted.
15. The selection of a sampling method will depend on the
nondietary pathway(s) of interest. Data must be generated to
consider all potential pathways of nondietary ingestion exposure
that are applicable (e.g., soil ingestion, hand-to-mouth transfer,
and object-to-mouth transfer of surface residues).
Subpart L--Biochemical Pesticides
n. By adding subpart L entitled ``Biochemical Pesticides.''
Sec. 158.910 [Redesignated from Sec. 158.690]
o. By redesignating Sec. 158.690 as Sec. 158.910 and adding Sec.
158.910 to subpart L.
Subpart M--Microbial Pesticides
p. By adding subpart M entitled ``Microbial Pesticides.''
Sec. 158.1010 [Redesignated from 158.740]
q. By redesignating Sec. 158.740 as Sec. 158.1010 and adding
redesignated Sec. 158.1010 to subpart M.
r. By adding subpart N to read as follows:
Subpart N--Environmental Fate
Sec. 158.1100 Environmental Fate Data Requirements Table.
(a) General. Sections 158.100 through 158.130 describe how to use
this table to determine the environmental fate data requirements for a
particular pesticide product. Notes that apply to an individual test
including specific conditions, qualifications, or exceptions to the
designated test are listed in paragraph (e) of this section.
(b) Use patterns. (1) The terrestrial use pattern includes products
classified under the general use patterns of terrestrial food crop,
terrestrial feed crop, and terrestrial nonfood. The aquatic use pattern
includes the general use patterns of aquatic food crop, aquatic nonfood
residential, and aquatic nonfood outdoors. The greenhouse use pattern
includes both food and nonfood uses. The indoor use pattern includes
food, nonfood, and residential indoor uses.
(2) Data are also required for the general use patterns of forestry
use and residential outdoor use.
(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; PAIRA=Pure active ingredient radio-labeled.
(d) Table.The following table list the data requirements that
pertain to environmental fate. The table notes are shown in paragraph
(e) of this section.
[[Page 12349]]
Environmental Fate Data Requirements
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Use pattern
------------------------------------------------------------------------------------------------------------
Guideline Number Data requirement Residential Test substance Test Note No.
Terrestrial Aquatic Greenhouse Indoor Forestry Outdoors
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Degradation Studies--Laboratory
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
835.2120 Hydrolysis [R] [R] [R] CR [R] [R] TGAI or PAIRA 1
-------------------------------
835.2240 Photodegradation R R NR NR R NR TGAI or PAIRA 2
in water
-------------------------------
835.2410 Photodegradation R NR NR NR R NR TGAI or PAIRA 3
on soil
-------------------------------
835.2370 Photodegradation CR NR CR NR CR CR TGAI or PAIRA 4
in air
-------------------------------
Metabolism Studies - Laboratory
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
835.4100 Aerobic soil [R] CR R NR [R] R TGAI or PAIRA 5
-------------------------------
835.4200 Anaerobic soil R NR NR NR NR NR TGAI or PAIRA --
-------------------------------
835.4300 Aerobic aquatic R [R] NR NR R NR TGAI or PAIRA --
-------------------------------
835.4400 Anaerobic R R NR NR R NR TGAI or PAIRA --
aquatic
-------------------------------
Mobility Studies................................................................................................................................................................................
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
835.1230 Leaching and [R] R R NR [R] R TGAI or PAIRA --
835.1240.................... adsorption/
desorption
-------------------------------
835.1410 Volatility - CR NR CR NR NR NR TEP 4
laboratory
-------------------------------
835.8100 Volatility - CR NR CR NR NR NR TEP --
field
-------------------------------
Dissipation Studies - Field
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
835.6100 Terrestrial R CR NR NR NR R TEP 5, 6
-------------------------------
835.6200 Aquatic CR R NR NR NR NR TEP 6, 7
(sediment)
-------------------------------
835.6300 Forestry NR NR NR NR CR NR TEP 6, 8
-------------------------------
835.6400 Combination and CR CR NR NR NR NR TEP 9
tank mixes
-------------------------------
Accumulation Studies
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1730 Fish [CR] [CR] NR NR [CR] NR TGAI or PAIRA 10
-------------------------------
850.1950 Aquatic CR CR NR NR CR NR TEP 11
nontarget
organisms
-------------------------------
Ground Water Monitoring
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
835.7100 Ground water CR NR NR NR CR NR TEP 6, 8, 12
monitoring
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
(e) Test notes. The following test notes apply to the data
requirements in the table to paragraph (d) of this section.
1. Study is required for indoor uses in cases where
environmental exposure is likely to occur. Such sites include, but
are not limited to, agricultural premises, in or around farm
buildings, barnyards, and beehives.
2. Not required when the electronic absorption spectra, measured
at pHs 5, 7, and 9, of the chemical and its hydrolytic products, if
any, show no absorption or tailing between 290 and 800 nm.
3. Not required when the chemical is to be applied only by soil
injection or is incorporated in the soil.
4. Requirement based on use patterns and other pertinent factors
including, but not limited to, Henry's Law Constant. In view of
methodological difficulties with the study of photodegradation in
air, prior consultation with the Agency regarding the protocol is
recommended before the test is performed.
5. Required for aquatic food and nonfood crop uses for aquatic
sites that are intermittently dry. Such sites include, but are not
limited to cranberry bogs and rice paddies.
[[Page 12350]]
6. Environmental chemistry methods used to generate data
associated with this study must include results of a successful
confirmatory method trial by an independent laboratory. The
environmental chemistry methods must include a statement of no data
confidentiality claims, i.e., non-CBI. Test standards and procedures
for independent laboratory validation are available as addenda to
the guideline for this test requirement.
7. Requirement for terrestrial uses is based on potential for
aquatic exposure and if pesticide residues have the potential for
persistence, mobility, nontarget aquatic toxicity or
bioaccumulation. Not required for aquatic residential uses.
8. Agency approval of a protocol is necessary prior to
initiation of the study.
9. Requirement based on use patterns and other environmental
factors that indicate potential exposure.
10. Not required when the octanol/water partition coefficients
of the pesticide and its major degradates are less than 1,000; or
there are no potential exposures to fish and other nontarget aquatic
organisms; or the hydrolytic half-life is less than 5 days at pH 5,
7, and 9.
11. Required if significant concentrations of the active
ingredient and/or its principal degradation products are likely to
occur in aquatic environments and may accumulate in aquatic
organisms.
12. Required if the weight of evidence indicates that the
pesticide and/or its degradates is likely to leach to ground water,
taking into account other factors such as the toxicity of the
chemicals(s), available monitoring data, and the vulnerability of
ground water resources in the pesticide use area.
s. Subpart O is added to read as follows:
Subpart O--Residue Chemistry
Sec. 158.1200 Definitions.
The following terms are defined for the purposes of this subpart:
Livestock, for the purposes of this section, includes all domestic
animals that are bred for human consumption, including, but not limited
to, cattle, swine, sheep, and poultry.
Plant or animal metabolite means a pesticide chemical residue that
is the result of biological breakdown of the parent pesticide within
the plant or animal.
Residue of concern means the parent pesticidal compound and its
metabolites, degradates, and impurities of toxicological concern.
Tolerance, for the purposes of this section, includes the
establishment of a new tolerance or tolerance exemption, or amended
tolerance or tolerance exemption.
Sec. 158.1210 Residue chemistry data requirements table.
(a) General. (1) Sections 158.100 through 158.130 describe how to
use this table to determine the residue chemistry data requirements for
a particular pesticide product. Notes that apply to an individual test
and include specific conditions, qualifications, or exceptions to the
designated test are listed in paragraph (e) of this section.
(2) All residue chemistry data requirements, as described in this
section, are required for an experimental use permit.
(b) Use patterns. (1) Data are required or conditionally required
for all pesticides used in or on food and for residential outdoor uses
where food crops are grown. Food use patterns include products
classified under the general use patterns of terrestrial food crop use,
terrestrial feed crop use, aquatic food crop use, greenhouse food crop
use, and indoor food use.
(2) Data may be required for nonfood uses if pesticide residues may
occur in food or feed as a result of the use. Data requirements for
these nonfood uses will be determined on a case-by-case basis. For
example, most products used in or near kitchens require residue data
for risk assessment purposes even though tolerances may not be
necessary in all cases. Food uses in general require a more extensive
database to characterize the extent of the exposure, whereas nonfood
uses which are of shorter duration, may require fewer studies. Uses
include products classified under the general use patterns of
terrestrial nonfood crop use, aquatic nonfood crop use, aquatic nonfood
outdoor use, greenhouse nonfood crop use, forestry use, indoor nonfood
use, and indoor residential use.
(c) Key. R=Required; CR=Conditionally required; NR=Not required;
TGAI=Technical grade of the active ingredient; PAI=Pure active
ingredient; PAIRA=Pure active ingredient radio-labeled; Residue of
concern= the active ingredient and its metabolites, degradates, and
impurities of toxicological concern; TEP=Typical end-use product.
(d) Table. The following table list the data requirements for
residue chemistry related to food uses. The table notes are shown in
paragraph (e) of this section.
Table--Residue Chemistry Data Requirements for Food Uses
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Use Pattern
----------------------------------------------------------------------------------------------------
Guideline Number Data Requirement Terrestrial Food Residential Test substance Test Note No.
or Feed Aquatic Food Greenhouse Food Indoor Food Outdoor
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Supporting Information
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
860.1100 Chemical identity R R R R R TGAI --
---------------------------------
860.1200 Directions for use R R R R R -- --
---------------------------------
860.1550 Proposed tolerance R R R CR NR -- 1
---------------------------------
860.1560 Reasonable grounds R R R CR NR -- 1
in support of
petition
---------------------------------
860.1650 Submittal of R R R CR NR PAI and residue of 1, 2
analytical concern
reference
standards
---------------------------------
Nature of the residue
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
860.1300 Nature of the R R R CR CR PAIRA 3, 4
residue in plants
---------------------------------
[[Page 12351]]
860.1300 Nature of the CR CR CR CR NR PAIRA or 1, 5, 6
residue in radiolabeled
livestock plant metabolite
---------------------------------
860.1850 Confined CR CR NR NR NR PAIRA 7
rotational crops
---------------------------------
Analytical methods
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
860.1340 Residue analytical R R R CR CR Residue of concern 1, 3, 8, 9, 10
methods
---------------------------------
860.1360 Multiresidue R R R CR NR Residue of concern 1, 11
method
---------------------------------
Magnitude of the residue
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
860.1380 Storage stability R R R CR CR TEP or residue of 1, 3, 10, 12
concern
---------------------------------
860.1500 Crop field trials R R R CR CR TEP 3, 10, 14
---------------------------------
860.1520 Processed food or CR CR CR CR NR TEP 1, 15
feed
---------------------------------
860.1480 Meat/milk/poultry/ CR CR CR CR NR TGAI or plant 1, 16, 17, 18
eggs metabolite
---------------------------------
860.1400 Potable water NR R NR NR NR TEP 19
---------------------------------
860.1400 Fish NR R NR NR NR TEP 5
---------------------------------
860.1400 Irrigated crops NR CR NR NR NR TEP 20
---------------------------------
860.1460 Food handling NR NR NR CR NR TEP 1, 21
---------------------------------
860.1540 Anticipated CR CR CR CR NR Residue of concern 1, 13, 22
residues
---------------------------------
860.1900 Field rotational CR CR NR NR NR TEP 23
crops
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
(e) Test notes. The following test notes apply to the data
requirements in the table to paragraph (d) of this section.
1. Required if indoor use could result in pesticide residues in
or on food or feed.
2. Material safety data sheets must accompany standards as
specified by OSHA in 29 CFR 1910.1200.
3. Required for residential outdoor use on food crops if home
gardens are to be treated or the home garden use is different from
the agricultural use pattern on which the tolerance is established.
4. Required for indoor uses where the pesticide is applied
directly to food, in order to determine metabolites and/or
degradates. Not required when only indirect contact with food would
occur (e.g., crack and crevice treatments).
5. Data for fish are required for all pesticides applied
directly to water inhabited, or will be inhabited, by fish that may
be caught or harvested for human consumption.
6. Required when a pesticide is to be applied directly to
livestock, to livestock premises, to livestock drinking water, or to
crops used for livestock feed. If results from the plant metabolism
study show differing metabolites in plants from those found in
animals, an additional livestock metabolism study involving dosing
with the plant metabolite(s) may also be required.
7. Required when it is reasonably foreseeable that a food or
feed crop could be subsequently planted on the site of the pesticide
application.
8. A residue analytical method suitable for enforcement purposes
is required whenever a numeric tolerance (including temporary and
time-limited tolerance) is proposed, and may be required for a
tolerance exemption.
9. New analytical methods to be used for enforcement purposes
must include results from an independent laboratory validation.
10. A residue method, storage stability data, and crop field
trials are required for the nonfood crop tobacco (green, freshly
harvested). Depending on the level of residues found on the green
tobacco, additional data may be required on cured/dried tobacco and
pyrolysis products (guideline 860.1000).
11. Data are required to determine whether FDA/USDA multiresidue
methodology would detect and identify the pesticides and any
metabolites.
12. Data are required for any magnitude of the residue study
unless analytical samples
[[Page 12352]]
are stored frozen for 30 days or less, and the active ingredient is
not known to be volatile or labile.
13. Studies using single serving samples of a raw agricultural
commodity may be needed for acutely toxic pesticides and/or their
metabolites. These residue studies must be conducted using a
statistical design accepted by the Agency.
14. Required for indoor uses which are direct postharvest
treatments of raw agricultural commodities (e.g., fungicidal waxes
or stored grain fumigants).
15. Data on the nature and level of residues in processed food/
feed are required if residues could potentially concentrate on
processing thus requiring the establishment of a separate tolerance
higher than that of the raw agricultural commodity. Studies,
however, may be waived if it can be demonstrated that residues do
not concentrate on processing.
16. Required when the pesticide use is a direct application to
livestock.
17. Data are required if pesticide residues are present in or on
livestock feed items. These studies, however, may be waived by the
Agency in cases where the residue levels are low or the animal
metabolism studies indicate negligible transfer of the pesticide
and/or metabolite(s) to tissues, milk, and eggs.
18. If results from the plant metabolism study show differing
metabolites in plants from those found in animals, an additional
livestock feeding study involving dosing with the plant
metabolite(s) may also be required.
19. Data are required whenever a pesticide may be applied
directly to water, unless it can be demonstrated that the treated
water would not be available for human or livestock consumption.
20. Data are required when a pesticide is to be applied directly
to water that could be used for irrigation or to irrigation
facilities such as irrigation ditches.
21. Data are required whenever a pesticide may be used in a food
handling or feed handling establishment.
22. Required when residues at the tolerance level may result in
a risk of concern. These data may include washing, cooking,
processing or degradation studies as well as market basket surveys
for a more precise residue determination.
23. Required if pesticide or metabolite residues of
toxicological concern are found in crops at the appropriate plant
back intervals from a confined rotational crop study (guideline
860.1850).
Subpart P--Pesticide Management and Disposal
t. By adding subpart P consisting of Sec. 158.1300 which is
reserved.
Subpart R--Spray Drift
u. By adding subpart R entitled ``Spray Drift.''
Sec. 158.1410 [Redesignated from 158.440]
v. By redesignating Sec. 158.440 as Sec. 158.1410 and adding
redesignated Sec. 158.1410 to subpart R.
w. Subpart U is added to read as follows:
Subpart U--Applicator Exposure
Sec. 158.1500 General requirements.
(a) If EPA determines that industrial standards, such as the
workplace standards set by OSHA, provide adequate protection from risk
under FIFRA for a particular pesticide use pattern, exposure data may
not be required for that use pattern. Applicants should consult with
the Agency on appropriate testing prior to the initiation of studies.
(b) The Agency may accept surrogate exposure data estimations from
other sources to satisfy applicator exposure data requirements if the
data meet the basic quality assurance, quality control, good laboratory
practice, and other scientific requirements set by EPA. In order to be
acceptable, the Agency must find that the surrogate exposure data
estimations have adequate information to address applicator exposure
data requirements and contain adequate replicates of acceptable quality
data to reflect the specific use prescribed on the label and the
applicator activity of concern, including formulation type, application
methods and rates, type of activity, and other pertinent information.
The Agency will consider using such surrogate data for evaluating human
exposure on a case-by-case basis.
Sec. 158.1510 Criteria for testing.
Applicator exposure data are required based on toxicity and
exposure criteria. Data are required if a product meets, as determined
by the Agency, at least one of the toxicity criteria in paragraph (a)
of this section and either of the exposure criteria in paragraph (b) of
this section.
(a) Toxicity criteria. (1) Evidence of potentially significant
adverse effects have been observed in any applicable toxicity studies.
(2) Scientifically sound epidemiological or poisoning incident data
indicate that adverse health effects may have resulted from handling of
the pesticide.
(b) Exposure criteria. (1) Dermal exposure may occur during the
prescribed use.
(2) Respiratory exposure may occur during the prescribed use.
Sec. 158.1520 Applicator exposure data requirements table.
(a) General. Sections 158.100 through 158.130 describe how to use
this table to determine the application data monitoring data
requirements for a particular pesticide product. Notes that apply to an
individual test and include specific conditions, qualifications, or
exceptions to the designated test are listed in paragraph (e) of this
section.
(b) Use patterns. (1) Occupational use patterns include products
classified under the general use patterns of terrestrial food crop,
terrestrial feed crop, terrestrial nonfood use, aquatic food crop,
aquatic nonfood use, aquatic nonfood outdoor, aquatic nonfood
industrial, forestry, greenhouse food, greenhouse nonfood, indoor food
use, indoor nonfood use, and indoor medical use. Occupational use
patterns also include commercial (``for hire'') applications to
residential outdoor and indoor sites.
(2) Residential use patterns include residential outdoor use and
indoor residential use. These use patterns are limited to
nonoccupational,i.e., nonprofessional, pesticide applications.
(c) Key. R=Required; CR=Conditionally required; TEP=Typical end-use
product.
(d) Table. The data requirements listed pertain to pesticide
products that meet the testing criteria outlined in Sec. 158.1510. The
table notes are shown in paragraph (e) of this section.
Applicator Exposure Data Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
Use pattern
Guideline Number Data requirement ----------------------------------------------- Test substance Test Note No.
Occupational Residential
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.1100 Dermal outdoor R R TEP 1, 2, 3, 4
exposure
------------------------------------
875.1200 Dermal indoor exposure R R TEP 1, 2, 5, 6
------------------------------------
875.1300 Inhalation outdoor R R TEP 1, 2, 3, 4
exposure
------------------------------------
[[Page 12353]]
875.1400 Inhalation indoor R R TEP 1, 2, 5, 6
exposure
------------------------------------
875.1500 Biological monitoring CR CR TEP 1, 2
------------------------------------
875.1600 Data reporting and R R TEP 7
calculations
------------------------------------
875.1700 Product use R R TEP --
information
--------------------------------------------------------------------------------------------------------------------------------------------------------
(e) Test notes. The following notes apply to the data requirements
in the table to paragraph (d) of this section:
1. Protocols must be submitted for approval prior to the
initiation of the study. Details for developing protocols are
available from the Agency.
2. Biological monitoring data may be submitted in addition to,
or in lieu of, dermal and inhalation exposure data, provided the
human pharmocokinetics of the pesticide and/or metabolite/analog
compounds (i.e., whichever method is selected as an indicator of
body burden or internal dose) allow for the back calculation to
actual dose.
3. Data are required for outdoor occupational site if the
product is applied outdoors.
4. Data are required for residential use sites if the product is
applied outdoors.
5. Data are required for occupational sites if the product is
applied indoors.
6. Data are required for residential use sites if the product is
applied indoors.
7. Data reporting and calculations are required when handler
exposure data are submitted.
Subpart V--Inert Ingredients
x. By adding subpart V consisting of Sec. 158.1600 which is
reserved.
Subpart W--Antimicrobial Pesticides
y. By adding subpart W consisting of Sec. 158.1700 which is
reserved.
Appendix A [Removed]
z. By removing Appendix A.
[FR Doc. 05-4466 Filed 3-10-05; 8:45 am]
BILLING CODE 6560-50-S