[Federal Register Volume 71, Number 45 (Wednesday, March 8, 2006)]
[Proposed Rules]
[Pages 12072-12117]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 06-2185]
[[Page 12071]]
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Part III
Environmental Protection Agency
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40 CFR Parts 158 and 172
Pesticides; Data Requirements for Biochemical and Microbial Pesticides;
Proposed Rule
Federal Register / Vol. 71, No. 45 / Wednesday, March 8, 2006 /
Proposed Rule
[[Page 12072]]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Parts 158 and 172
[EPA-HQ-OPP-2004-0415; FRL-7763-4]
RIN 2070-AD51
Pesticides; Data Requirements for Biochemical and Microbial
Pesticides
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: EPA is proposing to update and revise its data requirements
for the registration of microbial and biochemical pesticide products to
reflect current scientific knowledge. These proposed revisions are
intended to provide EPA with data and other information necessary to
support the registration of a biochemical and microbial pesticide
product, and will improve the Agency's ability to make regulatory
decisions about the human health and environmental effects of these
pesticide products. EPA is also proposing to update the definitions of
a biochemical pesticide and a microbial pesticide to more accurately
describe these categories of pesticides, and to make a conforming
change to the definition of microbial pesticide. EPA is announcing its
policy to provide assistance to applicants when needed in determining
what data are appropriate to support registration of a biochemical or
microbial pesticide and encouraging applicants to request pre-
submission meetings to discuss these data issues. EPA is announcing its
intent to provide assistance to applicants in some narrow circumstances
in preparation of an applicant's data waiver.
DATES: Comments must be received on or before June 6, 2006.
ADDRESSES: Submit your comments, identified by docket identification
(ID) number EPA-HQ-OPP-2004-0415, by one of the following methods:
Federal eRulemaking Portal:http://www.regulations.gov. Follow the
on-line instructions for submitting comments.
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. In
addition, please mail a copy of your comments on the information
collection provisions to the Office of Information and Regulatory
Affairs, Office of Management and Budget (OMB), Attn: Desk Officer for
EPA, 725 17th St. NW., Washington, DC 20503.
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. EPA-HQ-OPP-
2006-0415. 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.regulations.gov/, including any personal information
provided, unless the comment includes information claimed to be
Confidential Business Information (CBI) or other information whose
disclosure is restricted by statute. Do not submit information that you
consider to be CBI or otherwise protected through regulations.gov or e-
mail. The regulations.gov website is an ``anonymous access'' system,
which means EPA will not know your identity or contact information
unless you provide it in the body of your comment. If you send an e-
mail comment directly to EPA without going through regulations.gov your
e-mail address will be automatically captured and included as part of
the comment that is placed in the 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 the EPA Docket Center
homepage athttp://www.epa.gov/epahome/dockets.htm.
Docket: All documents in the docket are listed in the
regulations.gov index. Although listed in the index, some information
is not publicly available, e.g., CBI or other information whose
disclosure is restricted by statute. Certain other material, such as
copyrighted material, will be publicly available only in hard copy.
Publicly available docket materials are available either electronically
in http://www.regulations.gov or in hard copy at the Public Information
and Records Integrity Branch (PIRIB) (7502C), Office of Pesticide
Programs (OPP), Environmental Protection Agency, 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: Candace Brassard or Nathanael Martin,
U.S. Environmental Protection Agency (7506C), 1200 Pennsylvania Ave.
NW., Washington, DC 20460, telephone: 703-305-6598 or 703-305-6475, e-
mail: [email protected] or [email protected]. Do not e-
mail your comments to these contacts. Submit your comments according to
the instructions under ADDRESSES.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be affected by this notice if you are a producer or
registrant of a biochemical or microbial pesticide product. This
proposal also may affect any person or company who might petition the
Agency for new tolerances for biochemical or microbial pesticides, or
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 for
biochemical or microbial pesticides. The following is intended as a
guide to entities likely to be regulated by this action. The North
American Industrial Classification System (NAICS) codes are provided to
assist you in determining whether or not this action applies to you.
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.
Crop Production (NAICS 111).
Animal Production (NAICS 112).
Food Manufacturing and Processing (NAICS 311).
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 could also be affected. If
you have questions regarding the applicability of this action to a
particular entity, please consult the appropriate Branch Chief in the
U.S. EPA Biopesticides and Pollution Prevention Division of the Office
of Pesticide Programs at 703-308-8712, fax number at 703-308-7026 or
visit the following website: http://www.epa.gov/pesticides/biopesticides/.
[[Page 12073]]
B. What Should I Consider as I Prepare My Comments for EPA?
1. Submitting CBI. Do not submit this information to EPA through
www.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:
i. Identify the document by docket number and other identifying
information (subject heading, Federal Register date and page number).
ii. Follow directions. The Agency may ask you to respond to
specific questions or organize comments by referencing a Code of
Federal Regulations (CFR) part or section number.
iii. Explain why you agree or disagree; suggest alternatives and
substitute language for your requested changes.
iv. Describe any assumptions and provide any technical information
and/or data that you used.
v. If you estimate potential costs or burdens, explain how you
arrived at your estimate in sufficient detail to allow for it to be
reproduced.
vi. Provide specific examples to illustrate your concerns, and
suggest alternatives.
vii. Explain your views as clearly as possible, avoiding the use of
profanity or personal threats.
viii. Make sure to submit your comments by the comment period
deadline identified.
II. Overview of EPA's Proposal
EPA is proposing to update and revise its data requirements for the
registration of microbial and biochemical pesticide products to reflect
current scientific knowledge. These proposed revisions are intended to
provide EPA with data and other information necessary to support the
registration of a biochemical and microbial pesticide product, and will
improve the Agency's ability to make regulatory decisions about the
human health and environmental effects of these pesticide products.
Since the data requirements were first codified in 1984,
information needed to support the registration of a biochemical and
microbial pesticide has evolved as the general scientific understanding
of the potential hazards posed by pesticides has grown. Since 1984, EPA
has developed new and revised data requirements with public
participation, extensive involvement by the scientific community, and
review by the Scientific Advisory Panel (SAP) under Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA), which have been
imposed on a case-by-case basis. By codifying these data requirements,
the pesticide industry, along with other partners in the regulated
community, will have a better understanding of and could better prepare
for the registration process for biochemical and microbial pesticides.
In addition, the Agency is proposing certain new data requirements in
response to the need for strengthened risk assessment mandated by the
Food Quality Protection Act (FQPA) and FIFRA.
EPA is also proposing to update the definitions of a biochemical
pesticide and a microbial pesticide to more accurately describe these
categories of pesticides, and to make a conforming change to the
definition of microbial pesticide in 40 CFR part 172. EPA is announcing
its policy to provide assistance to applicants when needed in
determining what data are appropriate to support registration of a
biochemical or microbial pesticide and encouraging applicants to
request pre-submission meetings to discuss these data issues. EPA is
announcing its intent to provide assistance to applicants in some
narrow circumstances in preparation of an applicant's data waiver.
This proposed rule is one in a series of proposals to update and
clarify pesticide data requirements. EPA proposed data requirements for
conventional pesticides (70 FR 12276, March 11, 2005) and is developing
data requirements specific to antimicrobial pesticides. In the future,
EPA expects to develop data requirements for plant-incorporated
protectants.
III. Statutory Authorities and Regulatory Framework
EPA is authorized to regulate pesticides under two Federal
statutes. 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 FQPA to strengthen the protections offered,
with particular emphasis on protection of children.
This action is issued under the authority of sections 3, 4, 5, 12,
and 25 of FIFRA (7 U.S.C. 136-136y) and section 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
In general, under FIFRA, every pesticide product must be registered
(or specifically exempted from registration under FIFRA section 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 determination, as defined in the
statute, requires the Agency to consider the risks and benefits
associated with the use of a pesticide. 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 fate
properties, 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. Thispost-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 the 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 40 CFR part 158 requirements of the 1984 regulations.
Additional data for
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older pesticides were called in where gaps in the scientific data base
occurred. The Agency has 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 exemptions, FIFRA sec.
5 requires persons seeking experimental use of pesticides under field
conditions to obtain an experimental use permit (EUP). An EUP allows
limited distribution and 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 assess 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 exposure and cumulative risk 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.
As previously mentioned, in 1996, the FQPA modified the 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. (In this preamble, references to tolerances include
exemptions from tolerance since the standards and procedures for both
are essentially the same.) 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 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
prescheduled 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 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 will
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. What is the Context for Today's Proposal?
Under FIFRA, as previously stated, every pesticide product must be
registered (or specifically exempted from registration under FIFRA
section 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 registration. The establishment of tolerances, if
appropriate, is part of the registration process.
B. 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 the product 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 the 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, nontarget insect species
and to determine what happens to the pesticide in soil, water, and air.
C. What are the Data Requirements?
First promulgated in 1984, the data requirements in 40 CFR part 158
(49 FR 42856, October 24, 1984) 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,
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biochemical, microbial, etc.), scientific discipline (e.g.,
toxicology, etc.), and major use sites (e.g., outdoor vs. indoor,
terrestrial, aquatic, greenhouse). Part 158 also outlines the
associated procedures for submitting the data, requesting a waiver from
a requirement(s), and other associated procedures. Since there is much
variety in pesticide chemistry, exposure, and hazard, part 158 is
designed to be flexible. Table notes (referred to as test 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.
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. Data requirements address
both components of a risk assessment, i.e., what hazards do the
pesticide present, and estimated level of exposure to humans or
nontarget species. 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 extensive hazard data may not be required
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 EPA 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), which
includes representation of countries throughout the world (including
the United States). The process for developing and amending the test
guidelines included 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 provide recognized standards for conducting
acceptable tests, guidance on reporting data, definition of terms,
consistent with the purpose of the data requirement and the test
standard and recommended study protocols. As such, pesticide
registrants may also use a nonguideline 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 is expected to fully justify the methods
chosen in the study protocol. Nonguideline protocols may be accepted,
provided that the study protocol meets the purpose of the data
requirement 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 a http://www.epa.gov/opptsfrs/home/guidelin.htm. Please see the docket for the
complete crosswalk for old guideline numbers to new guideline numbers
(Ref. 2).
D. Why have EPA's 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. During the registration process, EPA recognized that some
of the 1984 data requirements were becoming out of date. The Agency
then called in additional information in order to complete the
registration process.
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,'' 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 and
reproductive testing (National Research Council, 1993, pp. 152-156)
(Ref. 3), which applies to biochemical and microbial pesticides. NRC
also suggested adding a thyroid screen to existing subchronic and
chronic toxicity tests and additional tests of 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
[[Page 12076]]
testing requirements recommended by the NRC have been incorporated into
the Agency's standard evaluation requirements and practices.
3. Scientific Advisory Panel Review of 1994. The FIFRA SAP
completed a review of a set of scientific issues regarding the
Environmental Protection Agency's Proposed Rule: Pesticide Registration
Data Requirements, 40 CFR part 158 (Ref. 4). The Panel commended the
Agency for presenting this regulation in such a clear and
understandable manner, and generally endorsed the revisions. The Panel
addressed individual scientific issues where necessary for both
biochemicals and microbial pesticides and the data needed to address
risk.
4. The Food Quality Protection Act of 1996 (FQPA). Passage of FQPA
in 1996 reformed the 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. Since the
early 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 nonoccupational
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 nonoccupational and residential exposure.
5. Pesticide reregistration. Recognizing that pesticides registered
in the past may not meet today's safety standards, EPA is reviewing and
reregistering older pesticides and taking action to reduce risks where
appropriate. On July 13, 2005, EPA published a notice of proposed
rulemaking (NPRM) to establish procedural regulations for conducting
registration review (70 FR 40251, July 13, 2005), as required in FIFRA
section 3(g). Registration review will replace EPA's one-time pesticide
reregistration and tolerance reassessment programs starting in 2006.
The Agency will conduct a review of each pesticide at least every 15
years to ensure that registrations continue to meet statutory standards
for registration. EPA plans to make decisions on almost 50 registration
review cases, or about 80 active ingredients, each year. Under the
reregistration process required by FIFRA section 4, EPA has been
reviewing older pesticides (those initially registered before November
1, 1984) to consider their health and environmental effects and to make
decisions about their future use. EPA is committed to completing the
reregistration process by the end of fiscal 2008.
V. Scope, Purpose, and Request for Comments on this Proposal
A. General Background on the Phased Rulemaking Approach
EPA is responsible for registration of the following categories of
pesticides: Biochemicals, microbials and plant-incorporated
protectants, conventional pesticides, and antimicrobial pesticides. The
various processes include differing data requirements that registrants
must take into account in their submittals.
On March 11, 2005, EPA published a proposed rule to update and
revise its data requirements for the registration of conventional
pesticides (70 FR 12276) (Ref. 5). In addition to proposing specific
changes to the data requirements for registration of conventional
pesticides, EPA proposed a number of other changes to the general
provisions of part 158. Specifically, subpart A of the proposed rule
for conventional chemicals describes general provisions including
definitions, format of data submissions, policies on Confidential
Business Information (CBI), flagging criteria, waivers, and minor uses.
Subpart B of the proposed rule for conventional chemicals describes
expanded use patterns, clarifications on using the data tables,
identifying data for Experimental Use Permits (EUPs), test guidelines,
and purpose of the registration data requirements. That proposed rule
also proposed to upgrade the structure of part 158, assigning
biochemical data requirements to subpart L, and microbial pesticide
data requirements to subpart M of part 158.
Today's proposed rule proposes to update and revise the data
requirements for the registration of biochemical and microbial
pesticides, and to maintain the structure proposed in the earlier
proposed rule for conventional pesticides, by placing the proposed data
requirements for biochemical and microbials in new subparts L and M,
respectively. When the proposed rule for conventional pesticides is
finalized, the general provisions of subparts A and B of that rule will
apply to the other data specific subparts, such as subparts L and M as
proposed today, unless otherwise specified. Future rulemakings will
address the data requirements for antimicrobials and plant-incorporated
protectants.
B. Summary of this Proposal
EPA is proposing a number of changes to the current data tables.
The proposed rule would:
1. Codify current data requirements that do not appear in part 158,
but which are routinely required.
2. Add new data requirements.
3. Revise certain existing data requirements, such as by updating
test notes.
4. Clarify the definitions of both ``biochemical pesticide'' and
``microbial pesticide'' to reflect our current application of those
terms, and make a conforming change in the part 172 definition of
``microbial pesticide.''
5. Add additional definitions needed to apply the data requirements
properly.
6. Make necessary reorganizing and formatting revisions, such as
renaming data requirements.
EPA will retain its current tiering system for both biochemical and
microbial pesticide data requirements.
C. What are the Purposes of this Proposal?
EPA has a number of objectives in proposing this regulation to
update and revise the data requirements in 40 CFR part 158.
1. Ensuring high quality data to meet EPA's mandates. Although most
of the specific requirements in part 158 have not changed since the
data requirements were first published in 1984, aspects of the
requirements may be out of date or may be unclear because the
underlying science has advanced (e.g., National Academy of Sciences
(NAS) in 1993 suggested changes to better protect children) or the
Agency's legislative mandate has been broadened to address new
concerns. For example, given the stricter mandates imposed by the 1988
FIFRA amendments and the 1996 FQPA amendments to FIFRA and FFDCA
(emphasis on exposure to population subgroups), 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.
In light of this background, the primary purpose of this proposal
is to
[[Page 12077]]
transparently identify the data EPA needs and will require to support a
determination of ``reasonable certainty of no harm'' under FFDCA and
``unreasonable adverse effects'' determination under FIFRA. In
developing this proposed rule, EPA has evaluated its data needs to
conduct the expanded risk assessments required by new statutory
mandates. Thus, the proposed changes entail both new tests and
broadened requirements for some current tests, reflecting the changes
in data requirement practices that have evolved since the 1984 data
requirement rule was promulgated and addressing data needed to meet
requirements created by statutory amendments to FIFRA and FFDCA.
2. Ensuring a sound scientific basis that is consistent with
advances in scientific understanding and works toward harmonization to
avoid duplicative data. Relatedly, these proposed revisions are
intended to ensure that the data requirements in part 158 reflect
current scientific understanding and scientific advances since the data
requirements were first issued in 1984. As discussed throughout this
document, these proposed revisions have been presented to, and reflect
the advice and recommendations of, the NAS and FIFRA SAP. Issues and
related materials that are brought by EPA to the FIFRA SAP undergo a
public review and comment opportunity before the FIFRA SAP issues its
report with recommendations to the Agency.
To the extent feasible, the proposed revisions are a reflection of
the scientific advances within OECD countries. The United States
participates in OECD activities to harmonize international testing
standards and, where appropriate, reference to the OECD testing
standards have been included in this proposal. However, since EPA
continues to allow applicants to submit and use their own study
protocols consistent with the purpose of the requirement to generate
data that they subsequently submit to EPA, and there are differences in
the mandate and authorities between EPA and the governing authorities
within OECD countries, the data submitted to EPA under part 158 would
be expected to satisfy OECD testing standards under most circumstances
for microbial testing (because OECD has agreed to use the U.S.
microbial pesticide testing guidelines) and for a number of countries
some of the U.S. biochemical testing guidelines would be satisfied. A
few of the governing authorities within the OECD countries may want
additional studies that would not normally be required in the United
States, but protocols for these studies are generally acceptable to all
countries.
3. Improving the depth and transparency of 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 improve the depth and transparency of the Agency's
understanding of the health and environmental effects of pesticides to
which individuals and the environment may be exposed. For example, the
proposed rule includes a test note for the human health assessment data
requirements indicating data are not required to support straight chain
lepidopteran pheromones when used at certain application rates. In
addition, EPA is proposing to continue using the tiered testing system,
as given in the current Sec. Sec. 158.690 and 158.740, since many of
the higher tiered data will not be required unless the results from the
lower tiered studies indicate a concern for adverse effects.
4. Improving utility of the part 158 data tables. As described in
the Notice of Proposed Rulemaking on Conventional Pesticides (70 FR
12276, March 11, 2005), EPA has proposed to reorganize and reformat
part 158 subpart A (General Provisions) and subpart B (How to Use Data
Tables), and reorganize and redesignate subpart D (Data Requirement
Tables) into several individual subparts (see Table 1 in Unit VI). In
the proposed reorganization, subpart L is designated for biochemicals
(Sec. 158.900) and subpart M (Sec. 158.1000) is designated for
microbials. Within both subpart L and M, there are definitions,
examples, applicability, and then the series of data requirements in
tables addressing product chemistry, residue chemistry, human health
assessment or toxicology, nontarget organism, and environmental fate.
Many of the revisions proposed in this document are intended to
improve the usefulness of part 158 data tables by better 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.
5. Reducing burdens where consistent with need for data. In
proposing new and revised data requirements, EPA expects that fewer
data waivers will be needed where the issue is well resolved, e.g.,
straight chain lepidopteran pheromones (SCLPs), and physical chemical
properties criteria outlined in test notes when data are not required.
There are also more transparent test notes indicating when data are
required, while providing assistance to avoid generation of data where
unnecessary. There is also an opportunity to reduce cost of preparation
of waiver requests by providing pre-submission/post-submission meetings
where appropriate.
D. What are Some of the Benefits of this Proposal?
Discussed in more detail in the document entitled ``Economic
Analysis of the Proposed Change in Data Requirements Rule for
Biochemical and Microbial Pesticides,'' which is available in the
docket for this rulemaking (Ref. 6), the following briefly highlights
the benefits anticipated from this proposal:
1. More refined assessments mean clearer understanding of real
risks. EPA's current applicator/user exposure data base is not
comprehensive, especially regarding exposures to pesticides in
nonagricultural settings. The new data that would be collected under
this proposal would allow the Agency to conduct improved exposure
assessments for applicators/users (i.e., especially for insect
repellents). This will benefit growers, other workers, and consumers by
allowing EPA to make better informed regulatory decisions that are
neither too stringent nor too lenient.
2. Clarity and transparency to regulated community means savings.
The enhanced clarity and transparency of the information presented in
part 158, subparts L and M 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, thereby registering safer pesticides sooner
and potentially reducing risks as well as 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 and nonagricultural products and registered pesticides as
tools for public health.
3. Enhanced international harmonization means less duplication. EPA
participates with OECD countries in the development of harmonized
international standards and, to the extent possible, we have included
these revisions in our proposal. The OECD Biopesticide Steering Group
has agreed to use U.S. EPA Harmonized Guidelines for the conduct of
microbial pesticide studies and we continue to work
[[Page 12078]]
together to harmonize our approach to evaluating and reviewing these
data. However, because other OECD countries do not use the tiered
approach to the data requirements, but instead decide on the data
needed for registration on a case-by-case basis, there may be
differences in the actual data required for registration for the United
States compared with other OECD countries. We are presently working
with key OECD biopesticide regulatory representatives to develop OECD
guidance for waiving data, which will bring actual data requirements
closer together. OECD has also recognized pheromones, a certain type of
biochemical pesticide, as warranting a separate, unique set of reduced
data requirements similar to the U.S. data requirements.
4. 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 nontarget 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.
5. 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/
users) may benefit from label information based on the data submitted
to the extent it helps inform their decisions about whether or how to
use particular pesticides to avoid potential exposure.
E. How will this Proposal Affect Existing Registrations?
This proposal codifies existing practices by requiring
data that are necessary to complete a risk assessment that are not
included in the current data requirements.
This proposal imposes new requirements for future
registrations, as is the case for applicator/user exposure data to
assess impacts from insect repellents.
In rare circumstances, the Agency may find it necessary to
call in data on certain existing registrations, as warranted by
emerging risk issues.
F. Request for Comments
The Agency invites the public to provide its views on the various
options proposed or present any data or information for the Agency to
consider during the development of the final rule. Specifically, the
Agency welcomes specific comments on the following topics of particular
interest to the Agency.
The Agency welcomes specific comments on the need for, value of,
and any alternatives to, the data requirements described in this
document to meet its mandates.
The Agency welcomes comments on the scientific basis of this
proposed rule.
The Agency welcomes specific comments on the clarity of the
proposed data requirements for biochemical and microbial pesticides and
the relationship between the proposed data requirements and EPA's
statutory determinations.
The Agency welcomes specific comments on the transparency of the
proposed definitions, examples, and applicability for both biochemical
and microbial pesticides.
The Agency welcomes comments on its economic analysis of the
proposed rule, as well as on its underlying assumptions, economic data,
and high- and low-cost options and alternatives. Describe any
assumptions and provide any technical information and data used in
preparing your comments. Explain estimates in sufficient detail to
allow for it to be reproduced for validation. 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
biochemical and microbial pesticide applicants.
VI. Background on Regulation of Biochemical and Microbial Pesticides
and Preparation of this Proposed Rule
A. Background of Regulating Biochemical and Microbial Pesticides
The Agency finalized the data requirements to support the
registration of biochemical and microbial pesticides (49 FR 42856,
October 24, 1984) more than 20 years ago. When promulgated in 1984, EPA
distinguished ``biochemical and microbial pesticides'' from
``conventional chemical pesticides'' by ``their unique modes of action,
low use volume, target species specificity or natural occurrence.'' EPA
recognized that biochemical pesticides are inherently different from
conventional pesticides since they are generally naturally-occurring
and have a non-toxic mode of action.
As a result, biochemicals are expected to pose lower potential risk
compared to conventional pesticides. Due to the non-toxic mode of
action and low risk to humans, certain studies are not included in the
Tier I data requirements for biochemical pesticides. This adjustment in
the tiered data requirements was intended to serve as a safety
mechanism. If Tier I testing indicates a toxic mode of action, the
biochemical would be treated as a conventional pesticide, and virtually
the same toxicology and residue data would be required as is required
for a conventional pesticide.
The Agency has confirmed in the past 20 years of regulating
biochemical pesticides that indeed biochemical pesticides can be
classified and regulated with the data requirement tables that have
been designated for biochemical pesticides. The Agency recognizes that
at the time of application for registration there are instances where a
biochemical may not fit the biochemical category and in such cases the
Agency evaluates the pesticide in question as a conventional pesticide.
Ultimately, if a pesticide were to exceed the criteria established for
a biochemical pesticide, the data requirements in the higher tiers
would be required and the process would take longer than if the
application were made as a conventional pesticide, since all data
requirements would not be clearly identified from the onset.
Microbial pesticides are living organisms and, as such, present
much different risk concerns than chemical toxicants. The main concern
for a microbial pesticide is whether it could survive within, and be
pathogenic to, a nontarget species or humans. As a result, required
studies specifically address the potential for these unique
[[Page 12079]]
risks. Some microorganisms do produce toxins. If comparisons of the
microorganisms indicates that taxonomically similar microorganisms have
been reported to be pathogenic, the data set is configured to allow for
use of conventional toxicity testing if needed to evaluate any toxins.
B. History of Development of Biochemical and Microbial Pesticide Data
Requirements and Guidelines
1. Biochemical pesticides history for regulatory activities. The
following provides the history in the regulatory development of the
data requirements for biochemical pesticides since 1984.
1984--Promulgation of 40 CFR part 158 subpart A: Sec.
158.65 Biochemical and Microbial Pesticides and subpart D: Sec.
158.690 Biochemical Pesticide Data Requirements and Microbial Data
Requirements (49 FR 42856, October 24, 1984).
1987--Report of SAP Recommendations: A Set of Issues Being
Considered by the Agency in Connection with Proposed Revision to
Subdivision M, Immunotoxicity Testing of Biochemical Pest Control
Agents (Ref. 7).
1989--Issuance of Subdivision M of the Pesticide Testing
Guidelines Microbial and Biochemical Pest Control Agents (Ref. 8).
Although titled as such, this guideline did not include a discussion on
biochemical guidelines. The Agency still relies on 1982 Pesticide
Assessment Guidelines Subdivision M Biorational Pesticides (Ref. 9) for
the guidelines pertaining to biochemicals (880 series) if there is not
a designated guideline in the conventional pesticide series (i.e., 870
series and 850 series).start here next
1994--Presentation to SAP to discuss data requirements for
all pesticides, including biochemical and microbial pesticides (Ref.
4). Some data requirements were presented to support conventional
pesticides, i.e., applicator/user exposure data to support insect
repellents (Ref. 10).
2. Microbial pesticides history for regulatory activities. The
following provides the history in the regulatory development of the
data requirements for microbials since 1984.
1984--Promulgation of 40 CFR part 158 subpart A: Sec.
158.65 Biochemical and Microbial Pesticides and subpart D: Sec.
158.690 Biochemical Pesticide Data Requirements and Microbial Pesticide
Data Requirements (49 FR 42856, October 24, 1984).
1987--Presentation to SAP in 1987 for microbial pesticides
in preparation for updating the guidelines (Ref. 7) on immunotoxicity
testing.
1989--Issuance of Subdivision M of the Pesticide Testing
Guidelines Microbial and Biochemical Pest Control Agents (Ref. 8). This
was a culmination of the 1987 SAP and public comments.
1994--Presentation to SAP to discuss data requirements for
all pesticides, including biochemical and microbial pesticides (Ref.
4).
This proposed rule proposes to codify the draft data requirements
outlined and presented to the FIFRA SAP in 1994 and in subsequent
meetings. However, EPA is proposing certain revisions for biochemicals
that are also discussed fully in the Agency's proposal for conventional
chemicals (70 FR 12276, March 11, 2005) (Ref. 5). The Agency developed
a complete list of data requirements for biochemicals and microbials
and the year each were presented to FIFRA SAP (Ref. 11). This
reference, the SAP final reports, and relevant documents presented to
the SAP are available in the docket for this proposed rulemaking.
C. EPA Activities in Preparation for this Proposed Rule
1. Consideration of redesigning data requirement tables. While
preparing for this proposed rule, the Agency considered redesigning
data requirements based on subcategories of biochemical and microbial
pesticides. Each subcategory was evaluated based on mode of action and
potential for risk to human health and the environment, with each
subcategory requiring different data to support registration. The
subcategories for biochemical pesticides were as follows: pheromones
(including arthropod, lepidopteran, and straight chain lepidopteran
pheromones), growth regulators (insect and plant), repellents (insect
and others), and other biochemicals (which includes all other
biochemicals). The microbial pesticides includes the following
subcategories: protozoa, viruses, bacteria, and fungi.
In the economic analysis for this proposed rule, the Agency
analyzed the test cost data submitted based on each subcategory to
determine the different data requirements (Ref. 12). Based on the
analysis, the Agency decided it was more appropriate to make the test
notes more clear and transparent, and only update the data requirement
tables without redesigning them based on subcategory.
2. Consistencies between current part 158 and proposed part 158
design of data requirement tables for biochemical and microbial
pesticides. EPA is proposing to continue using the tiered testing
system, as given in the current Sec. 158.690 and Sec. 158.740. For
these specific types of pesticides, it is appropriate to ask for
studies in a tiered scheme because many of the higher tiered data will
not be required unless the results from the lower tiered studies
indicate a concern for adverse effects.
3. Consultations with stakeholders. During the pre-rulemaking
process, the Agency actively sought consultations with industry,
academia, and non-profit organizations (i.e., environmental groups) on
the current regulatory requirements for data and requested input on the
universe of possible changes to the regulatory text. For parties
interested in discussing the development of this rule with EPA,
consultations were held in-person, by telephone conference, and via-
email. During these pre-proposal stage consultations, the Agency did
not request feedback on the changes being proposed today, whether the
proposed changes are newly imposed, newly codified data, or revisions
to existing data requirements. Feedback from these consultations
included the following topics: existing data requirements, industry
burden in fulfilling data requirements, tiered testing approach, and
issuance of guidance specific to test protocols. All the stakeholder
comments are available in the docket (Ref. 13).
D. Consultations with Applicants
In an effort to improve transparency, increase efficiencies and
reduce burdens, EPA is announcing a policy to provide assistance to
applicants when needed in determining what data or information are
appropriate to support registration of a biochemical or microbial
pesticide. EPA is encouraging applicants to request pre-submission
meetings to discuss these data issues. EPA is also announcing its
intent to provide assistance to applicants in some narrow circumstances
in preparation of an applicant's data waiver after submission of an
application.
EPA notes that applications for biochemical and microbial
pesticides frequently involve substances that present low risk (i.e.,
naturally-occurring, non-toxic mode of action, minimal exposure). Data
requirements - even as proposed--may overstate the Agency's need, or
may be satisfied by existing data in the open literature or other
available data or information. In some cases, the applicant may not be
aware of a potential rationale for a waiver or be able to identify
available data or information that may satisfy a data requirement in
lieu of generating new data. Thus, EPA encourages applicants to seek
pre-submission meetings to discuss the appropriate data or information
to support their product
[[Page 12080]]
and the opportunity for requesting data waivers.
1. Pre-submission process. During a pre-submission meeting, EPA may
be aware that certain data requirements are already satisfied by
available data or information. Sources of existing data include public
literature and/or studies submitted by another registrant, which may be
cited with data compensation procedures. EPA may also be aware of sound
scientific rationales that certain data requirements should not be
imposed. For example, the question the required data is intended to
answer might be addressed by a combination of other information or
data, and therefore might be able to be waived. In either case, during
the pre-submission meeting, EPA would discuss with the applicant the
grounds for citing other information or data to conclude that a data
requirement has been met or the grounds for requesting a waiver where
other information or data otherwise addresses the need for a specific
piece of data required by the regulations have been satisfied. The
applicant may then submit an application based on the discussion with
EPA. The application should include a signed copy of the minutes of the
pre-submission meeting listing each data requirement and the reason why
EPA and the company believe a waiver is appropriate. The applicant is
encouraged to submit a copy of the pre-submission meeting minutes to
EPA for concurrence prior to submission of its application for a
waiver.
To some extent, EPA currently offers this assistance to applicants
and is simply encouraging applicants to request pre-submission meetings
and suggesting a process for ensuring consistent reflection of
discussions at the pre-submission meeting.
2. Post-submission process. Even after submission of an application
for registration, EPA may find that either of these scenarios exist
(i.e., basis for citing to other data/information or waiver of a data
requirement). Again, EPA may discuss these issues with the applicant
and the applicant may choose to amend its application by citing to
other data/information or requesting a waiver.
EPA is also announcing its intention to assist applicants in the
actual preparation of a data waiver in some narrow circumstances.
Specifically, in the course of reviewing an application, EPA may find
that in its judgment, data otherwise required by part 158 would not be
necessary to grant the application or are available from other sources.
EPA would notify the applicant and explain the basis for its belief in
writing. If the data are compensable or exclusive in use, the applicant
may submit EPA's letter with the appropriate offer to pay or an
authorization, as an amendment to its application. If the Agency
explains in its correspondence that the data may be waived, the
applicant may use EPA's correspondence to support a waiver request by
signing the correspondence and submitting it as an amendment to its
application. Because the correspondence only includes citation or
discussion of existing data or information, EPA is proposing not to
consider such amendments to an application to be ``data'' subject to
the formatting provisions of Sec. 158.32(a) as proposed on March 11,
2005 (70 FR 12276).
This pre-submission and post-submission process for ensuring that
the data requirements are either satisfied or waived is specific to the
review of biochemical and microbial registration applications, due
primarily to the specific nature and circumstances unique to these
pesticides (e.g., information already known to the Agency) and thus the
Agency does not anticipate this process being widely applicable to
other types of pesticides, such as conventional or antimicrobial
pesticides.
EPA notes that in providing this assistance during the pre-
submission and post-submission process, it will only consider readily
accessible information, such as information found in Agency databases,
and will not search for applicable information, data, or literature.
Further, although intending to help applicants in supporting their
applications, EPA does not encourage applicants to rely on this process
to fill informational data gaps; doing so may be at the expense of
timely review or may ultimately result in rejection of an application
or petition.
Finally, providing assistance in this manner does not effectively
allow applicants to circumvent the data requirements or the requirement
to submit a waiver of a data requirement. The applicant must at all
times submit the waiver request; EPA is simply providing assistance in
what requirements are likely to be waived for a particular product or,
in some narrow circumstances, assistance in the preparation of the
waiver request. Throughout these mechanisms EPA is flexible in
implementing the regulation. Thus, the waiver provisions currently
codified and the recent proposed amendments to the waiver provisions do
not need to be amended.
One of the benefits of providing this pre-submission and post-
submission assistance is the reduction in burden. Prior to finalization
of this proposed rule (e.g., codifying that some data may no longer be
required or adding conditions that result in data not being required),
the number of opportunities for requesting waivers or citing to
existing data will not change. Thus, providing assistance in this
manner prior to finalization of this proposed rule may avoid the
generation, processing and review of unnecessary data, and thereby
ultimately save the Agency and applicant expenses, while providing the
same level of protection for human health and the environment. In
addition, although this proposal attempts to refine the test notes in
order to be more transparent when data are required and necessary to
support registration, there will continue to be opportunities to
reference existing data or information or request waivers based on
information that may be readily accessible to the Agency, and again
avoid the generation, processing, and review of unnecessary data or
information. Thus, the Agency expects to reduce burdens on both the
applicants and EPA during and after the rulemaking process.
E. Agency Coordination with the APHIS Permitting Process
As a result of the comments received during the Interagency review
process, the Agency and USDA have discussed the registration process of
microbial pesticides and the need for coordination when an Animal and
Plant Health Inspection Service (APHIS) movement permit under 7 CFR
part 340 is required by USDA. USDA suggested that the registrants
should be required to submit a copy of the applicable APHIS permits as
part of the registration application to EPA. The Agency is seeking
public comment on the most appropriate method to ensure APHIS
permitting and EPA registrations are coordinated. In particular, EPA is
interested in your specific suggestions on whether there should be a
requirement for pesticide registration applicants to include copies or
otherwise attest to the applicability of and their compliance with the
APHIS requirements when they submit their registration application to
EPA.
F. Differences Between the Proposed Biochemical Data Requirements and
the Proposed Conventional Data Requirements
There are several revisions that were included in the proposal to
amend part 158 for conventional pesticides, but were considered not
appropriate for biochemical pesticides. For example, neurotoxicity
studies (including acute, subchronic, delayed, and developmental
neurotoxicity studies; OPPTS Test
[[Page 12081]]
Guidelines 870.6100, 870.6200, 870.7620, etc.) are required to support
conventional pesticides. In addition, the recent proposal (70 FR 12276,
March 11, 2005) identifies developmental neurotoxicity to be critical
in some cases. If the Agency identifies a biochemical pesticide to be a
potential neurotoxicant, then the Agency would evaluate the pesticide
as a conventional pesticide, and it would then require the
neurotoxicity data to support registration. The Agency prepared an
overview of the proposed data requirements for biochemical pesticides
as compared to conventional pesticides (Ref. 14).
G. Similarities Between Both Biochemical and Microbial Proposed Rule
Development and Proposed Rule for Conventional Pesticides
The Agency proposes to retain certain data requirements when they
are appropriate. For instance, biochemical pesticides data requirements
for product chemistry are the same as is required for conventional
pesticides (Sec. 158.320 through Sec. 158.355).
Certain revisions for proposed conventional pesticides (70 FR
12276, March 11, 2005) were considered appropriate for biochemicals
and/or microbials and are included in this proposed rule, i.e.,
registrations introducing significant exposure require applicator/user
exposure data. As previously mentioned, the consistent designation of
CR and R within the data tables remains the same as it is in the
current part 158 for both conventional pesticides and microbial and
biochemical pesticides. The proposed conventionals retains the CR and R
designation, and this proposed rule retains this designation as well,
within the data tables.
H. Proposed Amendments and Reference to Harmonized Guidelines
The following units VII and VIII identify the proposed revisions to
the current data requirements for biochemicals and microbials. In each
preamble unit, the Agency explains the basis for the proposed
amendments and for ease of reference to the public, identifies the
harmonized guideline that is applicable to the proposed data
requirement. EPA is not proposing changes to these harmonized
guidelines as they have gone through a public review. The reference is
simply for ease in understanding the proposed revisions.
VII. Biochemical Pesticide Data Requirements (Subpart L)
A. Definition of Biochemical
The Agency is proposing to revise the definition of biochemical.
Although the current definition provides examples of biochemicals, it
does not really explain what a biochemical is. The language in the
current definition was constrained by the need for including microbial
pesticides in the same definition that defined biochemical pesticides.
The new format for this regulation allows for a separation of the two
classes of pesticides. The proposed definition of biochemical is
intended to reflect a more useful and transparent definition, in
accordance with the original scientific rationale for creating the
biochemical class of pesticides while being consistent with the
examples. The current definition is listed in Sec. 158.65 and reads as
follows:
Biochemical and microbial pesticides are generally distinguished
from conventional pesticides by their unique modes of action, low
use volume, target species specificity or natural occurrence. ...
(a) Biochemical pesticides include, but are not limited to, products
such as semiochemicals (e.g., insect pheromones), hormones (e.g.,
insect juvenile growth hormones), natural plant and insect
regulators, and enzymes. When necessary the Agency will evaluate
products on an individual basis to determine whether they are
biochemical or conventional chemical pesticides.
EPA is proposing to relocate the definition of biochemical to Sec.
158.900, which would immediately precede the data requirements in part
158 for the respective categories of biochemicals. EPA is also
proposing to amend the definition so that it would state the following:
A biochemical pesticide is a pesticide that:
(1) Is a naturally-occurring substance or structurally similar
and functionally identical to a naturally-occurring substance;
(2) has a history of exposure to humans and the environment
demonstrating minimal toxicity, or in the case of a synthetically
derived biochemical pesticides, is equivalent to a naturally-
occurring substance that has such a history; and
(3) Has a non-toxic mode of action to the target pest(s).
EPA is proposing to continue the requirement that a biochemical
pesticide be naturally-occurring. In addition, based on a long
established policy, EPA is proposing to include a clarification that a
``naturally-occurring'' biochemical pesticide may be synthetically
produced if it is ``equivalent'' (structurally similar and functionally
identical) to the naturally-occurring chemical. A synthetically derived
chemical may often be more pure or economically feasible to produce but
have the same properties as its naturally-occurring equivalent. An
example of a synthetic substance that meets the criteria for
classification as a biochemical is an insect pheromone manufactured by
man. These insect pheromones are structurally and functionally
identical to the substances that are produced by the insects, but the
currently registered products are not naturally-occurring because it
would be very difficult to extract them directly from an insect in a
usable form.
Second, the current regulation does not explicitly indicate that
inherent non-toxicity is a means of defining a biochemical. EPA is
proposing to add a criterion to the definition of biochemical that
requires that there be a history of exposure to the naturally-occurring
pesticide or, for synthetically-derived pesticides, to the equivalent
naturally-occurring pesticide, and that exposure demonstrates minimal
toxicity. The original intent for specifying natural occurrence in
Sec. 158.65 was to allow EPA to use information derived from the
pesticide's natural exposure to humans and non-target species to decide
if the pesticide is inherently toxic. This is described in the 1982
Pesticide Assessment Guidelines, Subdivision M for Biorational
Pesticides, section V(A)(2)(1) (Ref. 9), which states that the fact
that the chemical is naturally-occurring is to be used to predict
whether ``these compounds are generally not innately toxic.''
Therefore, the criterion for having a history of adequate exposure was
added in order to have confidence that if the naturally-occurring
pesticide were not ``innately'' toxic, it would have to be present in
the environment at sufficient levels and locations to predict
significant exposure to humans and/or non-target species. If the
pesticide is naturally-occurring but inherently toxic, EPA would use
the data requirements for the conventional pesticides to ensure it
could conduct an adequate assessment of the risks from the proposed use
of the pesticide.
Thus, rather than giving the impression that natural occurrence
alone defines whether the pesticide should be classified as a
biochemical pesticide, the Agency is proposing to include the criterion
that there be a history of exposure demonstrating minimal toxicity. In
order to make this determination, the naturally-occurring pesticide or
the naturally-occurring equivalent to the synthetically derived
pesticide must be present in the environment in sufficient quantities
so that if it is innately toxic, there would be a good chance that this
toxicity
[[Page 12082]]
would already have been recognized because of its effect on humans or
representative non-target organisms. EPA has often used public
literature to demonstrate that the substance is either widely used,
and/or widely known (supported by extensive information and low
toxicity) as part of the decision whether a pesticide may be adequately
reviewed using the reduced data set for biochemical pesticides. The
natural occurrence of a pesticide does not necessarily mean that it has
a non-toxic mode of action to the target pest. An example might be
pyrethrins, which are naturally-occurring toxins that occur in
chrysanthemum plants. The new criteria in the biochemical definition
would clearly allow us to classify this as a conventional chemical
pesticide that would be subject to the conventional pesticide data
requirements, which is consistent with past Agency decisions.
Third, the current regulation refers to a unique mode of action,
which is an attempt to describe the mode of action of both microbial
and biochemical pesticides together. EPA is proposing to add a
criterion to the definition of biochemical to better describe that the
unique mode of action for biochemical pesticides must be one that is
non-toxic to the target pest(s). This was the original intent for the
biochemical pesticide mode of action as described in the 1982 Pesticide
Assessment Guidelines, Subdivision M for Biorational Pesticides. That
guideline explained in section I(A)(1) (Ref. 9) that ``some of the
characteristics that typically distinguish biorational from
conventional pesticides are their unique non-toxic mode of action,
...,'' and in section V(A)(2)(1) that a characteristic of biochemical
pesticides is that ``their pesticidal action is not the result of
target organism toxification.'' Thus, the third element of the
definition adds that the biochemical must have a non-toxic mode of
action to the target pest. This toxic mode of action criterion would
preclude pyrethrins and other clearly toxic naturally-occurring
pesticides from being classified as biochemicals.
In addition to the proposed language noted previously, EPA is
proposing to amend the examples provided in the current definition of
biochemical to better represent the kinds of biochemical pesticides we
have actually seen since the original rule was published and move the
examples from the actual definition to a subsequent paragraph. The
proposed definition removes hormones from the example list because
hormones fall into the growth regulator class, which is already in the
list. The new ``Examples'' section is proposed to read as follows:
Biochemical pesticides include, but are not limited to: (1)
Semiochemicals (e.g., insect pheromones and kairomones), (2) natural
plant and insect regulators, (3) naturally-occurring repellents and
attractants, and (4) enzymes.
At the present time, the Agency will review requests for
classification as a biochemical pesticide, but does not believe this
needs to be part of the regulatory language because the proposed
revised definition is much more definitive than the current definition.
As a final note, although not always the case, EPA recognizes that
biochemical pesticides tend to have a limited range of target species,
are often effective against their target pest(s) in relatively low
quantities, and usually decompose rapidly after application in the
environment.
B. Applicability of Biochemical Pesticide Data Tables
EPA is also proposing to use table descriptors NR (not required), R
(required), and CR (conditionally required) to be used as markers along
a spectrum of the likelihood that a data requirement applies. In other
words, it should be assumed that a required (R) data requirement is
required typically all the time. There may be some narrow or rare
conditions identified in test notes when data are not required. For
example, acute oral toxicity data are required to support registration
for biochemical pesticides unless the proposed pesticide is a gas or
highly volatile (which is rare). In contrast, a conditionally required
(CR) data requirement is less likely to be triggered compared to a
required (R) data requirement. Conditionally required data are more
likely to include test notes indicating conditions when data are
typically required. For example, the 90-day dermal toxicity test is
currently conditionally required (CR) for biochemical pesticides. The
test note indicates it is required (R) to support uses involving
purposeful application to human skin or which would result in
comparable prolonged human exposure to the product (e.g., insect
repellents). Specific criteria are identified with the test note.
C. Product Chemistry Data Requirements
1. General. The Agency uses product chemistry information to
determine whether impurities of toxicological or environmental concern
are present in biochemical pesticides and their formulated products.
Product chemistry data requirements include product identity and
composition, the physical and chemical characteristics of data on the
pesticide, the identity of any intentionally added ingredients, and
impurities in the final pesticide product.
The Agency is continuing to list the data requirements in the table
for product identification, description of starting materials,
production and formulation process, discussion of formation of
impurities, preliminary analysis, certified limits, and physical and
chemical characteristics, as currently listed in Sec. 158.690. The
following is a discussion about the changes from the current data
requirements to support ``biochemical product analysis data
requirements'' to the proposed ``biochemical product chemistry data
requirements'' for biochemicals. The revised title of the proposed
table more accurately reflects the current types of data required to
support biochemical pesticides.
In addition, the proposed rule for conventional pesticides (70 FR
12276, March 11, 2005) identifies the following sections where this
proposed rule will also require the same information/data and are
indicated in the test notes within the proposed product chemistry data
requirement table: Sec. Sec. 158.320, 158.325, 158.330, 158.335,
158.340, 158.345, 158.350, 158.355.
2. Proposed product chemistry data requirements. The Agency
proposes to codify one study (particle size, fiber length, and diameter
distribution) and to make minor revisions to existing data requirements
to support product chemistry data requirements. The Agency is also
proposing to require studies to support experimental use permits (EUPs)
as well as registration for certain studies, (i.e., certified limits).
In addition, certain studies (i.e., enforcement analytical method)
would require a different test substance (for example, TGAI or both EP
and MP). One study, which is currently required to satisfy
environmental fate and expression data requirements, is proposed to be
moved from environmental fate and expression to the product chemistry
data requirements (ultraviolet (UV)/light absorption) table. The Agency
is also proposing to delineate the physical and chemical properties
into subcategories, depending on the formulation type (e.g., solid
versus liquid) and provide test notes identifying conditions when data
are required (i.e., flammability). In other words, the current product
chemistry data requirement table lists physical and chemical properties
as one data requirement, whereas the proposed rule identifies the
individual studies that make up physical and chemical
[[Page 12083]]
properties (e.g., color, odor, vapor pressure, pH). Additional test
notes concerning the physical and chemical properties identifying when
each data requirement is required (i.e., solid versus liquid at room
temperature, water insoluble substances (10-6 grams/liter
(g/l)) are also included.
i. New requirements. None.
ii. Newly codified requirements--particle size, fiber length, and
diameter distribution. The Agency proposes to add the conditional
requirement (CR) for data on particle size, fiber length, and diameter
distribution. This data requirement is proposed to be conditionally
required (CR), the condition being that the test substance is water
insoluble (<10-6 g/l) or fibrous with diameter >= 0.1 [mu]m
(micrometer). Data from this study are needed to complete the
environmental fate assessment to estimate potential pesticide drift to
nontarget areas.
iii. Revisions to existing requirements. a. ``Certification of
limits'' data are currently conditionally required (CR) to support all
proposed use patterns/applications, except for EUPs for nonfood crops.
The Agency proposes to change the conditionally required (CR) to
required (R) ``Certified limits'' data to support proposed use patterns
to ensure we have proper product chemistry information on all
registrations for enforcement purposes.start
b. UV/visible light absorption. The Agency currently requires (R)
these data to satisfy one of the nontarget organism, fate and
expression data requirements. The Agency proposes to relocate this data
requirement from environmental fate and expression data tables to the
proposed product chemistry data table. The endpoints measured by this
data, characterization, and identification of a compound are more
appropriately considered product chemistry data. This is not a new data
requirement, merely a relocation. This information will be used in
conjunction with the ``photodegradation in water'' study 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. The UV/visible light absorption spectrum will indicate
whether the pesticide is absorbed in this range.
c. Revision of names. The Agency proposes to revise names of
certain studies to correspond with OPPTS Test Guidelines (Ref. 2) and
to synchronize with the name changes taking place in the updating of
part 158 for conventional pesticides. The following three name changes
are proposed in this section: (1) `` Product identity'' to ``Product
identity and composition''; (2) ``Discussion of formation of
unintentional ingredients'' to ``Discussion of formation of
impurities''; and (3) ``Manufacturing process'' to ``Description of
starting materials, production and formulation process.''
D. Residue Chemistry Data Requirements
1. General. The Agency is proposing to codify two data requirements
which identify the use pattern under which they are proposed to be
required. EPA is also proposing to consolidate the nonfood use patterns
into the following four categories: terrestrial nonfood; greenhouse
nonfood; forestry; and domestic outdoor, and to do so for all residue
data requirements except for chemical identity and directions for use.
Those will remain conditionally required (CR) for all uses. This would
not change the number of times the data are required, but merely
consolidate the uses that have the same data required under the same
conditions.
In addition, the Agency is proposing to delete the test note
stipulating data conditionally required (CR) if the application rate of
0.7 ounces was exceeded. This test note is no longer considered
relevant. Therefore, all the proposed residue chemistry studies would
be required regardless of the application rate. It was originally
incorporated in the data requirements as explained in the October,
1982, Subdivision M guidelines (pages 31 and 32, Section VI, Residue
Analysis) as an estimate of a ``low application rate'' since the
original definition for biochemical and microbial pesticides (40 CFR
158.65) mentioned that they are generally distinguished from
conventional pesticides by various characteristics including ``low use
volume.'' The Agency has determined that the key to whether residue
data (which is needed only to support a numerical tolerance) are needed
for biochemical (and microbial) pesticides is toxicity, not exposure by
itself.
2. Residue data requirements-- i. New requirements. None.
ii. Newly codified requirements--a. Nature of the residue: plants;
livestock. These data are currently not required (NR) to support indoor
food use. The Agency, however, proposes to conditionally require (CR)
these studies to support registration of indoor food use. There have
been instances where certain biochemical pesticides are applied to food
crops indoors (e.g., for treatment of stored potatoes), and these
potato peels are then fed to cattle for feed. Therefore, the nature of
residues on plants is needed to determine potential residues on the
treated crop. The 0.7 ounces per acre restriction is no longer a
trigger for requiring the submittal of data. The Agency also proposes
to eliminate ``Nature of residue: livestock'' to support domestic
outdoor use, since the data are needed for potential food uses outside
of the home, and domestic outdoor use is for porches, patios, yards,
home gardens, etc. EPA also proposes to no longer require testing on
Pure Active Ingredient Radio Labeled (PAIRA) but instead to use the
TGAI because it is difficult to isolate pure active ingredient from a
naturally-occurring substance.
b. Residue analytical method. This data requirement is currently
conditionally required (CR) for terrestrial, aquatic, and greenhouse
food use with the 0.7 ounce per acre limitation (data not required if
applied at rate less than or equal to) restriction. The Agency proposes
these data to be required (R) for greenhouse use and continue to
conditionally require (CR) data for terrestrial, aquatic, and indoor
food use but without the less than 0.7 ounce active ingredient (a.i.)/
per acre/year exemption. It would remain conditionally required (CR)
for indoor food use. The residue analytical method data are needed to
address enforcement issues, i.e. ability to measure the pesticide.
iii. Revisions to existing requirements--a. Chemical identity and
Directions for use. These data are currently conditionally required
(CR) based on a series of conditions including if the application rate
exceeds 0.7 ounces (20 grams) active ingredient per acre per year. EPA
proposes not to include the application rate conditions (data required
only if application rate exceeds 0.7 ounce a.i./acre/year). EPA
proposes test note revisions for both the chemical identity and
directions for use, but preserves one test note addressing domestic
outdoor use. However, EPA is proposing to continue to conditionally
require (CR) this data only for all biochemicals for which residue data
are required since chemical identity and directions for use are
considered to be essential to understanding the pesticide. The Agency
has determined that throughout the years of registration activities for
all biochemicals, the chemical identity and the directions for use
information are always submitted before processing the application. The
directions for use are included as part of the labeling information
along with the submission.
b. Multiresidue method. Multiresidue methodology data are currently
part of
[[Page 12084]]
the residue analytical method requirement. The Agency proposes to
codify an existing multiresidue method study (guideline 860.1360) and
designate it as a separate requirement. These data, which are currently
submitted to support registration, are important in designing pesticide
monitoring and enforcement programs. 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 allow analysis of as many pesticides as possible, it is clearer to
list these as two separate data requirements. The test note indicates
that any analytical methodology must be evaluated for its ability to
detect metabolites included in the tolerance expression.
c. Magnitude of residue data. All the studies in this category
(guidelines 860.1400 through 860.1650) no longer have the application
rate of 0.7 ounces a.i./per acre/ per year exemption.
d. Submittal of analytical reference standards. The Agency
currently conditionally requires (CR) this data as ``submittal of
samples'' as a product analysis data requirement. The Agency is
proposing to revise the name to ``Submittal of Analytical Reference
Standards'' (quideline 860.1650) and continue to conditionally require
(CR) the data. The requirement for submittal of samples was moved to
the residue data requirements because it is considered a residue data
requirement rather than a product analysis data requirement.
Biochemical pesticides are generally of low toxicity because of their
non-toxic mode of action, but, if the Agency does identify toxicity
concerns, then an analytical reference standard requirement will be
triggered to analyze potential residues.
E. Human Health Assessment Data Requirements
1. General. The current ``Toxicology'' data requirement is proposed
to be renamed from ``toxicology'' to ``human health assessment'' to
include toxicology and applicator/user exposure data requirements.
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 health risk
assessment. For example, an insect repellent registration would require
significantly more human health assessment data compared to a
application for SCLP. The duration of the toxicity study approximates
the estimated duration of human exposure, while considering species
differences in maturational milestones and overall life span.
The proposed table in subpart L (Sec. 158.950) contains the human
health assessment data requirements EPA would rely on to identify
potential hazards to humans and domestic animals for biochemical
pesticides, and is expected to improve the Agency's understanding of
the potential pesticide hazard to animals and humans, including
subpopulations such as infants and children and possible environmental
effects. This proposal retains the requirements for pesticides in
current 40 CFR 158.690, as well as revisions that reflect the current
practices due to FQPA implementation and the evaluation of regulating
biochemical pesticides.
The Agency is continuing to require toxicity studies where use
patterns indicate high exposure, such as food use biochemical
pesticides, as well as exposure studies required to support certain use
patterns (e.g., insect repellents). The exposure data assess exposure
to both the person to and for whom the repellent is being applied as
well as the person who is applying the repellent (i.e., parent to
child) and it also assesses hand to mouth contact (i.e. children),
which often occurs under these circumstances. Other toxicity studies,
e.g., 90-day dermal, 90-day inhalation, 90-day oral toxicity for
nonfood use, etc., remain as conditionally required on a case-by-case
basis, depending on the category of pesticide (e.g., SCLPs, growth
regulators, repellents), the patterns of use (food and nonfood), and
estimated exposure and the results of lower tiered studies.
2. Human health assessment data requirements. The following
identifies the revisions from the current ``Biochemical pesticides
toxicology data requirements'' in 40 CFR 158.690 to the proposed
``Biochemical pesticides human health assessment data requirements.''
The title of the data table has been revised to reflect that the
primary use of the data is to assess the potential risk to humans. The
proposed revised table includes the toxicology data requirements and
exposure studies (the latter to support insect repellent uses). There
are few new studies which are proposed which were not identified until
the 1986 Science Advisory Panel discussing applicator/user exposure
data requirements (Ref. 10) and conditions under which data are
appropriate (except the companion animal safety data). The following
lists the individual data requirements, and what the proposed rule
requires and when it requires these data. There is also a discussion on
why the Agency proposes companion animal safety data in this proposed
rule as well.
i. New requirements.--a. Exposure (applicator/user). The Agency
proposes exposure studies (guidelines 875.1000 through 875.1500) to be
conditionally required (CR). These data are triggered when Tier I
toxicology data indicate that the biochemical may pose a hazard. The
Tier II human health assessment data (toxicology and/or exposure)
requirements are not required if the results from the Tier I toxicity
studies indicate no expected risk. The Agency recommends that
registrants consult with the Agency prior to study initiation to
determine what exposure studies are appropriate based on the nature of
the adverse effects seen in the Tier I data. The following are the
various types of applicator/user exposure data that could be required:
(1) Dermal exposure. The Agency proposes to conditionally require
(CR) data 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 applicator/
user exposure studies employ passive dosimetry techniques which
estimate the amount of a pesticide 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 using
patches that absorb pesticides or by removing the material that has
contacted the skin before it has been absorbed.
(2) Inhalation exposure. To estimate inhalation exposure to
pesticide residues, the Agency proposes to conditionally require (CR)
both outdoor and indoor inhalation exposure studies (guideline 875.1300
and 875.1400). It has become apparent to the Agency that insect
repellents when applied often result in inhalation exposure to the user
(either to the person it is being applied (e.g., child) as well as to
the person applying the insect repellent (e.g., adult)) and therefore
the Agency would like the flexibility to require these data for this
use when triggered by results from lower tier studies or estimated
exposure.
(3) 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 to
[[Page 12085]]
satisfy, dermal or inhalation exposure data requirements provided the
human pharmacokinetics of the pesticide residue are sufficiently
understood to permit calculation to determine the total internal dose.
Biological monitoring offers the advantage of assessing the actual
internal dose, as opposed to the estimated exposure or amount of
pesticide coming in contact with the surface of the skin or available
for inhalation in the lungs as measured using passive dosimetry
techniques. For example, biological monitoring could consist of
evaluating blood for cholinesterase activity; if it is low in a blood
sample, the person may have been exposed to a cholinesterase inhibitor
by any route including dermal or inhalation. Also, biological
monitoring may indicate whether a given substance has been absorbed
through the skin or inhaled in enough quantities to be of concern.
b. Companion animal safety data. Companion animal safety data
(guideline 870.7200) is being proposed to be part of conditionally
required (CR) special testing. This data would be triggered if the
product's use would result in exposure to domestic animals through, but
not limited to, direct application (e.g., topical application as in
insect repellents) or consumption of treated feed. This new data
requirement is based on recent Agency experiences with biochemical
pesticides, specifically, that there are currently no data requirements
addressing potential toxicity to domestic animal species from
biochemical pesticides. Fulfillment of this conditionally required data
would address such potential risk concerns. This is considered part of
the human health battery of studies, as it is considered for
conventionals.
ii. Newly codified data requirements.--a. Hypersensitivity
incidents. Currently, the Agency conditionally requires (CR) these data
when they are reported. The Agency proposes to augment this data
requirement to include incidents to be reported from conditionally
required (CR) to required (R) for all preregistered (EUP's) and
registered products. Incidents can occur from application of an EUP as
well as registered products, which, if reported, would be essential to
making a well informed finding. Registrants are reminded that FIFRA
section 6(a)(2) requires the submission of such information for
registered products (see 40CFR part 159).
b. Product use information. EPA is proposing to require (R) product
use information (guideline 875.1700) to provide information on how the
pesticide is used and applied per day. Data would at least include:
Typical application methods, typical values for application rates,
timing and number of applications per season or per year, any available
surveys that provide use information for insect repellents, and other
use information relevant to potential exposure following a repellent
application. Such use information enables the Agency to appropriately
trigger other conditional data requirements, i.e., identification of
potential exposure (risk), and conduct more accurate and realistic risk
assessments, thus enabling the Agency to levy appropriate limitations
on use to mitigate any potential risks. This data requirement is newly
codified since this information is already submitted with the label and
the Agency could not complete a risk determination (estimate exposure)
without the information.
c. Test note revisions and other conditions exempting data. The
Agency is proposing to add the following conditions at the onset to
Tier I, Tier II, and Tier III Human Health Assessment Data Tables:
Straight chain Lepidopteran pheromones are exempt if applied at a rate
less than or equal to 150 grams active ingredient/per acre/year (Ref.
15). EPA is no longer requiring these data for SCLPs because the past
20 years of scientific literature supports waiving the data. SCLP's do
not pose a risk to human health when applied at a rate not to exceed
150 grams active ingredient per acre. This is consistent with current
implementation, e.g., Sec. 180.1124 requirements.
The Agency proposes to provide a test note identifying when certain
data are required (acute oral, acute dermal, primary dermal
irritation), unless the test material is a gas or highly volatile
(vapor pressure >104 torr). The current data tables do not
specify the trigger for vapor pressure. Thus, the proposed rule
provides criteria and clarity.
iii. Revisions to existing requirements--a. Primary eye irritation
and primary dermal irritation. The Agency currently requires (R) these
data for MP or EP. The Agency is proposing to require (R) these data
for TGAI and MP test substances since effects may result from active
ingredient or other (inert) ingredients in the end-use product.
b. Dermal sensitization. The Agency conditionally requires (CR)
``Hypersensitivity study'' (152-15) in current Sec. 158.690. EPA
proposes to substitute dermal sensitization data (guideline 870.2600)
and to require (R) the data, since the dermal sensitization guideline
measures the same endpoints and more accurately describes the nature of
the type of data required in that it identifies dermal sensitivity. The
Agency considers this information a method for accurately classifying
the dermal sensitization potential of the pesticide and for determining
whether any observed adverse effects are inherent to the active
ingredient, or caused by the presence of other ingredients. In
addition, the Agency currently requires (R) this data for MP or EP. The
Agency is proposing to require (R) this data for TGAI and MP test
substances since effects may result from active ingredient or other
(inert) ingredients in the end-use product.
c. Mutagenicity. The Agency proposes to change the name of the
battery of studies from ``Studies to detect genotoxicity'' (152-17) to
specific mutagenicity studies including the following: Bacterial
Reverse Mutation Test (guideline 870.5100), In vitro Mammalian Cell
Gene Mutation Test (guideline 870.5300), and In-vivo Cytogenetics
(guideline 870.5385 and 870.5395) (Mammalian Bone Marrow Chromosomal
Aberration Test and Mammalian Erythrocyte Micronucleus Test,
respectively). The Agency proposes to split existing genotoxicity data
requirement (152-17) into four different data requirements. The
following are proposed as Tier I requirements: Bacterial Reverse
Mutagenicity (guideline 870.5100) and In vitro Mammalian Cell Gene
Mutation TEst (guideline 870.5300) are proposed to be required (R) for
food uses and conditionally required (CR) for nonfood uses. The
following are proposed Tier II requirements: In vivo Cytogenetics
(guideline 870.5385 and 870.5395). Second, the proposed Tier II
studies, mammalian spermatagonial chromosomal aberration and mammalian
bone marrow chromosomal aberration (guideline 870.5385 and 870.5395),
are conditionally required (CR) for food uses if Tier I data indicate
mutagenicity. The Agency is proposing these organizational changes
because the original genotoxicity data requirement was actually
composed of multiple studies and the actual data requirements are more
clearly described when separated as found in today's proposal. For
example, the current Tier II data is required on mammals and would be
unnecessary if the Tier I data shows no mutagenicity concerns. In
addition, the guideline under which the old genotoxicity data
requirement references is 152-17 in the 1982 guidelines and it says
``Data derived from short-term microbial mutagenicity tests are
required...'' and it mentions gene mutations, structural chromosomal
aberrations, and direct DNA damage and
[[Page 12086]]
repair (Ref. 9). The Agency designates these as mutagenicity tests
today and the overall way the Agency cumulatively test for mutagenicity
has evolved since then.
d. Prenatal developmental toxicity. The Agency proposes to change
the name of this requirement from ``Teratogenicity'' to ``Prenatal
developmental toxicity'' to better correspond with the focus of the
study and current terminology. The Agency currently conditionally
requires (CR) this study for Tier I. The Agency proposes to require (R)
this study for Tier I for food uses since food use has the highest
potential exposure to humans during pregnancy; this guideline will
provide sound data if needed to address prenatal development. EPA
encourages preregistration meetings to determine if the data
requirement can be waived because of minimal exposure; or existing data
on the product in the scientific literature indicating there is not a
concern for developmental toxicity. EPA will continue to conditionally
require (CR) these data for a nonfood use. EPA is also proposing to
conditionally require (CR) these data on a second test species for food
and nonfood uses as a Tier II data requirement based on the condition
that there are reproductive effects (e.g., fetotoxicity, retarded
development, structural abnormalities, behavioral abnormalities and/or
death) evident in Tier I, Prenatal Developmental Toxicity (guideline
870.3700).
The Agency currently does not require a reproduction study as Tier
III, and EPA is proposing to conditionally require (CR) a reproduction
and fertility data requirement as a Tier III study depending on the
results of the Tier I and II data requirements (i.e. subchronic
toxicity, prenatal development, mutagenicity studies) in order to
address potential risks that may be identified in lower tier studies.
In summary, for biochemical pesticides, the tiered principle of
testing requirements for developmental toxicity is as follows: identify
the hazard potential in Tier I for one species; if that study is
positive, another study is required (2nd species) for use in reducing
the uncertainties of species-to-species extrapolation (Tier II). If
positive mutagenicity or effects on reproductive organs are observed in
subchronic (Tier II) studies, then the reproduction study (Tier III)
would be required for greater certainty in risk characterization.
e. Immunotoxicity. The Agency currently requires (R) Immune
Response data (152-18). The Agency has renamed the guideline name and
number to Immunotoxicity (guideline 880.3550) and is proposing to
conditionally require (CR) such data as part of Tier II, with a test
note indicating this data is required if there are effects on
hematology, clinical chemistry, lymphoid organ weights and
histopathology observed in the 90-day studies, or if the results of the
Tier I mutagenicity tests are positive. The proposed change would make
it consistent with current evaluation process for determining if a
pesticide is expected to pose immunotoxicity. This is consistent with
the Office of Pesticide Programs historic waiver of this requirement
for SCLP's, as well as when there are no effects on hematology,
clinical chemistry, lymphoid organ weights, etc. or when there is no
evidence of mutagencity concerns in Tier I data.
The Immunotoxicity study (guideline 880.3550) provides information
on health hazards likely to arise from subchronic exposure to a
pesticide, usually after dosing by the oral route (emphasis added).
Tests are selected to provide quantitative and qualitative data on the
capacity of a pesticide to adversely affect components of antibody-
mediated and specific and non-specific cell-mediated immunity. This
purpose suggests that the oral route is preferred, but the conditions
for requiring immunotoxicity testing indicate that any route that is
relevant to each pesticide's use pattern (primary route of exposure
under conditions of use) is acceptable. (Results from one insect
repellent study that was done by the dermal route p-menthane-3,8-diol
(Ref. 16) did not show any effects on the immune system.)
EPA is also proposing to rename and move a Tier II immune response
data requirement (152-24) to a Tier III data requirement (immune
response guideline 880.3800). The Agency proposes to continue to
conditionally require (CR) these data depending on the results of the
study completed to satisfy the Tier II Immunotoxicity data requirement.
The Agency believes these data address the endpoints more suitably then
the results found in the Immune Response Study.
In summary, the Agency decided to raise the level of tiers for the
required immunotoxicity data from Tier I to II and from Tier II to Tier
III, based on the triggers used to require the immunotoxicity data. In
other words, the results of the 90 day studies requested under Tier I
may trigger Tier II immunotoxicity studies, but the Agency would not be
able to make that determination until the data from Tier I was
reviewed. This is different from what was proposed in conventional
pesticides (70 FR 12275, March 11, 2005), which requires the data
(though not the same guideline (conventional pesticides requires
guideline 870.7800)), since it is proposed to be required as Tier I.
The Agency discussed the variability, and decided for biochemical
pesticides, given their low risk, it was appropriate to defer until the
data in Tier I are reviewed and determined if there was a potential for
adverse effects to the immune system.
f. Carcinogenicity. The Agency proposes to change the name of the
``Oncogenicity study'' to ``Carcinogenicity study'' (guideline
870.4200) to reflect current terminology.
g. 90 Day-Oral Subchronic Testing. The Agency currently
conditionally requires (CR) these data for food uses. The Agency is
proposing to require (R) these data for food uses since people eat food
for periods longer than one day, and since biochemicals have a non-
toxic modes of action, there is a need for some data comparable to
dietary exposure to assure us that nothing adverse is likely to happen
when there are higher than normal levels of the biochemical in our
food. For instance, eating too much of a given vitamin can be toxic or
too much of an essential element like iron can have some unpleasant
effects.
F. Nontarget Organisms and Environmental Fate Data Requirements
1. General. The Agency uses a tiered system of ecological effects
and environmental fate testing to assess the potential exposure and
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.
Laboratory tests provide a screening tool for what can potentially
occur in the field, whereas the field study data indicate the potential
adverse effects in the field. 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 (e.g., Tier II, Tier III, and Tier IV) are needed. Tier I
ecological effects testing generally consists of the basic data
requirements that are necessary to determine the acute toxicity to
nontarget fish, invertebrate, plant, and wildlife species. Tier II
environmental fate data requirements (there are no Tier I environmental
fate data requirements) revolve around the characterization of the
pesticide in the environment, e.g., hydrolysis, soil and aquatic
metabolism
[[Page 12087]]
rate, photodegradation rate in soil and water, etc.
Higher tiered studies may be conditionally required when basic Tier
I data indicate there is potential for adverse effects to nontarget
species. Tier II data requirements include an array of environmental
fate data requirements and subchronic/chronic ecological effects tests
to further refine the potential for exposure and/or risk to the
environment. Tier III data requirements include a further array of
field studies that address ecotoxicity concerns for terrestrial and
aquatic animal species as well as nontarget plants and insects. These
data provide a foundation for ecological risk assessment, which allows
the Agency to determine any appropriate precautionary statements or
mitigation measures necessary to support registration concerning
toxicity or potential adverse effects to nontarget organisms (including
endangered species).
With respect to some of the environmental fate data requirements,
the Agency is providing two sets of guideline numbers where needed, the
first guideline numbers are what are currently used by the Agency. The
second set which are in (parentheses) are guidelines the Agency has in
draft stage and hope to finalize in the near future. To avoid confusion
on the types of data that are required, both numbers are provided for
each data requirement as an interim measure until the guidelines are
finalized.
2. Nontarget organisms and environmental fate data requirements.
The Agency is proposing to add the redwing blackbird, Agelaius
phoenicius, to the list of species that may be substituted for the
other species (i.e., mallard or bobwhite quail). This test species
could be used for the avian oral toxicity study because current data
requirements do not adequately characterize the risks that pesticides
pose to songbirds. Other changes include revisions in the test
substance, conditions under which the test is conducted, and
clarification of test notes.
i. New data requirements. None.
ii. Newly codified data requirements. a. Regulatory text revision.
The current part 158 for biochemicals does not include regulatory text
provisions within the data table section discussing the exemptions of
data to support arthropod pheromones (Sec. 158.960(a)(2)).The Agency
is proposing the following language to be part of the regulatory text
in the proposed rule:
(2) The data in this section (Sec. 158.960) are not required
for arthropod pheromones when applied at up to a maximum use rate of
150 grams active ingredient/acre/year except when the product is
expected to be available to avian species (i.e. granular
formulation).
It makes it clear from the onset under what conditions these data are
required. Based on a survey of data and the literature since 1984, EPA
believes that arthropod pheromones pose minimal risk to nontarget
species when applied at this rate or less (Ref. 15). As a result of
this finding, EPA has historically waived these data and is revising
the test note to reflect the current practice.
b. EP testing. Where nontarget and environmental fate data are
required, the Agency currently requires (R) that the TGAI be used as
the test substance, and does not generally require (R) or conditionally
require (CR) the EP to be tested. EPA is proposing to conditionally
require (CR) EP testing when any end-use formulation may contain other
ingredients that may be toxic to nontarget organisms or to support
arthropod pheromones that would be available to avian wildlife (e.g.,
granular product).
c. Anerobic aquatic metabolism (162-3 or guideline 835.4400) and
anerobic soil metabolism (162-2 or guideline 835.4200), are currently
not required (NR). The Agency is proposing to conditionally require
(CR) anerobic soil metabolism for terrestrial use and anerobic aquatic
metabolism for both terrestrial and aquatic uses. The Agency believes
that anerobic aquatic metabolism is necessary if the pesticide is
intended for application to standing water and/or low oxygen
environments, e.g., rice paddies, cranberry bogs, wetlands in natural
areas and would already be required under these circumstances under
typical registration practices for biochemicals.
iii. Revisions to existing requirements. The Agency is proposing a
reduction or clarification in following five data requirements: avian
oral, avian dietary, freshwater fish, freshwater invertebrate, and
plant toxicity testing. The Agency is proposing to not require (NR)
these studies for terrestrial uses of arthropod pheromones as defined
in Sec. 158.900. Other proposed changes are as follows:
a. Avian acute oral (guideline 850.2100)--Redwing Blackbird. Part
158 currently only offers two test species for testing, mallard and the
bobwhite quail. The Agency is proposing revisions to the Avian Acute
Oral data requirement, specifically to add an optional test species
(i.e. redwing blackbird), in order to address potential exposure to
passerine species in a terrestrial environment. In addition, the Agency
is proposing to conditionally require (CR) EP testing if the
formulation would be available to avian wildlife, e.g., granular
formulation. Testing on a passerine species (i.e., redwing blackbird)
may be required (R) for outdoor uses if the use pattern lends itself to
higher exposure to passerine species compared to upland game or
waterfowl species. EPA is requesting comments on whether this species
should replace the existing bobwhite/mallard species for a biochemical
pesticide, or otherwise be presented as an optional species for the
conduct of the test. If so, comments are also sought on the specific
criteria to be used to determine when the testing on this particular
species would be required.
In addition, the Agency is proposing to conditionally require (CR)
EP testing when the following apply: when any end-use formulation may
contain other ingredients that may be toxic to nontarget organisms or
when the end-use formulation is used to support arthropod pheromones
that would be available to avian wildlife (e.g., granular product).
b. Avian dietary (guideline 850.2200). Part 158 currently requires
(R) TGAI testing for this data requirement. In addition, the Agency is
proposing to conditionally require (CR) EP testing when the following
apply: when any end-use formulation may contain other ingredients that
may be toxic to nontarget organisms or when the end-use formulation is
used to support arthropod pheromones that would be available to avian
wildlife (i.e., granular product).
c. Fish acute toxicity test (freshwater) (guideline 850.1075),
aquatic invertebrate acute toxicity (freshwater)test (guideline
850.1010). The Agency currently requires (R) these data for all
terrestrial, aquatic, forestry, and domestic outdoor uses. The Agency
conditionally requires (CR) the data for greenhouse and indoor use. The
Agency proposes to add two test notes to the current standards. The
first proposed test note indicates when EP data are conditionally
required (CR), the second test note does not require testing for
compounds which are highly volatile.
d. Seedling emergence (guideline 850.4100) and vegetative vigor
(guideline 850.4250). Part 158 currently requires (R) these data as
Nontarget Plant Toxicity testing to support terrestrial and aquatic
nonfood uses and forestry uses. The Agency proposes to require (R)
these data for all outdoor uses. Currently there is one test note with
three conditions identifying when these data are required. The Agency
is proposing to eliminate these test note conditions, but add a test
note requiring
[[Page 12088]]
EP testing when the end-use formulation may contain other ingredients
that may be toxic to nontarget plants.
e. Nontarget insect testing (guideline 880.4350). Currently the
Agency conditionally requires (CR) nontarget insect testing (154-11)
data with two test note conditions. The Agency proposes to be more
transparent and require (R) these data, for all uses except indoor use.
This is because it has become apparent to the Agency throughout the
years, that is appropriate to require insect testing especially with
these types of biochemical pesticides, to ensure they are insect
specific. In addition, the actual test guideline recommends that the
guideline 850.3020 be conducted on the honeybee initially, but that
additional nontarget insect species may be required. The honeybee study
is required since that is what has been typically submitted and
addresses the issues for risk assessments for biochemical pesticides.
f. Sediment and soil adsorption/desorption for parent and
degradates; 161-1 or guideline 835.1230, and soil column leaching (
163-1 or guideline 835.1240) currently designated as adsorption-
desorption. These data are currently not required (NR) for greenhouse
use. Hydrolysis (161-1 or guideline 835.2120) and Aerobic Aquatic
Metabolism (162-4 or guideline 835.4300) are also not required (NR) for
greenhouse use. The Agency is proposing to conditionally require (CR)
these data for greenhouse use. The proposed test note is also revised
to indicate all these data are conditionally required (CR) depending on
the results of any of the Tier I data, not limited to environmental
fate data, since it is the experience of the Agency that there may be
other indicators other than exposure data which would trigger the need
for these data.
g. Laboratory volatilization from soil (163-2 or guideline
835.1410) designated as volatility in current data requirements, and
Aerobic soil metabolism, 161-1 or guideline 835.4100. The Agency
currently conditionally requires (CR) these data to support aquatic
uses and do not require (NR) these data to support greenhouse use. The
Agency is proposing to not require (NR) these data to support aquatic
uses, and to conditionally require (CR) these data to support
greenhouse use. Since the exposure is in the soil, it is appropriate
not to require data in the water/sediment and it is appropriate to
require these data for land type use. In other words, this revision is
consistent with the purpose and implementation, as well as with the
guidelines.
h. Photodegradation on soil (161-3 or guideline 835.2410) and
photodegradation in water (161-2 or guideline 835.2240) identified as
Soil photolysis and Aquatic photolysis in current guidelines. Part 158
currently conditionally requires (CR) these data for all uses except
greenhouse and indoor use. That study is designed to measure photolysis
of a pesticide on the surface of the soil. Water will attenuate the
amount of sunlight reaching underlying sediments in a water body,
thereby making photolysis of a sediment bound pesticide unlikely. In
that case, measuring photolysis of the pesticide in the water column
would be more appropriate. Therefore, the Agency proposes to not
require (NR) photodegradation of parent and degradates in soil for
aquatic (food and nonfood), since photodegradation cannot be measured
in the soil under the water, but the Agency is continuing to
conditionally require (CR) the direct photolysis rate of parent and
degradates in water, since photolysis can be measured. The Agency
proposes to add a condition for terrestrial, greenhouse, and forestry
uses, when the results of Tier I studies demonstrate a concern for
toxicity, and an evaluation of potential exposure (environmental fate)
is needed to make a risk determination. EPA also proposes to change the
names of these studies from ``soil photolysis'' to ``photodegradation
on soil'' as designated in (161-3 or guideline 835.2410) and from
``aquatic photolysis'' to ``photodegradation in water'' also identified
as direct photolysis rate of parent and degradates in water (161-2 or
guideline 835.2240). In essence, the proposed data requirements are in
line with the proposed use patterns, where the exposure is eminent.
i. Partition coefficient (n-octanol/water) (guidelines 830.7550,
830.7560, and 830.7570). Part 158 currently conditionally requires (CR)
this study when results from Tier1 tests indicate environmental fate
data are needed. The Agency proposes to relocate this requirement under
the product chemistry data requirements. As further explained in that
section of the preamble, the study would no longer be dependent on Tier
I studies, but would be conditionally required (CR) for organic
chemicals unless they dissociate in water or are partially or
completely soluble in water.
j. UV/light absorption (guideline 830.7050). Part 158 currently
conditionally requires (CR) this study for all uses except greenhouse
(food and nonfood) and indoor use. As explained elsewhere, the Agency
proposes to transfer this data requirement to product chemistry data
requirements and to require (R) this for all 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 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. The UV/visible light absorption
spectrum will indicate whether or not the pesticide absorbs in this
range.
k. Dispenser-water leaching (guideline 880.4425). Part 158
currently does not require (NR) this study to support greenhouse uses
and indoor use. The proposed rule conditionally requires (CR) this
study for greenhouse use and does not require (NR) for aquatic uses.
This proposed change brings the data table in line with the guideline
and only require the data when the pesticide is applied to land in a
passive dispenser.
l. Terrestrial wildlife, aquatic animal, nontarget plant, and
insect testing. The Agency currently divides Tier III studies into four
categories: terrestrial, aquatic animal, nontarget plant, and nontarget
insect testing. The Agency proposes to identify individual studies and
their respective guideline numbers that may be conditionally required
(CR) when results from lower tiered data indicate the potential need
for additional studies. The test notes have not been revised, therefore
the conditions under which these data are required will not be revised.
However, the Agency is updating the guideline numbers. As a result
guideline 850.2300 through 850.2500 apply to various terrestrial data
requirements (avian and mammal), guideline 850.1025 through 850.1500
for aquatic animal data requirements (freshwater and marine fish and
invertebrate species), and guideline 850.4225 through 850.4450 for
nontarget plant studies.
The Agency currently conditionally (CR) requires Tier III nontarget
insect testing depending on the results of the lowered testing for
nontarget insects. The Agency proposes to conditionally require (CR)
field pollinator testing (to address risks to bees) data (guideline
850.3040) as Tier III, if the product is expected to be transported
during application to air, soil, or water, which is determined in the
Tier II environmental fate studies. Based on industry information, and
fate data indication potential for exposure, we
[[Page 12089]]
might then require some type of Tier III testing. This testing would
have to be preceded by consultation with OPP, because it would be
directed at the problem identified earlier. We would need to consider
the species at risk, route of exposure, etc. Additional insect species
may have to be tested if necessary to address issues raised by use
patterns and potential exposure of important insect species, e.g.,
beneficial insects, endangered species. The guideline number is
guideline 850.4030.
m. Product performance. Currently the Agency relies on Sec.
158.640 for product performance data requirements for biochemicals and
microbial pesticides. The Agency is proposing to include product
performance in the regulatory text for both biochemicals and microbial
pesticides to improve transparency. Product performance verification
can be important, especially for public health pests, for some of the
biochemical and microbial pesticides since we have seen independent
reports that some do not work as well as the conventional pesticide
products.
VIII. Microbial Pesticides Data Requirements (Subpart M)
A. Definition of Microbial Pesticide
Amendment to part 158. The Agency is proposing a revision in the
definition of a microbial pesticide. The current definition at Sec.
158.65 of microbial pesticides is:
Biochemical and microbial pesticides are generally distinguished
from conventional pesticides by their unique modes of action, low use
volume, target species specificity or natural occurrence. In addition,
microbial pesticides are living entities capable of survival, growth
reproduction and infection. ... Microbial pesticides include microbial
entities such as bacteria, fungi, viruses, and protozoans. The data
requirements apply to all microbial pesticides, including those that
are naturally-occurring as well as those that are genetically modified.
Each ``new'' variety of subspecies, or strain of an already registered
microbial pest control agent must be evaluated, and may be subject to
additional data requirements.
The definition of a microbial pesticide in the proposed rule is as
follows:
Microbial pesticide means a microorganism intended for
preventing, destroying, repelling, or mitigating any pest, or
intended for use as a plant regulator, defoliant, or desiccant,
that: (1) Is a eucaryotic microorganism including, but not limited
to, protozoa, algae, and fungi; (2) Is a procaryotic microorganism,
including, but not limited to, bacteria; or (3) Is an autonomous
replicating microscopic element, including, but not limited to,
viruses.
This proposed definition of microbial pesticide is based on the
language in the current definition of microbial pesticide at Sec.
158.65 and the class of nonexempt biological control agents in Sec.
152.20(a)(2), but uses a structure for defining microbial pesticide
similar to that at 40 CFR 172.43. Specifically, the proposed definition
replicates the structure used in Sec. 172.43 that identifies the
intent of the microbial pesticide, for example, as the prevention or
destruction of a pest. The proposed definition also combines the
structure and examples at Sec. 152.20 with the current regulatory
structure to clarify the intended scope of the current regulatory
definition and relationship to Sec. 152.20. For example, the proposed
definition includes references to eucaryotic and procaryotic
microorganisms, terms not found in the current definition at Sec.
158.65 but found in Sec. 152.20(a)(3). The proposed definition also
clarifies that microbial pesticides include viruses and other similar
infective elements, while the ''autonomous replicating`` language is
intended to exclude pesticide components of microscopic cells that are
not able to replicate as separate entities, such as genetic constructs
inserted intentionally into the cells. None of these proposed
amendments are intended to change the scope of the current regulatory
definitions of microbial pesticide at Sec. 158.65 or of the exemption
provision at Sec. 152.20(a)(3).
EPA is also proposing not to include in the definition of microbial
pesticide the phrase from current Sec. 158.65 distinguishing microbial
pesticides from conventional pesticides because the original definition
was more of a description of those characteristics that might be shared
by both biochemical pesticides and microbial pesticides. In this rule,
we have described biochemical pesticides separately and we can now be
more specific in defining microbial pesticides.
EPA notes that microorganisms are known to produce many pesticidal
substances. These pesticidal substances, when used independently of the
microorganism, are considered to be biochemical pesticides,
conventional chemical pesticides, or antimicrobial pesticides,
depending on the mode of action and the use. The microorganism would
then usually be considered part of the manufacturing process. For
example, streptomycin, an antibiotic produced by a bacterium,
Streptomyces griseus, is registered as a conventional chemical
fungicide.
B. Applicability of Microbial Pesticide Data Tables
EPA is proposing to create a new applicability provision expressly
providing that the microbial pesticide data tables apply to microbial
pesticides, as described previously, and to add to that paragraph
specifics on the types of microbials subject to the subpart M data
requirements.
First, the language in current Sec. 158.65 states that ``each new
variety of subspecies, or strain of an already registered microbial
pest control agent must be evaluated, and may be subject to additional
data requirements.'' The proposed refinement now reads ``each new
isolate of a microbial pesticide is treated as a new strain and must be
registered independently of any similar registered microbial pesticide
strain and supported by data required in this subpart.'' This
refinement is simply intended to clarify the intent of the current
regulatory language.
The second sentence added to the applicability provision states
that genetically modified microbial pesticides may be subject to
additional data or information requirements on a case-by-case basis
depending on the particular microorganism and/or its parent
microorganism(s), the proposed pesticide use pattern, and the manner
and extent to which the organism has been genetically modified. That
language is moved from current Sec. 158.65.
The final sentence reads ``pest control organisms such as insect
predators, nematodes, and macroscopic parasites are exempt from the
requirements of FIFRA as authorized by section 25 (b) of FIFRA and
specified in Sec. 152.20 (a) of this chapter.'' That sentence is moved
from current Sec. 158.65 as well.
In addition, the current regulatory text at Sec. 158.65 specifies
that the microbial ``data requirements apply to all microbial
pesticides, including those that are naturally-occurring as well as
those that are genetically modified.'' This language is not needed in
the definition; the use of the data requirements for microbial
pesticides is fully described in the section immediately following the
definition.
Other portions of the current text at Sec. 158.65 are proposed to
be moved to the applicability subsection of subpart M, Sec. 158.1000,
or the other provision that seems generic Sec. 158.1010 to avoid
confusion on the definition of microbial pesticide. Specifically, EPA
is proposing to move current Sec. 158.65(b)(2) to proposed Sec.
159.1010.
EPA is also proposing to use table descriptors NR (not required), R
[[Page 12090]]
(required), and CR (conditionally required) to be used as markers along
a spectrum of the likelihood that a data requirement applies. In other
words, it should be assumed that a required (R) data requirement is
required typically all the time. There may be some narrow or rare
conditions identified in test notes when data are not required. For
example, acute injection toxicity (intraperitoneal or intravenous) not
required when the microbial pesticide is a virus. In contrast, a
conditionally required (CR) data requirement is less likely to be
triggered compared to a required (R) data requirement, but more likely
include test notes indicating conditions when data are typically
required. For example, the primary dermal irritation is currently
conditionally required (CR) for microbial pesticides. The test note
indicates it is required (R) when dermal irritation is reported from
the acute dermal toxicity study. Specific criteria are identified with
the test note.
C. Amendment of Part 172
The Agency is also proposing to replace the definition for a
microbial pesticide at 40 CFR 172.43 with the definition proposed here.
The proposed definition is broader than the definition at Sec. 172.43
in that it uses the term ``includes'' rather than ``means'' and
identifies a category for autonomous replicating microscopic elements,
rather than just including viruses. EPA is proposing a broader
definition because it has been EPA's experience that there are
microorganisms other than viruses that could be used as a pesticide but
that would otherwise be excluded by the definition at Sec. 172.43.
D. Product Analysis Data Requirements
1. General. The Agency uses product analysis information to
determine whether impurities of toxicological or environmental concern
are present in the pesticide and formulated products. Product analysis
data requirements include product identity and composition data,
physical and chemical characteristics of a pesticide, plus any
intentionally added ingredients and impurities in the final pesticide
product. Included in this category are the specific, detailed
requirements for product identity and chemical analysis. The title of
the data requirements, ``microbial pesticides product chemistry data
requirements,'' is proposed to be revised to ``microbial pesticides
product analysis data requirements'' to better reflect the extra
identification procedures necessary to analyze living organisms. The
following discussion addresses the proposed data requirements.
2. Product analysis data requirements. Currently, the Agency groups
all the physical and chemical properties studies under one section. The
Agency proposes instead to list the individual studies that are
included in the category of data requirements to support registration
(guideline 830.6302 through 830.7300). The Agency currently requires
(R) all product chemistry data to support registration, except for
analysis of samples and submittal of samples, which is proposed to be
required under residue chemistry data requirements.
i. New requirements. None.
ii. Newly codified requirements. None.
iii. Revisions to existing requirements. a. Product identity,
manufacturing process, and deposition of a sample in a nationally
recognized culture collection. Currently these data are required as
guideline numbers 151-20, 151-21, and 151-22. The Agency proposes that
these data requirements would remain the same as before. However, we
are proposing to list each as a separate study: product identity;
manufacturing process; and, discussion of formation of unintentional
ingredients. The Agency proposes to list them as follows: product
identity (guideline 885.1100), manufacturing process and deposition of
a sample in a nationally recognized culture collection (guideline
885.1200), and discussion of formation of unintentional ingredients
(guideline 885.1300).
b. Physical and chemical characteristics. The Agency currently
requires (R) physical and chemical characteristics data. The Agency
proposes to require (R) that the same studies and same endpoints be
evaluated, however the Agency is trying to be more clear by identifying
the individual pieces of the data requirement and separately identify
each in the data table. Specifically the studies are identified as:
color, physical state, odor, stability, storage stability, miscibility,
corrosion characteristics, pH, viscosity, and density (guidelines
830.6302 through 870.7300).
c. Analysis of samples. This study (guideline 885.1400) is
currently conditionally required (CR) for EUPs and registrations. The
Agency proposes to revise this data requirement to be required (R),
since it is critical to have an analysis of samples to understand the
composition of the microbial pesticide and the potential for
contamination with other microorganisms.
d. Certification of limits. This study is currently required (R)
except for nonfood uses. The Agency is proposing to expand this data
requirement to be required (R) for all uses. These studies are needed
to confirm the claims made on the label and to validate the
confidential statement of formula.
e. Analytical methods. The analytical methods would typically
assure that you could quantify the confidential statement of formula.
This study is currently required (R), and the Agency proposes to
continue to require (R) these data, but under product identity and
discussion of unintentional ingredients data requirements, which
provide these data.
f. Submittal of samples. This provision is typically intended to
enable EPA to identify the active ingredient and provide standards to
governmental agencies needing to monitor chemical pesticide residues
and is conditionally required (CR). The Agency proposes to require (R)
these data as a product analysis requirement to be deposited in a
nationally recognized culture collection to allow EPA to validate
strain identity if issues arise (guideline 885.1200).
Since the Agency does not have capacity to store the variety of
microbial pesticides that may be submitted, EPA did not set up a
nationally recognized culture collection. There are several nationally
recognized culture collections in this country (and abroad) such as the
American Type Culture Collection and a microbial collection maintained
in Peoria, Ill., by the USDA. These facilities have a vast number of
microbial and cell cultures that are dedicated to transferring,
maintaining and identifying. Rather than duplicate this effort, EPA
chose to refer microbial pesticide producers to these facilities who
have the routine expertise to keep and distribute (or protect)
microbial cultures. There is a certain element of required expertise
but really the cost and small number of our microbial pesticides would
make it prohibitively expensive for the Agency to do this collection
rather than direct the companies to these specialized facilities.
E. Residue Chemistry Data Requirements
1. General. The Agency uses residue chemistry information to
determine the potential bioavailability of pesticide residues on food.
Included in this subpart are the detailed requirements for chemical
identity, analytical methods for plants and animals, nature of residue,
stability, and magnitude of residue.
2. Residue chemistry data requirements. The residue chemistry
[[Page 12091]]
data table currently requires residue data under one data requirement.
The Agency is proposing to delineate the residue data to clearly
identify the endpoints being measured. In other words, there is only
one data requirement, and in the proposed rule there are several data
requirements listed (guideline 885.2000 through 885.2350), but no more
additional data are actually required. In addition, the current test
note in part 158 delays the residue study requirement until Toxicology
Tier II and Tier III data are required (R). The Agency is proposing the
data requirement not be dependent on the Tier Data in II and III, but
to conditionally require (CR) these data when the results of testing
(indicated in test note).
i. New requirements. None.
ii. Newly codified requirements. None.
iii. Revisions to existing requirements. Part 158 currently
requires residue data (153-4) for microbial pesticides, but does not
lay out clearly the various underlying studies for fulfilling the
actual requirement. EPA proposes the following be listed to provide
greater clarity and transparency of the data that are actually required
(R) to support registration: Background for residue analysis of
microbial pest control agents (guideline 885.2000), chemical identity
(guideline 885.2100), nature of residue (guideline 885.2200, 885.2250),
analytical methods (guideline 885.2300,885.2350), storage stability,
magnitude of residue (guideline 885.2500, 885.2550, 885.2600). These
data are currently required (R), therefore there is no revision in the
proposed rule.
F. Toxicology Data Requirements
1. General. 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, and
domestic animals, for all microbial pesticides. These data requirements
include acute toxicity/infectivity studies (oral, dermal, inhalation,
pulmonary injection), a cell culture study, and hypersensitivity
incidents (guideline 885.3050 through 885.3500) to be submitted. In
addition, acute toxicity studies (oral, dermal, and inhalation) and the
primary eye and dermal irritation studies (guidelines 870.1100 through
870.2500) are also required. The Agency wants to specially note that we
are inviting public comment as to whether or not hypersensitivity
incidents (guideline 885.4300) is addressed adequately via the Sec.
152.125, FIFRA section 6 (a)(2) data requirement, also discussed in the
preamble for biochemical pesticides.
The following identifies the revisions to the current Sec. 158.740
for microbial toxicology data requirements. Revisions include name
changes, test note clarifications, revisions under which use pattern
data are triggered (e.g., food use versus non-food use), and
clarification of other circumstances under which data are required.
2. Toxicology data requirements. The Agency generally discourages a
registrant from pursuing registration of a microbial pesticide that is
a known human pathogen, even one reported to be an opportunistic human
pathogen, because it would be difficult to support a risk assessment
that would show no unreasonable risk to humans. However, in some cases,
a candidate microbial pesticide may:
(a) Be very closely related to a human pathogen but lack the toxins
or invasive factors responsible for that disease;
(b) Be taxonomically distinct from known human pathogens, but may
have picked up a toxin or other factor that could cause mammalian
disease as detected by Tier I and II studies; or,
(c) Provide significant benefits that would offset some risk that
might additionally be mitigated by certain use/exposure considerations.
The Agency has encountered several cases where microbial pesticides
are a member of a taxonomic group containing mammalian toxins. In these
instances, data gathering beyond the codified data requirements may be
required to account for potential human health risks. For most
applications, this kind of testing is not needed.
Generally, toxicology data from Tier I is sufficient to address the
hazards related to the human health risk assessment for pathogenicity
and infectivity of microbial pesticides. The most common reason for
needing Tier II or higher tests is the appearance of unexplained
toxicity, unusual persistence, lethality, or adverse effects related to
treatment with the microbial pesticide in the Tier I studies.
Some microbial products may be lethal to rodents at the Tier I and/
or Tier II levels, where the mode of action may not be sufficiently
clear to allow for specific toxin or other infectivity factors to be
analyzed. Furthermore, due to the nature of some microorganisms, the
possibility exists that rodents may not be a truly representative test
animal for determining effects on humans of a microbial pesticide.
The Agency proposes to conditionally require (CR) Infectivity/
pathogenicity as a Tier III data requirement. This requirement allows
for the possible use of alternative test species, including primates as
described in the testing guidelines.
In addition, there are ten revisions, primarily name changes to the
data requirements.
i. New requirements--Infectivity/pathogenicity. Currently this
study is not required. The Agency is proposing to conditionally require
(CR) a Tier III infectivity/pathogenicity analysis (guideline 885.3000)
when the microbial pesticide appears to be a mammalian pathogen that
might sufficiently affect humans or nontarget mammals. While it is
possible that the registrant would not want to pursue a microbial
registration if such testing were triggered, the Agency believe it is
appropriate to establish a Tier III toxicity study requirement to
evaluate the microbial pesticides potential effects in higher animals.
The Agency believes this type of data would rarely be required.
However, if all criteria established in the revised test notes has been
exceeded, it is appropriate to require the data.
ii. Newly codified requirements. None.
iii. Revisions to existing requirements-- a. Acute oral toxicity/
pathogenicity. Currently this study is required (R) with no test notes.
For clarity, the Agency is proposing a name change to the more
descriptive one used in the updated guidelines (guideline 885.3050).
EPA also proposes a reduction in the number of test substances required
to be tested. Currently, part 158 requires both MP or EP and TGAI. The
proposed rule would only require (R) the TGAI to be tested. TGAI is
only required for the acute oral toxicity/pathogenicity and can be done
with MP or EP to avoid the ``normal'' acute oral toxicity for the EP if
all endpoints and dosing are confirmed. The endpoint examined in the
toxicity/pathogenicity include clearance and immune functioning of the
test rodent. These endpoints, once determined, are not necessary for
more than the TGAI. The MP and the EP are not expected to dramatically
alter the pathogenicity character of the microbe so the extra testing
does not add to the safety assessment. The Agency is also proposing to
add a test note, indicating the acute oral study toxicity/pathogenicity
can be combined with the unit dose portion of acute oral toxicity study
(guideline 870.1100) if the new protocol is designed to address the
endpoints of concern.
b. Acute pulmonary toxicity/pathogenicity. The Agency currently
requires (R) the acute inhalation study
[[Page 12092]]
(152-31) under Tier I. The Agency is proposing acute pulmonary
toxicity/pathogenicity (guideline 885.3150) to be required in lieu of
the acute inhalation study. EPA also proposes a reduction in number of
test substances required to be tested, currently both MP or EP and TGAI
are required. The proposed rule would only require (R) the TGAI to be
tested. These endpoints, once determined, are not needed for more than
the TGAI. As discussed previously, the MP and the EP are not expected
to dramatically alter the pathogenicity character of the microbe so the
extra testing does not add to the safety assessment.
c. Acute injection toxicity/pathogenicity (Intravenous or
Intraperitoneal). The Agency currently requires (R) I.V., I.C., I.P.
injection study. The Agency is proposing acute injection toxicity/
pathogenicity (either intraperitoneal or intravenous) to also be
required (R), with the test note indicating the pathway under what
conditions the intravenous or intraperitoneal would be required.
Intracerebral is no longer required since it has been determined that
exposure would most likely result in intravenous or intraperitoneal
exposure. Under this revised data requirement, the data would not be
required if the active ingredient of the pesticide product is a virus.
d. Primary dermal irritation. The Agency currently requires (R)
this data under Tier I. The Agency is proposing to conditionally
require (CR) these data as Tier I, with proposed test notes better
defining the conditions when the data requirement would apply. This
study would be conditionally required (CR) only if dermal irritation
was indicated in the acute dermal toxicity study, since it would be
evident in the results of the acute dermal toxicity study if primary
dermal toxicity effects could occur.
e. Acute inhalation toxicity. Currently the Agency conditionally
requires (CR) an acute inhalation study (151-41) in Tier II on MP or EP
product when data in a Tier I acute inhalation study indicate potential
adverse effects (e.g., survival, replication, infectivity, toxicity).
The Agency is proposing to require (R) the acute inhalation toxicity
study (guideline 870.1300) as a Tier I, limiting it to testing MP or
EP, no longer requiring TGAI testing, but with a test note indicating
data are required only if the product can be inhaled.
f. Hypersensitivity study and hypersensitivity incidents. Currently
the Agency requires (R) the hypersensitivity study and conditionally
requires (CR) hypersensitivity incidents. The Agency is proposing to
not require (NR) the hypersensitivity study and to require (R)
hypersensitivity incident reporting data. The hypersensitivity study
are currently submitted as part of product characterization on known
microbial hazards such as toxins and allergens.
As indicated, the Agency proposes to revise hypersensitivity
incidents from the current conditionally required (CR) to proposed
required (R), even under conditions of EUP's. While these types of data
are already required under Sec. 152.125, FIFRA 6(a)(2), the status of
hypersensitivity incidents reporting is unclear for microbial products
that have not been registered or are under an EUP. Therefore, the
Agency included a requirement for hypersensitivity incident reporting
for EUP's in lieu of the hypersensitivity study. As previously
indicated, EPA is inviting comment as to whether or not this study is
needed, since the data must already be submitted to the Agency as
6(a)(2) data.
g. Cell culture. The Agency proposes to rename the currently
required (R) tissue culture study for all viruses to the cell culture
data requirement (guideline 885.3500), since this study is a more
appropriate name for the tissue culture study and would only be
required when the product's active ingredient is a virus.
h. Reproductive fertility effects. The Agency currently
conditionally requires (CR) teratogenicity data. The Agency is
proposing to conditionally require (CR) reproductive and fertility
effects data (guideline 885.3650). This study replaces both guidelines
152-47 and 152-53. This is actually a replacement, since the data are
basically assessing the same endpoints. The Agency is also proposing to
not require these data as Tier II, but as Tier III since the triggers
for this study rely on toxicity endpoints which are collected in Tier
II studies, i.e., guideline 885.3600.
G. Nontarget Organisms and Environmental Fate Data Requirements
1. General. The Agency uses a tiered system of ecological effects
testing to assess the potential risks of pesticides to nontarget
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, or whether the
pesticide should be registered for certain use patterns at all.
Higher tiered nontarget organisms and environmental fate studies
may be required when basic human health assessment 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 would be required only when the
potential for adverse effects is indicated by the results of lower tier
studies, or to confirm the need for mitigation measures. In some cases,
the results of field studies may also give rise to the need for further
testing.
2. Nontarget organisms and environmental fate data requirements.
The proposed nontarget organisms and environmental fate data table
reflects the data that are currently required to support registration
of new microbials. Conditions under which data may be required are
stipulated in the test notes. In addition, there are a few studies that
would be replaced by more appropriate studies to measure the endpoint
of concern, and other studies would be deleted. These data revisions
are not be expected to substantively increase the nature or burden of
the existing data requirements.
i. New requirements. None.
ii. Newly codified requirements. None.
iii. Revisions to existing requirements. a. Avian Inhalation
Toxicity/Pathogenicity. The Agency currently requires (R) an avian
injection test. The Agency proposes to replace the avian injection test
(154-17) with the avian inhalation test (guideline 885.4100) to provide
a more appropriate endpoint to assess risks to avian species. The
Agency is also proposing to conditionally require (CR) this data only
when the microbial pesticide appears to have toxins that indicate
potential pathogenicity. The inhalation study models a more realistic
route of exposure in the wild than intraperitoneal injection.
b. Fish life-cycle study and aquatic invertebrate range testing.
The Agency proposes to replace conditionally required (CR) aquatic
embryo larvae and life cycle studies (154-28) with conditionally
required (CR) fish life-cycle studies (guideline 885.4700) and
definitive aquatic animal tests (154-27) with aquatic invertebrate
range testing (guideline 885.4650) to provide more appropriate
endpoints for assessing risks to aquatic species (fish and
[[Page 12093]]
invertebrates). The ``fish'' life cycle study is more appropriate
because it identifies a particular taxonomic class to be tested as
opposed to ``aquatic embryo and life cycle studies'' which do not
identify the taxonomic class or species to be tested. ``Definitive
aquatic animal tests'' does not say what animal group (species) is to
be tested and does not say what test is to be done (``definitive'' is
not a test name), whereas ``aquatic invertebrate range testing'' is
more appropriate because it specifically instructs the registrant to
determine which aquatic invertebrate species are susceptible to the
pesticide and which are not susceptible. In summary, the Agency is
proposing to revise the titles of the data requirements in order to
account for species and life cycles being tested.
c. Simulated or actual field testing for plants (guideline
850.2500). The Agency currently conditionally requires (CR) nontarget
plant studies (154-31) as Tier III when data in Tier II indicate there
is a concern. The Agency proposes to rename the data requirement to
simulated or actual field testing for plants (guideline 850.2500),
which is currently conditionally required (CR) on a case-by-case basis.
The test notes associated with the proposed requirement are more
explicit as to when the conditions would be met. In addition, these
data are proposed to be conditionally required (CR) as Tier IV.
d. Product performance. Currently the Agency relies on Sec.
158.640 for product performance data requirements for biochemicals and
microbial pesticides. The Agency is proposing to include product
performance in the regulatory text for both biochemicals and microbial
pesticides to improve transparency. Product performance verification
can be important for some of the biochemical and microbial pesticides
since we have seen independent reports that some do not work as well as
the conventional pesticide products. It is particularly useful to have
product performance data for those products that want to be considered
as presenting less risk than a conventional pesticide product.
e. Subchronic toxicity/pathogenicity. The Agency proposes to change
the name of the subchronic oral toxicity study (152-42) to correspond
with the current name of the test guideline.
f. Carcinogenicity. The Agency proposes to change the name of the
oncogenicity study to carcinogenicity study (guideline 870.4200) to
correspond with the current name of the test guideline.
IX. Peer Review
A. National Research Council Recommendations
As discussed in Unit V.A.3, the National Academy of Sciences issued
a report in 1993 entitled, ``Pesticides in the Diets of Infants and
Children.'' The study, conducted by the National Research Council, was
initiated to address the question of whether the current regulatory
system adequately protected infants and children from pesticide
residues in food. The Council reviewed current EPA practices and data
requirements related to dietary risk assessment as well as testing
modifications planned by the Agency. The panel of experts concluded
that, at that time, EPA approaches to data requirements and risk
assessments emphasized the evaluation of the effects of pesticides in
mature animals and, in general, there was a lack of data on pesticide
toxicity in developing organisms. The Council also expressed the need
to investigate the effects of pesticide exposure on immunotoxic
responses in infants and children (Ref. 3).
B. FIFRA Scientific Advisory Panel
1. 1994 SAP Review. In 1994, EPA held a two 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.
While these data requirements were presented to SAP to support
conventional pesticides, the majority of changes to the data
requirements presented in this notice were submitted for review as
subpart M: Microbial and Biochemical Pesticides Data Requirements.
These revisions were generally endorsed by the SAP (Ref. 4). A copy of
the 1994 SAP final report can be found in the docket for this
rulemaking (docket ID number EPA-HQ-OPP-2004-0415).
The limited issues that were addressed in1994 Panel's specific
comments are as follows:
Intraperitoneal study. The issue revolved around whether
an intraperitoneal study is appropriate to use when microbial size or
physical properties preclude the use of intravenous study. At that
time, SAP believed the intraperitoneal study was appropriate to use
when microbial size or physical properties preclude the use of
intravenous study. This option is included in the proposed rule.
Bird species. The issue revolved around whether the second
bird study gives significant additional information for microbial
effects, i.e., are the two birds species likely to respond differently
to typical biocontrol microbials. At the time, SAP suggested that it
was appropriate to use only the more sensitive bird species (the quail)
for data requirements. This recommendation has been included in the
test note.
Fish species. The issue revolved around whether the second
fish study was likely to provide significant information for
microbials. At the time, SAP suggested that it was appropriate to use
the more sensitive fish species (trout) for data requirements. The SAP
recommendation was incorporated into the test note.
Additionally, SAP encouraged the Agency to carefully evaluate the
data requirements for genetically engineered microbials. The SAP
believed this emerging technology was still, in many respects, an
unknown entity. In the future, EPA will develop data requirements for
plant-incorporated protectants.
2. 1987 SAP Review--Immunotoxicity testing of biochemical pest
control agents (BPCAs) (Ref. 7). Proposed Guidelines for Immunotoxicity
Testing of Biochemical Pest Control Agents were presented to the SAP.
In particular the issues revolved around the use of a single sex of
test animal in the lower tiered studies. At that time, the 1987 SAP
decided that there was no scientific rationale for examining both male
and female animals, though this may not apply to compounds that
demonstrate estrogenic activity. In this case females may be the sex of
choice since they would be more sensitive to immunotoxic effects than
males by this class of compounds. A second issue raised at this meeting
was the inclusion of a limit test in Tier I, in which no adverse
immunological effects are observed at a single high dose, then no
further testing is required. The Agency was seeking advice on the
scientific criteria that would support the inclusion or exclusion of a
limit test in Tier I studies. At that time, the SAP deemed it
appropriate for all assays in Tier I to be included since no single
test can fully evaluate all cellular or functional components of the
immune system. A dose that produces a large amount of general toxicity
would be of concern since the general toxicity might indirectly
contribute to the immunotoxicity. Immunotoxicity data
[[Page 12094]]
should be cautiously evaluated in this context.
3. 1986 SAP Review--Applicator/user exposure monitoring guidelines.
The Series 875, Group A, Applicator/User Exposure Monitoring Guidelines
were presented to SAP in January 1986. After EPA addressed SAP
comments, the guidelines were finalized. The guidelines were published
by the National Technical Information Service (NTIS) in 1987 (Ref. 10).
A comprehensive listing of data requirements and the year that each
specific data requirement was reviewed by SAP is available in the
docket for this proposed rule (Ref. 11). Additionally, copies of
documents reviewed by SAP and the final reports can be found on EPA's
website at http:// www.epa.gov/scipoly/sap.
X. 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.
The Agency believes it has taken steps, based on current scientific
knowledge and experience, to minimize testing on biochemical and
microbial pesticides. With respect to these types of pesticides, the
Agency has implemented a tiered testing approach, thereby potentially
reducing the number of studies required for registration. 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 pesticide 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 pesticide as a screen to judge whether the
pesticide 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.
The Agency plays an important role in the Federal Interagency
Coordinating Committee on 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; and (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 pesticide 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 would continue to be added to the test guidelines.
XI. 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 (mostly conventional chemical
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 site on which it was authorized to be
used.
In general, a biochemical pesticide is not expected to pose
endangered species concerns because it is a naturally-occurring
chemical or a synthetically-derived equivalent; has a history of
exposure to humans and the environment demonstrating minimal toxicity;
and has a non-toxic mode of action to the target pest(s). However, the
Agency has occasionally required such data for microbial pesticides
(e.g., Metarhizium anisopliae). The microbial pesticides typically have
a limited host range and affect only certain species limiting the
potential of such pesticides to pose endangered species concerns. The
Agency anticipates that these data could be requested in the future in
connection with other registration and reregistration actions for both
biochemical and microbial pesticides if lower tier studies show
potential adverse effects to nontarget organisms.
In response to a Data Call-In notice on certain conventional
pesticides for data on the location of all listed species, an industry
taskforce 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. Thus, the Agency is
requesting comment on its utility and appropriateness.
While EPA is using the best available scientific and commercial
information to assess risks to listed species, uncertainties still
exist. 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
[[Page 12095]]
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 nontarget and
endangered plant species exposed to herbicides.
Toxicity data to characterize potential effects to aquatic
invertebrates (i.e., freshwater mussels).
Toxicity data to characterize potential effects to
reptiles and amphibians.
The Agency seeks comment on:
1. The relative value of each of these research areas in better
refining assessments of potential risks to listed species.
2. Input on specific research directions in these areas, including
methodologies, protocols etc., that would be appropriate and useful in
assessing the potential risks to listed species.
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.
XII. Research Involving Human Subjects
This proposed rule (see proposed Sec. 158.950) would establish
data requirements for applicator/user exposure studies for biochemical
pesticides proposed as insect repellents. This data requirement is
consistent with Sec. 158.500 of the proposed rule for conventional
pesticides (70 FR 12275, March 11, 2005).
On January 26, 2006, the EPA Administrator signed a final rule
entitled Protections for Humans Subjects in Research (71 FR 6138,
February 6, 2006), (Ref. 23) that significantly strengthens and expands
the protections for subjects of ``third-party'' human research (i.e.,
research that is not conducted or supported by EPA) by (1) prohibiting
new research involving intentional exposure of pregnant women or
children that is intended for submission to EPA under the pesticide
laws; (2) extending the provisions of the Federal Policy for the
Protection of Human Subjects of Research (the ``Common Rule'') to other
human research involving intentional exposure of non-pregnant adults
that is intended for submission to EPA under the pesticide laws; (3)
requiring submission to EPA of protocols and related information about
covered human research before it is initiated; and (4) establishing an
independent Human Studies Review Board to review both proposals for new
research and reports of covered human research on which EPA proposes to
rely under the pesticide laws.
This rule forbids EPA to rely, in its actions under the pesticide
laws, on intentional-exposure human research that either involves
pregnant women or children as subjects or is otherwise considered
unethical, except in narrowly defined circumstances. Some studies
required under this part will also be subject to subparts K, L, and M
of 40 CFR part 26--the newly promulgated final rule for the protection
of human subjects of research. Subpart K extends the substantive
provisions of the ``Common Rule''--the ethical standard that governs
research with human subjects conducted or supported by EPA and other
Federal departments and agencies to third-party research that involves
intentional exposure of non-pregnant adults as subjects, and that is
intended for submission to EPA under the pesticide laws. Subpart K also
requires submission to EPA of proposals for any covered research, at
least 90 days before it is initiated, for review by EPA staff and the
Human Studies Review Board. Subpart L categorically prohibits any
third-party research that involves intentional exposure of pregnant
women, fetuses, or children as subjects, and that is intended for
submission to EPA. Subpart M specifies the range of information
required to be submitted along with reports of completed research with
human subjects to document the ethical conduct of the research.
XIII. Summary of Proposed Changes
The Agency has prepared a document, entitled Summary of the
Proposed Changes (Ref. 1), to compare the current data requirements to
support the registration of biochemicals and microbials, respectively,
with the revised data requirements presented in this proposed rule. The
changes include: revision in test notes, revision in guideline names,
revisions in tiering the various data requirements, etc. Along with the
proposed changes to the data required, the Agency also proposes to
revise the definitions of biochemical pesticides and microbial
pesticides and to add definitions of pheromones, arthropod pheromones,
and straight chain lepidopteran pheromones.
XIV. Summary of Options
What Options did the Agency Evaluate?
The Agency evaluated three regulatory options to revising the
existing data requirements. The three options are generally
characterized by estimated annual cost or regulatory burden reduction
and frequency of requiring data. The options as presented are intended
to reflect broad conceptual approaches, and within each broad option
there are other options for requiring or reducing data requirements. In
addition, whether considered broadly or more narrowly, EPA's approach
is based on the primary need for sufficient information to make the
FIFRA/FFDCA findings while at the same time being mindful of
opportunities to reduce burden and testing where data is not value
added. Again, as noted previously, the point is to emphasize first the
need to meet statutory mandates.
This section will briefly cover these three options. The specific
cost differences between these three regulatory options are discussed
in the executive summary of the Economic Analysis for this rulemaking
(Ref. 6). Overviews of estimated annual cost or regulatory burden
reduction for the proposed rulemaking as a whole may be found in Unit
XVI., Regulatory Assessment.
1. Option 1 (reduced regulatory burden, potential risk). This low-
cost approach was designed to maximize burden reduction based upon the
specific nature of biochemical and microbial pesticides. Based on the
non-toxic mode of action and naturally-occurring characteristics of
many of these compounds, the Agency could perform a complete risk
assessment based on a minimal amount of nontarget organisms and
environmental fate data. For biochemical pesticides, the Agency would
not require Tier I nontarget organisms and Tier II environmental fate
data. For example, under this approach, the Agency would not receive
any exposure or infectivity/pathogenicity data for biochemical
pesticides. For microbial pesticides, the Agency would significantly
reduce the
[[Page 12096]]
frequency of time (up to 50 percent) that proposed Tier I nontarget
organisms and Tier II environmental fate data are required. The
nontarget organism tests monitor the effects of proposed pesticides on
nontarget birds, wild mammals, fish, insects and plants. The
environmental fate tests are used to assess the persistence of
biochemicals and microbial pesticides in the environment. This option
would only minimally reduce the regulatory burden as compared to the
changes being proposed today (described in Option 3). The Agency does
not believe the decrease in burden outweighs the loss in benefits to
public health and the environment from reduced availability of data for
assessing environmental hazard and risk through registration decisions.
The cost savings realized in this option are only marginally lower than
the savings realized in the proposed option.
2. Option 2 (significant regulatory burden, adequate risk
assessment). This high-cost approach was evaluated based on an Agency
approach of maximizing the completeness of the database. Under this
approach, the Agency would require Tier I human health and
environmental data requirements 100 percent of the time. For example,
under this approach, the Agency would receive all exposure and
infectivity/pathogenicity data, with immunotoxicity required as Tier II
and Tier III data. This approach would result in significantly higher
costs to pesticide registrants and increased burden to the Agency
compared to the proposed approach. Additionally, unlike Option 1 and
the proposed option, EPA believes that this high-cost approach would
substantially raise the cost of registering a biochemical or microbial
pesticide, resulting in fewer products being registered and reducing
the potential for these biopesticides (generally lower risk) to compete
in the marketplace to provide alternatives to conventional pesticides
(generally higher risk). The extra cost and time required to register a
biochemical or microbial pesticide under this option may discourage use
of these safer pesticides, resulting in more, not less environmental
risk.
3. Option 3 (proposed option). The proposed option provides the
Agency with flexibility and is a middle ground between Option 1,
representing a minimal cost but potentially significant loss of
environmental hazard information, and Option 2, representing the
maximum availability of information, but at significantly higher cost.
The Agency would require, under certain conditions, human health and
environmental data from all tiering levels (I, II, III, IV). The
frequency that data is required would be based on current scientific
knowledge and conditions specific to the active ingredient and use
patterns. For example, the Agency proposes to require immunotoxicity as
Tier II and Tier III data, conditionally require infectivity/
pathogenicity data, and conditionally require exposure data for insect
repellents. The proposed option is a codification of current practice,
and is a balance that provides sufficient data for Agency to complete
an environmental risk assessment while ensuring the lowest feasible
cost and burden to applicants and the Agency.
The Agency believes the changes proposed today best serve to
protect human health and the environment and allow for a complete and
accurate assessment of risks, while benefitting a large number of
parties, including the regulated industry, pesticide users, the general
public, other Federal, State, and foreign governments, and others who
are affected by or interested in pesticide use or regulation.
Additionally, the net benefit of the proposed changes is expected to
include a cost savings for existing and future biochemical and
microbial pesticide registrants versus the current codified
requirements.
Comparing the proposed option to Option 1 (low cost option), EPA
believes that the modified and newly-imposed nontarget organisms and
environmental fate Tier I data requirements contained in the proposed
approach are needed to ensure informed risk assessment and risk
management decisions on biochemical and microbial pesticide
registrations.
Comparing the proposed option to Option 2 (high cost option), EPA
believes that the cost and burden of requiring the Tier I human health
and environmental data for all biochemical and microbial registrations
would not warrant the modest benefits of marginally valuable
information. EPA believes that Option 2 would reduce the adverse
externalities of pesticides and unknown risks to consumers only
slightly more than the proposed approach. However, the benefits of this
additional data are speculative. Based on the specific nature and
scientific knowledge of biochemical and microbial pesticides, these
additional data (over and above what the proposed option requires)
would most likely inform registration decisions very little.
XV. References
The Agency has established a docket for this rulemaking under
docket ID number EPA-HQ-OPP-2004-0415. 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. 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 as described under ADDRESSES.
1. U.S. EPA, 2005. ``Summary of Proposed Changes to Biochemical and
Microbial Pesticide Data Requirements.'' FEAD/OPP/U.S. EPA, Washington,
D.C.
2. U.S. EPA, 2003. ``OPPTS Test Guidelines.'' OPP/U.S. EPA,
Washington, D.C.
3. National Research Council, ``Pesticides in the Diets of Infants
and Children,'' National Academy Press, Washington, D.C., 1993. Excerpt
pp. 152-156.
4. FIFRA Scientific Advisory Panel (SAP). 1994 SAP Final, November
29, 1994 FIFRA Scientific Advisory Panel Meeting, November 29-30, 1994,
held in Arlington, Virginia.
5. U.S. EPA. 2005. Part II. Environmental Protection Agency.
Pesticides; Data Requirements for Conventional Pesticides; Proposed
Rule. (70 FR 12276, March 11, 2005).
6. U.S. EPA, 2005. ``Economic Analysis of the Proposed Rule
Changing Data Requirements for Biochemical and Microbial Pesticides.''
FEAD/OPP/U.S. EPA, Washington, D.C.
7. FIFRA Scientific Advisory Panel (SAP). ``A Set of Scientific
Issues Being Considered by the Agency in Connection with Proposed
Revision to Subdivision M, Immunotoxicity Testing of Biochemical Pest
Control Agents (BPCA's).'' Review from open meeting on March 24, 1987
in Arlington, Virginia.
8. U.S. EPA, 1989. ``Subdivision M of the Pesticide Testing
Guidelines, Microbial and Biochemical Pest Control Agents.'' EFED/OPP/
U.S. EPA, Washington, D.C.
9. U.S. EPA, 1982. ``Pesticide Assessment Guidelines, Subdivision
M, Biorational Pesticides.'' HED/OPP/U.S. EPA, Washington, D.C.
10. U.S. EPA, 1986. ``Series 875, Group A, Applicator/user Exposure
Monitoring Guidelines.'' Presented to the FIFRA Scientific Advisory
Panel (SAP), January, 1986. OPP/U.S. EPA, Washington, D.C.
11. U.S. EPA, 2005. ``Overview of Proposed Data Requirements and
FIFRA SAP Review.'' FEAD/OPP/U.S. EPA, Washington, D.C.
12. U.S. EPA, 2005. ``Analysis of Data Requirements for Biochemical
and
[[Page 12097]]
Microbial Pesticides from 1997-2004.'' FEAD/OPP/U.S. EPA, Washington,
D.C.
13. U.S. EPA, 2005. ``Data Requirements for Biochemical and
Microbial Pesticides; Proposed Rule; Consultations.'' FEAD/OPP/U.S.
EPA, Washington, D.C.
14. U.S. EPA, 2005. ``Comparison between Current Conventional
Pesticides Data Requirements and Proposed Biochemical and Microbial
Pesticide Data Requirements.'' FEAD/OPP/U.S. EPA, Washington, D.C.
15. OECD [2002-a] Guidance for Registration Requirements for
Pheromones and Other Semiochemicals Used for Arthropod Pest Control.
OECD Series on Pesticides, Number 12. Organization for Economic
Cooperation and Development. February 26, 2002.
16. U.S. EPA, 2000. ``p-Menthane-3,8-diol (011550) Biopesticide
Registration Eligibility Document.'' BPPD/OPP/U.S. EPA, Washington,
D.C. Issued May, 2000.
17. OECD [2002-b] Registration of Agricultural Pesticides,
Biological Pesticides--Progress on Development of Dossier/Monograph
Guidance for Microbials and Pheromones. Working Group on Pesticides.
Organization for Economic Cooperation and Development. January 3, 2002.
18. U.S. EPA, 2002. ``Supporting Statement for an Information
Collection Request: Tolerance Petitions for Pesticides on Food/Feed
Crops and New Inert Ingredients.'' OMB Control No. 2070-0024, EPA ICR
No. 0597. OPP/U.S. EPA, Washington, D.C.
19. U.S. EPA, 2002. ``Supporting Statement for an Information
Collection Request: Application for New or Amended Pesticide
Registration.'' OMB Control No. 2070-0060, EPA ICR No. 0277. OPP/U.S.
EPA, Washington, D.C.
20. U.S. EPA, 2001. ``Supporting Statement for an Information
Collection Request: ''Data Generation for Reregistration; Phase 4 and 5
Reregistration.`` OMB Control No. 2070-0107, EPA ICR No. 1504. OPP/U.S.
EPA, Washington, D.C.
21. U.S. EPA, 2001. ``Supporting Statement for an Information
Collection Request: Data Call-Ins for the Special Review and
Registration Review Programs.'' OMB Control No. 2070-0057, EPA ICR No.
0057. OPP/U.S. EPA, Washington, D.C.
22.U.S. EPA, 2004. ``Supporting Statement for an Information
Collection Request: Plant- Incorporated Protectants; CBI Substantiation
and Adverse Effects Reporting.'' OMB Control No. 2070-0142, EPA ICR No.
1693, Washington, D.C.
23. U.S. EPA, 2005. Protections for Subjects in Human Research:
Final Rule. (71 FR 6138, February 6, 2006). Document ID No. OPP-2003-
0132.
XVI. FIFRA Review Requirements
In accordance with FIFRA section 25(a), the Agency submitted a
draft of this proposed regulation to the FIFRA SAP, the USDA, the
Committee on Agriculture in the House of Representatives, and the
Committee on Agriculture, Nutrition, and Forestry in the United States
Senate.
The FIFRA SAP waived its review of this proposal because the
significant scientific issues involved have already been reviewed by
the SAP and additional review isn't necessary. USDA participated fully
in the interagency review process under Executive Order 12866, during
which EPA and USDA discussed the registration process of microbial
pesticides and the need for a coordination process when an APHIS
movement permit under 7 CFR part 340 is required by USDA. As a part of
related comments, USDA suggested that the Agency consider requiring the
registrants to submit a copy of the applicable APHIS permits as part of
the registration application for a microbial pesticide because it would
facilitate coordination and improve compliance with the applicable USDA
requirements. As discussed in Unit IIX., the Agency is specifically
seeking public comment on the most appropriate method to ensure APHIS
permitting and EPA registrations are properly coordinated.
XVII. Regulatory Assessment
A. Regulatory Planning and Review
Under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993), the Office of Management and
Budget (OMB) has determined that this proposed rule is a ``significant
regulatory action'' because the proposed revision of the existing
regulation to update the data requirements may raise novel legal or
policy issues arising out of legal mandates, the President's
priorities, or the principles set forth in the Executive Order.
Accordingly, 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 docket for this rulemaking as
required by sec. 6(a)(3)(E) of the Executive Order.
In addition, EPA has prepared an economic analysis of the potential
costs, benefits, and impacts associated with this proposed action,
which is contained in a document entitled Economic Analysis of the
Proposed Rule Changing Data Requirements for Biochemical and Microbial
Pesticides (Ref. 6). A copy of this Economic Analysis is available in
the docket for this action, and is briefly summarized here.
The economic analysis considered the incremental effects between
the baseline and future biochemical and microbial pesticide
registration activity based on the proposed rule and two alternatives.
All costs associated with presently codified 40 CFR part 158 data
requirements applicable to biochemical and microbial pesticides were
considered in the baseline. Future biochemical and microbial
registration activity and associated costs were calculated based on a
historical examination of actual pesticide registration actions between
1997 and 2004 combined with anticipated effects of new, revised, or
modified 40 CFR part 158 subparts L and M data requirements. Review of
1997 to 2004 registration activity considered the type and frequency of
the various biochemical and microbial pesticide registration actions
that occurred, the related applicability of the various data
requirements for those actions, the type and regularity of waivers
granted by EPA for certain data requirements, and information about the
applicants involved in those actions. Where applicable, these trends
and patterns were used to predict future registration activity.
Additional effects of the proposed rule due to newly proposed, revised,
or modified 40 CFR part 158 subparts L and M data requirements were
estimated based on EPA experience and best judgment.
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 proposed revisions
include newly codified data requirements (i.e., data requirements that
are not currently in part 158, but have been, in practice, required on
a case-by-case basis), changes to existing requirements (i.e., a 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, or a change in use pattern for an existing requirement),
and newly imposed data requirements (i.e., data requirement have never
been previously imposed).
To calculate the potential costs associated with this proposal, EPA
first identified the tests necessary to generate the data required, and
then gathered information on the prices that laboratories typically
charge a firm to conduct these tests. The prices varied
[[Page 12098]]
depending on conditions specific to the substance tested. Variations
can be related to differences in the assumptions about the test
performed (e.g., protocol, species used), or can simply be a difference
in the price charged by the laboratory. Average, high, and low cost
estimates were obtained for each test where possible. EPA assumed that
the data required would always need to be newly generated, but often
the data are already available because the registrant generated it for
its own use. In such cases, the firm would simply need to submit those
data to EPA, which involves less burden than generating it.
EPA then used historical data on pesticide registration actions
that occurred over an eight year period (1997-2004) to identify the
entities that sought pesticide registration actions in the past (Ref.
12). 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) and use pattern (how the product will be
used). To estimate the average incremental cost of a new registration,
a baseline testing rate (i.e., the percentage of time a particular test
was historically required under the current rule) was estimated by EPA
scientists based on their past experience with biochemical and
microbial pesticide registrations and their involvement in developing
the new data requirements. This baseline data requirement rate was
compared with the percentage of time each test was required for
registrations between 1997 and 2004. EPA assumes that under the
proposed rule, data requirements would be imposed at the same frequency
they have been required from 1997 to 2004. Additionally, EPA scientists
estimated the frequency that newly imposed data requirements would be
required.
Part of the Economic Analysis included preparation of 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
XVII.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. 6).
Using the currently codified requirements as the baseline for the
impact analysis, the total annual impact to the pesticide industry is
estimated to be a regulatory compliance cost reduction of about $3.04
million per year, with an estimated average cost reduction of $60,000
per firm per year.
EPA also considered a low cost alternative and a high cost
alternative to the proposed rule. The low cost alternative would waive
certain data requirements for biochemical pesticides and reduce the
rate at which certain data requirements are required for microbial
pesticides. The estimated impact of the low cost alternative is
estimated to be a regulatory compliance cost reduction approximately
$3.20 million, with an estimated average cost reduction of $63,000 per
firm per year. The high cost alternative would require certain groups
of data requirements 100 percent of the time, removing the discretion
of Agency scientists to decide if the data are needed for a specific
registration. This alternative would result in an estimated annual cost
increase over current rule requirements of approximately $3.44 million
per year, or an estimated cost increase of $67,000 per firm.
The estimated potential costs of the proposed rule acknowledges
registrant is likely to request that the Agency waive certain data
requirements if the registrant believes that the data are not necessary
for determining the effects of a pesticide on human health and the
environment. EPA estimated the annual cost savings due to waived data
requirements based on both the historical rate and type of waivers
granted for the period from 1997-2004, and on an analysis of how the
proposed rule is expected to modify the rate at which waivers are
granted. EPA estimated that the annual cost savings due to waived data
requirements based on the historic waiver rates to be approximately
$29.6 million, or $580,000 per firm per year. At the modified waiver
rates predicted under the proposed rule, EPA estimated an annual cost
savings of $23.96 million, or $470,000 per firm per year.
Since the likely impact of the proposed rule on businesses overall
is expected to be mostly beneficial, the Agency believes that the rule
would have no effect on the availability of pesticides to users. On
balance, the Agency believes that cost savings resulting from the
proposed changes to 40 CFR part 158 subparts L and M can be realized
without compromising the protection of human health and the
environment.
B. Paperwork Reduction Act
This proposed rule does not contain any information collection
requirements that require additional approval by the Office of
Management and Budget (OMB) under the Paperwork Reduction Act, 44
U.S.C. 3501 et seq. 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 contained in Title 40 of the CFR, after
appearing in the preamble of the final rule, may be listed in 40 CFR
part 9, 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 additional
information collection and paperwork burden. The information collection
requirements, i.e., the paperwork collection activities, contained in
this proposal related to the new data necessary to register a pesticide
product are already approved by OMB under several existing information
collection requests (ICR). Specifically, the program activities which
would generate a paperwork burden under this proposal are covered by
the following ICRs:
The activities associated with the establishment of a tolerance are
currently approved under OMB Control No. 2070-0024 (EPA ICR No. 0597)
(Ref. 18);
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) (Ref. 19);
The activities associated with the generation of data for
reregistration are currently approved under OMB Control
[[Page 12099]]
No. 2070-0107 (EPA ICR No. 1504) (Ref. 20);
The activities associated with the generation of data for special
review or registration review are currently approved under OMB Control
No. 2070-0057 (EPA ICR No. 0922) (Ref. 21); and
Notification of genetically modified microbial pesticides. OMB
Control No. 2070-0142 (EPA ICR No. 1693) (Ref. 22).
These existing ICRs cover the paperwork activities contained in
this proposal because these activities already occur as part of
existing program activities. These program activities are an integral
part of the Agency pesticide program and the corresponding ICRs are
regularly renewed as required under the PRA, such that these OMB
Control Nos. are maintained valid. The approved burden in these ICRs
were increased in 1996 to accommodate the potential increased burden
related to the implementation of the new safety standard imposed in
1996 by FQPA and additional burden revisions related to the proposed
rule are not necessary.
Based on these existing approvals, the Agency estimates that the
total 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.
Direct your comments on the Agency's need for this information, the
accuracy of the provided burden estimates, and any suggested methods
for minimizing respondent burden, including the use of automated
collection techniques, to EPA using the docket that has been
established for this proposed rule (docket ID number EPA-HQ-OPP-2004-
0415) at http://www.epa.gov/edocket/.
The Agency will consider and address comments received on the
information collection requirements contained in this proposal when it
develops the final rule.
C. Regulatory Flexibility Act
Pursuant to section 605(b) of the Regulatory Flexibility Act (RFA),
5 U.S.C. 601 et seq., after considering the potential economic impacts
of today's proposed rule on small entities, 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 XVII.A., and a copy of which is available in the
docket for this rulemaking. The following is a brief summary of the
factual basis for this certification.
Small entities include small businesses, small organizations, and
small governmental jurisdictions. For purposes of assessing the impacts
of today's proposed rule on small entities, small entity is defined in
accordance with the RFA as: (1) A small business as defined by the
Small Business Administration's (SBA) regulations at 13 CFR 121.201;
(2) a small governmental jurisdiction that is a government of a city,
county, town, school district, or special district with a population of
less than 50,000; and (3) a small organization that is any not-for-
profit enterprise which is independently owned and operated and is not
dominant in its field.
Based on the industry profile that EPA prepared using historical
data as part of the Economic Analysis prepared for this rulemaking, EPA
has 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 impacts 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.
EPA then used historical data to estimate the impacts of the
proposed rule on these small businesses. Out of 51 firms with
biochemical or microbial registration actions between 1997 to 2004,
financial data for determining company size was available for 40 firms,
with 23 of those firms classified as small businesses. According to the
analysis, all of these small entities would have realized a reduction
in costs based on the proposed rule changes compared to the current
part 158 data requirements. Given these estimated impacts on small
businesses, EPA concluded that the proposed revisions may benefit and
would not likely have a significant adverse economic impact on a
substantial number of small entities.
Nonetheless, EPA is particularly interested in receiving comment
from small businesses as to the estimated cost savings, expected
benefits, and overall impacts of this proposed rule. Any comments
regarding the economic impacts that this proposed regulatory action may
impose on small entities should be submitted to the Agency in the
manner specified in the ADDRESSES section.
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
XVII, the total annual impact to the pesticide industry is estimated to
be a regulatory compliance cost reduction of about $3.04 million per
year. 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
sections 202 and 205 of UMRA.
E. Federalism Implications
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 would 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. Because instances where a State is a registrant
are extremely rare, 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. Tribal Implications
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 would not have substantial direct effects on
tribal governments, on the relationship between the Federal government
and the Indian tribes, or on the distribution
[[Page 12100]]
of power and responsibilities between the Federal government and Indian
tribes, as specified in the Order. 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 tribal governments, EPA specifically solicits comment on
this proposed rule from tribal officials.
G. Protection of Children
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 XVII.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 would 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 would 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. Energy Implications
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. Environmental Justice
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.
List of Subjects
40 CFR Part 158
Administrative practice and procedure, Agricultural commodities,
Pesticides and pests, Reporting and recordkeeping requirements.
40 CFR Part 172
Confidential business information, Pesticides and pests, Reporting
and recordkeeping requirements, Administrative practice and procedure,
Agricultural commodities, Intergovernmental relations, Labeling.
Dated: March 1, 2006.
Stephen L. Johnson,
Administrator.
Therefore, it is proposed that 40 CFR chapter I, parts 158 and 172
be amended as follows:
PART 158--[AMENDED]
1. By revising the authority citation for part 158 to read as
follows:
Authority: 7 U.S.C. 136-136y; 21 U.S.C. 346a.
2. By adding Sec. 158.3 to part 158, subpart A to read as follows:
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:
Active ingredient means any substance (or group of structurally
similar substances, if specified by the Agency) that would prevent,
destroy, repel or mitigate any pest, or that functions as a plant
regulator, desiccant, defoliant, or nitrogen stabilizer, within the
meaning of FIFRA section 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
[[Page 12101]]
ingredient only, or may contain inert ingredients, such as stabilizers
or solvents.
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. 158.65 [Removed]
3. By removing Sec. 158.65.
4. By adding subparts L and M to part 158 to read as follows:
Subpart L--Biochemical Pesticides
Sec.
158.900 Biochemical pesticides subject to subpart L.
158.910 Biochemical pesticides data requirements.
158.930 Product chemistry data requirements table.
158.940 Residue data requirements table.
158.950 Human health assessment data requirements table.
158.960 Nontarget organisms and environmental fate data requirements
table.
158.970 Biochemical pesticides product performance data
requirements.
Subpart M-- Microbial Pesticides
Sec.
158.1000 Definition and applicability.
158.1010 Microbial pesticide data requirements.
158.1020 Product analysis data requirements table.
158.1030 Residue data requirements table.
158.1040 Toxicology data requirements table.
158.1050 Nontarget organisms and environmental fate data
requirements table.
158.1060 Microbial pesticides product performance data requirements.
Subpart L--Biochemical Pesticides
Sec. 158.900 Biochemicalpesticides subject to subpart L.
(a) This subpart applies to all biochemical pesticides as defined
in paragraphs (b), (c) and (d) of this section.
(b) Definition. A biochemical pesticide is a pesticide that:
(1) Is a naturally-occurring substance or structurally-similar and
functionally identical to a naturally-occurring substance;
(2) Has a history of exposure to humans and the environment
demonstrating minimal toxicity, or in the case of a synthetically-
derived biochemical pesticides, is equivalent to a naturally-occurring
substance that has such a history; and
(3) Has a non-toxic mode of action to the target pest(s).
(c) Pheromone is a compound produced by a living organism which,
alone or in combination with other such compounds, modifies the
behavior of other individuals of the same species.
(1) Arthropod pheromone is a pheromone produced by a member of the
taxonomic phylum Arthropoda.
(2) Lepidopteran pheromone is an arthropod pheromone produced by a
member of the insect order Lepidoptera.
(3) Straight Chain Lepidopteran pheromone is a lepidopteran
pheromone designated by an unbranched aliphatic chain (between 9 and 18
carbons) ending in an alcohol, aldehyde, or acetate functional group
and containing up to three bonds in the aliphatic backbone.
(d) Examples. Biochemical pesticides include, but are not limited
to:
(1) Semiochemicals (insect pheromones and kairomones),
(2) Natural plant and insect regulators,
(3) Naturally-occurring repellents and attractants, and
(4) Enzymes
(e) Applicability. The Agency may review on a case-by-case basis,
naturally-occurring pesticides that do not clearly meet the definition
of a biochemical in an effort, to ensure, to the greatest extent
possible, that only the minimum testing sufficient to make
scientifically sound regulatory decisions would be conducted. The
Agency will reviewapplications for registration of naturally-occurring
pesticides to determine whether to review the pesticide under this
subpart L.
Sec. 158.910 Biochemicalpesticides data requirements.
(a) Sections 158.930 through 158.970 identify the data requirements
that are required to support registration of biochemical pesticides.
Variations in the test conditions are identified within the test notes.
Definitions that apply to all biochemical data requirements can be
found inSec. 158.930.
(b) Each data table includes ``use patterns'' under which the
individual data are required, with variations including food and
nonfood uses for terrestrial and aquatic applications, greenhouse,
indoor, forestry, and residential outdoor applications under certain
circumstances.
(c) The categories for each data requirement are ``R'', which
stands for required, and ``CR'' which stands for conditionally
required. If a bracket appears around the R or CR, the data are
required for both the registration and experimental use permit
requests. Generally, ``R'' indicates that the data are more likely
required than forthose data requirements with CR. However, in each
case, the regulatory text preceding the data table and the test notes
following the data table must be used to determine whether the data
requirement must be satisfied.
(d) Each table identifies the test substance that is required to be
tested to satisfy the data requirement. Test substances may include:
technical grade active ingredient (TGAI), manufacturing-use product
(MP), end-use product (EP), typical end-use product (TEP), residue of
concern, and pure active ingredient (PAI) or (All) indicating all of
the above. Commasbetween the test substances (i.e., TGAI, EP) indicate
that data may be required on the TGAI or EP or both depending on the
conditions set forth in the test note. Data requirements which list two
test substances (i.e., TGAI and EP) indicate that both are required to
be tested. Data requirements that list only the manufacturing product
(MP) as the test substance apply toproducts containing solely the
technical grade of the active ingredient and manufacturing-use products
to which other ingredients have been intentionally added. Data
requirements listing the EP as the test substance apply to any EP with
an ingredient in the end-use formulation other than the active
ingredient that is expected to enhance the toxicity of the product.
(e) The data requirements are organized into a tier-testing system
with specified additional studies at higher tiers being required if
warranted by adverse effects observed in lower tier studies. The lower
tier studies are a subset of those required for conventional
pesticides, and the studies overall are generally selected from those
required for conventional pesticides.
(f) Two sets of guideline numbers are provided for some of the
environmental fate data requirements. For ease of understanding, the
current guidelines will be used as an interim measure until the new
guidelines (in parentheses) are finalized.
[[Page 12102]]
Sec. 158.930 Product chemistrydata 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 (e) 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) Key. R=Required; [R]=Required for registrations andexperimental
use permits; CR=Conditionally required; [CR]=Conditionally required for
registrations and experimental use permits; NR=Not required;
MP=Manufacturing-use product; EP=End-use product; TEP=Typical end-use
product; TGAI=Technical grade of the active ingredient; Residue of
concern= the active ingredient and its metabolites, degradates, and
impurities of toxicological concern; All= all of the above. Specific
conditions, qualifications, or exceptions to the designated test
procedures appear in paragraph (e) of this section, and apply to the
individual tests in the following table:
(d) Table. The following table shows the data requirements for
biochemical product chemistry. The test notes are shown in paragraph
(e) of this section .
Table--Biochemical Product Chemistry Data Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
Test Substance to support
Guideline Number Data Requirement All Use Patterns ---------------------------------------------- Test notes
MP EP
--------------------------------------------------------------------------------------------------------------------------------------------------------
Product Identity and Composition
--------------------------------------------------------------------------------------------------------------------------------------------------------
880.1100 Product identity and [R] TGAI, MP TGAI, EP 1,2
composition
--------------------------------------------------------------------------------------------------------------------------------------------------------
880.1200 Description of [R] TGAI, MP TGAI, EP 2,3
starting materials,
production and
formulation process
--------------------------------------------------------------------------------------------------------------------------------------------------------
880.1400 Discussion of [R] TGAI and MP TGAI and MP 4
formation of
impurities
--------------------------------------------------------------------------------------------------------------------------------------------------------
Analysis and Certified Limits
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.1700 Preliminary analysis [CR] TGAI and MP TGAI and MP 5,8
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.1750 Certified limits [R] MP EP 6
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.1800 Enforcement [R] MP EP 7
analytical method
--------------------------------------------------------------------------------------------------------------------------------------------------------
Physical and Chemical Characteristics
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6302 Color [R] TGAI TGAI 8
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6303 Physical state [R] TGAI TGAI and EP 8
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6304 Odor [R] TGAI TGAI 8
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6313 Stability to normal [R] TGAI TGAI 8,17
and elevated
temperatures, metals
and metal ions
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6315 Flammability [CR] MP EP 9
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6317 Storage stability [R] MP EP --
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6319 Miscibility [CR] MP EP 10
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6320 Corrosion [R] MP EP --
characteristics
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7000 pH [CR] TGAI and MP TGAI and EP 8,11
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7050 UV/Visible light [R] TGAI TGAI --
absorption
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7100 Viscosity [CR] MP EP 12
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7200 Melting point/melting [CR] TGAI TGAI 8,13
range
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7220 Boiling point/boiling [CR] TGAI TGAI 8,14
range
--------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 12103]]
830.7300 Density/relative [R] TGAI and MP TGAI and EP 8,18
density/bulk density
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7520 Particle size, fiber [CR] TGAI TGAI 8,15
length, and diameter
distribution
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7550 Partition coefficient [CR] TGAI TGAI 16
830.7560........................... (n-Octanol /Water)
830.7570...........................
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7840 Water solubility [R] TGAI TGAI 8
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7950 Vapor pressure [R] TGAI TGAI 8,19
--------------------------------------------------------------------------------------------------------------------------------------------------------
(e) Test notes. The following test notes are applicable to the data
requirements for biochemical product chemistry and are referenced in
the last column of the table in paragraph (d) of this section.
1. Data must be provided in accordance with Sec. 158.320.
2. If the MP and EP are produced by an integrated formulation
system(non-registered source), these data are also required on TGAI.
3. Data must be provided in accordance with Sec. 158.325,Sec.
158.330, and Sec. 158.335.
4. Data must be provided in accordance with Sec. 158.340.
5. Data must be provided in accordance with Sec. 158.345. Also,
required to support the registration of each manufacturing-use
product (including registered TGAIs) and end-use products produced
by an integrated formulation system. Data on other end-use products
would be required on a case-by-case basis. For pesticides in the
production stage, a preliminary product analytical method and data
would suffice to support an experimental use permit.
6. Data must be provided in accordance with Sec. 158.350.
7. Data must be provided in accordance with Sec. 158.355.
8. If the TGAI cannot be isolated, data are required on the
practical equivalent of the TGAI. EP testing may also be
appropriate.
9. Required if the product contains combustible liquids.
10. Required if the product is an emulsifiable liquid and is to
be diluted with petroleum solvents.
11. Required if the test substance is soluble or dispersible in
water.
12. Required if the product is a liquid.
13. Required when the technical chemical is a solid at room
temperature.
14. Required when the technical chemical is a liquid at room
temperature.
15. Required for water insoluble test substances
(<10-6 g/l) andfibrous test substances with diameter
>=0.1 [mu]m.
16. Required for organic chemicals unless they dissociate in
water or are partially or completely soluble in water.
17. 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.
18. True density or specific density are required for all test
substances. Data on bulk density is required for MPs or EPs that are
solid at room temperature.
19. Not required for salts.
Sec. 158.940 Residue datarequirements table.
(a) General. Sections 158.100 through Sec. 158.130 describe how to
use this table to determine the biochemical pesticides residue data
requirements for a particular pesticide product and the substance that
needs to be tested. These data requirements apply to all biochemicals,
e.g., semiochemicals, natural plant and insect regulators, naturally-
occurring repellents and attractants, and enzymes. 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) 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. Data are also conditionally required for
aquatic nonfood use if there is direct application to water.
(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 would 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 and aquatic food use, greenhouse food use, indoor food use,
and indoor residential use.
(c) Key. R=Required; [R]=Required for registrations andexperimental
use permits; CR=Conditionally required; [CR]=Conditionally required for
registrations and experimental use permits; NR=Not required;
MP=Manufacturing-use product; EP=End-use product; TEP=Typical end-use
product; TGAI=Technical grade of the active ingredient; Residue of
concern= the active ingredient and its metabolites, degradates, and
impurities of toxicological concern; All= all of the above. Specific
conditions, qualifications, or exceptions to the designated test
procedures appear in paragraph (e) of this section, and apply to the
individual tests in the following table:
(d) Table. The following table shows the data requirements for
biochemical residue for specific uses. The test notes are shown in
paragraph (e) of this section.
[[Page 12104]]
Table--Biochemical Residue Data Requirements for Specific Uses
--------------------------------------------------------------------------------------------------------------------------------------------------------
Use patterns containing data requirements
-----------------------------------------------------------------------
Guideline Number Data Requirement Terrestrial Aquatic Test Substance Test notes
------------------------------------ Greenhouse Food Indoor Food
Food/Feed Food
--------------------------------------------------------------------------------------------------------------------------------------------------------
Supporting Information
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1100 Chemical [CR] [CR] [CR] [CR] TGAI 1,2,4
identity
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1200 Directions for [CR] [CR] [CR] [CR] TGAI 1,3,4
use
--------------------------------------------------------------------------------------------------------------------------------------------------------
Nature of Residue
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1300 Nature of the [CR] [CR] [CR] [CR] TGAI 1,4,5,6
residue in
plants
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1300 Nature of the [CR] [CR] [CR] [CR] TGAI 1,7,8,10
residue in
livestock
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1340 Residue CR CR R [CR] Residue of 4,9,10
analytical concern
method- plants
Residue
analytical
method-
livestock.
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1360 Multiresidue CR CR R CR Residue of 10,11
method concern
--------------------------------------------------------------------------------------------------------------------------------------------------------
Magnitude of the Residue
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1400 Potable water NR [CR] NR NR TGAI 1,12
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1400 Fish NR [CR] NR NR TGAI 1,13
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1400 Irrigated crops NR [CR] NR NR TGAI 1,14
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1460 Food handling NR NR NR [CR] TGAI 1,15
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1480 Meat/milk/ [CR] [CR] [CR] [CR] TGAI or plant 1,7,8,10
poultry/eggs metabolites
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1500 Crop field [CR] [CR] [CR] [CR] TGAI 1,3,4
trials
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1520 Processed food/ [CR] [CR] [CR] [CR] TGAI 1,16
feed
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1540 Anticipated [CR] [CR] [CR] [CR] Residue of 1,10,17
residues concern
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1550 Proposed [CR] [CR] [CR] [CR] Residue of 1,18
tolerances concern
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1560 Reasonable [CR] [CR] [CR] [CR] Residue of 1,10
grounds in concern
support of the
petition
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1650 Submittal of [CR] [CR] [CR] [CR] TGAI 10,19
analytical
reference
standards
--------------------------------------------------------------------------------------------------------------------------------------------------------
(e) Test notes. The following test notes are applicable to the data
requirements for biochemical residue for specific uses as referenced in
the last column of the table contained in paragraph (d) of this
section.
1. Residue chemistry data requirements apply to biochemical
pesticide products when Tier II or Tier III toxicology data are
required, as specified for biochemical agents in the biochemical
human health assessment data requirements, Sec. 158.950.
2. The same chemical identity data are required for biochemical
product chemistry data requirements,Sec. 158.930 with an emphasis
on impurities.
3. Required information includes crops to be treated, rate of
application, number and timing of applications, preharvest
intervals, and relevant restrictions.
4. Residue data for outdoor residential uses are required if
home gardens are to be treated and the home garden use pattern is
different from use patterns where tolerances have been established.
5. Required unless it is an arthropod pheromone applied at a
rate less than or equal to 150 grams active ingredient per acre.
6. Required for indoor uses where the pesticide is applied
directly to food, in order to determine metabolites and/or
degradates.
7. Data on metabolism in livestock are required when residues
occur on a livestock feed or if the pesticide is to be applied
directly to livestock. 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.
8. Livestock feeding studies are required whenever a pesticide
residue is present in livestock feed or when direct application to
livestock uses occurs.
9. A residue method suitable for enforcement of tolerances is
required whenever a numeric tolerance is proposed.
10. Required for indoor uses if the indoor use could result in
pesticide residues in or on food or feed.
[[Page 12105]]
11. Data are required to determine whether FDA/USDA multiresidue
methodology would detect and identify the pesticides and any
metabolites.
12. Data on residues in potable water are required whenever a
pesticide is to be applied directly to water, unless it can be
determined that the treated water would not be used (eventually) for
drinking purposes, by man or animals.
13. Data on residues in fish are required whenever a pesticide
is to be applied directly to water inhabited, or that will be
inhabited, by fish that may be caught or harvested for human
consumption.
14. Data on residues in irrigated crops 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.
15. Data on residues in food/feed in food handling
establishments are required whenever a pesticide is to be used in
food/feed handling establishments.
16. Data on the nature and level of residue in processed food/
feed are required when detectible residues could concentrate on
processing.
17. Anticipated residue data are required when the assumption of
tolerance level residues would result in predicted exposure at an
unsafe level of exposure. Data on the level or residue in food as
consumed would be used to obtain a more precise estimate of
potential dietary exposure.
18. The proposed tolerance must reflect the maximum residue
likely to occur in crops in meat, milk, poultry, or eggs.
19. Required when a residue analytical method is required.
Sec. 158.950 Human healthassessment data dequirements table.
(a) General. (1) Sections 158.100 through 158.130 describe how to
use this table to determine the human health assessment data
requirements for a particular pesticide product.
(2) The data in this section (158.950) are not required for
straight chain lepidopteran pheromones when applied up to a maximum use
rate of 150 grams active ingredient/acre/year.
(b) Use patterns. (1) Food use patterns, in general, include
products classified under the following general uses: terrestrial food
crop use; terrestrial feed crop use; aquatic food crop use; greenhouse
food crop use.
(2) Nonfood use patterns include products classified under the
general use patterns of terrestrial nonfood crop use; aquatic nonfood
residential use; aquatic nonfood outdoor use; aquatic nonfood
industrial use; greenhouse nonfood crop use; forestry use; residential
outdoor use; residential indoor use; indoor food use; indoor nonfood
use; indoor medical use.
(c) Key. R=Required; [R]=Required for registrations and
experimental use permits; CR=Conditionally required; [CR]=Conditionally
required for registrations and experimental use permits; NR=Not
required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use product; TGAI=Technical grade of the active ingredient; Residue
of concern= the active ingredient and its metabolites, degradates, and
impurities of toxicological concern; All= all of the above. Specific
conditions, qualifications, or exceptions to the designated test
procedures appear in paragraph (e) of this section, and apply to the
individual tests in the following table:
(d) Table. The following table shows the data requirements for
biochemical human health assessment. The test notes are shown in
paragraph (e) of this section.
Table--Biochemical Human Health Assessment Data Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
Use Patterns Test substance to support
Guideline Number Data Requirement -------------------------------------------------------------------------------- Test notes
Food Nonfood MP EP
--------------------------------------------------------------------------------------------------------------------------------------------------------
Tier I
--------------------------------------------------------------------------------------------------------------------------------------------------------
Acute Testing
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.1100 Acute oral [R] [R] TGAI and MP> TGAI and EP 1
toxicity-rat
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.1200 Acute dermal [R] [R] TGAI and MP TGAI and EP 1,2
toxicity
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.1300 Acute inhalation [R] [R] TGAI and MP TGAI and EP 3
toxicity--rat
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.2400 Primary eye [R] [R] TGAI and MP TGAI and EP 2
irritation--rabbi
t
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.2500 Primary dermal [R] [R] TGAI and MP TGAI and EP 1,2
irritation
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.2600 Dermal R R TGAI and MP TGAI and EP 2,4
sensitization
--------------------------------------------------------------------------------------------------------------------------------------------------------
none Hypersensitivity [R] [R] All All 5
incidents
--------------------------------------------------------------------------------------------------------------------------------------------------------
Subchronic Testing
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.3100 90-day oral (one [R] CR TGAI TGAI 6
species)
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.3250 90-day dermal--rat CR CR TGAI TGAI 7
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.3465 90-day inhalation-- CR CR TGAI TGAI 8
rat
--------------------------------------------------------------------------------------------------------------------------------------------------------
Developmental Toxicity
--------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 12106]]
870.3700 Prenatal [R] [CR] TGAI TGAI 9
developmental--ra
t preferably
--------------------------------------------------------------------------------------------------------------------------------------------------------
Mutagenicity Testing
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.5100 Bacterial reverse [R] [CR] TGAI TGAI 10
mutation test
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.5300 In vitro mammalian [R] [CR] TGAI TGAI 10,11
cell gene
mutation test
--------------------------------------------------------------------------------------------------------------------------------------------------------
Tier II
--------------------------------------------------------------------------------------------------------------------------------------------------------
Mutagenicity Testing (In vivo cytogenetics)
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.5385 Mammalian bone CR CR TGAI TGAI 13
marrow
chromosomal
aberration
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.5395 Mammalian CR CR TGAI TGAI 13
erythrrocyte
micronucleus
--------------------------------------------------------------------------------------------------------------------------------------------------------
Developmental Toxicity
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.3700 Prenatal [CR] [CR] TGAI TGAI 9
developmental
--------------------------------------------------------------------------------------------------------------------------------------------------------
Special Tests
--------------------------------------------------------------------------------------------------------------------------------------------------------
880.3550 Immunotoxicity CR CR TGAI TGAI 12,13
--------------------------------------------------------------------------------------------------------------------------------------------------------
Applicator/User Exposure
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.1000 Background for CR CR TGAI TGAI 15
application
exposure
monitoring test
guidelines
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.1100 Dermal outdoor CR CR TGAI TGAI 15
exposure
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.1200 Dermal indoor CR CR TGAI TGAI 15
exposure
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.1300 Inhalation outdoor CR CR TGAI TGAI 15
exposure
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.1400 Inhalation indoor CR CR TGAI TGAI 15
exposure
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.1500 Biological CR CR TGAI TGAI 15
monitoring
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.1700 Product use [R] [R] TGAI TGAI --
information
--------------------------------------------------------------------------------------------------------------------------------------------------------
Tier III
--------------------------------------------------------------------------------------------------------------------------------------------------------
Chronic Testing/Special Testing
--------------------------------------------------------------------------------------------------------------------------------------------------------
880.3800 Immune response CR CR TGAI TGAI 14
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.3800 Reproduction and CR CR TGAI TGAI 16
fertility effects
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.4100 Chronic oral-- CR CR TGAI TGAI 17
rodent and
nonrodent
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.4200 Carcinogenicity--t CR CR TGAI TGAI 18
wo species--rat
and mouse
preferred
--------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 12107]]
870.5380 Mammalian CR CR TGAI TGAI 19
spermatogonial
chromosome
aberration test
--------------------------------------------------------------------------------------------------------------------------------------------------------
Special Testing
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.7200 Companion animal CR CR Choice Choice 20
safety
--------------------------------------------------------------------------------------------------------------------------------------------------------
(e) Test notes. The following test notes are applicable to the data
requirements for biochemical human health assessment as referenced in
the last column of the table in paragraph (d) of this section.
1. Required unless the test material is a gas or highly volatile
(vapor pressure >104torr).
2. Required unless the test material is corrosive to skin or has
pH <2 or >11.5.
3. Required when the pesticide, under conditions of use, would
result in respirable material (e.g., gas, volatile substance or
aerosol/particulate), unless it is a straight chain lepidopteran
pheromone.
4. Required if repeated contact with human skin is likely to
occur under conditions of use.
5. Hypersensitivity incidents must be reported as adverse
effects data.
6. Required for non-food uses that are likely to result in
repeated oral exposure to humans.
7. Required to support uses involving purposeful application to
the human skin or which would result in comparable prolonged human
exposure to the product (e.g., insect repellents) and if any of the
following criteria are met:
(i) Data from a 90-day oral study are not required.
(ii) The active ingredient is known or expected to be
metabolized differently by the dermal route of exposure than by the
oral route and the metabolite is of toxicological concern.
(iii) The use pattern is such that the dermal route would be the
primary route of exposure.
8. Required if there is a likelihood of significant levels of
repeated inhalation exposure to the pesticide as a gas, vapor, or
aerosol.
9. Required if the use of the product under widespread and
commonly recognized practice may reasonably be expected to result in
significant exposure to female humans (e.g., occupational exposure
or repeated application of insect repellents directly to the skin).
Tier II data is required on a different test species from Tier I
data when developmental effects are observed in the first study and
information on species-to-species extrapolation is needed.
10. It is required to support nonfood uses if either (i) the use
is likely to result in significant human exposure; or (ii) if the
active ingredient (or its metabolites) is structurally related to a
known mutagen or belongs to any chemical class of compounds
containing a known mutagen. Additional mutagenicity tests that may
have been performed plus a complete reference list must also be
submitted. Subsequent testing may be required based on the available
evidence.
11. Choice of assay using either (1) mouse lymphoma L5178Y
cells, thymidine kinase (tk) gene locus, maximizing assay conditions
for small colony expression or detection; (2) Chinese hamster ovary
(CHO) or Chinese hamster lung fibroblast (V79) cells, hypoxanthine-
guanine phosphoribosyl transferase (hgprt) gene locus, accompanied
by an appropriate in vivo test for clastogenicity; or (3) CHO cells
strains AS52, xanthine-guanine phosphoribosyl transferase (xprt)
gene locus.
12. Required if there are effects on hematology, clinical
chemistry, lymphoid organ weights and histopathology are observed in
the 90-day studies.
13. Required if results from the Tier I mutagenicity tests are
positive. Allowed choice of assays, initial considerations usually
given to rodent bone marrow, using either metaphase analysis
(aberrations) or micronucleus assay.
14. Required if adverse effects are observed in the Tier II
immunotoxicity study. The protocol for evaluating adverse effects to
the immune response should be developed after evaluating the effects
noted in the immunotoxicity study.
15. These data are required when any human health effects
assessment data indicate that the biochemical may pose a potential
hazard to the applicator/user. It is recommended that the Agency be
consulted prior to study initiation to determine what studies are
appropriate based on the nature of the adverse effects seen in the
human health assessment data and the available exposure data.
Studies performed to support registration of insect repellents may
require modifications to these guidelines.
16. Required if there is evidence of: (a) endocrinological
effects from the subchronic toxicity studies, (b) developmental
effects in the prenatal developmental toxicity study(s), or (c)
genotoxicity to mammals based on results from the mutagenicity
tests. The use of a combined study that utilizes the two-generation
reproduction study in rodents (guideline 870.3800) as a basic
protocol for the addition of other endpoints or functional
assessments in the immature animal is encouraged.
17. Required if the potential for adverse chronic effects is
indicated based on any of the following:
(i) The subchronic effect level established in the following
Tier I studies: 90-day feeding toxicity study, the 90-day dermal
toxicity study, or the 90-day inhalation toxicity study.
(ii) The pesticide use pattern (e.g., rate, frequency, and site
of application).
(iii) The frequency and level of repeated human exposure that is
expected.
18. Required if the product meets either of the following
criteria:
(i) The active ingredient (or any of its metabolites,
degradation products, or impurities) produce(s) in Tier I subchronic
studies a morphologic effect (e.g., hyperplasia or metaplasia) in
any organ that potentially could lead to neoplastic change.
(ii) Adverse cellular effects suggesting carcinogenic potential
are observed in Tier II immunotoxicity and Tier III immune response
study or in Tier II mammalian mutagenicity assays.
In addition, a 90-day range finding study in both rats and mice
is required to determine the 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.
19. Required if results from lower tiered mutation or
reproductive studies indicate there is potential for chromosomal
aberration to occur.
20. 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.
Sec. 158.960 Nontarget organismsand environmental fate data
requirements table.
(a) General. (1) Sections 158.100 through 158.130 describe how to
use this table to determine the terrestrial and aquatic nontarget
organisms and 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. In general,
[[Page 12108]]
for all outdoor end-use products including turf, the following studies
are required: one avian acute oral, one avian dietary, one acute
freshwater fish, one acute freshwater invertebrate study, plant
toxicity testing and a honeybee acute contact study.
(2) The data in this section are not required for arthropod
pheromones when applied at up to a maximum use rate of 150 grams active
ingredient/acre/year except when the product is expected to be
available to avian species (i.e., granular formulation).
(b) Use patterns. The terrestrial use pattern includes products
classified under the general use patterns of terrestrial food crop,
terrestrial feed crop, and terrestrial nonfood/nonfeed 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 nonfood use. The remaining terrestrial uses
include: forestry and residential outdoor use. Data are also required
for the general use patterns of aquatic food and nonfood crop use.
(c) Key. R=Required; [R]=Required for registrations and
experimental use permits; CR=Conditionally required; [CR]=Conditionally
required for registrations and experimental use permits; NR=Not
required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use product; TGAI=Technical grade of the active ingredient; Residue
of concern= the active ingredient and its metabolites, degradates, and
impurities of toxicological concern; All= all of the above. Specific
conditions, qualifications, or exceptions to the designated test
procedures appear in paragraph (e) of this section, and apply to the
individual tests in the following table:
(d) Table. The following table shows the data requirements for
biochemical nontarget organisms and environmental fate. The test notes
are shown in paragraph (e) of this section.
Table--Biochemical Nontarget Organisms and Environmental Fate Data Requirements
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Use Groups containing data requirements
---------------------------------------------------------------------------------------------------------
Guideline Number Data Requirement Terrestrial Aquatic Greenhouse Indoor Test Substance Test notes
--------------------------------------------------------------- Forestry, ---------------------
Food/feed, nonfood Food, nonfood Food, nonfood residential outdoor Food, nonfood
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Tier I
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Avian Testing
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.2100 Avian acute oral [R]................ [R]................ CR................. [R]................ CR................. TGAI, EP.......... 1,2,3,4
toxicity
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.2200 Avian dietary [R]................ [R]................ CR................. [R]................ CR................. TGAI, EP.......... 1,2,3,4
toxicity
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Aquatic Organism Testing
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1075 Fish acute [R]................ [R]................ CR................. [R]................ CR................. TGAI, EP.......... 2,3,4,5
toxicity,
freshwater
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1010 Aquatic [R]................ [R]................ CR................. [R]................ CR................. TGAI, EP.......... 2,3,4,5
invertebrate acute
toxicity,
freshwater
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Nontarget Plant Testing
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.4100 Terrestrial Plant R................. R................. NR................. R................. NR................. TGAI, EP.......... 5
Toxicity, Seedling
emergence
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.4150 Terrestrial Plant R................. R................. NR................. R................. NR................. TGAI, EP.......... 5
Toxicity,
Vegetative vigor
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Insect Testing
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
880.4350 Nontarget Insect R................. R................. R................. R................. NR................. TGAI.............. 14
Testing
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Tier II
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Environmental Fate Testing
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
163-1 (835.1230) Sediment and soil CR................. CR................. CR................. CR................. NR................. TGAI.............. 6
adsorption/
desorption for
parent and
degradates
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
163-1 (835.1240) Soil column CR................. CR................. CR................. CR................. NR................. TGAI.............. 6
leaching
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
163-2 (835.1410) Laboratory CR................. NR................. CR................. CR................. NR................. TEP.............. 7
volatilization
from soil
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 12109]]
161-1 (835.2120) Hydrolysis CR................. CR................. CR................. CR................. NR................. TGAI.............. 6
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
161-1 (835.4100) Aerobic soil CR................. NR................. CR................. CR................. NR................. TGAI.............. 6
metabolism
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
161-2 (835.2240) Photodegradation in CR................. CR................. CR................. CR................. NR................. TGAI.............. 6
water
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
161-3 (835.2410) Photodegradation on CR................. NR................. CR................. CR................. NR................. TGAI.............. 6
soil
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
162-2 (835.4200) Anerobic soil CR................. NR................. NR................. NR................. NR................. TGAI.............. 6
metabolism
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
162-4 (835.4300) Aerobic aquatic CR................. CR................. CR................. CR................. NR................. TGAI.............. 6
metabolism
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
162-3(835.4400) Anerobic aquatic CR................. CR................. NR................. NR................. NR................. TGAI.............. 6
metabolism
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
880.4425 Dispenser -water CR................. NR................. CR................. CR................. NR................. EP................ 8
leaching
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Nontarget Plant
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.4225 Seedling emergence R................. R................. NR................. R................. NR................. TGAI.............. 9
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.4250 Vegetative vigor R................. R................. NR................. R................. NR................. TGAI.............. 9
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Tier III
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Aquatic Fauna Chronic, Life Cycle, and Field Studies
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1300 Freshwater fish/ CR................. CR................. NR................. CR................. NR................. TGAI.............. 10
850.1400........................ invertebrate
850.1500........................ testing
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1025 Marine/Estuarine CR................. CR................. NR................. CR................. NR................. TGAI.............. 10
850.1035........................ fish/invertebrate
850.1045........................ animal testing
850.1055........................
850.1350........................
850.1400........................
850.1500........................
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1950 Aquatic field fish/ CR................. CR................. NR................. CR................. NR................. EP............... 10
invertebratetestin
g
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Terrestrial Wildlife
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.2300 Avian Reproduction CR................. CR................. NR................. CR................. NR................. TGAI.............. 11
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.2400 Wild mammal acute CR................. CR................. NR................. CR................. NR................. TGAI.............. 11
toxicity
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.2500 Terrestrial field CR................. CR................. NR................. CR................. NR................. EP................ 11
testing
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Beneficial Insects
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.3040 Field testing for CR................. CR................. NR................. CR................. NR................. TEP.............. 12
Pollinators
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Nontarget Plants
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 12110]]
850.4225 Nontarget plant CR................. CR................. NR................. CR................. NR................. TGAI.............. 13
850.4250........................
850.4300........................
850.4450........................
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
(e) Test notes. The following test notes are applicable to the data
requirements for biochemical nontarget organisms and environmental fate
as referenced in the last column of the table contained in paragraph
(d) of this section.
1. Required for the EP when any end-use formulation may contain
other ingredients that may be toxic to nontarget organisms or to
support arthropod pheromones that would be available to avian
wildlife, (e.g., a granular product).
2. Tests for pesticides intended solely for indoor application
would be required on a case-by-case basis, depending on use pattern,
physical/chemical properties, production volume, and other pertinent
factors.
3. Not required for any use groups if the pesticide is highly
volatile (estimated volatility >5 X 10-5 atm
m3/mol).
4. Preferred test species are bobwhite quail, mallard, or
redwing blackbird for avian acute oral toxicity studies; bobwhite
quail or mallard for avian dietary studies, rainbow trout for acute
freshwater fish studies; and Daphnia magna for acute freshwater
invertebrate studies.
5. Required for the EP when the end-use formulation may contain
other ingredients that may be toxic to nontarget organisms.
6. Required on a case-by-case basis when results from Tier I
studies indicate adverse effects.
7. Required when results of any one or more of the nontarget
organism studies in Tier I indicate potential adverse effects on
nontarget organisms and the pesticide is to be applied on land.
8. Required when results of any one or more of the nontarget
organism studies in Tier I indicate potential adverse effects on
nontarget organisms and the pesticide is to be applied in a passive
dispenser.
9. Required to support registration of known phytotoxicants,
i.e. herbicides, desiccants, defoliants, and plant growth
regulators.
10. Required if environmental fate characteristics indicate that
the estimated environmental concentration of the pesticide in the
aquatic environment is >0.01 of any EC50 or
LC50 determined in the aquatic nontarget organism
testing.
11. Required if either of the following criteria are met:
(i) Environmental fate characteristics indicate that the
estimated concentration of the pesticide in the terrestrial
environment is >0.20 the avian dietary LC50 or equal to
or >0.20 the avian oral single dose LD50 (converted to
ppm).
(ii) The pesticide or any of its metabolites or degradation
products are stable in the environment to the extent that
potentially toxic amounts may persist in the avian or mammalian
feed.
12. Required when results of Tier I nontarget organism studies
indicate potential adverse effects on nontarget insects and results
of Tier II tests indicate exposure of nontarget insects. Additional
insect species may have to be tested if necessary to address issues
raised by use patterns and potential exposure of important nontarget
insect species, (e.g., threatened or endangered species).
13. Required if the product is expected to be transported from
the site of application by air, soil, or water. The extent of
movement would be determined by the results of the Tier II
environmental fate studies.
14. Required depending on pesticide mode of action, method and
timing of application, and results of any available efficacy data.
Typically the honeybee acute toxicity guideline (guideline 850.3020)
satisfies this requirement, however additional nontarget insect
species may have to be tested if necessary to address issues raised
by use patterns and potential exposure of important nontarget insect
species, e.g., endangered species.
Sec. 158.970 Biochemicalpesticides product performance data
requirements.
Product performance data must be developed for all biochemical
pesticides. However, the Agency typically does not require applicants
to submit such efficacy data unless the pesticide product bears a claim
to control public health pests, such as pest microorganisms infectious
to man in any area of the inanimate environment or a claim to control
vertebrates (including but not limited to: rodents, birds, bats,
canids, and skunks) or invertebrates (including but not limited to:
mosquitoes and ticks) that may directly or indirectly transmit diseases
to humans. However, each registrant must ensure through testing that
his products are efficacious when used in accordance with label
directions and commonly accepted pest control practices. The Agency
reserves the right to require, on a case-by-case basis, submission of
efficacy data for any pesticide product registered or proposed for
registration.
Subpart M--Microbial Pesticides
Sec. 158.1000 Definition andApplicability.
(a) This subpart applies to all living or dead microbial pesticides
as described in paragraphs (b) and (c) of this section.
(b) Definition. Microbial pesticide is a microorganism intended for
preventing, destroying, repelling, or mitigating any pest, or intended
for use as a plant regulator, defoliant, or desiccant, that:
(1) Is a eucaryotic microorganism including, but not limited to,
protozoa, algae, and fungi;
(2) Is a procaryotic microorganism, including, but not limited to,
bacteria; or
(3) Is an autonomous replicating microscopic element, including,
but not limited to, viruses.
(c) Applicability. (1) In addition to the definition above, the
definitions in Sec. 158.3 also apply to this subpart.
(2) Each new isolate of a microbial pesticide is treated as a new
strain and must be registered independently of any similar registered
microbial pesticide strain and supported by data required in this
subpart.
(3) Genetically modified microbial pesticides, may be subject to
additional data or information requirements on a case-by-case basis
depending on the particular microorganism and/or its parent
microorganism(s), the proposed pesticide use pattern, and the manner
and extent to which theorganism has been genetically modified.
Additional requirements may be required on a case-by-case basis.
(4) Pest control organisms such as insect predators, nematodes, and
macroscopic parasites are exempt from the requirements of FIFRA as
authorized by section 25(b) of FIFRA and specified in Sec. 152.20 (a)
of this chapter.
[[Page 12111]]
Sec. 158.1010 Microbial pesticidedata requirements.
(a) For all microbial pesticides. (1) The following Sec. Sec.
158.1010 through 158.1050 identify the data requirements that are
required to support registration of microbial pesticides. The
variations in the test conditions are identified within the test notes.
(2) Each data table includes ``use patterns'' under which the
individual data are required, with variations including all use
patterns, food and nonfood uses for terrestrial and aquatic
applications, greenhouse, indoor, forestry, and residential outdoor
applications under certain circumstances.
(3) The categories for each data requirement are ``R'', which
stands for required, and ``CR'' which stands for conditionally
required. If a bracket appears around the R or CR, the data are
required for both the registration and experimental use permit
requests. Generally, ``R'' indicates that the data are more likely
required than for those data requirements with CR. However, in each
case, the regulatory text preceding the data table and the test notes
following the data table must be used to determine whether the data
requirement must be satisfied.
(4) Each table identifies the test substance that is required to be
tested to satisfy the data requirement. Test substances may include:
technical grade active ingredient (TGAI), manufacturing-use product
(MP), end-use product (EP), typical end-use product (TEP), residue of
concern, and pure active ingredient (PAI) or (All) indicating all of
the above. Commas between the test substances (i.e., TGAI, EP) indicate
that data may be required on the TGAI or EP or both depending on the
conditions set forth in the test note. Data requirements which list two
test substances (i.e., TGAI and EP) indicate that both are required to
be tested. Data requirements that list only the manufacturing product
(MP) as the test substance apply to products containing solely the
technical grade of the active ingredient and manufacturing-use products
to which other ingredients have been intentionally added. Data
requirements listing the EP as the test substance apply to any EP with
an ingredient in the end-use formulation other than the active
ingredient that is expected to enhance the toxicity of the product.
(b) Additional data requirements for genetically modified microbial
pesticides. Additional requirements for genetically modified microbial
pesticides may include but are not limited to: genetic engineering
techniques used; the identity of the inserted or deleted gene segment
(base sequence data or enzyme restriction map of the gene); information
on the control region of the gene in question; a description of the
``new'' traits or characteristics that are intended to be expressed;
tests to evaluate genetic stability and exchange; and selected Tier II
environmental expression and toxicology tests.
Sec. 158.1020 Product analysisdata requirements table.
(a) General. Sections 158.100 through 158.130 describe how to use
this table to determine the product analysis data requirements and the
substance to be tested for a particular microbial pesticide. Specific
conditions, qualifications, or exceptions to the designated test are
identified in (d) of this section, and the test notes appear in
paragraph (e) of this section.
(b) Key. R=Required; [R]=Required for registrations andexperimental
use permits; CR=Conditionally required; [CR]=Conditionally required for
registrations and experimental use permits; NR=Not required;
MP=Manufacturing-use product; EP=End-use product; TEP=Typical end-use
product; TGAI=Technical grade of the active ingredient; All= all of the
above. Specific conditions, qualifications, or exceptions to the
designated test procedures appear in paragraph (e) of this section, and
apply to the individual tests in the following table:
(c) Table. The following table shows the data requirements for
microbial product analysis. The test notes are shown in paragraph (d)
of this section.
Table--Microbial Product Analysis Data Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
All Use patterns Test substances to support
Guideline Number Data Requirement -------------------------------------------------------------------------------- Test notes
Food Use Nonfood Use MP EP
--------------------------------------------------------------------------------------------------------------------------------------------------------
Product Chemistry and Composition
--------------------------------------------------------------------------------------------------------------------------------------------------------
885.1100 Product Identity [R] [R] MP EP --
--------------------------------------------------------------------------------------------------------------------------------------------------------
885.1200 Manufacturing [R] [R] TGAI and MP TGAI and EP 1,2
process
--------------------------------------------------------------------------------------------------------------------------------------------------------
Deposition of a [R] [R] TGAI TGAI --
sample in a
nationally
recognized
culture
collection
--------------------------------------------------------------------------------------------------------------------------------------------------------
885.1300 Discussion of [R] [R] TGAI and MP TGAI and EP 2
formation of
unintentional
ingredients
--------------------------------------------------------------------------------------------------------------------------------------------------------
Analysis and Certified Limits
--------------------------------------------------------------------------------------------------------------------------------------------------------
885.1400 Analysis of [R] [R] TGAI and MP TGAI and EP 2,3
samples
--------------------------------------------------------------------------------------------------------------------------------------------------------
885.1500 Certification of [R] R MP EP --
limits
--------------------------------------------------------------------------------------------------------------------------------------------------------
Physical and Chemical Characteristics
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6302 Color [R] [R] TGAI TGAI --
--------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 12112]]
830.6303 Physical state [R] [R] TGAI TGAI --
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6304 Odor [R] [R] TGAI TGAI --
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6313 Stability to [R] [R] TGAI TGAI --
normal and
elevated
temperatures,
metals and metal
ions
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6317 Storage stability [R] [R] TGAI and MP TGAI and EP --
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6319 Miscibility [R] [R] MP EP 4
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6320 Corrosion [R] [R] MP EP 5
Characteristics
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7000 pH [R] [R] TGAI TGAI --
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7100 Viscosity [R] [R] MP EP 6
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7300 Density/relative [R] [R] TGAI TGAI --
density/bulk
density (specific
gravity)
--------------------------------------------------------------------------------------------------------------------------------------------------------
(d) Test notes. The following test notes are applicable to the
data requirements for microbial product analysis as referenced in
the last column of the table contained in paragraph (c) of this
section.
1. If an experimental use permit is being sought, and if the
pesticide is not already under full-scale production, a schematic
diagram and/or description of the manufacturing process suffices.
2. If an experimental use permit is being sought, and if the
product is not already under full-scale production, a discussion of
unintentional ingredients is required to be submitted to the extent
this information is available.
3. Required to support registration of each manufacturing-use
product and end-use product. This analysis must be conducted at the
point in the production process after which there would be no
potential for microbial contamination or microbial regrowth. For
pesticides in the production stage, a preliminary product analytical
method and data would suffice to support an experimental use permit.
For full registration, generally an analysis of samples is a
compilation of batches, over a period of time, depending on the
frequency of manufacturing.
4. Only required for emulsifiable liquid forms of microbial
pesticides.
5. Required when microbial pesticides are packaged in metal,
plastic, or paper containers.
6. Only required for liquid forms of microbial pesticides.
Sec. 158.1030 Residue datarequirements table.
(a) General. Sections 158.100 through 158.130 describe how to use
this table to determine the residue chemistry data requirements and the
substance to be tested for a particular microbial pesticide. Specific
conditions, qualifications, or exceptions to the designated test appear
in (d) of this section, and the procedures appear in paragraph (e) of
this section.
(b) Key. R=Required; [R]=Required for registrations and
experimental use permits; CR=Conditionally required; [CR]=Conditionally
required for registrations and experimental use permits; NR=Not
required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use product; TGAI=Technical grade of the active ingredient; All=
all of the above. Specific conditions, qualifications, or exceptions to
the designated test procedures appear in paragraph (d) of this section,
and apply to the individual tests in the following table:
(c) Table. The following table shows the data requirements for
microbial residue. The test notes are shown in paragraph (d) of this
section.
Table--Microbial Residue Data Requirements
----------------------------------------------------------------------------------------------------------------
Test Substance
Guideline Number Data Requirement All Use Patterns Data to support MP Test notes
or EP
----------------------------------------------------------------------------------------------------------------
885.2000 Background for [CR] EP 1
Residue analysis
of microbial pest
control agents
----------------------------------------------------------------------------------------------------------------
885.2100 Chemical Identity [CR] EP 1
----------------------------------------------------------------------------------------------------------------
885.2200 Nature of the [CR] EP 1
Residue in plants
----------------------------------------------------------------------------------------------------------------
885.2250 Nature of the [CR] EP 1
Residue in
animals
----------------------------------------------------------------------------------------------------------------
[[Page 12113]]
885.2300 Analytical [CR] TGAI 1
methods--plants
----------------------------------------------------------------------------------------------------------------
885.2350 Analytical [CR] TGAI 1
methods-animals
----------------------------------------------------------------------------------------------------------------
885.2400 Storage Stability [CR] EP 1
----------------------------------------------------------------------------------------------------------------
885.2500 Magnitude of [CR] EP 1
residue in plants
----------------------------------------------------------------------------------------------------------------
885.2550 Magnitude of [CR] EP 1
residues in meat,
milk, poultry,
eggs
----------------------------------------------------------------------------------------------------------------
885.2600 Magnitude of [CR] EP 1
residues in
potable water,
fish, and
irrigated crops
----------------------------------------------------------------------------------------------------------------
(d) Test notes. The following test note is applicable to the data
requirements for microbial residue as referenced in the last column of
the table contained in paragraph (c) of this section.
1. Required when the results of testing:
i. Indicate the potential to cause adverse human health effects
or the product characterization indicates the microbial pesticide
has a significant potential to produce a mammalian toxin; andii. The
use pattern is such that residues may be present in or on food or
feed crops.
Sec. 158.1040 Toxicology datarequirements 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) This category includes products classified
under the following general uses: terrestrial food and nonfood crop
use; terrestrial feed crop use; aquatic food and nonfood crop use;
greenhouse food and nonfood crop use; forestry; residential outdoor and
indoor; and indoor food use.
(2) Nonfood use patterns include products classified under the
general use patterns of terrestrial nonfood crop use; aquatic nonfood
residential use; aquatic nonfood outdoor use; aquatic nonfood
industrial use; greenhouse nonfood crop use; forestry use; residential
outdoor use; residential indoor use; indoor food use; indoor nonfood
use.
(c) Key. R=Required; [R]=Required for registrations andexperimental
use permits; CR=Conditionally required; [CR]=Conditionally required for
registrations and experimental use permits; NR=Not required;
MP=Manufacturing-use product; EP=End-use product; TEP=Typical end-use
product; TGAI=Technical grade of the active ingredient; All= all of the
above. Specific conditions, qualifications, or exceptions to the
designated test procedures appear in paragraph (e) of this section, and
apply to the individual tests in the following table:
(d) Table. The following table shows the data requirements for
microbial toxicology. The test notes are shown in paragraph (e) of this
section.
Table--Microbial Toxicology Data Requirements
----------------------------------------------------------------------------------------------------------------
Guideline Number Data Requirement All Use patterns Test substance Test notes
----------------------------------------------------------------------------------------------------------------
Tier I
----------------------------------------------------------------------------------------------------------------
885.3050 Acute oral [R] TGAI 1
toxicity/
pathogenicity
----------------------------------------------------------------------------------------------------------------
885.3150 Acute pulmonary [R] TGAI --
toxicity/
pathogenicity
----------------------------------------------------------------------------------------------------------------
885.3200 Acute injection [R] TGAI 2
toxicity/
pathogenicity/
(intravenous)
Acute injection
toxicity/
pathogenicity /
(intraperitoneal).
----------------------------------------------------------------------------------------------------------------
885.3400 Hypersensitivity [R] All 3
incidents
----------------------------------------------------------------------------------------------------------------
885.3500 Cell culture [R] TGAI 4
----------------------------------------------------------------------------------------------------------------
870.1100 Acute oral [R] MP , EP 1,5
toxicity
----------------------------------------------------------------------------------------------------------------
870.1200 Acute dermal [R] MP , EP 5
toxicity
----------------------------------------------------------------------------------------------------------------
870.1300 Acute inhalation [R] MP , EP 5,7
toxicity
----------------------------------------------------------------------------------------------------------------
870.2400 Acute eye [R] MP , EP 5
irritation
----------------------------------------------------------------------------------------------------------------
870.2500 Primary dermal [CR] MP , EP 5,6
irritation
----------------------------------------------------------------------------------------------------------------
[[Page 12114]]
Tier II
----------------------------------------------------------------------------------------------------------------
885.3550 Acute toxicology CR TGAI 8
----------------------------------------------------------------------------------------------------------------
885.3600 Subchronic CR TGAI 9
toxicity/
pathogenicity
----------------------------------------------------------------------------------------------------------------
Tier III
----------------------------------------------------------------------------------------------------------------
885.3650 Reproductive CR TGAI 10,14
fertility effects
----------------------------------------------------------------------------------------------------------------
870.4200 Carcinogenicity CR TGAI 11,14
----------------------------------------------------------------------------------------------------------------
870.7800 Immunotoxicity CR TGAI 12,14
----------------------------------------------------------------------------------------------------------------
885.3000 Infectivity/ CR TGAI 13,14
pathogenicity
analysis
----------------------------------------------------------------------------------------------------------------
(e) Test notes. The following test notes are applicable to the data
requirements for microbial toxicology as referenced in the last column
of the table contained in paragraph (d) of this section:
1. The acute oral toxicity/pathogenicity study is required to
support the TGAI. However, it can be combined with the unit dose
portion of the acute oral toxicity study, with an EP or MP test
material to fulfill the requirement for the TGAI and the MP or EP in
a single study, if the new protocol is designed to address the
endpoints of concern.
2. Data not required for products whose active ingredient is a
virus. For test materials whose size or consistency may prevent use
of an i.v. injection, the i.p. injection procedure may be employed.
3. Hypersensitivity incidents for registered products must be
reported if they occur.
4. Data must be submitted only for products whose active
ingredient is a virus.
5. The 870 series studies for the MP and EP are intended to
provide data on the acute toxicity of the product. Waivers for any
or all of these studies may be granted when the applicant can
demonstrate that the combination of inert ingredients is not likely
to pose any significant human health risks. Where appropriate, the
limit dose approach to testing is recommended.
6. Data are required only if dermal irritation is found after
dosing in acute dermal toxicity study.
7. Required when the product consists of, or under conditions of
use would result in, an inhalable material (e.g., gas, volatile
substances, or aerosol particulate).
8. Data required when significant toxicity, in the absence of
pathogenicity and significant infectivity, is observed in acute
oral, injection, or pulmonary studies (Tier I). Route(s) of exposure
correspond to routes where toxicity was observed in Tier I studies.
The toxic component of the TGAI is to be tested.
9. Data required when significant infectivity and/or unusual
persistence is observed in the absence of pathogenicity or toxicity
in Tier I studies. Routes of exposure (oral and/or pulmonary)
correspond to routes in Tier I studies where adverse effects were
noted. Data may also be required to evaluate adverse effects due to
microbial contaminants or to toxic byproducts.
10. Data are required when any of the following criteria are
met:
(i) Significant infectivity of the microbial pest control agent
(MPCA) was observed in test animals in the Tier II subchronic study
and in which no significant signs of toxicity or pathogenicity were
observed.
(ii) The microbial pesticide is a virus which can persist or
replicate in mammalian cell culture lines.
(iii) The microbial pesticide is not amenable to thorough
taxonomic classification, and is related to organisms known to be
parasitic for mammalian cells.
(iv) The microbial pesticide preparation is not well purified,
and may contain contaminants which are parasitic for mammals.
11. Data may be required for products known to contain or
suspected to contain carcinogenic viruses or for microbial
components that are identified as having significant toxicity in
Tier II testing.
12. Data may be required for products known to contain or
suspected to contain viruses that can interact in an adverse manner
with components of mammalian immune system.
13. An analysis of human infectivity/pathogenicity potential
using scientific literature, genomic analysis, and/or actual
specific cell culture/animal data may be required for products known
to contain or suspected of containing intracellular parasites of
mammalian cells for products that exhibit pathogenic characteristics
in Tier I and/or Tier II, for products which are closely related to
known human pathogens based on the Product Analysis data, or for
known human pathogens that have been ``disarmed'' or rendered non-
pathogenic for humans.
14. Test standards may have to be modified depending on the
characteristics of the microorganism. Requirements may vary for
these studies depending on the active ingredient being tested.
Consultation with the Agency is advised before performing these Tier
III studies.
Sec. 158.1050 Nontarget organismsand environmental fate data
requirements table.
(a) General. Sections 158.100 through 158.130 describe how to use
this table to determine the terrestrial and aquatic nontarget organisms
data requirements for a particular microbial 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. Aquatic uses include: food and feed, nonfood uses
(e.g., outdoor, residential, and industrial). Terrestrial uses include:
Food, Feed, Non-Food, Forestry, Residential outdoor, greenhouse (food
and food), Indoor (food and nonfood), and Industrial.
(c) Key. R=Required; [R]=Required for registrations and
experimental use permits; CR=Conditionally required; [CR]=Conditionally
required for registrations and experimental use permits; NR=Not
required; MP=Manufacturing-use product; EP=End-use product; TEP=Typical
end-use product; TGAI=Technical grade of the active ingredient; All=
all of the above. Specific conditions, qualifications, or exceptions to
the designated test procedures appear in paragraph (e) of this section,
and apply to the individual tests in the following table:
(d) Table. The following table shows the data requirements for
microbial nontarget organisms and environmental fate. The test notes
are shown in paragraph (e) of this section.
[[Page 12115]]
Table--Microbial Nontarget Organisms and Environmental Fate Data Requirements
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Aquatic Terrestrial
---------------------------------------------------------------------------------------------------------------------------------------------------
Non-Food
Guideline Number Data Requirement -------------------- Test Substance Test notes
Food, Feed Out Food, Feed, Non- Forestry Residential Greenhouse Indoor Food, Industrial
door,Residential, food outdoor Food, Non-Food Non-Food
Industrial
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Tier I
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4050 Avian oral R [R] [R] [R] [R] CR CR CR TGAI 1,2
toxicity.........
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4100 Avian inhalation CR CR CR CR CR CR CR CR TGAI 1,2,3
toxicity/
pathogenicity
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4150 Wild mammal CR CR CR CR CR NR NR CR TGAI 1,4
toxicity/
pathogenicity
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4200 Freshwater fish R [R] [R] [R] CR CR CR CR TGAI 1, 2,5
toxicity/
pathogenicity
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4240 Freshwater R [R] [R] [R] CR CR CR CR TGAI 1, 2,5
invertebrate
toxicity/
pathogenicity
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4280 Estuarine/Marine CR CR CR CR CR NR NR CR TGAI 1,6
fish testing
Estuarine and
marine
invertebrate
testing.
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4300 Nontarget plant CR CR CR [R] CR NR CR CR TE 1,7
testing..........
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4340 Nontarget insect [R] [R] [R] [R] R CR NR CR TGAI 1,8
testing
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4380 Honey bee testing [R] [[R] [R] [R] R CR NR CR TGAI 1
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Tier II
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.5200 Terrestrial CR CR CR CR CR NR NR CR TGAI or TEP 9
environmental
expression tests
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.5300 Freshwater CR CR CR CR CR NR NR CR TGAI or TEP 10
environmental
expression tests
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.5400 Marine or CR CR CR CR CR NR NR CR TGAI or TEP 11,12
estuarine
environmental
expression tests
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Tier III
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4600 Avian chronic CR CR CR CR CR NR NR CR TGAI 12, 13
pathogenicity
and reproduction
test
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4650 Aquatic CR CR CR CR CR NR NR CR TGAI 12, 14
invertebrate
range testing
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4700 Fish life cycle CR CR CR CR CR NR NR CR TGAI 12, 14/ROW>
studies
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4750 Aquatic ecosystem CR CR CR CR CR NR NR CR TGAI 15
test ................
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Tier IV
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 12116]]
850.2500 Field testing for CR CR CR CR CR NR NR CR TGAI or TEP 11, 16
850.1950...................... terrestrial
wildlife and
Field testing
for aquatic
organisms
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.2500 Simulated or CR CR CR CR CR NR NR CR TEP 16, 17, 20
actual field
tests (birds,
mammals)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1950 Simulated or CR CR CR CR CR NR NR CR TEP 16, 18, 19, 20
actual field
test (aquatic
organisms)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.2500 Simulated or CR CR CR CR CR NR NR CR TEP 16, 18,19, 20
actual field
tests (insect
predators,
parasites)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.3040 Simulated or CR CR CR CR CR NR NR CR TEP 16, 18,19, 20
actual field
tests (insect
pollinators)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.4300 Simulated or CR CR CR CR CR NR NR CR TEP 16, 18, 19, 20
actual field
tests (plants)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
(e) Test notes. The following test notes are applicable to the data
requirements for microbial nontarget organism and environmental fate as
referenced in the last column of the table contained in paragraph (d)
of this section.
1. Tests for pesticides intended solely for indoor application
would be required on a case-by-case basis, depending on use pattern,
production volume, and other pertinent factors. Tests to support
EUP's are based on the application timing and acreage.
2. The preferred species for the avian oral study is either the
bobwhite quail or mallard duck. The preferred species for the avian
inhalation toxicity/pathogenicity study and the avian chronic
toxicity/pathogenicity study is the bobwhite quail. There is also
the option to test the redwing black bird if there is a concern for
passerine species. The rainbow trout is preferred for freshwater
fish testing. However, two species (rainbow trout and bluegill
sunfish are the preferred species) must be tested for uses involving
direct freshwater exposure. Daphnia magna is the preferred species
for freshwater invertebrate testing.
3. Data required when the nature of the microbial pesticide and/
or its toxins indicates potential pathogenicity to birds.
4. Required on a case-by-case basis if results of tests required
bySec. 158.1040 are inadequate or inappropriate for assessment of
hazards to wild animals.
5. Required when there will be significant exposure to aquatic
organisms (fish and invertebrates).
6. Required if the product is intended for direct application
into the estuarine or marine environment or expected to enter this
environment in significant concentrations because of expected use or
mobility pattern.
7. Required if the microbial pesticide is taxonomically related
to a known plant pathogen.
8. Data are not required unless an active microbial ingredient
controls the target insect pest by a mechanism of infectivity; i.e.
may create an epizootic condition in nontarget insects.
9. Required if toxic or pathogenic effects are observed in any
of the following tests for microbial pesticides:
(i) Avian acute oral or avian inhalation studies.
(ii) Wild mammal studies.
(iii) Nontarget plant studies (terrestrial).
(iv) Honey bee studies.
(v) Nontarget insect studies.
10. Required when toxic or pathogenic effects are observed in
any of the following Tier I tests for microbial pest control agents:
(i) Freshwater fish studies.
(ii) Freshwater aquatic invertebrate studies.
(iii) Nontarget plant studies (aquatic).
11. Required if product is applied on land or in fresh water or
marine/estuarine environments and toxic or pathogenic effects are
observed in any of the following Tier I tests for microbial
pesticides:
(i) Estuarine and marine animal toxicity and pathogenicity.
(ii) Plant studies--estuarine or marine species.
12. An appropriate dose-response toxicity test is required when
toxic effects on nontarget terrestrial wildlife or aquatic organisms
(including plants) are reported in one or more Tier I tests and
results of Tier II tests indicate exposure of the microbial agent to
the affected nontarget terrestrial wildlife or aquatic organisms.
The protocols for these tests may have to be modified in accordance
with results from the nontarget organism and environmental
expression studies.
13. Required when one or more of the following are present:
(i) Pathogenic effects are observed in Tier I avian studies.
(ii) Tier II environmental expression testing indicate that
long-term exposure of terrestrial animals is likely.
14. Required when product is intended for use in water or
expected to be transported to water from the intended use site, and
when pathogenicity or infectivity was observed in Tier I aquatic
studies.
15. Required if, after an analysis of the microbial pesticide's
ability to survive and multiply in the environment and what
ecological habitat it would occupy, the intended use patterns, and
the results of previous nontarget organisms and environmental
expression tests, it is determined that use of the microbial agent
may result in adverse effects on the nontarget organisms in aquatic
environments. Testing is to determine if applications of the
microbial pest control would be expected to disrupt the balance of
populations in the target ecosystem.
16. Tier IV studies may be conducted as a condition of
registration aspost-registration monitoring if the potential for
unreasonable
[[Page 12117]]
adverse effects appears to be minimal during that period of use due
to implementation of mitigation measures.
17. Required when both of the following conditions occur:
(i) Pathogenic effects at actual or expected field residue
exposure levels are reported in Tier III; and
(ii) The Agency determines that quarantine methods would not
prevent the microbial pesticide from contaminating areas adjacent to
the test area.
18. Short term simulated or actual field studies are required
when it is determined that the product is likely to cause adverse
short-term or acute effects, based on consideration of available
laboratory data, use patterns, and exposure rates.
19. Data from a long-term simulated field test (e.g., where
reproduction and growth of confined populations are observed) and/or
an actual field test (e.g., where reproduction and growth of natural
populations are observed) are required if laboratory data indicate
that adverse long-term, cumulative, or life-cycle effects may result
from intended use.
20. Since test standards would be developed on a case-by-case
basis, consultation with the Agency and development of a protocol is
advised before performing these Tier IV studies.
Sec. 158.1060 Microbial pesticidesproduct performance data
requirements.
Product performance data must be developed for all microbial
pesticides. However, the Agency has waived all requirements to submit
efficacy data unless the pesticide product bears a claim to control
public health pests, such as pest microorganisms infectious to man in
any area of the inanimate environment or a claim to control vertebrates
(including but not limited to: rodents, birds, bats, canids, and
skunks) or invertebrates (including but not limited to: mosquitoes and
ticks) that may directly or indirectly transmit diseases to humans.
However, each registrant must ensure through testing that his products
are efficacious when used in accordance with label directions and
commonly accepted pest control practices. The Agency reserves the right
to require, on a case-by-case basis, submission of efficacy data for
any pesticide product registered or proposed for registration.
PART 172--[AMENDED]
5. The authority citation continues to read as follows:
Authority: 7 U.S.C. 136c, 136w. Section 172.4 is also issued
under 31 U.S.C. 9701.
6. In Sec. 172.43 revise the definition for ``microbial
pesticide'' to read as follows:
Sec. 172.43 Definitions.
* * * * *
Microbial pesticide means a microorganism intended for preventing,
destroying repelling, or mitigating any pest, or intended for use as a
plant regulator, defoliant, or desiccant, that:
(1) Is a eucaryotic microorganism including, but not limited to,
protozoa, algae and fungi;
(2) Is a procaryotic microorganism, including, but not limited to,
bacteria; or
(3) Is an autonomous replicating microscopic element, including,
but not limited to, viruses.
* * * * *
[FR Doc. 06-2185 Filed 3-7-06; 8:45 am]
BILLING CODE 6560-50-S