[Federal Register Volume 72, Number 207 (Friday, October 26, 2007)]
[Rules and Regulations]
[Pages 60988-61025]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-20828]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 158
[EPA-HQ-OPP-2004-0415; FRL-8109-8]
RIN 2070-AD51
Pesticides; Data Requirements for Biochemical and Microbial
Pesticides
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final Rule.
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SUMMARY: This is the final rule for Biochemical and Microbial Pesticide
Data Requirements. The Agency published a proposed rule on March 8,
2006, on the data requirements to support registration of biochemical
and microbial pesticides and proposed to update definitions for both
biochemical and microbial pesticides. The Agency received comments from
20 commenters, representing State and Federal agencies, industry, and
private consultants.
DATES: This rule is effective on December 26, 2007.
ADDRESSES: EPA has established a docket for this action under Docket
identification number EPA-HQ-OPP-2004-0415. All documents in the docket
are listed on the regulations.gov web site. Although listed in the
index, some information is not publicly available, i.e., CBI or other
information whose disclosure is restricted by statute. Certain other
material, such as copyrighted material, is not placed on the Internet
and will be publicly available only in hard copy form. Publicly
available docket materials are available either electronically through
www.regulations.gov or in hard copy at the Office of Pesticide Programs
(OPP) Regulatory Public Docket (7502P), Room S-4400, One Potomac Yard
(South Building), 2777 S. Crystal Drive, Arlington, VA 22202. This
Docket 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 (7506P), 1200 Pennsylvania Ave.,
NW., Washington, DC 20460, telephone: 703-305-6598 or 703-305-6475, e-
mail: [email protected] or [email protected].
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are a
producer or registrant of a biochemical or microbial pesticide product.
This action may also affect any person or company that might petition
the Agency for new tolerances for biochemical or microbial pesticides,
or hold a pesticide registration with existing tolerances, any person
or company interested in obtaining or retaining a tolerance in the
absence of a registration. Potentially affected entities may include,
but are not limited to:
Crop Production (NAICS code 111).
Animal Production (NAICS code 112).
Food Manufacturing and Processing (NAICS code 311).
Chemical Producers (NAICS code 32532), e.g., pesticide
manufacturers or formulators of pesticide products, importers, or any
person or company that seeks to register a pesticide or obtain a
tolerance for a pesticide.
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. To determine
whether you or your business may be affected by this action, you should
carefully examine the applicability provisions in Unit II. If you have
any questions regarding the applicability of this action to a
particular entity, consult the persons listed under FOR FURTHER
INFORMATION CONTACT or visit the following Web site: http://www.epa.gov/pesticides/biopesticides/.
B. How Can I Access Electronic Copies of this Document and Other
Related Information?
All documents in the docket are listed in the docket index at
http://www.regulations.gov under docket number EPA-HQ-OPP-2004-0415.
Although listed in the index, some information is not publicly
available, e.g., CBI or other information whose disclosure is
restricted by statute. Certain other material, such as copyrighted
material, is not placed on the Internet and will be publicly available
only in hard copy form. Publicly available docket materials are
available either in the electronic docket at http://www.regulations.gov, or, if only available in hard copy, at the Office
of Pesticide Programs (OPP) Regulatory Public Docket in Rm. S-4400, One
Potomac Yard (South Building), 2777 S. Crystal Drive, Arlington, VA.
The hours of operation of this docket facility are from 8:30 a.m. to
4:00 p.m., Monday through Friday, excluding legal holidays. The Docket
telephone number is 703-305-5805.
II. Overview of This Document
EPA published a notice of proposed rulemaking in the Federal
Register on March 8, 2006 (71 FR 12072) for Data Requirements for
Biochemical and Microbial Pesticides. This document is the final rule
and the response to comments on the proposed rule. EPA received
comments from 20 commenters, raising 58 comments on various data
requirement issues for biochemical and microbial pesticides. A total of
11 comments concerning the definition of a biochemical pesticide and 5
comments concerning the
[[Page 60989]]
definition of a microbial pesticide were received. Of the 20
commenters, 15 were from industry or private consulting firms, 4 were
from State/Federal/international governments, and 1 was from a public
interest group.
In response to comments, EPA is modifying some aspects of the rule
relating to types of products being tested, i.e., technical grade
active ingredient (TGAI) versus typical end-product (TEP), modifying
some test notes where appropriate, adding or deleting some data
requirements, and modifying the definition of a microbial pesticide.
The final rule updates 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 172.43. The rule also informs the public
how the Agency will assist applicants in determining what data are
appropriate to support registration of a biochemical or microbial
pesticide. EPA encourages applicants to request pre-submission meetings
to discuss these data issues. The final rule also provides for
assistance to applicants, in some narrow circumstances, in preparation
of an applicant's data waiver.
As an ancillary matter, this final rule is making certain technical
changes necessitated by EPA's decision to create new part 161 to
contain data requirements specific to antimicrobial pesticides. New
part 161 is discussed fully in the final rule for conventional
pesticides published elsewhere in this issue of the Federal Register.
By transferring essentially intact the current part 158 requirements,
EPA would also be transferring material pertaining to biochemical and
microbial pesticides that is not intended to be covered by part 161.
Specifically, EPA is removing Sec. Sec. 161.65, 161.690 and 161.740,
the freestanding sections devoted exclusively to biochemical and
microbial pesticides.
This final rule is one in a series of proposed and final rules to
update and clarify pesticide data requirements.
III. The Proposed Rule and Related Proposal for Conventional Chemicals
On March 8, 2006, the Agency published a notice of proposed
rulemaking for Biochemical and Microbial Pesticide Data Requirements
(71 FR 12072). The Agency received submissions from 20 commenters. This
final rule describes briefly the background of the final rule and
responds to key issues raised by commenters.
A. General Background on the Phased Rulemaking Approach
EPA is responsible for registration of the following categories of
pesticides: biochemicals, microbials, plant-incorporated protectants,
conventional pesticides, and antimicrobial pesticides. These
pesticides, although regulated under the same statutory standards under
FIFRA and FFDCA, pose different levels of risk and exposure that lead
to significant differences in data needs. EPA has embarked on a series
of rulemakings intended to update data requirements for the various
types of pesticides. This final rule is the second and builds on the
previous update for conventional chemicals.
Elsewhere in this issue of the Federal Register EPA published a
final rule to update and revise its data requirements for the
registration of conventional pesticides. In addition to specific
changes to the data requirements for registration of conventional
pesticides, EPA made a number of other changes to the general
provisions of part 158. Specifically, subpart A of the 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 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.
EPA proposed to also upgrade the structure of part 158, assigning
biochemical data requirements to subpart L and microbial pesticide data
requirements to subpart M of part 158. As a result of the comments on
the proposed rule for conventional pesticides, EPA has restructured
part 158. Biochemical pesticide data requirements will now be under
subpart U and microbial pesticide data requirements will be under
subpart V.
B. General Provisions and Format
As described in the final rule on Conventional Pesticides published
elsewhere in this issue of the Federal Register, EPA has reorganized
and reformatted part 158, subpart A (General Provisions) and subpart B
(How to Use Data Tables), and reorganized and redesignated subpart D
(Data Requirement Tables) into a number of individual subparts.
Many of the revisions 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.
C. Required and Conditionally Required Data Requirements
As with conventional pesticides, the R/CR terminology is a general
presentation of the likelihood that a data requirement will apply. The
use of R does not necessarily indicate that a study is always required,
but that it is more likely to be required than not. The use of CR means
a study is less likely to be required. However, both R and CR
designations must be read in the context of the accompanying test notes
to the table. An applicant may assume that a data requirement with R
will typically be required all the time. The test notes accompanying
that R designation may provide supplementary information or identify
some condition(s) when the study is not required. A CR designation will
generally include more extensive test notes describing the limited
conditionality of the requirement. The final rule continues this
longstanding practice. EPA revised some of the test notes to clarify
the conditions under which the data would be required.
IV. Regulation of Biochemical and Microbial Pesticides and Response to
Comments Discussion
A. Background of Regulating Biochemical and Microbial Pesticides
This document is the final rule for the Biochemical and Microbial
Pesticide Data Requirements. This document also finalizes definitions
of both a biochemical and microbial pesticide. The Agency issued a
Notice of Proposed Rulemaking on Biochemical and Microbial Pesticide
Data Requirements, 71 FR 12072; March 8, 2006. This notice was an
update of the biochemical and microbial pesticide data requirements to
support the registration of biochemical and microbial pesticides
originally promulgated in 1984.
B. Consultations with Applicants
In the preamble to the proposed rule, the Agency discussed a
process for consultations with applicants. The public responses were in
favor of the Agency recognizing that applicants often needed assistance
in determining what information or data are appropriate to support
registration of a biochemical or microbial pesticide.
[[Page 60990]]
Therefore, EPA will continue to encourage applicants to request pre-
submission meetings to discuss these data issues. EPA will also
continue to provide assistance to applicants in some narrow
circumstances in preparation of an applicant's data waiver after
submission of an application.
EPA encourages applicants to seek pre-submission meetings to
discuss the appropriate data or information to support their product
and the opportunity for requesting data waivers. During the 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 by the applicant in accordance with
relevant data compensation procedures. EPA may also be aware of sound
scientific rationales that render certain testing unnecessary.
Ultimately, the applicant may submit an application based on the
discussion with EPA, along with a signed copy of the minutes (which
have been concurred on by the Agency) of the pre-submission meeting
listing each data requirement and the reason why EPA and the company
believe a waiver is appropriate.
In addition, the Agency is offering a post-submission process. Even
after submission of an application for registration, EPA may find that
either of these scenarios may exist (i.e., basis for citing to other
data or 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.
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 this process is intended 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 request for waiver of a data requirement. The applicant
must at all times submit the waiver request; EPA is simply providing
assistance in identifying what requirements are likely to be waived for
a particular product or, in some narrow circumstances, assistance in
the preparation of the waiver request. Because we are using the pre-and
post-submission process to assist applicants in filing their own waiver
requests, we are not amending the existing waiver provisions at 40 CFR
158.45.
C. Agency Coordination with the APHIS Permitting Process
EPA requested comment on whether the Agency should coordinate with
USDA for reviewing microbial pesticides prior to registration. The
Agency was prompted by USDA's need for coordination when an Animal and
Plant Health Inspection Service (APHIS) movement permit under 7 CFR
part 340 is needed. USDA suggested that registrants be required to
submit a copy of the applicable APHIS permits as part of the
registration application to EPA. After discussing this issue with USDA,
EPA is developing a process for coordinating the review of these
applications with USDA to avoid delays.
D. Other Issues
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 those currently used by the Agency. The
second guideline numbers, which are in parentheses, are the draft
guidelines that have completed peer review and will be published as EPA
final guidelines in the near future. Guideline numbers are provided in
part 158 as information/guidance to applicants, and both guideline
numbers are provided for each data requirement in this rule as an
interim measure until the draft guidelines are finalized. In general,
draft guidelines do not represent official Agency position until
finalized. In either case, an applicant is not compelled to use the
cited guidelines, but may choose to use an alternative methodology that
will provide the information needed to complete the risk assessment. In
such cases, applicants are encouraged to consult with EPA beforehand.
Applicants may also consult with EPA about using an alternative
methodology in draft guideline that has completed peer review.
As with the existing guidelines, draft guidelines are developed
through a rigorous scientific process, including public comment and
extensive peer review by the Scientific Advisory Panel, and many have
been harmonized internationally. As such, they represent the Agency's
recommended approach to developing data that will generally be likely
to satisfy the Agency's data needs for risk assessment, and an
applicant choosing to use the Agency guidelines may have greater
confidence that the resulting data will adequately address our needs.
This may also be the case for the draft guidelines referenced in
parentheses in this rule. Once finalized, the Agency would correct the
guideline references as appropriate.
E. Issues Identified that Apply to Both Biochemical and Microbial
Pesticide Data Requirements.
The Agency did receive comments that applied to both biochemical
and microbial pesticide data requirements. These issues are discussed
as follows:
1. Endangered species assessments--summary of comments. Incidental
to its proposed data requirements for conventional pesticides, EPA
discussed the possibility of future data and information needs to
develop and/or refine risk assessments for endangered species. EPA did
not propose any data requirements specific to endangered species but
described its current level of information and data usage. EPA
requested comment on the value and utility of location and usage
information, and on additional types of research that might yield
greater refinement in risk assessments for endangered species. One
commenter questioned whether the Agency's endangered species discussion
in the preamble applies to biochemical and microbial pesticides only,
or for conventional pesticides as well. Two commenters indicated the
Agency should require toxicity data for surrogate species, and in
particular reptile and amphibian data.
Summary of response to comments. EPA appreciates the responses it
received from the commenter on this topic. As endangered species data
requirements were not proposed, EPA has not responded to the comment as
part of this final rule but will consider them in the context of its
ongoing risk assessments. If EPA finds that it needs
[[Page 60991]]
to amend part 158 to normalize endangered species data requirements,
the Agency will consider these comments in the development of a future
proposed rule. The Agency has in the past and will continue to rely on
the avian, fish, and invertebrate testing to indicate the potential
toxicity for other non-target species.
2. Product performance--summary of comments. Without proposing
changes to existing product performance data requirements (Sec.
158.640), the Agency augmented language for both biochemical and
microbial pesticide data requirements for product performance with the
regulatory text. One commenter indicated that the Agency requires data
for uses other than for public health pests. Another comment was that
EPA's language in the proposed preamble required clarification,
indicating some products are not as efficacious as conventional
pesticides. Another commenter indicated that the label should be
supported by the efficacy data provided to the Agency.
Summary of response to comments. The Agency agrees that product
performance data are required for all uses, but are only required to be
submitted for review at the time of registration to support public
health claims. These provisions, i.e. new Sec. Sec. 158.2070 and
158.2160 for biochemical and microbial pesticides, respectively, are
not replacing the data requirement tables in Sec. 158.640, but only
adding additional text for clarifying when submission of product
performance data are typically necessary for biochemical and microbial
pesticides. EPA is finalizing the language as proposed. EPA agrees with
the commenters that the data must be submitted to support the label
claims for registration of these public health pesticides.
EPA did not propose to change the existing data requirements and
neither the existing data table nor the proposed regulating text would
require the applicant to submit data comparing product efficacy. The
Agency agrees with the commenter that there should not have been a
distinction between biochemical and conventional pesticides in their
efficacy, but that the efficacy varies between all pesticides and their
products, and with respect to public health claims, the label should
reflect the efficacy of the product.
3. Addition of passerine species and appropriate nomenclature of
test species within nontarget ecological effects data requirements--
summary of comments. The Agency proposed to add another possible test
species for the avian acute oral toxicity study, the red-winged
blackbird, a passerine species. EPA also proposed to continue to
include the identification of other possible avian test species
(bobwhite quail and mallards), and for fish species (rainbow trout and
bluegill sunfish). One commenter requested that EPA revise the word
``songbird'' to read ``passerine.'' Another commenter indicated that
the Agency should require historical control data on the red-winged
blackbird for the past 5 years to develop a baseline for future testing
on the species.
Summary of response to comments. The Agency recommends that if the
registrant and the Agency deem it appropriate to test a passerine
species, the registrant meet with the Agency before initiating the
study to determine if the passerine species is appropriate based on the
current scientific methodology and use pattern of the proposed
registration. This test species may be required if the use pattern
would result in higher exposure to this order of avian species.
In addition, after reviewing the comments submitted, the Agency
decided to discontinue specific species designation for all non-target
organisms. The test notes in the final rule only indicate upland game,
waterfowl, or passerine species for avian concerns and coldwater and
warmwater fish for fish concerns.
In summary, passerine species data are still conditionally required
in the final rule for both biochemical and microbial pesticides. The
individual test notes indicate when these data would be appropriate.
With respect to developing test data over 5 years, EPA will consider
such protocol concerns when it revises its test guidelines. The Agency
is finalizing the proposed addition of the passerine species.
4. Reptile/amphibian testing--summary of comments. The Agency did
not propose to require separate reptile testing. One commenter
indicated that amphibian testing needed to be included in the data
requirements for evaluating effects to non-target ecological species.
Summary of response to comments. The Agency has in the past and
will continue to rely on avian, fish, and invertebrate testing to
indicate the potential toxicity for other non-target species.
Additional information will be required as needed.
5. New studies providing little or no practical value-- summary of
comments. EPA proposed to require a few newly codified studies, i.e.,
applicator/user exposure data to refine data requirements, i.e.,
mutagenicity data requirements. One commenter believed the Agency was
using a ``check box'' approach to requiring data rather than regulatory
need.
Summary of response to comments. The Agency reviewed the data
typically submitted or determined to be necessary to support
registration requests received over 7 years. EPA's proposed rule was
based on that review. In some cases, EPA proposed new data requirements
to codify existing practices and in other cases EPA proposed to amend
test notes, for example, to clarify existing data requirements. EPA's
analysis and proposed rule were based on decisions that the data and
the modifications to the tables were necessary. Without more specific
comment, EPA can not further respond to this comment.
6. Providing adequate guidance when data are required/use pattern
clarification--summary of comments. When EPA revised the proposed rule,
there was a concerted effort to provide informative test notes, which
would clarify when data are required. However, a commenter did not
provide specific data requirement issues but indicated the Agency was
not clear on the expanded use patterns. This commenter also indicated
that the waiver policy was unclear.
Summary of response to comments. As indicated earlier in this
preamble, the Agency provided a section on ``Consultation with
Applicants'' in the proposal which the commenter indicated was missing.
It is a description of the pre-submission and post-submission process
within the Agency encouraging the registrant to meet with the Agency as
early as possible in the process in order to minimize delays and avoid
unnecessary test costs. In most cases the numbers of use patterns were
actually combined for transparency, i.e., food use and non-food use.
The test notes provided for biochemical and microbial pesticides are
more detailed than in the current regulation.
7. There are no accepted protocols or guidelines for many data
requirements--summary of comments. One commenter indicated that the
Agency published data requirements without supporting published
guidelines. This commenter cited the environmental fate guidelines.
Summary of response to comments. The Agency proposed newly codified
data data requirements guidelines for applicator/user exposure data;
particle size, fiber length, and diameter distribution; product use
information; and companion animal safety. There were also some new
guideline numbers identified for environmental fate data
[[Page 60992]]
requirements. All of these data requirements have guidelines available.
At the time of the publication of the proposed rule, the environmental
fate guidelines were not finalized. The Agency did provide the existing
guideline numbers that denoted the test methods at that time. The
environmental fate guidelines (835 series) are anticipated to be
published this year. In the interim, we have provided the current
guideline numbers and the proposed guideline numbers in the data table.
Once the final guidelines are published, the Agency will amend the
Guideline references in the datea tables, as appropriate. As indicated
previously, the guideline references are provided in part 158 as
information/guidance to applicants. As with existing guidelines, an
applicant is not compelled to use the cited draft guidelines, but may
choose to use an alternative methodology that will provide the
information needed to complete the risk assessment. (See Unit IV.D.).
8. Codifying existing practice--summary of comments. EPA made
revisions, which included codified, newly codified, or new data
requirements. One commenter stated that the Agency was mistaken in its
distinction between ``new requirements'' and ``newly codified
requirements.'' The commenter provided the example that the
immunotoxicity study (guideline 885.3550), is a new requirement, as no
such data requirement previously existed, regardless of whether the
guideline was available.
Summary of response to comments. In developing this rule, the
Agency received the data typically submitted or determined to be
necessary to support registration requests received over the last 7
years. If the data had never been submitted to support registration,
then the data requirement would be considered new. However, if the data
had been submitted or required to support recent registrations, and
were not listed in the 1984 promulgated rule, then the Agency would
classify that data requirement as newly codified.
As for the specific example of immunotoxicity, these data are
currently required and are being submitted to support existing
registrations and is currently required in 40 CFR 158.690. EPA has been
requiring or applicants have been submitting immunotoxicity data based
on specific conditions, consistent with the 880.3550 guideline in more
recent years, so the Agency classified this as a newly codified data
requirement as a Tier II and Tier III data requirement.
9. Animal welfare concerns--summary of comments. The Agency
received comment on individual studies suggesting alternative
approaches to substitute for them. This comment was designed to
recommend reducing the number of animals used in studies.
Summary of response to comments. All new studies required under
today's rule for biochemical and microbial pesticides were all standard
guideline studies that are also part of the data requirements for
conventional pesticides. The EPA's Biopesticides and Pollution
Prevention Division (BPPD) uses, where possible, the same studies that
are used for conventional pesticides to allow for similar risk
assessment procedures; to support the validated, time-tried, methods;
to reduce the complexity of studies that testing laboratories must
provide; to avoid excessive expenses for the typically small businesses
that market these biopesticides; and to avoid instituting novel, non-
validated procedures for a relatively small group of pesticides. As
discussed in the preamble to the final rule for the data requirements
for the registration of conventional pesticide products, Unit XIII,
Discussion of Comments on Animal Welfare Concerns, the Agency is
committed to avoiding unnecessary animal testing, while taking into
consideration principles of sound science and the requirements of FIFRA
to protect humans and the environment. The complete Unit XIII response
to these comments also applies to microbial and biochemical pesticide
data requirements. BPPD will consider test methods that do not use
animals and is working with the rest of the Agency to move towards
these goals. In addition, BPPD will continue to be available for pre
and post submission meetings to allow an applicant to submit only those
data needed to support that particular product.
V. Biochemical Pesticide Data Requirements (new Subpart U)
A. Definition of Biochemical (Sec. 158.2000)
Summary of proposed definition. EPA proposed to revise the
definition of biochemical pesticide and received 11 comments on the
definition. EPA's proposed definition was as follows:
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 pesticide, 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).
As explained in the proposed rule, EPA proposed to clarify the
``naturally-occurring'' clause of the prior definition by adding a
criterion that the pesticide have a history of exposure demonstrating
minimal toxicity. EPA believes that if a pesticide is present in the
environment in sufficient quantities, there would be a good chance that
any innate toxicity would already have been recognized due to observed
effects on humans or representative non-target organisms. A pesticide
that meets this, as well as other specified criteria, is more
appropriate for the tiering data structure that EPA uses for
biochemicals than a pesticide that does not have such history of
exposure or a pesticide that has a history of exposure in which such
exposure has revealed toxicity concerns.
The tiering structure can be beneficial if data submitted to
satisfy the early tiers allow EPA to determine that the pesticide does
not cause unreasonable adverse effects on the environment. This
determination at the early tiered stage can reduce the total amount of
data generated to satisfy registration as compared to pesticides that
do not meet the biochemical definition.
If the pesticide is naturally occurring but otherwise does not
clearly meet the biochemical definition, EPA is not likely to use the
biochemical pesticides tiering structure for testing; instead, EPA
would likely apply the data requirements for conventional pesticides
for an adequate assessment of the risks from the proposed use of such a
pesticide. However, note that in some limited cases, EPA may assess a
pesticide under the biochemical pesticide tiering structure even though
the pesticide is not a biochemical pesticide. Specifically, EPA added
paragraph (c) to 40 CFR 158.2000 to allow some limited use of the
biochemical tiering structure for pesticides not clearly meeting the
biochemical definition but for which only minimal additional data would
be necessary. Please refer to the preamble of the proposed rule for
further explanation.
EPA also proposed that to meet the definition of ``biochemical''
the pesticide must have a non-toxic mode of action to the target pest.
EPA proposed this criterion to conform to the original intent for
defining biochemical, that the term describes a pesticide that is ``not
the result of target organism
[[Page 60993]]
toxification.'' As EPA explained in the proposed rule, 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. See the proposed preamble and regulatory text for
a more complete discussion of the proposed definition.
Summary of comments. Eleven commenters identified concerns for the
revised definition of a biochemical pesticide. In particular, the
commenters believed in most cases that the proposed definition was more
restrictive than the current definition. Of particular concern was the
addition of the criterion that a biochemical pesticide must have a non-
toxic mode of action. A suggestion was made that the definition be
reworded to include the phrase ``mitigating mode of action'' as in
``Has a non-toxic or mitigating mode of action to the target pest.''
The commenters suggested that this would allow inclusion of a physical
mode of action. Another commenter indicated that the new definition
would not allow pesticides that cause suffocation.
In addition, most of these commenters believed that the proposed
definition, which included the language ``Has a history of exposure ...
demonstrating minimal toxicity'' and ``Has a non-toxic mode of action
to the target pest(s),'' would also make the criteria for defining a
biochemical more restrictive, possibly disallowing insect pheromones,
juvenile growth hormones, and most plant and animal extracts to be
classified as biochemical pesticides. One commenter indicated that the
definition should include both natural occurrence and non-toxic mode of
action as part of the definition for low risk.
One commenter generally supported the new definition but suggested
that EPA also consider setting some limits to exposure since some
naturally-occurring substances may be much more toxic if their use
patterns result in high exposure levels. Another commenter expressed a
concern that saponins would not be considered as biochemical pesticides
under the proposed definition.
Summary of response to comments. EPA disagrees with the general
comment that the proposed definition is more restrictive than EPA's
operation under the prior definition. EPA reviewed all 180 biochemical
pesticide registrations since 1948 and determined that only two
pesticides currently evaluated as biochemicals would not fit the
definition of a biochemical pesticide as proposed. Though these two
have been evaluated as biochemical pesticides, the data required were
equivalent to what was required to support conventional pesticides.
Based on this survey of biochemical pesticides, the Agency expects that
there will be no significant differences in the scope of pesticides EPA
evaluated as biochemical pesticides prior to the effect of this rule
and the scope of those EPA evaluates as biochemical pesticides under
this new definition. This applies equally to the scope of insect
pheromones, juvenile growth hormones, and plant and animal extracts
evaluated under the prior definition and that would be evaluated under
the new definition.
The Agency would like to clarify that the provision that a
biochemical pesticide is a naturally-occurring substance as well as a
compound that is structurally-similar and functionally identical to a
naturally-occurring substance, also applies to pheromones. The
pheromone definition in today's rule has been modified to make this
explicit. In addition, the straight chain lepidopteran pheromone
definition will be slightly corrected to correspond with the
internationally-recognized definition as used in the tolerance
exemption at Sec. 180.1153. The word ``double'' is added to ``three
bonds'' to read as ``three double bonds''. The Agency is also replacing
``designated by'' with ``consisting of'' in order to make the
definition more transparent. The revised definition will read: `` A
straight chain lepidopteran pheromone is a lepidopteran pheromone
consisting of an unbranched aliphatic chain (between 9 and 18 carbons)
ending in an alcohol, aldehyde, or acetate functional group and
containing up to three double bonds in the aliphatic backbone.''
EPA does not believe that the recommended inclusion of a
``mitigating mode of action'' is needed. First, the Agency interprets
the phrase ``non-toxic mode of action'' to include such pest control
mechanisms as attraction, repellency (including irritants), growth
regulation/development changes, induction of systemic acquired
resistance, and physical modes of action such as desiccation, coatings,
or smothering, e.g., by naturally-occurring oils. The Agency recognizes
that physical modes of action, e.g. suffocation, may be lethal to the
target pest, but since they do not involve toxic chemical/poison-
induced effects in the context of this program, they are considered to
be a non-toxic mode of action. This is how EPA has interpreted ``unique
modes of action'' as used in the prior definition. EPA notes that the
Biochemical Classification Committee (consisting of EPA scientists) was
formed in 1995 and has been responsible for determining whether a
proposed pesticide is eligible to be evaluated as a biochemical
pesticide and has consistently applied this interpretation of the
existing definition. EPA proposed to include the phrase ``non-toxic
mode of action'' instead of the phrase ``unique modes of action''
because EPA believes the former and proposed phrase better/more
accurately describes our historical approach for defining ``biochemical
pesticides,'' and intended no change in the scope of the term
historically applied. In addition, to the fact that the proposed phrase
captures commenter's concern, commenters did not adequately define the
word ``mitigate'' as it would apply to pesticidal modes of action.
Thus, EPA believes using a reference to mitigating mode of action is
unnecessary and may only add confusion in implementation.
Finally, for practical reasons, EPA does not believe that setting a
limit based on the amount of existing exposure as compared to that
contemplated by the proposed use pattern is necessary as recommended by
the commenter. Implementation of this concept would be very difficult
since the classification of the product would depend on the uses
proposed with the initial application, which often change subsequent to
the risk assessment process. It would be impractical to have to
reclassify an active ingredient from a biochemical pesticide to a
chemical pesticide based on use patterns. In practice, EPA will
initially classify a pesticide as a biochemical pesticide, but will
apply additional data requirements, up to and including those for
conventional pesticides, to adequately assess the risk. In no case will
an initial determination of biochemical status preclude the Agency from
requiring data not specifically included in subpart U if necessary.
Another commenter stated the belief that saponins (naturally-
occurring glycosides within plants) should be considered biochemical
pesticides and that the new definition precludes such a finding. The
Agency believes not all saponins would necessarily be registered as
biochemical pesticides. Each one has to be evaluated carefully. This
illustrates the importance of having sufficient exposure of naturally
occurring chemicals to determine if any unreasonable toxicity is
observed. Some saponins are known to be poisonous to people if
swallowed, and some saponins can cause severe dermal irritation, and
others may not be absorbed at low levels in the diet. Many saponins are
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especially toxic to fish. Any changes in the application or scope of
the definition would be addressed through notice and comment
rulemaking.
B. Individual Biochemical Data Requirements
As noted in Unit II, 20 commenters responded to the proposal. The
following sections are responses to comments raised:
1. TEP and EP testing versus TGAI testing--summary of comments.
Many commenters raised concerns about the variability in test material
used for testing typical end-use product (TEP) or end-use product (EP)
or technical grade active ingredient (TGAI) and whether to require the
use of the same test material as that required for conventional
pesticide data requirements.
Summary of response to comments. The Agency compared the test
materials required for conventional pesticides and determined that
requiring the same testing material (i.e., TEP, EP, or TGAI) for
biochemical pesticides to be used is appropriate in some circumstances.
However, upon review EPA determined that there are instances where the
types of testing material should not be the same. This difference is
because there usually is no ``typical end-use product'' for biochemical
pesticides. Most biochemical pesticide EPs are difficult to replicate.
Therefore, TGAI is being required for many instances in which the
conventional pesticide regulations require TEP or EP. EPA has made
revisions where appropriate in the final rule.
2. Particle size, fiber length, and diameter distribution--summary
of comments. EPA proposed to add a new requirement for particle size,
fiber length and diameter distribution, due to spray drift concerns.
This new data requirement is consistent with conventional pesticides
data requirements with the exception of the test material to be used;
the Agency is requiring TGAI data for biochemical pesticides given the
difficulties of producing a replicated TEP or EP. One commenter
questioned the need for this data requirement.
Summary of response to comments. As indicated in the proposed
preamble, the data from these studies are needed to complete the
environmental fate assessment to estimate the potential pesticide drift
to non-target areas. The Agency should have included in the
justification that these data are also useful for determining the
potential for acute inhalation toxicity to human health and the
environment. The Agency is being consistent with its assessment, since
it reached the same conclusion in response to comments for conventional
pesticides.
Specifically, particle size is generally expressed as mean mass
aerodynamic diameter (MMAD), which is a practical way to account for
the different possible shapes such as fibers, clumps, etc. The particle
size distribution is used as a set of criteria to determine
respirability for purposes of establishing the need and/or the
acceptability of inhalation toxicity studies (acute and, if the main
route of exposure is inhalation, subchronic toxicity studies), and
again, these data can also be used for spray drift evaluation.
3. Immunotoxicity data requirements--summary of comment. EPA
proposed to move the immune response requirements from Tier I and Tier
II to Tier II and Tier III and added two test notes indicating when the
data are required. One commenter stated immunotoxicity tier II data are
difficult to interpret. Another commenter believed that this should be
identified as a ``new requirement'' rather than as ``codifying an
existing data requirement.''
Summary of response to comments. EPA is finalizing the amendments
as proposed. The name of this study has changed, but the
``immunotoxicity testing'' data requirement is identical to the
original ``immune response'' testing. To provide more guidance on when
the studies are actually required, the final rule includes two test
notes. As a result the data will be conditionally required as Tier II
and Tier III data requirements.
4. Companion animal safety data requirement--summary of comments.
The Agency proposed to add companion animal safety data requirements
based on past experiences indicating the data were needed for a risk
assessment. One commenter requested that the Agency define companion
animal species and surrogate species to be tested.
Summary of response to comments. The Agency did not define the
species to be tested in a test note since it relies on the Pesticide
Assessment Guidelines (870.7200) to identify various appropriate
species, which traditionally have been required to support flea and
tick treatments for pets (i.e., dogs and cats). EPA has not changed the
final rule as a result of the comments received, except we provided
more specific guidance on test substance, (i.e., TGAI instead of
choice).
5. Applicator/user exposure data requirements--summary of comments.
EPA proposed to add data requirements to address applicator/user
exposure. EPA proposed a series of data requirements within this
category to be tested on TGAI. EPA proposed to require background
information as part of the applicator/user exposure monitoring data
requirements. One commenter requested that EPA clarify its expectation
that applicator exposure data requirements are primarily intended to
generate data to support evaluation of insect repellents. One commenter
indicated these data were not needed for all use patterns.
Summary of response to comments. EPA has decided to not finalize
its proposal to require background information for the applicator/user
exposure monitoring test (guideline 875.1000) since the same data are
already required to be submitted under the various other data
requirements, i.e., dermal outdoor exposure, dermal indoor exposure,
etc. (guidelines 875.1100 through 875.1500). EPA has made no further
revisions to any other proposals on this series of data requirements.
The final rule conditionally requires the data to be submitted when
the use of the biochemical pesticide could result in exposure levels
that might exceed those historically encountered, and if so, other
additional information would be necessary (e.g., directions for use,
application rates, or other exposure information) to determine
potential risks.
Thus, in general, when the use of any biochemical pesticide can be
expected to exceed historical exposure to humans or the environment,
the Agency would require exposure information to assure minimal risk
associated with that use. Although it is true that insect repellents
are typically applied at levels that can be expected to exceed those
historically encountered, many other pesticide use patterns may also
result in exposure levels exceeding these historically encountered use
patterns. Again, these data requirements are not limited to insect
repellents.
6. Product use information data requirement--summary and Response
to comments. The Agency proposed to require product use information
(guideline 875.1700). EPA received comments that this information was
not necessary because this same basic use information is available as
part of the registration or experimental use permit application. EPA
agrees with the commenters and has removed this requirement from the
final rule.
7. Mutagenicity data requirements--summary of comments . EPA
proposed to provide more guidance for mutagenicity testing by
specifying what kinds of studies would be required at Tier I and Tier
II. This information was previously described in the 1982 published
Subdivision M guidelines that indicated that Tier I would be in
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vitro testing and Tier II would be in vivo testing. EPA proposed to add
two of the three in vitro studies to the table for mutagenicity Tier I
testing, and the two in vivo studies were added to the data table for
mutagenicity Tier II testing. Three comments were received. One
commenter mistakenly thought we had an in vivo study at Tier I but did
urge us to use non-animal methods at Tier I referencing an EPA tiered
testing proposal by Dearfield, et al. (Ref. 1). Another commenter
recommended that we include an in vitro chromosome aberration test at
Tier I to better address chromosomal endpoints. The third commenter was
concerned that an in vivo chromosomal aberration or clastogenicity
study was moved to Tier II and recommended an in vivo test be included
at Tier I.
Summary of response to comments. Although the commenters were not
totally accurate about the presence of in vivo chromosome studies being
at the Tier I level (they were not actually at Tier I in the original
nor the proposed guidelines, although the original table was not
definitive by itself), the Agency believes the recommendation of the
second commenter will address all these concerns. Therefore, the in
vitro mammalian chromosome aberration study, guideline 870.5375, will
be included in the Tier I Mutagenicity Testing battery of acceptable
tests to better address chromosomal endpoints. This will correspond
better to the mutagenicity testing description for the conventional
pesticide data requirements, and will provide a more complete Tier I
assessment.
8. Primary eye, dermal and skin sensitization data requirements--
summary of comments. The Agency proposed to require both TGAI and EP
testing, for EPs and TGAI and MP testing for MPs. The prior rule did
not require TGAI testing. One commenter did not understand why the
Agency expanded the data requirements to add the TGAI as the requisite
test material.
Summary of response to comments. The Agency indicated in the
preamble of the proposed rule that inert ingredients as well as active
ingredients could cause adverse effects not necessarily noted by TGAI
alone. Therefore, testing on both TGAI and EP or MP is necessary to
determine the safety of the pesticide for these endpoints. As a result,
EPA is finalizing both TGAI and EP or MP testing.
9. Limit testing--summary and response to comments. The Agency did
not propose any revisions on limit testing for avian acute toxicity
testing, but one commenter indicated support for the new methods in
reducing the number of test animals used for conducting the study. The
Agency minimizes testing as much as possible and often encourages the
use of maximum hazard testing using only the high dose level,
anticipating that no significant effects will be seen.
10. Sediment/soil adsorption/desorption data--summary of comments.
EPA proposed a revision in the sediment toxicity data requirement in
Tier I from ``not required'' to ``conditionally required'' for
greenhouse use. The Agency also revised the test note. One commenter
requested that the Agency clarify why these data would be required for
greenhouse use.
Summary of response to comments. The Agency indicated the data may
be conditionally required for greenhouse use to determine if the parent
compound remains bound while grown in greenhouse conditions and is
available for uptake in the plant. Likewise, it may need to be
determined how rapidly the parent degrades in the growing medium, into
what forms it may degrade, and whether the degradates are bound in the
growing medium or taken up by the plant.
VI. Microbial Pesticides Data Requirements (Subpart V)
A. Definition of Microbial Pesticide
1. Summary of proposal. The Agency proposed to revise the
definition of a microbial pesticide 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:
i. Is a eucaryotic microorganism including, but not limited to,
protozoa, algae, and fungi.
ii. Is a procaryotic microorganism, including, but not limited to
bacteria.
iii. Is an autonomous replicating microscopic element, including,
but not limited to, viruses.
EPA proposed this revision to 40 CFR 158.65 to better conform to
the description of the class of non-exempt biological control agents in
152.20(a)(3), and to use a structure for defining microbial pesticide
similar to that at 40 CFR 172.43. EPA explained that the proposed
revisions are not intended to change, and in EPA's view does not
change, the scope of the previous regulatory definitions and
descriptions of microbial pesticides at Sec. Sec. 158.65,
152.20(a)(3), or Sec. 172.43. EPA also proposed changes to Sec.
172.43 so that the definition would conform to the newly proposed
definition of microbial pesticide, but did not intend to change the
scope of that provision. These revisions are intended to include all
microorganisms as microbial pesticides based on the currently accepted
taxonomic nomenclature as of the date of publication of this rule.
EPA also proposed to refine the current regulatory text relating to
the need to separately register new species or isolates and to separate
that provision from the definition section to avoid confusion on the
definition of microbial pesticide.
In the preamble to the proposed rule, EPA noted that microorganisms
are known to produce many chemical pesticidal substances. These
pesticidal substances, when distributed or sold 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.
See Unit VIII.A. of the preamble to the proposed rule (71 FR 12072,
March 8, 2006) for a more complete discussion of the changes proposed
for the definition of microbial pesticide.
2. Summary of comments. The Agency received a total of five
comments on the proposed definition of a microbial pesticide. Some
commenters expressed concerns that the microbial pesticide definition
might not adequately describe all microbial pesticides. One recommended
including bacteriophages. Another commenter asked if nematodes (which
may have symbiotic microorganisms living in them) are covered by the
definition. Several commenters generally agreed with the provision in
EPA's prior definition that specifies that each new isolate of a
microorganism should be evaluated as a new strain. However, one of
these commenters was concerned that, particularly for baculoviruses,
there may be a few cases in which some microorganisms could be
evaluated at a family or genus level for some test data requirements
such as for human health toxicity/pathogenicity testing, even if each
microorganism is a different strain, while in other cases an isolate
might not ``always meet the definition for a strain.'' The commenter is
concerned that maintaining the provision from the prior definition
might require more testing than is necessary.
3. Summary of response to comments. To address the concerns about
the adequacy of the microbial pesticide definition, the Agency added
the
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procaryotic class Archaea as an example to the class Bacteria since
this is another division of procaryotes that is on the level of
bacteria, at least according to some taxonomic schemes. Although this
does not change the scope of the definition as implemented and proposed
by EPA, this will ensure that this part of the definition is much
clearer by explicitly including that entire group of microscopic living
organisms. EPA also considered including bacteriophages in the
``autonomous replicating'' class under the revised microbial
definition, which, as proposed, only included ``viruses'' as an
example. However, EPA decided that it would not be appropriate from a
taxonomic viewpoint. Bacteriophages are viruses that infect
prokaryotes. Including a subcategory of viruses, i.e. the
bacteriophages, as well as ``viruses'' would tend to confuse the
language in the regulation and adds nothing to the scope of the
definition. In addition, the original language in the preamble to the
proposed rule was not quite accurate in describing viruses, i.e. ``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.'' Because viruses
replicate utilizing some components of a host cell, the ``autonomous
replicating'' language would not accurately capture the relevant
biology or the viruses we have registered. Therefore, EPA is changing
the phrase ``autonomous replicating microscopic element'' to
``parasitically replicating microscopic element'' in part 3 of the
definition. Under this definition, genetic constructs inserted
intentionally into a microbial agent to provide pesticidal traits are
not included because they do not parasitically replicate; however, the
genetically altered microbial agent itself would be regulated as a
microbial pesticide. We also changed the language in the definition
from ``microorganism'' to ``microbial agent.'' This better agrees with
the language in 40 CFR 152.20(a) which exempts ``Certain biological
control agents'' from regulation under FIFRA.
In response to the comment concerning nematodes, EPA will offer
some general guidance on nematodes here. Nematodes have been identified
as a macroscopic biocontrol organism that is exempt from regulation in
accordance with Sec. 152.20(a) on the basis that another Federal
regulatory agency is adequately regulating them. However, EPA is aware
that the insecticidal activity of some commercially marketed nematodes
is due to insecticidal microorganisms that live in a symbiotic
relationship inside the nematode gut, (e.g., Xenorhabdus spp. and
Photorhabdus spp., entomopathogenic bacteria associated with nematodes
of the families Steinernematidae and Heterorhabditidae). In response to
previous inquiries from researchers working with these biocontrol
organisms, EPA determined that these symbiotic bacteria are considered
a part of the mode of action of the exempt nematodes and are therefore
covered by the exemption in Sec. 152.20. Many exempt biocontrol
organisms have naturally-occurring microbial flora living within them.
However, if these bacteria were isolated, grown separately, and
reinoculated into the nematodes as a delivery system, EPA has
determined that the exemption does not apply and, thus, a registration
would be required (USEPA, 1990)(Ref. 2). Likewise, genetic engineering
of the symbiotic insecticidal microorganisms would also require them to
be regulated as microbial pesticides.
EPA carefully considered the comment raising the issue of whether
an isolate occasionally could be evaluated to satisfy a subset of data
requirements at a higher taxonomic level than strain level and whether
an isolate might sometimes be included as part of a very similar
strain. EPA believes the proposed microbial pesticide definition
applicability provision is sufficiently flexible to ensure adequate
consideration and data on new isolates, while allowing use of existing
data to support registration if similar to an existing strain that is
already registered. The wording of the provision relating to
applicability of the microbial data requirements 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 wording
does not preclude the possibility of using data from another isolate to
support the assessment if it can be shown that the two isolates are
sufficiently closely related. In this way it ensures that each isolate
will be independently considered for registration purposes. The
differences in taxonomy between different microorganism
classifications, particularly for baculoviruses, would make any attempt
to further clarify this provision very complex and potentially
confusing as the systematic nomenclature of these organisms change over
time. The Agency intends to use its best scientific judgment in each
instance to determine if one isolate is sufficiently closely related to
another isolate to allow sharing of data or waiving of data
requirements.
B. Amendment of Parts 172 and 152
The definition of a microbial pesticide has been revised as
follows:
(1) ``Microbial agent'' replaces ``microorganism;''
(2) ``Eubacteria and Archaebacteria'' replaces bacteria; and
lastly,
(3) ``parasitically'' replaces ``autonomous''.
These revisions were incorporated and were also replaced in other
sections of 40 CFR. To better coordinate the regulations, EPA proposed
to replace the definition for a microbial pesticide at 40 CFR 172.43
with an updated definition. In addition, the Agency has also identified
Sec. 152.403 as another location in 40 CFR where the definition of a
microbial pesticide is cross-referenced. Accordingly, this provision
also needs to be corrected to reference the new Sec. 158.2000 and
Sec. 158.2100. EPA has also proposed to delete Sec. 158.65 in the
proposed rule for conventional pesticides. EPA received no comments on
this change to parts 152 and 172.
C. Individual Issues Submitted on Microbial Pesticides Data
Requirements
A number of issues were identified that were focused on the
guidelines, i.e., number of applications, maximum dosing of pesticides
during testing, etc. These issues are outside the scope of this rule
and EPA will consider them in the context of guideline development.
The following issues were identified for specific data requirements
for microbial pesticides. The Agency responds to these comments in this
preamble. When appropriate, the Agency has revised the regulatory text.
1. EP versus TGAI testing for data requirements--summary of
comments. EPA proposed to require testing on TGAI for various data
requirements instead of MP, or TEP or vice versa.
Summary of response to comments. One commenter indicated that the
EP should be tested instead of the TGAI for physical and chemical
properties data requirements. The Agency agrees with the commenter and
understands that for meeting the chemical and physical properties data
requirements, some product analyses should be done on the product
proposed for registration, either an MP or EP. However, some product
analyses should be done with TGAI. EPA proposed no change to the test
substance currently being required. Rather, EPA simply broke out the
various tests that make up the body of the product analyses data.
Therefore, the data being required are on TGAI or
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EP just as often as before, but with the revised table, it is more
clear when TGAI or TGAI and MP/EP data are required for each specific
test is listed (odor, color, etc.).
2. Analytical methods data requirement--summary of comments. EPA
proposed to move the data requirement for analytical methods from the
Product Analysis Data Table to the Residue Data Table. One commenter
indicated that the analytical method should be required as a chemical
and physical properties data requirement.
Summary of response to comments. The Agency is continuing to
require these data but believes it more appropriate to require the data
as a residue chemistry data requirement where it primarily would be
needed if the microorganism could produce residues of concern, such as
toxins. For general analysis of less problematic microorganisms, the
new requirement for deposition of a sample to a culture collection
where it would be available for use with standard microbial analytical
comparison methods is sufficient to allow post registration analysis.
This is to ensure that the product being registered is what was tested
and evaluated.
3. Quality assurance/quality control issue--summary of comments.
EPA did not propose a revision in the manufacturing process data
requirement. One commenter indicated that a detailed description of
quality assurance/quality control (QA/QC) program as part of the
manufacturing/production process should be clearly specified as a data
requirement.
Summary of response to comments. The Agency agrees with the
commenter that the QA/QC program is especially critical for microbial
agents. The existing regulations address these concerns by requiring
confirmation that QA/QC is an essential part of the manufacturing
process description as well as the discussion on formation of
unintentional products and impurities.
4. Acute injection toxicity/pathogenicity data requirement--summary
of comments. EPA proposed to eliminate the intracerebral administration
and rely on the intravenous or intraperitoneal administration for the
acute injection toxicity/pathogenicity study. One commenter agreed that
elimination of the intracerebral injection assay was reasonable, but
indicated it was unclear why the data were not required to support
registration of viruses. Another commenter indicated that the
pathogenicity/toxicity study via the intravenous (i.v.) or subcutaneous
(s.c.) route should not be required for viruses.
Summary of response to comments. The requirement for the
intracerebral injection assay is eliminated since it is difficult to
accomplish and has questionable utility for detecting effects given the
high likelihood of adverse effects from the method itself.
The Agency is not requiring pathogenicity/toxicity data for viral
agents based on the difficulty of establishing the clearance endpoint
for viruses. In these tests, the individual organ macerates must be
tested for infectivity by a bioassay in the target pest. The Agency
finds that the results from the cell culture assays are more sensitive
and present a greater potential for the virus to express infectivity
and cytopathic effects. The final rule is the same as the proposed rule
for this data requirement.
5. Hypersensitivity incidents data requirement--summary of
comments. EPA proposed to revise the hypersensitive incident data
requirement from ``conditionally required'' (CR) to ``required'' (R) to
better describe the occurrence and when it is actually required. One
commenter requested more guidance on when to report hypersensitivity
incidents to the Agency, and indicated that the elimination of the
sensitization study could not be supported.
Summary of response to comments. For clarification, EPA did not
require a ``sensitization'' study for microbial pesticides in either
the original or the proposed rule. The original rule required a
hypersensitivity study and reporting of hypersensitivity incidents. The
proposed rule proposed to remove the requirement for hypersensitivity
studies but continue the requirement for reporting of data for
hypersensitivity incidents. The reference was changed from CR to R for
the hypersensitivity reporting to better indicate that the data are
required with no exceptions for all use patterns, if any
hypersensitivity incidents occur. The Agency expects that many
microbial pesticides may be respiratory sensitizers, although there are
no consistently reliable laboratory tests available for this endpoint.
Therefore, in general, the Agency requires protective equipment to
lessen exposure to microbial agents for applicators with a high
likelihood of repeated exposure. The requirement for reporting of human
hypersensitivity incidents is to track microorganisms that may require
more protective measures than those generally followed. The Agency
agrees with the comment that more guidance on when to report would be
helpful and is adding to the footnote the following language from the
``when required'' section of the 1982 Subdivision M Guideline 152.37
referenced in the original data requirements for Hypersensitivity
Incidents and as slightly revised in the 1989 Guidelines (152A-15):
``3. Hypersensitivity incidents, including immediate-type and delayed-
type reactions, of humans or domestic animals that occur during the
testing or production of the TGAI, MP, or EP, or are otherwise known to
the applicant, must be reported if they occur.'' Additional guidance is
provided by 40 CFR 152.50(f)(3), which specifies that an applicant must
include in a registration application any factual information of which
he is aware regarding unreasonable adverse effects of the pesticide on
humans or the environment.
6. Mutagenicity data requirements--summary of comments. EPA
proposed to no longer require mutagenicity data on the whole
microorganism. One commenter disagreed with the Agency, and indicated
that mutagenicity data should be required on the whole organism. The
commenter indicated that, especially for a new microorganism, basic
genotoxicity studies (in vitro) might indicate the presence of
metabolites/toxins with mutagenic properties that otherwise would not
have been detected. Thus, basic studies should be kept on the list, at
least as conditionally required. This same commenter indicated a
concern for immunocompromised people and the possible production of
antibiotic substances or the spread of antibiotic resistance to human
or animal pathogens that could occur.
Summary of response to comments. The Agency's experience with
standard mutagenicity testing shows that it is not appropriate for
whole microorganisms or often even for slurries. These mixtures often
interfere with the results from the tests. If toxins that may be
mutagenic are identified as part of the Tier I testing and/or are known
to be present in taxonomically related microorganisms, they can be
tested as part of the acute testing requirements at Tier II. The
Agency's approach is to require testing that identifies whether known
problematic toxins are present in that isolate. The significant part of
a microbial assessment comes from the taxonomic description of the
organism that is used to search the literature to identify any
problematic toxins that warrant individual assessment.
EPA evaluates potential effects on immunocompromised people as part
of the assessment process of a microbial pesticide, considering its
relationship to known human pathogens, the test data, and the potential
exposure from its use.
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EPA agrees most naturally-occurring microorganisms have evolved some
sort of antibiotic mechanisms to help them survive in the presence of
other microorganisms. However, rarely would significant levels of an
antibiotic be produced from uses of microbial pesticides that might
produce a disease problem. If a microorganism that could produce
significant levels of a clinically important antibiotic was proposed
for a pesticidal use that might affect medicinal uses of that
antibiotic, it would be handled on a case-by-case basis by
knowledgeable EPA scientists. After careful consideration, the
mutagenicity data requirements remain the same in the final rule as in
the proposed rule.
7. Infectivity/pathogenicity data requirement--summary of comments.
EPA proposed to conditionally require infectivity/pathogencity data as
a Tier III data requirement. One commenter was opposed to the new data
requirement for infectivity/pathogenicity.
Summary of response to comments. The Agency understands the
concerns of conditionally requiring higher tiers of mammalian testing.
EPA believes, however, that there may be instances in which a microbial
pesticide is intended for control of a mammalian pest, and such tests
may be needed to assure the safety for non-target mammalian species.
This same commenter also strongly opposed the use of primates for this
testing and oncogencity/carcinogenicity testing. The Agency doubts a
registrant would go to the extremes of performing a primate study to
try to support registration of a mammalian pathogen. The data
requirements in the final rule remain the same as in the proposed rule.
8. TEP testing for non-target ecological effects. EPA proposed some
revisions to provide the option for testing either the TEP or TGAI for
non-target ecological effects. One commenter recommended TEP or EP
testing for all products with potential aquatic or terrestrial non-
target exposure.
Summary of response to comments: The Agency agrees with the
commenter that EP testing should be required when significant non-
target exposure is to be expected. Therefore, the Agency has added a
new test note to require EP or TEP testing when the EP may contain
other ingredients that may be toxic to non-target organisms. The Agency
has added TEP to freshwater fish/pathogenicity and invertebrate/
pathogenicity testing data requirements.
9. Honeybee toxicity testing--summary of comments. The Agency
proposed one test note revision to the honeybee toxicity study for
indoor use and Experimental Use Permits (EUPs). One commenter indicated
the data requirement refers mainly to oral effects, and that the Agency
should consider dermal/topical effects as well, suggesting it would
improve harmonization with other data requirements, if the dermal/
topical acute toxicity test was also included as an option.
Summary of response to comments. The data table does not specify
the route of exposure for the honeybee toxicity testing. The route of
exposure for this test is addressed in its OPPTS Microbial Pesticide
Harmonized Test Guideline, 885.4380, which is available on the EPA's
web site at http://www.epa.gov/opptsfrs/home/guidelin.htm and which is
referenced in the data table. This guideline recommends using an oral
dose if the microbial pesticide is expected to act by a dietary route
of exposure or consists of particles of such a size that they might be
carried back to the hive like pollen. However, we recognize that most
honeybee oral dosing methods would likely also result in some dermal
exposure. Furthermore, the guideline does not rule out using a
conventional dermal/topical exposure as an option if the mode of action
of the microbial pesticide indicates that it would be more appropriate.
10. Environmental expression data requirements--summary of comments
. EPA did not propose to change when the Tier II environmental fate,
i.e. expression, testing would be triggered by Tier I acute toxicity
testing. However, one commenter indicated that the data requirements on
environmental expression are very limited. The commenter recommended,
to improve harmonization with the European Union (EU), that EPA should
add substantial guidance to the test notes 9, 10, and 11 (or references
to relevant literature) on what environmental fate data should be
collected, presented, and submitted, in case a Tier II evaluation is
required.
Response to comments: The guidance that the commenter recommends be
added to the regulatory text is found in our guidelines, specifically
guidelines 885.5200, 885.5300, and 85.5400, which are referenced in the
data tables. Historically, EPA has provided detailed guidance on a
case-by-case basis. The EU and the US have agreed to use the same
microbial pesticide testing guidelines, so these would be the best
place to address this concern. The EPA will continue to address EU
harmonization through the OECD Biopesticides Steering Group.
11. Reduction in number of test animals used for testing--summary
of comments. EPA did not propose any revisions to the test guidelines
within this proposed rule. Two commenters supported the development of
new methods to reduce the number of animals used for pesticide testing
while maintaining the diversity of test species.
Summary of response to comments. The revision of the guidelines is
a separate activity. The OPPTS Microbial Test Guidelines already
recommends a single high dose for the initial test using a minimal
number of test animals and provides for enough replicates with
sufficient statistical power. Specifically, high dose tests (basically
high dose screening tests using a low number of test animals and
replicates) by their very nature provide sufficient statistical power
to avoid type II (beta) errors.
12. Non-target organisms and environmental fate testing. Both the
original and the proposed testing for non-target effects and
environmental fate are organized into tiers, with the effects testing
at the Tier I level and the environmental exposure testing at the Tier
II level. One commenter requested the Agency conduct the fate and
exposure studies at Tier I and put the non-target studies using living
test organisms at Tier II and higher. The commenter suggested limiting
Tier I data requirements to strictly non-vertebrate studies, e.g.,
environmental expression studies, and substituting some in vitro
studies such as a fish egg and a protozoan toxicity study for in vivo
fish studies.
Summary of response to comments. The Agency does not believe this
suggestion would allow an adequate assessment to be done. The basis for
the microbial pesticide ecological risk assessment is to first
determine if there are any significant adverse effects with a maximum
hazard approach. The maximum hazard approach to testing uses one dosing
group of animals (mice, rats, birds, etc) tested at a very high dosage
of the test substance on the presumption that no adverse effects will
be seen. If no significant adverse effects are seen at the maximum
dosage, exposure data are not required. The Agency minimizes testing as
much as possible and often encourages the use of maximum hazard testing
when no significant effects are expected to be seen at that level. This
is especially pertinent to microbial pesticides which rarely show any
significant effects in the high dose and it has dramatically reduced
the number of test animals used and also reduced the cost of the
testing.
Definitive environmental expression studies are very difficult to
perform for naturally-occurring microorganisms that can increase in
numbers in the
[[Page 60999]]
environment under varying conditions, in contrast to chemical
pesticides for which environment fate studies are designed to determine
only how fast they degrade and/or are transported. An environmental
expression study on a microorganism rarely, if ever, would be
sufficiently conclusive to allow bypassing the easier-to-perform in
vivo effects studies. However, a careful preregistration analysis of
the proposed uses and known environmental characteristics of the
specific microorganism usually allows for some data waivers of the Tier
I studies to be granted. The proposal for substituting the two in vitro
studies to replace a study on fish is worth further study as an
alternative to the standard fish study, but it is not clear at this
time if it would accurately detect the potential for microbial
infectivity and pathogenicity.
13. Addition of other test species--summary of comments. One
commenter suggested adding testing of freshwater algae, terrestrial
micro-organisms, and the active micro-organisms in sewage treatment
plants, as these may be exposed as well to general use, biochemical, or
microbial pesticides.
Summary of response to comments. Current knowledge indicates that
the inherent variability in physical and biological environments, the
adaptability of microbes, and redundant degradation pathways in
microbial and mesofaunal communities, leads to no significant or
lasting impact on ecosystems from introduction of pesticidal microbes
even where changes to these populations can be meaningfully tracked.
(Refs. 3 and 4). Moreover, microbial ecosystems are highly variable.
Any transitory, limited, effects from the introduction of a typical
microbial pesticide into the environment would be very difficult to
detect and analyze. The active microorganisms in sewage treatment
plants are also part of a complex specialized microbial community that
is very competitive and is also very unlikely to be influenced by any
one given microbial pesticide.
VII. Experimental Use Permits
In promulgating its final rule on conventional pesticides, EPA
segregated the Experimental Use Permit (EUP) data requirements into a
separate subpart C. This was done in response to comments suggesting
this change for clarity and to avoid confusion about the purpose of the
brackets. For consistency and ease of use, EPA has adopted this new
format for biochemical and microbial pesticides. Accordingly, the
brackets have been removed from the product chemistry, residue,
toxicology, non-target organism, and environmental fate data tables.
The new data requirements for experimental use permits are listed
in Sec. 158.2080 for biochemical pesticides and Sec. 158.2170 for
microbial pesticides.
VIII. Implementation
After the effective date, the data requirements in this final rule
will apply to all new registrations of biochemical pesticides and
microbial pesticides. The Agency does not intend to apply these
requirements retroactively to all existing pesticide registrations but
the Agency may find it necessary to call in some data on certain
existing registrations, as warranted by emerging risks of concern on
particular pesticides or as a result of possible programmatic changes
and priorities on existing pesticides.
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. Although the data requirements in part 158 are imposed
primarily as a part of initial registration, EPA is authorized under
FIFRA sec. 3(c)(2)(B) to require a registrant to develop and submit
additional data to maintain a registration. This post-registration data
call-in authority recognizes that the scientific underpinnings of risk
assessment change, and is another means by which EPA may keep data for
use in risk assessment current with evolving science.
EPA will consider as part of its review of a pending application
whether and how to apply these updated data requirements. EPA expects
that few changes will be needed, as these updated requirements reflect
current practice.
IX. References
The following is a listing of the documents that are specifically
referenced in this final rule. These documents and other supporting
materials are included in the docket established for this rulemaking
under docket ID No. EPA-HQ-OPP-2004-0415 at http://www.regulations.gov.
1. Dearfield, K.L., Cimino, M.C., McCarroll, N.E., et al.
``Genotoxicity risk assessment: a proposed classification strategy.''
Mutation Research 521, 121-135 (2002).
2. December 3, 1990 EPA memo: Schneider to Hutton.
3. Gagliardi, J.V., Buyer, J.S. Angle, J.S. and Russek-Cohen, E.
2001a. Structural and functional analysis of whole-soil microbial
communities for risk and efficacy testing following microbial
inoculation of wheat roots in diverse soils. Soil Biol. Biochem. 33:25-
40.
4. Gagliardi J.V., Angle J.S., Germida J.J., Wyndham R.C., Chanway
C.P., Watson R.J., Greer C.W., McIntyre T, Yu H.H., Levin M.A., Russek-
Cohen E, Rosolen S, Nairn J, Seib A, Martin-Heller T, Wisse G. 2001b.
Intact soil-core microcosms compared with multi-site field releases for
prerelease testing of microbes in diverse soils and climates. Can J
Microbiol. 47(3):237-52.
5. U.S. EPA, 2006. ``Economic Analysis of the Final Data
Requirements For Biochemical And Microbial Pesticides Rule.'' FEAD/OPP/
U.S. EPA, Washington, D.C.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
X. FIFRA Review Requirements
In accordance with FIFRA sec. 25(a), the Agency submitted a draft
of this final rule to the FIFRA Scientific Advisory Panel (SAP), the
Secretary of Agriculture, and 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 final rule because the
significant scientific issues involved have already been reviewed by
the SAP and additional review is unnecessary.
[[Page 61000]]
XI. Statutory and Executive Order Review
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 action is a significant
regulatory action because it might raise novel legal or policy issues
arising out of legal mandates, the President's priorities, or the
principles set forth in the Executive Order. Accordingly, EPA submitted
this action to OMB for review under Executive Order 12866 and any
changes made in response to OMB recommendations have been documented in
the docket for this action as required by sec. 6(a)(3)(E) of the
Executive Order.
In addition, EPA has prepared an analysis of the potential costs
and benefits associated with this action, entitled Economic Analysis of
the Final Data Requirements For Biochemical And Microbial Pesticides
Rule (Economic Analysis). (Ref. 4). A copy of this analysis is
available in the docket for this rule and is briefly summarized here.
For the proposed rule, EPA estimated that the total annual impact
to the pesticide industry is a regulatory compliance cost reduction of
$3.04 million per year, with an estimated average cost reduction of
$60,000 per firm, per year. During the public comment period for the
proposed rule, no comments were received on the economic analysis. The
majority of the comments on the proposed rule focused on definitional
issues; none of the clarifications made in this final rule affect the
Agency's estimate on the total annual impact to the pesticide industry.
Accordingly, no substantive changes have been made to the Economic
Analysis for this rulemaking.
As such, the likely impact of this final rule on businesses overall
is expected to be mostly beneficial. EPA believes that the final rule
would have no effect on the availability of pesticides to users. On
balance, the Agency believes that cost savings resulting from the final
changes to the data requirements presented in this final rule can be
realized without compromising the protection of human health and the
environment.
B. Paperwork Reduction Act (PRA)
This final rule does not contain any new information collection
requirements that require additional approval by OMB under the
Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq. Under the PRA, an
agency may not conduct or sponsor, and a person is not required to
respond to a collection of information unless it displays a currently
valid OMB control number, or is otherwise required to submit the
specific information by a statute. The OMB control numbers for EPA's
regulations codified in Title 40 of the CFR, after appearing in the
preamble of the final rule, are further displayed either by publication
in the Federal Register or by other appropriate means, such as on the
related collection instrument or form, if applicable. The display of
OMB control numbers in certain EPA regulations is consolidated in a
list at 40 CFR 9.1.
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 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.
The information collection requirements (i.e., the paperwork
collection activities) related to the submission of data necessary to
register a pesticide product are already approved by OMB under several
existing information collection requests (ICR). Specifically, the
activities that would generate a paperwork burden under this rule 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. 5).
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. 6).
The activities associated with the generation of data for
reregistration are currently approved under OMB Control No. 2070-0107
(EPA ICR No. 1504) (Ref. 7).
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. 8).
The activities associated with notification of genetically
modified microbial pesticides are currently approved under OMB Control
No. 2070-0142 (EPA ICR No. 1693) (Ref. 9).
These existing ICRs cover the paperwork activities contained in
this rule 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.
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.
C. Regulatory Flexibility Act
Pursuant to section 605(b) of the Regulatory Flexibility Act (RFA),
5 U.S.C. 601 et seq., the Agency hereby certifies that this rule 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
IX.A. above, and a copy of which is available in the docket for this
rulemaking. The following is a brief summary of the factual basis for
this certification.
Under the RFA, small entities include small businesses, small not-
for-profit organizations, and small governmental jurisdictions. For
purposes of assessing the impacts of today's 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
pesticide registration data as part of the Economic Analysis prepared
for this rulemaking, EPA has determined that this rule is not expected
to impact any small not-for-profit organizations or small governmental
jurisdictions. The
[[Page 61001]]
historical data indicates that these types of entities do not engage in
the activities covered by this rulemaking. As such, the small entity
impacts analysis evaluates 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 rule
on these small businesses. 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 realize a reduction in costs based on the
rule changes compared to the current part 158 data requirements. Given
these estimated impacts on small businesses, EPA concluded that the
revisions in this rule may benefit and would not likely have a
significant adverse economic impact on a substantial number of small
entities.
D. Unfunded Mandates Reform Act (UMRA)
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
XI.A., 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
pesticide applicants or registrants, the final 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 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 in which a State is a registrant are
extremely rare, this final rule may seldom affect a State government.
Thus, Executive Order 13132 does not apply to this rule.
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 final 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 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 rule.
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 final rule because this action is not
designated as an ``economically significant'' regulatory action as
defined by Executive Order 12866 (see Unit XI.A.). Further, this rule
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 requirements in this rule are intended to address risks that, if
not addressed, could have a disproportionate negative impact on
children. EPA will use the data and information obtained by this 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
designated as an ``economically significant'' regulatory action under
Executive Order 12866 (see Unit XI.A.), nor is it likely to have any
significant adverse effect on the supply, distribution, or use of
energy.
I. National Technology Transfer and Advancement Act (NTTAA)
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 a biochemical or microbial pesticide registration but does not
propose to require specific methods or standards to generate those
data. Therefore, this regulation does not impose any technical
standards that would require Agency consideration of voluntary
consensus standards. EPA is not precluding the use of any method,
whether it constitutes a voluntary consensus standard or not, as long
as it meets the performance criteria specified. The Agency invited
comment on its conclusion regarding the applicability of voluntary
consensus standards to this rulemaking effort and did not receive any
comments on this point.
J. Environmental Justice
This 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 is not required
to and has not considered environmental justice-related issues.
Although not directly impacting environmental justice-related concerns,
the Agency believes that the requirements in this rule will assist EPA
and others in assessing potential risks associated with exposures to
biochemical and microbial pesticides.
XII. Congressional Review Act (CRA)
The Congressional Review Act, 5 U.S.C. 801 et seq., generally
provides that before a rule may take effect, the Agency promulgating
the rule must
[[Page 61002]]
submit a rule report, which includes a copy of the rule, to each house
of Congress and the Comptroller General of the United States. EPA will
submit a report containing this rule and other required information to
the U.S. Senate, the U.S. House of Representatives, and the Comptroller
General of the United States prior to publication of the rule in the
Federal Register. This rule is not a major rule as defined by 5 U.S.C.
804(2).
List of Subjects in 40 CFR Part 158
Administrative practice and procedure, Agricultural commodities,
Pesticides and pests, Reporting and recordkeeping requirements.
Dated: October 10, 2007.
Stephen L. Johnson,
Administrator.
0
Therefore, Title 40, chapter I, part 158 is amended as follows:
0
1. The authority citation for part 158 continues to read as follows:
Authority: 7 U.S.C. 136-136y; 21 U.S.C. 346a.
0
2. By adding subparts U and V to part 158 to read as follows:
Subpart U--Biochemical Pesticides
Sec.
158.2000 Biochemical pesticides definition and applicability.
158.2010 Biochemical pesticides data requirements.
158.2030 Biochemical pesticides product chemistry data requirements
table.
158.2040 Biochemical pesticides residue data requirements table.
158.2050 Biochemical pesticides human health assessment data
requirements table.
158.2060 Biochemical pesticides nontarget organisms and
environmental fate data requirements table.
158.2070 Biochemical pesticides product performance data
requirements.
158.2080 Experimental use permit data requirements - biochemical
pesticides.
158.2081 Experimental use permit biochemical pesticides product
chemistry data requirements table.
158.2082 Experimental use permit biochemical pesticides residue data
requirements table.
158.2083 Experimental use permit biochemical pesticides human health
assessment data requirements table.
158.2084 Experimental use permit biochemical pesticides nontarget
organisms and environmental fate data requirements table.
Subpart V-- Microbial Pesticides
Sec.
158.2100 Microbial pesticides definition and applicability.
158.2110 Microbial pesticides data requirements.
158.2120 Microbial pesticides product analysis data requirements
table.
158.2130 Microbial pesticides residue data requirements table.
158.2140 Microbial pesticides toxicology data requirements table.
158.2150 Microbial pesticides nontarget organisms and environmental
fate data requirements table.
158.2160 Microbial pesticides product performance data requirements.
158.2170 Experimental use permit data requirements-microbial
pesticides.
158.2171 Experimental use permit microbial pesticides product
analysis data requirements table.
158.2172 Experimental use permit microbial pesticides residue data
requirements table.
158.2173 Experimental use permit microbial pesticides toxicology
data requirements table.
158.2174 Experimental use permit microbial pesticides nontarget
organisms and environmental fate data requirements table.
Subpart U--Biochemical Pesticides
Sec. 158.2000 Biochemical pesticides definition and applicability.
This subpart applies to all biochemical pesticides as defined in
paragraphs (a), (b), and (c) of this section.
(a) Definitions. The following terms are defined for the purposes
of subpart U of this part.
(1) A biochemical pesticide is a pesticide that:
(i) Is a naturally-occurring substance or structurally-similar and
functionally identical to a naturally-occurring substance;
(ii) 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
(iii) Has a non-toxic mode of action to the target pest(s).
(2) A Pheromone is a compound produced by a living organism or is a
synthetically derived substance that is structurally similar and
functionally identical to a naturally-occurring pheromone, which, alone
or in combination with other such compounds, modifies the behavior of
other individuals of the same species.
(i) An Arthropod Pheromone is a pheromone produced by a member of
the taxonomic phylum Arthropoda.
(ii) A Lepidopteran Pheromone is an arthropod pheromone produced by
a member of the insect order Lepidoptera.
(iii) A Straight Chain Lepidopteran Pheromone is a lepidopteran
pheromone consisting of an unbranched aliphatic chain (between 9 and 18
carbons) ending in an alcohol, aldehyde, or acetate functional group
and containing up to three double bonds in the aliphatic backbone.
(b) 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.
(c) Applicability. The Agency may review, on a case-by-case basis,
naturally-occurring pesticides that do not clearly meet the definition
of a biochemical pesticide 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 review applications for registration of naturally-occurring
pesticides to determine whether to review the pesticide under this
subpart U.
Sec. 158.2010 Biochemical pesticides data requirements.
(a) Sections 158.2030 through 158.2070 identify the data
requirements that are required to support registration of biochemical
pesticides. Sections 158.2080 through 158.2084 identify the data
requirements that are required to support Experimental Use Permits
(EUPs). Variations in the test conditions are identified within the
test notes. Definitions that apply to all biochemical data requirements
can be found in Sec. 158.2000.
(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. 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.
(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
[[Page 61003]]
product (TEP), residue of concern, and pure active ingredient (PAI) or
all of the above (All). 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.
(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.
Sec. 158.2030 Biochemical pesticides product chemistry data
requirements table.
(a) General. (1) Sections 158.100 through 158.130 describe how to
use this table to determine the product chemistry data requirements for
a particular pesticide product. Notes that apply to an individual test
and include specific conditions, qualifications, or exceptions to the
designated test are listed in paragraph (e) of the section.
(2) Definitions in Sec. 158.300 apply to data requirements in this
section.
(b) Use patterns. Product chemistry data are required for all
pesticide products and are not use specific.
(c) Key. R=Required; CR=Conditionally required; 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.
(d) Table. The following table shows the data requirements for
biochemical pesticides product chemistry. The test notes are shown in
paragraph (e) of this section.
Table--Biochemical Pesticides Product Chemistry Data Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
Test Substance
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 EP 4
formation of
impurities
--------------------------------------------------------------------------------------------------------------------------------------------------------
Analysis and Certified Limits
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.1700 Preliminary analysis CR TGAI and MP TGAI and EP 5, 8
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.1750 Certified limits R MP EP 6
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.1800 Enforcement analytical R MP EP 7
method
--------------------------------------------------------------------------------------------------------------------------------------------------------
Physical and Chemical Characteristics
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6302 Color R TGAI TGAI 8
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6303 Physical state R TGAI and MP 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
--------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 61004]]
830.7220 Boiling point/boiling CR TGAI TGAI 8, 14
range
--------------------------------------------------------------------------------------------------------------------------------------------------------
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 pesticides 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. Sec. 158.325,
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.
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
(>10-6g/l) and fibrous 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. 158.2040 Biochemical pesticides residue data requirements table.
(a) General. Sections 158.100 through 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 biochemical
pesticides, i.e. naturally occurring insect repellents and attractants,
semiochemicals (e.g., insect pheromones), natural and plant growth
regulators. 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 that could
subsequently result in exposure to food.
(2) Data are conditionally 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.
(c) Key. R=Required; CR=Conditionally required; NR=Not required;
MP=Manufacturing end-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) Data requirements table. The following table shows the data
requirements for biochemical pesticides residue. The test notes are
shown in paragraph (e) of this section.
[[Page 61005]]
Table--Biochemical Residue Data Requirements for Specific Uses
--------------------------------------------------------------------------------------------------------------------------------------------------------
Use Patterns
-----------------------------------------------------------------------
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 -- 1, 3, 4
use
--------------------------------------------------------------------------------------------------------------------------------------------------------
Nature of the 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 or plant 1, 7, 8, 10, 13
residue in metabolite
livestock
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1340 Residue CR CR R CR Residue of 4, 9, 10
analytical concern
method
--------------------------------------------------------------------------------------------------------------------------------------------------------
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 TEP 1, 3, 4
trials
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1520 Processed food/ CR CR CR CR TEP 1, 16
feed
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1540 Anticipated CR CR CR CR Residue of 1, 10, 17
residues concern
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1550 Proposed CR CR CR CR -- 1, 18
tolerances
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1560 Reasonable CR CR CR CR -- 1, 10
grounds in
support of the
petition
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1650 Submittal of CR CR CR CR TGAI and 10, 19
analytical residue of
reference concern
standards
--------------------------------------------------------------------------------------------------------------------------------------------------------
(e) Test notes. The following test notes are applicable to the data
requirements for biochemical pesticides product chemistry and are 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. 158.2050.
2. The same chemical identity data are required for biochemical
product chemistry data requirements, Sec. 158.2030, 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. Required for residential outdoor uses on food crops if the
corresponding agricultural use is not approved or the residential
use is expected to produce higher residues based on the label
directions .
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. Not required when only indirect contact with food would
occur (e.g., crack and crevice treatments).
7. Required when a pesticide is to be applied directly to
livestock, to livestock premises, to livestock drinking water, or to
crops used for livestock feed.
8. 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.
9. A residue analytical method suitable for enforcement of
tolerances is required whenever a numeric tolerance (including
temporary and time-limited tolerances) is proposed.
10. Required if indoor use could result in pesticide residues in
or on food or feed.
11. Data are required to determine whether FDA/USDA multiresidue
methodology would detect and identify the pesticides and any
metabolites.
[[Page 61006]]
12. Data are required whenever a pesticide may be applied
directly to water, unless it can be demonstrated that the treated
water would not be available for human or livestock consumption.
13. Data on fish are required for all pesticides applied
directly to water inhabited, or which will be inhabited by fish that
may be caught or harvested for human consumption .
14. Data are required when a pesticide is to be applied directly
to water that could be used for irrigation or to irrigation
facilities such as irrigation ditches.
15. Data are required whenever a pesticide may 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 potentially
concentrate on processing thus requiring the establishment of a
separate tolerance higher than that of the raw agricultural
commodity.
17. Required when residues at the tolerance level may result in
risk of concern. These data may include washing, cooking,
processing, or degradation studies as well as market basket surveys
for a more precise residue determination.
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. 158.2050 Biochemical pesticides human health assessment data
requirements table.
(a) General. (1) Sections 158.100 through 158.130 describe how to
use this table to determine the biochemical human health assessment
data requirements for a particular biochemical pesticide product.
(2) The data in this section 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; CR=Conditionally required; 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 pesticides human health assessment. The test notes are
shown in paragraph (e) of this section.
Table--Biochemical Pesticides Human Health Assessment Data Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
Use Patterns Test Substance
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 -
rabbit
--------------------------------------------------------------------------------------------------------------------------------------------------------
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 - CR CR TGAI TGAI 7
rat
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.3465 90-day inhalation - CR CR TGAI TGAI 8
rat
--------------------------------------------------------------------------------------------------------------------------------------------------------
Developmental Toxicity
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.3700 Prenatal R CR TGAI TGAI 9
developmental -
rat preferably
--------------------------------------------------------------------------------------------------------------------------------------------------------
Mutagenicity Testing
--------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 61007]]
870.5100 Bacterial reverse R CR TGAI TGAI 10
mutation test
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.5300 In vitro mammalian R CR TGAI TGAI 10, 11
870.5375........................ cell assay
--------------------------------------------------------------------------------------------------------------------------------------------------------
Tier II
--------------------------------------------------------------------------------------------------------------------------------------------------------
Mutagenicity Testing (In vivo cytogenetics)
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.5385 In vivo Mammalian CR CR TGAI TGAI 13
870.5895........................ Cytogenetics
--------------------------------------------------------------------------------------------------------------------------------------------------------
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
--------------------------------------------------------------------------------------------------------------------------------------------------------
875.1100 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
--------------------------------------------------------------------------------------------------------------------------------------------------------
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 - CR CR TGAI TGAI 18
two species - rat
and mouse
preferred
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.5380 Mammalian CR CR TGAI TGAI 19
spermatogonial
chromosome
aberration test
--------------------------------------------------------------------------------------------------------------------------------------------------------
Special Testing
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.7200 Companion animal CR CR NR TGAI or EP 20
safety
--------------------------------------------------------------------------------------------------------------------------------------------------------
(e) Test notes. The following test notes are applicable to the data
requirements for biochemical pesticides 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 >10-4torr (mm/Hg)).
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
[[Page 61008]]
developmental effects are observed in the first study and
information on species-to-species extrapolation is needed.
10. Required to support nonfood uses if either:
i. The use is likely to result in significant human exposure; or
ii. 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:
i. Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene
locus, maximizing assay conditions for small colony expression or
detection;
ii. Chinese hamster ovary (CHO) or Chinese hamster lung
fibroblast (V79) cells, hypoxanthine-guanine phosphoribosyl
transferase (hgprt) gene locus, accompanied by an appropriate in
vitro test for clastogenicity; or
iii. 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. The micronucleus rodent bone marrow assay is preferred;
however, rodent bone marrow assays using metaphase analysis
(aberrations) are acceptable.
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 the data used for the human
health assessment indicates that the biochemical may pose a
potential hazard to the applicator/user.
16. Required if there is evidence of:
i. Endocrinological effects from the subchronic toxicity
studies.
ii. Developmental effects in the prenatal developmental toxicity
study(s), or
iii. 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 oral toxicity study, 90-day dermal toxicity study,
or 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. 158.2060 Biochemical pesticides nontarget organisms and
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 biochemical
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, 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; CR=Conditionally required; 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 pesticides nontarget organisms and environmental fate. The
test notes are shown in paragraph (e) of this section.
Table--Biochemical Pesticides Nontarget Organisms and Environmental Fate Data Requirements
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Use Patterns
---------------------------------------------------------------------------------------------------------
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
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 61009]]
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, 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
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
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) Anaerobic 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) Anaerobic 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
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 61010]]
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
invertebrate
testing
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
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
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
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 pesticides 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 10-5atm
m3/mol).
4. Preferred test species are Upland game, waterfowl, or
passerine for avian acute oral toxicity studies; Upland game and
waterfowl for avian dietary studies; and coldwater fish species for
acute freshwater fish 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. In
view of methdological difficulties with the study of
photodegradation in air, prior consultation with the Agency
regarding the protocol is recommended before the test is performed.
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
> 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. 158.2070 Biochemical pesticides product performance data
requirements.
Product performance data must be developed for all biochemical
[[Page 61011]]
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.
Sec. 158.2080 Experimental use permit data requirements--biochemical
pesticides.
(a) Sections 158.2081 through 158.2084 describe the experimental
use permit (EUP) data requirements for biochemical pesticides.
Variations in the test conditions are identified within the test notes.
Definitions that apply to all biochemical data requirements can be
found in Sec. 158.2000.
(b) For general information on the data requirement tables, see
Sec. 158.2010(b)-(f).
Sec. 158.2081 Experimental use permit biochemical pesticides product
chemistry data requirements table.
(a) General. (1) Sections 158.100 through 158.130 describe how to
use this table to determine the product chemistry data requirements for
a particular biochemical 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.
(b) Use patterns. Product chemistry data are required for all
pesticide products and are not use specific.
(c) Key. R=Required; CR=Conditionally required; 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
experimental use permit biochemical pesticides product chemistry. The
test notes are shown in paragraph (e) of this section .
Table--EUP Biochemical Pesticides Product Chemistry Data Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
Test Substance
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 EP 4
formation of
impurities
--------------------------------------------------------------------------------------------------------------------------------------------------------
Analysis and Certified Limits
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.1700 Preliminary analysis CR TGAI and MP TGAI and EP 5, 8
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.1750 Certified limits R MP EP 6
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.1800 Enforcement analytical R MP EP 7
method
--------------------------------------------------------------------------------------------------------------------------------------------------------
Physical and Chemical Characteristics
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6302 Color R TGAI TGAI 8
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6303 Physical state R TGAI and MP 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
--------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 61012]]
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
--------------------------------------------------------------------------------------------------------------------------------------------------------
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 experimental use permit biochemical pesticides 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
(>10-6g/l) and fibrous 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. 158.2082 Experimental use permit biochemical pesticides residue
data requirements table.
(a) General. Sections 158.100 through 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 biochemical
pesticides, i.e. naturally occurring insect repellents and attractants,
semiochemicals (e.g., insect pheromones), natural and plant growth
regulators. 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 that could
subsequently result in exposure to food.
(2) Data are conditionally 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.
(c) Key. R=Required; CR=Conditionally required; NR=Not required;
MP=Manufacturing end-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) Data table. The following table shows the data requirements for
biochemical pesticides residue. The test notes are shown in paragraph
(e) of this section.
[[Page 61013]]
Table--EUP Biochemical Pesticides Residue Data Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
Use Patterns
-----------------------------------------------------------------------
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 -- 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 or plant 1, 7, 8, 9, 13
residue in metabolite
livestock
--------------------------------------------------------------------------------------------------------------------------------------------------------
Magnitude of the Residue
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1400 Potable water NR CR NR NR TGAI 1, 11
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1400 Fish NR CR NR NR TGAI 1, 12
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1400 Irrigated crops NR CR NR NR TGAI 1, 13
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1460 Food handling NR NR NR CR TGAI 1, 14
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1480 Meat/milk/ CR CR CR CR TGAI or plant 1, 7, 8, 9
poultry/eggs metabolites
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1500 Crop field CR CR CR CR TEP 1, 3, 4
trials
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1520 Processed food/ CR CR CR CR TEP 1, 15
feed
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1540 Anticipated CR CR CR CR Residue of 1, 9, 16
residues concern
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1550 Proposed CR CR CR CR -- 1, 17
tolerances
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1560 Reasonable CR CR CR CR -- 1, 9
grounds in
support of the
petition
--------------------------------------------------------------------------------------------------------------------------------------------------------
860.1650 Submittal of CR CR CR CR TGAI and 9, 18
analytical residue of
reference concern
standards
--------------------------------------------------------------------------------------------------------------------------------------------------------
(e) Test notes. The following test notes are applicable to the data
requirements for biochemical pesticides product chemistry and are
referenced 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. 158.2050.
2. The same chemical identity data are required for biochemical
product chemistry data requirements,Sec. 158.2030 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. Required for residential outdoor uses on food crops if the
corresponding agricultural use is not approved or the residential
use is expected to produce higher residues based on the label
directions.
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. Not required when only indirect contact with food would
occur (e.g., crack and crevice treatments).
7. Required when a pesticide is to be applied directly to
livestock, to livestock premises, to livestock drinking water, or to
crops used for livestock feed. If results from the plant metabolism
study show differing metabolites in plants form 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. Required if indoor use could result in pesticide residues in
or on food or feed.
10. Data are required to determine whether FDA/USDA multiresidue
methodology would detect and identify the pesticides and any
metabolites.
11. Data are required whenever a pesticide may be applied
directly to water, unless it can be demonstrated that the treated
water would not be available for human or livestock consumption.
12. Data on fish are required for all pesticides applied
directly to water inhabited, or which will be inhabited, by fish
that may be caught or harvested for human consumption.
13. Data are required when a pesticide is to be applied directly
to water that could be used for irrigation or to irrigation
facilities such as irrigation ditches.
14. Data are required whenever a pesticide may be used in food/
feed handling establishments.
15. Data on the nature and level of residue in processed food/
feed are required when detectible residues could potentially
concentrate on processing thus requiring the
[[Page 61014]]
establishment of a separate tolerance higher than that of the raw
agricultural commodity.
16 Anticipated residue data are required when the assumption of
tolerance level residues would result in predicted exposure at an
unsafe level of exposure. Data, using single serving samples of a
raw agricultural commodity, on the level or residue in food as
consumed would be used to obtain a more precise estimate of
potential dietary exposure. These data may also include washing,
cooking, processing or degradation studies as well as market basket
surveys for a more precise residue determination.
17. The proposed tolerance must reflect the maximum residue
likely to occur in crops, in meat, milk, poultry, or eggs.
18. Required when a residue analytical method is required.
Sec. 158.2083 Experimental use permit biochemical pesticides human
health assessment data requirements 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 biochemical pesticide product.
(2) The data in this section 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; CR=Conditionally required; 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
experimental use permit biochemical pesticides human health assessment.
The test notes are shown in paragraph (e) of this section.
Table--EUP Biochemical Pesticides Human Health Assessment Data Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
Use Patterns Test Substance
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 -
rabbit
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.2500 Primary dermal R R TGAI and MP TGAI and EP 1, 2
irritation
--------------------------------------------------------------------------------------------------------------------------------------------------------
none Hypersensitivity R R All All 4
incidents
--------------------------------------------------------------------------------------------------------------------------------------------------------
Subchronic Testing
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.3100 90-day oral (one R NR TGAI TGAI --
species)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Developmental Toxicity
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.3700 Prenatal R CR TGAI TGAI 5
developmental -
rat preferably
--------------------------------------------------------------------------------------------------------------------------------------------------------
Mutagenicity Testing
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.5100 Bacterial reverse R CR TGAI TGAI 6
mutation test
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.5300 In vivo mammalian R CR TGAI TGAI 6, 7
cell assay
--------------------------------------------------------------------------------------------------------------------------------------------------------
Tier II
--------------------------------------------------------------------------------------------------------------------------------------------------------
Developmental Toxicity
--------------------------------------------------------------------------------------------------------------------------------------------------------
870.3700 Prenatal CR CR TGAI TGAI 5
developmental
--------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 61015]]
(e) Test notes. The following test notes are applicable to the data
requirements for experimental use permit biochemical pesticides 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 > 10-4torr (mm/Hg)).
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. Hypersensitivity incidents must be reported as adverse
effects data.
5. 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.
6. Required to support nonfood uses if either:
i. The use is likely to result in significant human exposure; or
ii. 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.
7. Choice of assay using either:
i. Mouse lymphoma L5178Y cells, thymidine kinase (tk) gene
locus, maximizing assay conditions for small colony expression or
detection;
ii. Chinese hamster ovary (CHO) or Chinese hamster lung
fibroblast (V79) cells, hypoxanthine-guanine phosphoribosyl
transferase (hgprt) gene locus, accompanied by an appropriate in
vivo test for clastogenicity; or
iii. CHO cells strains AS52, xanthine-guanine phosphoribosyl
transferase (xprt) gene locus.
Sec. 158.2084 Experimental use permit biochemical pesticides
nontarget organisms and 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 biochemical
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, for all
outdoor end-use products including turf, the following studies are
required: one avian acute oral, one avian dietary, one acute freshwater
fish, and one acute freshwater invertebrate 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; CR=Conditionally required; 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
experimental use permit biochemical pesticides nontarget organisms and
environmental fate. The test notes are shown in paragraph (e) of this
section.
Table--EUP Biochemical Pesticides Nontarget Organisms and Environmental Fate Data Requirements
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Use Patterns
---------------------------------------------------------------------------------------------------------
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.................. NR................. R.................. NR................. TGAI, EP.......... 1, 2, 3
toxicity
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.2200 Avian dietary R.................. R.................. NR................. R.................. NR................. TGAI, EP.......... 1, 2, 3
toxicity
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Aquatic Organism Testing
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1075 Fish acute R.................. R.................. NR................. R.................. NR................. TGAI, EP.......... 2, 3, 4
toxicity,
freshwater
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
850.1010 Aquatic R.................. R.................. NR................. R.................. NR................. TGAI, EP.......... 2, 4
invertebrate acute
toxicity,
freshwater
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 61016]]
(e) Test notes. The following test notes are applicable to the data
requirements for experimental use permit biochemical pesticides
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. Not required for any use groups if the pesticide is highly
volatile (estimated volatility >5 X 10-5atm
m3/mol).
3. Preferred test species are: upland game, waterfowl, or
passerine for avian acute oral toxicity studies; upland game or
waterfowl for avian dietary studies; and coldwater fish for acute
freshwater fish studies.
4. Required for the EP when the end-use formulation may contain
other ingredients that may be toxic to nontarget organisms.
Subpart V--Microbial Pesticides
Sec. 158.2100 Microbial pesticides definition and applicability.
(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 microbial agent 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,
Eubacteria and Archaebacteria; or
(3) Is a parasitically replicating microscopic element, including,
but not limited to, viruses.
(c) Applicability. (1) This part applies to microbial pesticides as
specified in paragraphs (c)(2), (3) and (4) of this section.
(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 microbial agent and/or its parental
strains, the proposed pesticide use pattern, and the manner and extent
to which the organism has been genetically modified.
(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.
Sec. 158.2110 Microbial pesticides data requirements.
(a) For all microbial pesticides. (1) The following Sec. 158.2120
through Sec. 158.2150 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 of the above (All).
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 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. 158.2120 Microbial pesticides product analysis data 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 paragraph (d) of this section, and the test notes appear
in paragraph (e) of this section.
(b) Key. R=Required; CR=Conditionally required; 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 pesticides product analysis. The test notes are shown in
paragraph (d) of this section.
[[Page 61017]]
Table--Microbial Pesticides Product Analysis Data Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
Test Substance
Guideline Number Data Requirement All Use Patterns ---------------------------------------------- Test Notes
MP EP
--------------------------------------------------------------------------------------------------------------------------------------------------------
Product Chemistry and Composition
--------------------------------------------------------------------------------------------------------------------------------------------------------
885.1100 Product Identity R MP EP --
--------------------------------------------------------------------------------------------------------------------------------------------------------
885.1200 Manufacturing process R TGAI and MP TGAI and EP --
--------------------------------------------------------------------------------------------------------------------------------------------------------
Deposition of a R TGAI TGAI --
sample in a
nationally recognized
culture collection
--------------------------------------------------------------------------------------------------------------------------------------------------------
885.1300 Discussion of R TGAI and MP TGAI and EP --
formation of
unintentional
ingredients
--------------------------------------------------------------------------------------------------------------------------------------------------------
Analysis and Certified Limits
--------------------------------------------------------------------------------------------------------------------------------------------------------
885.1400 Analysis of samples R TGAI and MP TGAI and EP 1
--------------------------------------------------------------------------------------------------------------------------------------------------------
885.1500 Certification of R MP EP --
limits
--------------------------------------------------------------------------------------------------------------------------------------------------------
Physical and Chemical Characteristics
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6302 Color R TGAI TGAI --
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6303 Physical state R TGAI TGAI --
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6304 Odor R TGAI TGAI --
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6313 Stability to normal R TGAI TGAI --
and elevated
temperatures, metals
and metal ions
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6317 Storage stability R TGAI and MP TGAI and EP --
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6319 Miscibility R MP EP 2
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6320 Corrosion R MP EP 3
Characteristics
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7000 pH R TGAI TGAI --
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7100 Viscosity R MP EP 4
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7300 Density/relative R TGAI TGAI --
density/bulk density
(specific gravity)
--------------------------------------------------------------------------------------------------------------------------------------------------------
(d) Test notes. The following test notes are applicable to the data
requirements for microbial pesticides product analysis as referenced in
the last column of the table contained in paragraph (c) of this
section.
1. 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
full registration, generally an analysis of samples is a compilation
of batches, over a period of time, depending on the frequency of
manufacturing.
2. Only required for emulsifiable liquid forms of microbial
pesticides.
3. Required when microbial pesticides are packaged in metal,
plastic, or paper containers.
4. Only required for liquid forms of microbial pesticides.
Sec. 158.2130 Microbial pesticides residue data requirements 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 paragraph (d) of this section, and the procedures appear in
paragraph (e) of this section.
(b) Key. R=required; CR=Conditionally required; 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 pesticides residue. The test notes are shown in paragraph (d)
of this section.
[[Page 61018]]
Table--Microbial Pesticides Residue Data Requirements
----------------------------------------------------------------------------------------------------------------
Test Substance
Guideline Number Data Requirement All Use Patterns Data to Support MP Test Notes
or EP
----------------------------------------------------------------------------------------------------------------
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
----------------------------------------------------------------------------------------------------------------
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 pesticides 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; and
ii. The use pattern is such that residues may be present in or
on food or feed crops.
Sec. 158.2140 Microbial pesticides toxicology data requirements
table.
(a) General. Sections 158.100 through 158.130 describe how to use
this table to determine the toxicology data requirements for a
particular pesticide product. Notes that apply to an individual test
and include specific conditions, qualifications, or exceptions to the
designated test are listed in paragraph (d) of this section.
(b) Key. R=Required; CR=Conditionally required; 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 pesticides toxicology. The test notes are shown in paragraph
(d) of this section.
Table--Microbial Pesticides 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, 6
toxicity
----------------------------------------------------------------------------------------------------------------
870.2400 Acute eye R MP , EP 5
irritation
----------------------------------------------------------------------------------------------------------------
870.2500 Primary dermal R MP , EP 5
irritation
----------------------------------------------------------------------------------------------------------------
Tier II
----------------------------------------------------------------------------------------------------------------
885.3550 Acute toxicology CR TGAI 7
----------------------------------------------------------------------------------------------------------------
885.3600 Subchronic CR TGAI 8
toxicity/
pathogenicity
----------------------------------------------------------------------------------------------------------------
[[Page 61019]]
Tier III
----------------------------------------------------------------------------------------------------------------
885.3650 Reproductive CR TGAI 9, 13
fertility effects
----------------------------------------------------------------------------------------------------------------
870.4200 Carcinogenicity CR TGAI 10, 13
----------------------------------------------------------------------------------------------------------------
870.7800 Immunotoxicity CR TGAI 11, 13
----------------------------------------------------------------------------------------------------------------
885.3000 Infectivity/ CR TGAI 12, 13
pathogenicity
analysis
----------------------------------------------------------------------------------------------------------------
(d) Test notes. The following test notes are applicable to the data
requirements for microbial pesticides toxicology as referenced in the
last column of the table contained in paragraph (c) 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 intravenous injection, the intraperitoneal injection procedure
may be employed.
3. Hypersensitivity incidents, including immediate type and
delayed-type reactions of humans or domestic animals, occur during
the testing or production of the TGAI, MP, or EP, or are otherwise
known to the applicant 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. 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).
7. 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 route(s) where toxicity was observed in Tier I
studies. The toxic component of the TGAI is to be tested.
8. 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.
9. Data are required when one or more 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.
10. 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.
11. Data may be required for products known to contain or
suspected to contain viruses that can interact in an adverse manner
with components of the mammalian immune system.
12. 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.
13. 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. 158.2150 Microbial pesticides nontarget organisms and
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; CR=Conditionally required; 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 pesticides nontarget organisms and environmental fate. The
test notes are shown in paragraph (e) of this section.
[[Page 61020]]
Table--Microbial Pesticides Nontarget Organisms and Environmental Fate Data Requirements
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Use Patterns
---------------------------------------------------------------------------------------------------------------------------------------------------
Aquatic Terrestrial
Guideline Number Data Requirement --------------------------------------------------------------------------------------------------------------------------------------------------- Test Substance Test Notes
Residential Greenhouse Indoor
Food/Feed Nonfood Food/Feed/ Forestry ------------------------------------------------------ Industrial
Nonfood Outdoor Food/Nonfood Food/Nonfood
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
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 or TEP 1, 2, 5
toxicity/
pathogenicity
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4240 Freshwater R R R R CR CR CR CR TGAI or TEP 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 TEP 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
studies
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4750 Aquatic ecosystem CR CR CR CR CR NR NR CR TGAI 15
test
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Tier IV
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
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)
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 61021]]
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 pesticides 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.
2. The preferred species for the avian oral study is either the
upland game or waterfowl. The preferred species for the avian
inhalation toxicity/pathogenicity study and the avian chronic
toxicity/pathogenicity study is the upland game. There is also the
option to test the passerine if there is a concern. The coldwater
fish is preferred for freshwater fish testing. However, two species
(coldwater and warmwater fish species are the preferred species)
must be tested for uses involving direct freshwater exposure.
Freshwater invertebrate testing is also required.
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
by Sec. 158.2140 are inadequate or inappropriate for assessment of
hazards to wild mammals.
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 one
or more 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 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 as post-registration monitoring if the potential for
unreasonable 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 observed 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.
[[Page 61022]]
Sec. 158.2160 Microbial pesticides product 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.
Sec. 158.2170 Experimental use permit data requirements--microbial
pesticides.
(a) For all microbial pesticides. (1) The following Sec. 158.2171
through Sec. 158.2174 identify the data requirements that are required
to support experimental use permits for microbial pesticides. The
variations in the test conditions are identified within the test notes.
(2) For general information on the data requirement tables, see
Sec. 158.2110(a)(2)-(4).
(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. 158.2171 Experimental use permit microbial pesticides product
analysis data 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; CR=Conditionally required; 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
experimental use permit microbial pesticides product analysis. The test
notes are shown in paragraph (d) of this section.
Table--EUP Microbial Product Analysis Data Requirements
--------------------------------------------------------------------------------------------------------------------------------------------------------
Test Substance
Guideline Number Data Requirement All Use Patterns ---------------------------------------------- Test Notes
MP EP
--------------------------------------------------------------------------------------------------------------------------------------------------------
Product Chemistry and Composition
--------------------------------------------------------------------------------------------------------------------------------------------------------
885.1100 Product Identity R MP EP --
--------------------------------------------------------------------------------------------------------------------------------------------------------
885.1200 Manufacturing process R TGAI and MP TGAI and EP 1, 2
--------------------------------------------------------------------------------------------------------------------------------------------------------
Deposition of a sample R TGAI TGAI --
in a nationally
recognized culture
collection
--------------------------------------------------------------------------------------------------------------------
885.1300 Discussion of R TGAI and MP TGAI and EP 2
formation of
unintentional
ingredients
--------------------------------------------------------------------------------------------------------------------------------------------------------
Analysis and Certified Limits
--------------------------------------------------------------------------------------------------------------------------------------------------------
885.1400 Analysis of samples R TGAI and MP TGAI and EP 2, 3
--------------------------------------------------------------------------------------------------------------------------------------------------------
885.1500 Certification of R MP EP --
limits
--------------------------------------------------------------------------------------------------------------------------------------------------------
Physical and Chemical Characteristics
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6302 Color R TGAI TGAI --
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6303 Physical state R TGAI TGAI --
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6304 Odor R TGAI TGAI --
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6313 Stability to normal R TGAI TGAI --
and elevated
temperatures, metals
and metal ions
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6317 Storage stability R TGAI and MP TGAI and EP --
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.6319 Miscibility R MP EP 4
--------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 61023]]
830.6320 Corrosion R MP EP 5
Characteristics
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7000 pH R TGAI TGAI --
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7100 Viscosity R MP EP 6
--------------------------------------------------------------------------------------------------------------------------------------------------------
830.7300 Density/relative R TGAI TGAI --
density/bulk density
(specific gravity)
--------------------------------------------------------------------------------------------------------------------------------------------------------
(d) Test notes. The following test notes are applicable to the data
requirements for experimental use permit microbial pesticides 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. 158.2172 Experimental use permit microbial pesticides residue
data requirements 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; CR=Conditionally required; 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
experimental use permit microbial pesticides residue. The test notes
are shown in paragraph (d) of this section.
Table--EUP Microbial Pesticides Residue Data Requirements
----------------------------------------------------------------------------------------------------------------
Test Substance
Guideline Number Data Requirement All Use Patterns Data to Support MP Test Notes
or EP
----------------------------------------------------------------------------------------------------------------
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
----------------------------------------------------------------------------------------------------------------
885.2300 Analytical methods CR TGAI 1
- plants
----------------------------------------------------------------------------------------------------------------
885.2350 Analytical methods- CR TGAI 1
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 experimental use permit microbial pesticides 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; and
ii. The use pattern is such that residues may be present in or
on food or feed crops.
Sec. 158.2173 Experimental use permit microbial pesticides toxicology
data requirements table.
(a) General. Sections 158.100 through 158.130 describe how to use
this table to determine the toxicology data requirements for a
particular microbial pesticide product. Notes that apply to
[[Page 61024]]
an individual test and include specific conditions, qualifications, or
exceptions to the designated test are listed in paragraph (d) of this
section.
(b) Key. R=Required; CR=Conditionally required; 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 pesticide toxicology. The test notes are shown in paragraph
(d) of this section.
Table--EUP Microbial Pesticides Toxicology Data Requirements
----------------------------------------------------------------------------------------------------------------
Guideline Number Data Requirement All Use Patterns Test Substance Test Notes
----------------------------------------------------------------------------------------------------------------
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, 6
toxicity
----------------------------------------------------------------------------------------------------------------
870.2400 Acute eye R MP, EP 5
irritation
----------------------------------------------------------------------------------------------------------------
870.2500 Primary dermal CR MP, EP 5
irritation
----------------------------------------------------------------------------------------------------------------
(d) Test notes. The following test notes are applicable to the data
requirements for experimental use permit microbial pesticides
toxicology as referenced in the last column of the table contained in
paragraph (c) 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 intravenous injection, the intraperitoneal injection procedure
may be employed.
3. Hypersensitivity incidents, including immediate type and
delayed type reactions of humans or domestic animals occur during
the testing or production of the TGAI, MP, or EP, or are otherwise
known to the applicant 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. Required when the product consists of, or under conditions of
use that would result in an inhalable material (e.g., gas, volatile
substances, or aerosol particulate).
Sec. 158.2174 Experimental use permit microbial pesticides nontarget
organisms and 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; CR=Conditionally required; 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
experimental use permit microbial pesticides nontarget organisms and
environmental fate. The test notes are shown in paragraph (e) of this
section.
[[Page 61025]]
Table--EUP Microbial Pesticides Nontarget Organisms and Environmental Fate Data Requirements
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Use Patterns
---------------------------------------------------------------------------------------------------------------------------------------------------
Aquatic Terrestrial
Guideline Number Data Requirement --------------------------------------------------------------------------------------------------------------------------------------------------- Test Substance Test Notes
Residential Greenhouse Indoor
Food/Feed Nonfood Food/Feed/Nonfood Forestry ------------------------------------------------------ Industrial
Outdoor Food/Nonfood Food/Nonfood
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4050 Avian oral NR R R R R NR NR NR TGAI 1, 2
toxicity.........
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4200 Freshwater fish NR R R R NR NR NR NR TGAI 1, 2, 3
toxicity/
pathogenicity
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4240 Freshwater NR R R R NR NR NR NR TGAI 1, 2, 3
invertebrate
toxicity/
pathogenicity
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4300 Nontarget plant NR NR NR R NR NR NR NR TEP 1, 4
testing..........
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4340 Nontarget insect R R R R NR NR NR NR TGAI 1, 5
testing
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
885.4380 Honey bee testing R R R R NR NR NR NR TGAI 1
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
(e) Test notes. The following test notes are applicable to the data
requirements for microbial pesticides 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
upland game or waterfowl. The preferred species for the avian
inhalation toxicity/pathogenicity study and the avian chronic
toxicity/pathogenicity study is the upland game. There is also the
option to test a passerine species if there is a concern. The
coldwater fish is preferred for freshwater fish testing. However,
two species (coldwater and warmwater fish are the preferred species)
must be tested for uses involving direct freshwater exposure.
Freshwater invertebrates are preferred for invertebrate testing.
3. Required when there will be significant exposure to aquatic
organisms (fish and invertebrates).
4. Required if the microbial pesticide is taxonomically related
to a known plant pathogen.
5. 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.
[FR Doc. E7-20828 Filed 10-25-07; 8:45 am]
BILLING CODE 6560-50-S