|
 |
|
Pesticide Registration (PR) Notice 97-3
Fax-On-Demand
Telephone: (202) 401-0527
Item: 6101
September 4, 1997
Pesticide Registration (PR) Notice 97-3
NOTICE TO MANUFACTURERS, FORMULATORS, PRODUCERS AND
REGISTRANTS OF PESTICIDE PRODUCTS
ATTENTION: Persons Responsible for Registration of Pesticide Products
SUBJECT: Guidelines for Expedited Review of Conventional Pesticides
under the Reduced-Risk Initiative and for Biological
Pesticides
I. PURPOSE
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) as
amended by the Food Quality Protection Act of 1996 (FQPA) requires the
Environmental Protection Agency (EPA) to develop procedures and guidelines
for expedited review of any pesticide. These procedures and guidelines
must be in place within one year after the date of enactment of the FQPA
(by August 3, 1997). EPA has already established a Reduced Risk Initiative
for conventional pesticides, has formed the Biopesticides and Pollution
Prevention Division to review biological pesticides and has established the
Antimicrobial Division to review antimicrobial pesticides. The purpose of
this PR Notice is to provide the process and criteria to guide applicants
in developing their submissions to these programs.
This PR Notice supersedes the reduced-risk criteria published in
Federal Register Notices 57 FR 32140, July 20, 1992 and 58 FR 5854, January
22, 1993 and PR Notice 93-9, July 21, 1993. In addition, it defines the
types of pesticide products reviewed by the Biopesticides and Pollution
Prevention Division and describes how an applicant can apply for
biochemical pesticide classification.
The goal of the Reduced-Risk Pesticide Initiative and the
Biopesticides and Pollution Prevention Division is to encourage the
development, registration and use of lower-risk pesticide products which
would result in reduced risks to human health and the environment when
compared to existing alternatives. The major incentive which EPA offers
for these pesticides is expedited registration review. The major goal of
the Antimicrobial Division is to provide expedited review of all types of
antimicrobial registration actions.
II. APPLICABILITY
This notice applies to all applicants for initial registration and
amended registration for conventional pesticides, as described more fully
in Sections IV-X, and for biological pesticides, as described in Section
XI. The term "conventional pesticides" as used in this notice includes all
pesticides other than biological pesticides and antimicrobial pesticides
(as defined in FQPA). Since certain pesticide products, such as wood
preservatives and antimicrobials, are not defined as antimicrobial products
in FQPA but are handled in the Antimicrobial Division, for the purposes of
this notice they are considered conventional pesticides.
III. EFFECTIVE DATE
This PR Notice is effective immediately.
IV. BACKGROUND ON THE REDUCED-RISK INITIATIVE
In July 1992, the Office of Pesticide Programs (OPP) published a
Federal Register notice announcing the need for incentives for the
development and registration of reduced-risk pesticides. In a subsequent
Federal Register notice (January 1993) OPP announced the initiation of the
Reduced-Risk effort, and in July 1993 OPP published PR Notice 93-9 which
provided interim reduced-risk criteria and guidance for submissions.
Since July 1993, applicants have sent thirty-nine new chemical or new
use submissions to OPP for consideration as reduced-risk pesticides. Of
the thirty-nine, twenty-two have been accepted by OPP as reduced-risk
candidates; and sixteen have been rejected. Of the twenty-two accepted
reduced-risk submissions, fourteen have been registered. The following is
a list of the registered pesticides by accepted common names (if available)
and their trade name (in parenthesis):
(1) Hexaflumuron (Recruit) - below ground bait station termiticide
(2) Flumiclorac-pentyl (Resource) - post emergent herbicide on corn,
soybeans
(3) Methyl Anthranilate (Rejex-It) - bird repellent on cherries,
grapes, blueberries, forestry
(4) Tebufenozide (Confirm) - insecticide on walnuts
(5) Hymexazol (Tachigaren) - fungicide seed treatment on sugar beets
(6) Fludioxonil (Maxim) - fungicide seed treatment on corn, sorghum
(7) (Cadre) - herbicide on peanuts
(8) (Mefenoxam) - fungicide on multiple crops
(9) Spinosad (Spinosad) - insecticide on cotton
(10) Azoxystrobin (Heritage) - fungicide on turf
(11) Alpha-Metolachlor (CGA 77102) - herbicide on multiple crops.
(12) Hexaflumuron (Recruit) - above ground bait station new use
termiticide
(13) Imazamox (Raptor) - herbicide on soybeans
(14) Azoxystrobin (Heritage) - fungicide on grapes, bananas, peaches,
tomatoes, pecans and peanuts
The major advantage for reduced-risk pesticides is expedited
registration review. For FY95 and FY96 (prior to the passage of FQPA in
August 1996) the average total time required to register a new conventional
pesticide was thirty-eight months. For reduced-risk pesticides the average
total time for registration was only fourteen months. Since passage of
FQPA three new AI, reduced-risk pesticides were registered in seventeen,
eighteen and seventeen months, somewhat longer than the pre-FQPA average
but still substantially shorter than the conventional pesticide times. The
faster registration times reflect, in part, the expedited review status
granted reduced-risk actions. Not only is the initial submission granted a
high review priority but also any resubmission that may be necessary.
If the applicant is simultaneously seeking registration in Canada, and
if the application has been determined by Canada to be complete, the
reduced-risk action can also qualify for work-sharing between the two
countries. While this work-sharing program is still in the "pilot" stage,
it could result in further reduced review times and greater harmonization.
V. CHARACTERISTICS OF ACCEPTABLE AND UNACCEPTABLE SUBMISSIONS FOR THE
REDUCED-RISK INITIATIVE
OPP has assessed fourteen of the twenty-two reviews conducted by the
Reduced Risk Committee of submissions that were determined to be
reduced-risk. Those factors that most significantly contributed to EPA's
decision
to grant reduced risk status are summarized below in descending order:
o human health effects
- very low mammalian toxicity
- toxicity generally lower than alternatives (10-100X)
- displaces chemicals that pose potential human health
concerns [e.g., organophosphates (OPs), probable
carcinogens (B2s)]
- reduces exposure to mixers, loaders, applicators and reentry
workers
o non-target organism effects (birds)
- very low toxicity to birds
- very low toxicity to honeybees
- significantly less toxicity/risk to birds than alternatives
- not harmful to beneficial insects, highly selective pest
impacts
o non-target organism effects (fish)
- very low toxicity to fish
- less toxicity/risk to fish than alternatives
- potential toxicity/risk to fish mitigatable
- similar toxicity to fish as alternatives but significantly
less exposure
o groundwater (GW)
- low potential for GW contamination
- low drift, runoff potential
- runoff mitigatable
o lower use rates than alternatives, fewer applications
o low pest resistance potential (i.e., new mode of action)
o highly compatible with IPM
o efficacy.
OPP has also assessed eleven of the sixteen reviews conducted by the
Reduced Risk Committee of submissions that were determined not to be
reduced-risk. Those factors that most significantly contributed to an
unacceptable decision by the committee are summarized below in descending
order:
o human health effects
- inadequate/inappropriate comparisons with alternatives
- inadequate documentation of effects
- human health risk reduction case weak
- risk reduction case inadequate when compared to alternatives
o non-target organism effects (birds and fish)
- toxic to birds
- toxic to fish
- risk reduction case inadequate when compared to alternatives
o potential GW problems
o unlikely to displace higher risk alternatives
o lack of efficacy data
o phytotoxicity.
This survey of past decisions should assist future applicants in
preparing their submissions.
VI. PROCEDURES AND GUIDELINES FOR EXPEDITED REVIEW OF
CONVENTIONAL AND ANTIMICROBIAL PESTICIDES
A. Background
In general, FIFRA section 3(c)(3)(A) requires EPA after receipt of an
application for registration of a pesticide "as expeditiously as possible"
either to register it or to notify the applicant that the application does
not comply with the Act. FIFRA also establishes expedited review
procedures for a variety of Agency activities associated with the
registration of pesticides, including expedited review for certain end-use
pesticides that are identical or substantially similar to currently
registered pesticides ("me too" registrations) as provided in FIFRA section
3(c)(3)(B)(II), and for antimicrobial pesticides as provided for in FIFRA
section 3(h)(2). EPA also has several programs to expedite the
registration process for biological pesticides by the Biopesticides and
Pollution Prevention Division, antimicrobial pesticides by the
Antimicrobial Division and fast track procedures to expedite the
registration of certain amendments to existing conventional pesticide
registrations. As a result of these programs, EPA is already expediting
many pesticide applications for registration.
FIFRA section 3(c)(10) establishes an expedited review for
applications for registration and amendments to registrations for
pesticides that "may reasonably be expected to accomplish one or more of
the following:
(i) Reduce the risks of pesticides to human health.
(ii) Reduce the risks of pesticides to nontarget organisms.
(iii)Reduce the potential for contamination of groundwater, surface
water or other valued environmental resources.
(iv) Broaden the adoption of integrated pest management strategies,
or make such strategies more available or more effective."
The statute does not establish deadlines for review of registration
applications or amendments that meet the above criteria. Section 3(c)(10),
however, requires EPA to notify the applicant whether the application for
expedited review is complete no later than 30 days after receipt of the
application.
B. Procedures
EPA intends to establish a two-step procedure for expedited review
pursuant to FIFRA section 3(c)(10).
1. Step One - Application. For step 1, the Agency will
determine whether an application for registration or amended registration
qualifies for expedited review based upon whether use of the pesticide
proposed by the application may reasonably be expected to accomplish one or
more of the criteria listed in Section VI.A. above.
To initiate the process, the applicant must submit an application for
expedited review demonstrating how the use of the pesticide may reasonably
be expected to accomplish one or more of the criteria listed in section
VI.A. above. The applicant also must submit a reduced-risk rationale
pursuant to the guidelines and procedures specified in sections VII - IX of
this notice. The step 1 rationale may be a sentence or a paragraph in the
reduced-risk rationale summary as long as the claims are documented
elsewhere in the reduced-risk rationale.
Certain types of pesticide applications for registration and amended
registration already receive expedited review pursuant to existing Agency
programs. Because the Agency is already expediting review of these
registrations, it is not necessary to include them in the review program
established pursuant to FIFRA section 3(c)(10). Applications that already
receive expedited review include applications for registration or amended
registration for biological or antimicrobial pesticides, "me-too"
applications for registration or amended registrations of end-use
pesticides under FIFRA section 3(c)(3)(B)(I) that are identical or
substantially similar to other EPA registered pesticide products, and
applications for certain pesticides under FIFRA section 3(c)(3)(B)(II).
The FQPA amendments require EPA to make expedited decisions on
antimicrobial pesticides as defined in FIFRA section 2(mm). Specifically,
FIFRA section 3(h)(2) establishes goals for the time periods during which
EPA must review different types of applications for antimicrobials covered
by the statutory definition and make decisions whether to approve or deny
the applications. Generally, these review and decision deadlines are 30%
to 60% shorter than historic Agency performance in processing such
applications.
While FIFRA antimicrobial review deadlines do not become legally
binding until May 1998, as a matter of policy, the Agency has committed to
and, in fact, is meeting the goals specified in FIFRA section 3(h)(2) as
well as the expedited deadlines already mandated in FIFRA section
3(c)(3)(B). For every application received by the Agency since November 1,
1996, the Agency has made a registration decision within the review periods
provided by the statute. EPA will continue to expedite review of
applications for registrations and amendments to registrations for
antimicrobial pesticides pursuant to its commitment.
The Agency's improved performance in review of antimicrobials is the
result of several new initiatives. First, EPA has established within the
Office of Pesticide Programs a new Antimicrobials Division (AD) that is
responsible for all regulatory decisions relating to antimicrobial and
related pesticides. In addition to regulatory staff, the new AD
organization includes scientific personnel capable of performing most of
the analyses needed to make a registration decision. Thus, AD is capable
of providing "one-stop shopping" for registration decisions. Second, the
new AD management team has instituted a number of process improvements,
including a dedicated expedited review team of "me-too" applications, that
have resulted in a significantly improved performance.
Thus, because EPA's current organizational and resource allocations,
and process improvements are providing expedited review for antimicrobials,
all types of applications for antimicrobial pesticides (as defined in FQPA)
will be outside the scope of this PR Notice.
What types of applications for expedited review will the Agency
accept? An application for expedited review may be submitted only for the
following types of actions:
(a) an application to register a conventional pesticide that contains
an active ingredient not contained in any currently registered
pesticide, provided the pesticide is not a biopesticide or an
antimicrobial pesticide (as defined in FQPA). [See sections VII
through IX for reduced-risk rationale guidelines]; or
(b) an application to amend the registration of a currently
registered conventional pesticide for an additional new use,
provided the pesticide is not a biopesticide or an antimicrobial
pesticide (as defined in FQPA). [See sections VII through IX for
reduced-risk rationale guidelines]; or
a non-fast-track application for registration of a new
formulation provided the pesticide is not a biopesticide or an
antimicrobial pesticide (as defined in FQPA). [See section X for
expedited review rationale guidelines].
2. Step 2 - Reduced-Risk Determination If an application for
expedited review qualifies under step 1, the Agency will expedite the
review of the reduced-risk rationale presented by the applicant to
determine whether the pesticide qualifies under the reduced- risk criteria
described in sections VII and X below. The Agency's Reduced-Risk Committee
will expedite the review of the reduced-risk rationale and complete its
review within thirty days of receipt of a complete reduced-risk rationale.
If the Agency decides that a pesticide qualifies for reduced-risk status,
then it will further expedite review of the remainder of the application
for registration or amended registration as described in section IV of this
notice.
If the Agency denies a submission reduced-risk status, applicants
will be given only one opportunity to rebut this decision, and the
applicant will have four weeks to resubmit their rebuttal. Due to limited
program resources, the Agency can only allow one opportunity to rebut a
decision. Pesticides that EPA determines do not qualify for reduced-risk
status during step 2 will be processed in accordance with existing Agency
procedures.
VII. GUIDELINES FOR REDUCED RISK RATIONALES
While participation in the reduced-risk pesticides program is
voluntary, those who elect to participate must fully address all of the
following areas: (a) executive summary, (b) human health effects; (c)
environmental fate and effects; (d) other hazards; (e) risk discussion (f)
pest resistance and management (e.g., IPM); and (g) comparative
performance, (h) other information and how application complies with FQPA.
The Agency will consider all of these areas in determining the
acceptability of these applications. However, these may not be the
exclusive factors in all cases. If an applicant identifies additional
criteria that substantiate the argument that their product is indeed a
reduced-risk pesticide, then EPA invites the applicant to submit a
rationale with any supporting data to verify such a claim. The Agency will
consider this additional information.
An applicant's documentation must contain both a discussion of the
inherent reduced-risk properties of their product, as well as a comparison
of those properties with the properties of the commonly-used alternatives
where appropriate. Comparisons must be made to conventional chemical
pesticides, antimicrobial pesticides, biological pesticides, and cultural
practices currently being used for pest control at the same use site(s) and
for the same pest(s).
Please note that the Agency does not expect the applicant to perform
any additional testing to derive the data necessary to develop rationales
for the Reduced-Risk Program. The applicant must summarize all data in the
applicant's possession or control or available through the open literature
for the product being submitted to the Agency. If data addressing one of
the stated factors has been developed, but is not required for registration
of the pesticide in the United States, the applicant must provide a summary
of these data as part of the Reduced-Risk Rationale. If any of the
required information is not known, that fact must be noted in the
rationale.
If the rationale does not include a discussion of each of these
factors or provide reasoning as to why the factor should not be considered
in the Agency's decision, OPP will consider the rationale to be incomplete
and not responsive to this PR Notice. However, if the applicant believes
that the factor does not apply to the new pesticide, the registrant must
provide a short rationale describing this reasoning.
In situations where the Agency has already reviewed data on the active
ingredient, the applicant should use the Agency's review to address the
relevant factor(s). Applicants must also provide Master Record
Identification (MRID) numbers for each study, where appropriate.
A. Executive Summary. Provide an executive summary that addresses
the following considerations:
1. Chemical Name.
2. Chemical Abstracts Service Registry Number.
3. Chemical Structure.
4. Chemical Class or Family Name of the Active Ingredient.
5. Mode/Mechanism of Pesticidal Action for the Active
Ingredient (if known).
6. Proposed Use Pattern (including site(s) of application and
pest(s) controlled), Application Methods, Application Rates,
Frequency of Application, and Product Formulation
Percentages. Also indicate whether the new chemical will
be used in combination with other registered pesticides.
7. Brief Overview Summary of the Health, Ecological and
Environmental Fate Effects.
8. Tier 1 statement stating which of the four FQPA criteria are
being met by this application.
9. Reduced-Risk Statement, articulating the specific factors
that lead the applicant to the conclusion that the active
ingredient offers the opportunity for risk reduction.
10. Data Matrix, providing tabular information on all data
available for the active ingredient. The table should
include the guideline reference number, the study title,
MRID number (if available), outcome of the Agency's
evaluation (i.e., in review, acceptable, supplemental, data
waived, etc.), and date of the Agency's review (if
applicable).
B. Human Health. Clearly identify the portion of the rationale
which addresses the potential effects of the active ingredient on human
health. When specifying the dose levels used in the toxicity studies,
present the no-observable-effects level (NOEL) and the
lowest-observable-effects level (LOEL). Doses need to be specified in
terms of mg/kg/day. Also, describe qualitatively and quantitatively the
array of effects at all dose levels tested. In the format described in
Part IX of this PR Notice, address each of the following aspects of the
active ingredient and its use:
1. Acute Toxicity of the active ingredient and the
formulations. Provide the toxicity category for each of the
acute toxicity studies conducted on the active ingredient
and the formulated products.
2. Reproductive, Developmental, Mutagenic and Neurotoxic
Properties of the active ingredient.
3. Oncogenic and Other Subchronic and Chronic Effects of the
active ingredient.
4. Toxicity of Mammalian and Plant Metabolites.
C. Environmental Fate and Effects. Clearly identify the portion of
the rationale which addresses the potential ecological effects of the
active ingredient and its environmental fate. The discussion should also
address potential environmental degradates or metabolites of the active
ingredient. Address each of the following aspects of the active
ingredients and its use:
1. Mammalian Acute Toxicity
2. Avian Acute and Subacute Toxicity
3. Avian Reproductive Toxicity
4. Fish Acute and Chronic Toxicity
5. Aquatic Invertebrate Toxicity
6. Honeybee Acute Contact Toxicity
7. Effects on Terrestrial Plant Growth
8. Effects on Aquatic Plant Growth
9. Potential Exposure to Non-target Organisms
10. Environmental Persistence (Soil and Water)
11. Mobility in Soil and Water
12. Transport in Air (Spray Drift and Volatility)
13. Bioaccumulation as Indicated by the Octanol/Water Partition
Coefficient
D. Other Hazards. Clearly identify the portion of the rationale
which addresses other potential human health and environmental hazards
produced by the following:
1. Potential to Deplete Stratospheric Ozone thus increasing
ultraviolet radiation.
2. Potential to Present a Hazard through Storage,
Transportation, Mixing, Use or Disposal based on its
physical or chemical characteristics:
a. stability
b. flammability
c. corrosion characteristics
d. explodability
e. oxidizing or reducing action
f. storage stability
3. Potential to Affect Endangered and/or Threatened Plant and
Animal Species as designated under the Endangered Species
Act.
E. Risk Discussion. Clearly identify the portion of the rationale
which addresses the following items:
1. Discuss the information which supports the claims that the
active ingredient presents reduced toxicity, reduced
exposure to humans or non-target organisms, and/or reduced
environmental burden. When discussing the ecological levels
of concern (LOCs), present the methods used to derive them
and provide interpretations of what the LOCs mean.
2. Where alternative, registered pesticides or pest control
practices exist, make a quantitative and/or qualitative
comparison between the risks posed by the active ingredient
under consideration and all the other pesticides commonly
used, and/or the other current pest control practices.
3. The comparisons with alternative technology should also
include biological pesticides as well as cultural and
mechanical pest management practices.
F. Pest Resistance and Management. Clearly identify the portion of
the rationale which addresses the following items:
1. Describe how the active ingredient addresses the development
of pest resistance, either to the active ingredient itself
or to existing pesticides registered for the same use.
2. Discuss the suitability of the active ingredient for use in,
or encouraging the adoption of, Integrated Pest Management
(IPM) programs. This discussion should include information
on the effects of the pesticide on natural predators,
parasites and pathogens of each target pest, if such
information is known. The degree of risk and/or usage
reduction to be achieved by the IPM program must also be
addressed.
G. Comparative Performance Data (efficacy data). These data are
important to assure that risk reduction has a reasonable opportunity to be
accomplished by adoption of the new pesticide by growers.
1. It is desirable to have summaries of comparative performance
data in which the performance of the candidate pesticide is
compared to that of alternative control measures under
actual-use or simulated actual-use conditions.
2. Summaries of the available efficacy data if comparative
performance data are not available.
Summaries should include statistical analysis of significant
differences between the new pesticide and the commonly used alternatives.
Summaries should also include experimental methodologies such as
application rates, application intervals, pest pressure, weather
conditions, varieties of the crop used, etc. Unfavorable results must be
included. Efficacy experiments performed under substantially different
conditions should not be combined (examples include differences in pest
pressure, geography, strain/race of pest and weather). Guidance for this
requirement can be obtained from standardized published tests such
"Fungicide and Nematicide Tests," "Insecticide and Acaricide Tests" and
methods section sections of juried professional journals.
H. Other Information. Submission of the following additional
information will assist the Agency in making its decision on the active
ingredient:
1. A copy of the proposed product label(s).
The Agency will consider all of these criteria using a
weight-of-evidence approach.
VIII. GUIDELINES FOR FQPA RATIONALE FOR REDUCED RISK PESTICIDES
Reduced-risk submissions should also provide a rationale that
explains how this registration action complies with the requirements of
FQPA. Such rationale should follow guidance provided in Appendix A of PR
Notice 97-1 (January 31, 1997). Such rationale should address at a minimum
aggregate risk, special sensitivities, endocrine effects and potential
common mechanisms of toxicity with other registered pesticides. Appendix A
is provided as an attachment to this notice.
IX. FORMATTING AND SUBMITTAL PROCEDURES FOR REDUCED-RISK PESTICIDES
Formatting (A) and submittal (B) procedures for Reduced-Risk
Rationales are provided below. These procedures will enable EPA to easily
identify the application for priority consideration. Also, applicants
should note that it is unlawful to falsify any portion of an application.
FIFRA Sections 12(a) (2)(M), 12(a)(2)(R) and 18 U.S.C. Section 1001 make
such actions unlawful and can result in civil or criminal penalties. The
Agency will not consider an application under the Voluntary Reduced-Risk
Pesticide Initiative if the applicant does not follow these procedures.
A. Format. The reduced-risk rationale document must include the
following elements in the order indicated: Title Page, Statement or
Supplemental Statement of Data Confidentiality Claims, Cover Sheet to
Confidential Attachment and Confidential Business Information (CBI)
Reduced-Risk Attachment. Any supporting data must comply with PR Notice
86-5 requirements.
The Reduced-Risk Rationale must be bound as a separate entity and
consecutively paginated beginning with the title page as page 1. The total
number of pages must be represented on the title page. Do not include CBI
on the title page. On the title page, include titles and author(s).
B. Submitting a Reduced-Risk Rationale Registration Application. The
Reduced-Risk Rationale should accompany the registration application and
supporting data packages. This PR Notice does not supersede established
submittal procedures as addressed in PR Notice 91-5; rather, this PR Notice
provides additional guidance for submitting the reduced-risk rationale.
OPP uses distribution codes to facilitate the delivery of registration and
other submissions within the program. When preparing your submission to
mail or deliver to OPP, direct your submission to the Document Processing
Desk and including the following distribution code: REDUCED-RISK APPL.
The submission delivered via the U.S. Postal Service should be
directed to OPP using the following address:
Document Processing Desk (REDUCED-RISK APPL.)
Office of Pesticide Programs (7504C)
U.S. Environmental Protection Agency
401 M Street, S.W.
Washington, D.C. 20460-0001
Submissions via personal or courier delivery should be directed to the
Document Processing Desk between the hours of 8:00 a.m. and 4:00 p.m.,
Monday through Friday, excluding federal holidays. OPP's Document
Processing Desk is located at the following address:
Office of Pesticide Programs
Document Processing Desk (REDUCED-RISK APPL.)
Room 266A, Crystal Mall 2
1921 Jefferson Davis Highway
Arlington, VA 22202
C. Rebuttals may be submitted to Rick Keigwin, Registration Division
(7505C), U.S. Environmental Protection Agency, 401 M Street, S.W.,
Washington, DC 20460.
X. GUIDELINES FOR EXPEDITED REVIEW OF NON-FAST-TRACK NEW FORMULATIONS
FOR CURRENTLY REGISTERED CONVENTIONAL PESTICIDES
Some new, non-fast-track, formulations and amendments to currently
registered conventional pesticide products could result in reduced risk.
To qualify, an application for expedited review under this section must
first demonstrate that it meets one or more of the step 1 criteria listed
in section VI.A of this notice. Secondly, the registrant must demonstrate
that the new formulation, when compared with all of the existing
formulation(s) for the active ingredient, results in significant risk
reduction. Examples of risk reduction that would most likely qualify for
expedited review include new formulations that result in (a) at least a 35%
reduction in the amount of active ingredient applied, (b) at least a ten
fold reduction in risks to mixers, loaders and applicators, (c) at least a
50% reduction in the product's potential to leach into groundwater or run
off into surface water or (d) a significant reduction in risk to non-target
species. Actions that are accepted will qualify for expedited review but
will not be classified as reduced risk.
The process for submission of a non-fast-track formulation or new
end-use product differs from the new active ingredient/new uses procedures.
For consideration of a non-fast-track new formulation/end-use product, the
registrant shall make a submission to the Product Manager with documented
rationale for consideration of expedited review. The Product Manager will
review the request and determine if the submission qualifies for expedited
review. Consultation with other Product Managers or Branch Chiefs in
Registration Division may be necessary. The Product Manager will notify
the applicant of the expedited review status within 30 days. If denied
expedited review status, there will be one opportunity for rebuttal; the
submitter has four weeks to resubmit their rebuttal to the PM. Finally, if
the applicant holds the registrations for the old formulations that this
new formulation will replace, a request for cancellation of the old
formulations is also required. This cancellation request will not be
processed until a registration is issued on the new formulation.
XI. BIOLOGICAL PESTICIDES
A. Background. In November, 1994, EPA established a pilot division,
the Biopesticides and Pollution Prevention Division (BPPD), with part of
its mission to expedite the registration and reregistration of biological
pesticides (biopesticides). Biopesticides are any of the following: (1)
naturally occurring or genetically altered microorganisms, (2)
plant-pesticides (pesticidal substances produced in a plant and the genetic
material necessary for the production of those substances), or (3)
biochemical pesticides. In addition, BPPD does review the registration
submissions for some other pesticidal substances which warrant a reduced
data set as described below in Part C.
BPPD is now a permanent part of the Office of Pesticide Programs. To
date, BPPD has been successful at expediting the registration of biological
pesticides. Since the Division was established in the fall of 1994, 37 new
biological pesticides have been registered including the first
plant-pesticide products. New biopesticide active ingredients are
typically registered in less than 11 months which is substantially less
time than the average review time for conventional pesticides.
B. Priority for Review in BPPD. EPA believes that biological
pesticides generally pose less risk than most conventional pesticides.
Therefore, EPA established BPPD to provide an expedited review to all
biological pesticide products. BPPD's priority of actions is based upon
the order submissions are received rather than a comparison of risk among
the biopesticides. When a particular pesticide registrant requests that a
certain one of its submissions receives top priority amongst that company's
other biological actions, BPPD honors the requests. Also, if a
biopesticide would replace the use of a hazardous pesticide requested for
an emergency exemption under FIFRA Section 18, BPPD would make a
case-by-case determination on whether to further expedite the regulatory
decision.
C. Characteristics of Biopesticides
1. Microbial Pesticides. Microbial pesticides contain a
bacterium, fungus, virus, protozoan or alga as the active ingredient.
Approximately 50 microbial pesticide active ingredients are registered by
EPA. The most widely known of these are varieties of the bacterium,
Bacillus thuringensis or Bt, which can control certain moths, beetles, and
mosquitoes. Data requirements for microbial pesticides are found in 40 CFR
158.740. BPPD encourages potential registrants to contact the Division for
a preregistration submission meeting to discuss these data requirements,
and the scientific rationales for study waivers.
2. Plant-Pesticides. In November of 1994, EPA published a
proposed rule for regulation of plant-pesticides. In that document, EPA
encouraged potential registrants to follow the proposed rule until the
final rule is published. To date, seven plant-pesticide registrations have
been issued. Once the final rule is published, EPA will propose guidelines
for registration of plant-pesticides which will be incorporated into 40 CFR
Part 158. The guidelines will be open to public comments and appropriate
public meetings will be held prior to final guidelines being issued. In
the meantime, potential registrants should work closely with BPPD to
determine the data requirements for their products.
3. Biochemical Pesticides. Biochemical pesticides are
distinguished from conventional chemical pesticides by their nontoxic mode
of action toward target organisms (usually species specific), e.g. growth
regulation or mating disruption, and by the natural occurrence of the
pesticidal substance. In contrast, conventional pesticides generally are
toxic and may affect a wider range of target species. Biochemical
pesticides generally fall into distinct biologically functional classes:
Semiochemicals (chemicals emitted by a plant or animal that modify the
behavior of receptor organisms of similar or different species), hormones,
natural plant regulators, natural insect growth regulators, and enzymes.
In many instances, biochemical pesticides may be synthesized rather than
isolated from nature. In order for synthesized pesticides to be considered
as biochemical pesticides, they must be demonstrated to be structurally
similar and functionally identical to a naturally occurring biochemical
pesticide.
Although there are no strict criteria for the definition of
biochemical pesticides, most biochemical pesticides are applied at very low
rates, are highly volatile, or are applied in bait, trap, or "encapsulated"
formulations, thus resulting in less exposure (and less likelihood of
adverse effects to humans and the environment than from use of most
conventional pesticides). In keeping with their unique properties,
biochemical pesticides have been assigned a set of data requirements which
are organized in a tiered testing scheme to ensure, to the greatest extent
possible, that only the minimum data sufficient to make scientifically
sound regulatory decisions will be required. The data requirements are
outlined in 40 CFR Part 158.690.
4. Pesticides Which Warrant Reduced Data Requirements. The
Agency recognizes that many naturally occurring pesticidal chemicals may be
highly toxic to their target organisms and does not intend to include these
as biochemical pesticides. BPPD has elected to review certain of these
naturally occurring pesticides that may operate via a toxic mode of action
toward target organisms, but which a priori also would be candidates for an
initial tiered data set, as required for biochemical pesticides. These
"biochemical-like" pesticides have not yet been formally classified into a
subcategory of pesticides for nomenclature purposes. These pesticides
usually have uncomplicated structures and are commonly present in the
environment or the human diet at significant levels or have been widely
used for non-pesticidal purposes. Thus, any clinical or nontarget effects
are very likely to have been noticed and should be well documented. BPPD
has found that potential registrants for these products generally follow
the same data requirements as the biochemicals, but a preregistration
meeting with the Division is highly recommended before extensive testing
and before formal submission of an application.
D. Guidelines for Classification as a Biochemical or a
"Biochemical-like" Pesticide to be Reviewed by BPPD. On request, the
Biopesticides and Pollution Prevention Division (BPPD) will evaluate
products on an individual basis to classify them as biochemical pesticides,
pesticides warranting reduced data requirements ("biochemical-like"), or
conventional chemical pesticides.
BPPD has formed a Biochemical Classification Committee to evaluate
written requests for classifying products proposed for BPPD review as
biochemicals and similar products. A classification request should include
information to support the natural occurrence of the chemical and
information bearing on its mode of action toward the target pest.
Additional information to support low toxicity or low exposure levels may
be useful if available. This could include GRAS (generally regarded as
safe) status (please cite the listing number) or information on application
rates and/or degradation rates. Published studies or private data should
be attached if the supporting information is not commonly known or obvious.
E. Evaluation Standards
1. Natural Occurrence. Naturally occurring substances may be
inorganic or organic. As noted above, if the chemical is not naturally
occurring, information must be provided showing that it is structurally
similar and functionally identical to a naturally occurring substance. The
Biochemical Classification Committee recognizes that "natural occurrence"
may technically include substances that occur at very low levels in the
environment, but in such amounts or locations that humans and/or nontarget
organisms have not been exposed to significant levels of these chemicals.
The committee may decide that these substances are not biochemical
pesticides if there is any indication that natural exposure levels are
insufficient to indicate potential effects from the expected product
exposure.
2. Nontoxic Mode of Action. A nontoxic mode of action is one
that does not kill the target pest. The most obvious are repellents and
attractants. The committee has also included in the nontoxic mode of
action category, those chemicals that may be lethal to the target, but
operate via a physical mode of action to control the target pest. For
example, certain oils and/or sticky substances can kill insects by clogging
their respiratory spiracles and trachea, but such substances are not likely
to have adverse effects on non-target organisms or humans. Desiccants also
are considered as acting via a nontoxic mode of action. Plant growth
regulators are usually considered to have a nontoxic mode of action;
however, some plant growth regulators may act as herbicides at higher
application rates. Thus, higher application rates may result in additional
data requirements (as required for conventional chemical herbicides) or
reclassification as a conventional chemical pesticide.
F. Formatting and Submittal of Request for Biochemical
Classification. The classification request should be in the form of a
letter and should be sent directly to the Biopesticides and Pollution
Prevention Division (7511W), Office of Pesticide Programs, US Environmental
Protection Agency, 401 M St SW, Washington, DC 20460. It should be labeled
"Attn.: Biochemical Classification Committee."
G. EPA Response to Request for Biochemical Classification.
Submissions for classification are reviewed by a team of scientists from
several divisions within OPP. The recommendations of the Committee are
brought to management for approval. Decisions can include classification
as a biochemical, classification as a "biochemical-like" substance that
warrants reduced data requirements, but is not a biochemical, or
classification as a conventional pesticide. The potential registrant is
informed by letter of the decision. Because these are preapplication
requests for classification, the information submitted and the results may,
upon request, be treated as confidential business information.
H. Rebuttals to Denials for Biochemical Classification. In some
cases, inadequate information is supplied so that a Committee
recommendation cannot be made. In these cases the potential registrant is
asked to submit additional information. If a potential registrant
disagrees with classification as a conventional pesticide (essentially a
denial of classification as a biochemical), a rebuttal can be submitted to
the Biochemical Classification Committee for reconsideration.
XII. FOR FURTHER INFORMATION
For further information on reduced-risk submissions for conventional
pesticides, contact Peter Caulkins, Associate Director, Registration
Division at (703)305-6550. For further information on antimicrobial
pesticides, contact Bill Jordan, Associate Director, Antimicrobials
Division at (703)308-6411. For further information on microbial and
plant-pesticides, contact Phil Hutton, Chief, Microbial Pesticides Branch,
BPPD at (703) 308-8260 and for biochemicals, contact Roy Sjoblad, Chief,
Biochemical Pesticides Branch, BPPD at (703) 308-8269.
Daniel M. Barolo, Director
Office of Pesticide Programs
APPENDIX A
CONTENT OF SUPPLEMENTAL INFORMATION
As indicated at the beginning of the PR Notice, registrants,
applicants and petitioners are not currently required to submit any
additional information. Nevertheless, since the new statute requires the
Agency to consider additional information in order to make the necessary
decisions, EPA recognizes that many registrants, applicants and petitioners
may wish to provide the supplemental information to the Agency even without
a requirement to do so. For those registrants, applicants or petitioners
who wish to supplement their original submissions with additional
information, this Appendix describes what information the Agency would
consider helpful additions for its review.(*1)
(*1) An agency may not conduct or sponsor, and a person is not
required to respond to, a collection of information unless it either
displays a currently valid OMB control number or is imposed on the
person by statute (5 CFR 1320.6(a) & (e)). The collection of
information relating to the registration, reregistration, and
tolerance programs have are approved under OMB Control Numbers
2070-0024 (expires: 6/30/99); 2070-0032 (expires: 5/3/98); 2070-0040
(expires: 11/30/99); 2070-0060 (expires: 5/31/98); 2070-0122 (expires:
11/30/97); 2070-0107 (expires: 7/31/99). If you should have any
comments on the collection activities, please send them to the
Director, OPPE Regulatory Information Division, U.S. Environmental
Protection Agency (Mailcode 2137), 401 M St., S.W., Washington, D.C.
20460. Include the OMB control number in any correspondence. Note
that this address is ONLY for comments on the collection activity. Do
not submit your information to this address.
All tolerances or tolerance exemptions and associated registration
actions under FIFRA section 3 or reregistration actions under FIFRA section
4, whether pending or future, will need to comply with the new safety
standard of section 408(b)(2) of the Federal Food, Drug and Cosmetic Act.
In addition, because EPA intends to apply a similar standard to actions
involving non-food use pesticides that may pose significant non-dietary
risks to infants and children, all registration and reregistration actions
also will need to comply with this standard with respect to the Agency's
consideration of infants and children exposure to the pesticide.
In preparing a package to be submitted, those seeking a registration,
reregistration, tolerance, or an exemption from the requirement of a
tolerance for a food use pesticide, or a registration or reregistration of
a non-food use pesticide that may result in significant exposure to
children, may need to provide additional information and/or materials to
address adequately the factors and specific questions contained here.
Those who wish to submit additional information should keep in mind that
the Agency will consider each factor listed below (and perhaps others as
Agency policies are developed) in addition to any data and information
already required. In addition, it is important to note that the
information identified here may not be definitive in all cases. Additional
information or more detailed information may be needed in individual cases.
If a registrant, applicant, or petitioner can identify additional
information that would assist the Agency in addressing the FQPA provisions,
EPA welcomes such information. Although the submission of this information
is not currently required by the regulations, if such information is not
submitted, the Agency must rely on previously submitted data, if
applicable, or on broad or default assumptions when considering the factors
listed. As a result, favorable action on an application, petition, or
reregistration decision may be significantly delayed or precluded
altogether.
It would be helpful for any submitted documentation to contain a
discussion of each of the following factors as it relates to the pesticide
and proposed tolerance or tolerance exemption. If information on any
factor is not known, that fact, along with an explanation, should be noted
in the rationale. It is important to note that EPA does not expect the
registrant, applicant, or petitioner at this time to perform any additional
testing to derive the data necessary to develop its rationales. However,
if it has in its possession data from preliminary reports of ongoing
studies, articles from published literature, unpublished report
information, previously unsubmitted studies, or supplemental data that are
otherwise pertinent to the Agency's concerns, the party is encouraged to
submit them. Likewise, if a registrant, applicant, or petitioner believes
that a factor is not applicable to its product, a discussion as to why this
view is held should also be included. The Agency will consider all
relevant factors in determining an application's completeness and in
setting priorities for review.
Based on the new safety standard, EPA will need the following
additional information in order to make appropriate regulatory decisions:
(For details on each factor, please refer to the explanations below in
parts A and B.)
1. An informative summary of the petition or application, including a
summary of the supporting data, information, accompanying rationales,
and a statement providing permission to publish such summary, and
2. Information and discussion pertaining to a specific safety
determination for infants and children including their special
susceptibilities and exposure patterns to the particular pesticide.
A. Food Use Pesticides: Registration and Reregistration Actions,
Experimental Use Permits, Tolerance (or Exemption)
Petitions and Reassessments
In the format described in Appendix C of this PR Notice, address each
of the following with respect to the pesticide and its use(s):
Special Sensitivities
a) Chronic Endpoints
For a chemical pesticide: Discuss and/or provide evidence as to
whether or not the current Reference Dose (RfD) is sufficient to
adequately protect infants and children. Discuss and/or provide
evidence as to whether or not infants and children are more
susceptible to the chemical. If you believe that an additional safety
factor of 10X, to take into account potential pre- and post-natal
toxicity to infants and children is not necessary, provide evidence to
support the additional safety factor, if any, you believe to be more
appropriate. Please bear in mind that the Agency may accept a
different margin of safety only if, based on reliable data, EPA
concludes that the margin will be safe for infants and children.
For a biochemical pesticide:(*2)
(*2) A biochemical is a naturally-occurring compound, or
substantially similar to a naturally-occurring compound, with a
non-toxic mode of action to the target pest.
Does the toxicity testing indicate that the establishment of an RfD is
warranted? If so, then discuss whether or not the RfD is sufficient
to adequately protect infants and children. Discuss and/or provide
evidence as to whether or not infants and children are more
susceptible to the biochemical pesticide.
For a microbial pesticide:(*3)
(*3) Certain subpopulations are more susceptible to certain
disease-causing microorganisms; however, these are not the types
of microorganisms that are considered for registration or use as
microbial pesticides. The Agency has not registered, and does
not expect to register a microbial active ingredient that is
known to be a common human pathogen. To address the potential
risk from microbial pesticides, the Agency requires a battery of
acute toxicity/pathogenicity studies in order to perform a
risk assessment. If results of the acute exposure studies
indicate a toxicity concern, then subchronic or chronic studies
are required.
Discuss the potential for chronic dietary risks for infants and
children. Discuss and/or provide evidence as to whether or not
infants and children are more susceptible to the microbial pesticide
than is the adult population.
b) Acute Endpoints
Discuss the potential for greater acute dietary risk for infants and
children. If the chemical or biochemical pesticide demonstrates acute
effects, then discuss the endpoint used to perform the assessment
including relevance to infants and children and the details as to how
the exposure assessment was conducted and whether the estimated risk
is within the Agency's levels of concern.
c) Carcinogenic Endpoints
If the chemical or biochemical has been determined to be a carcinogen
and has a cancer potency factor (Q1*), discuss the aggregate excess
lifetime cancer risk resulting from exposure to the chemical from
residues in food and drinking water (ground and surface water) and
from residential and other non-occupational source(s).
Aggregate Exposure
a) Water
For a chemical or biochemical pesticide: Discuss the potential for
the transfer of residues (of both the parent pesticide and any
degradates) to drinking water. The discussion should include, but not
be limited to, information indicating whether the pesticide is
persistent and/or mobile, relevant product chemistry, and any
available modeling data.
Has the chemical or any of its degradates been detected in ground
water or surface water? Would this chemical or any of its degradates
likely pass through primary or secondary drinking water treatment into
finished water? Are any States conducting water monitoring programs
for this pesticide? If so, data collected by the States and all
relevant information should also be included.
For a microbial pesticide: Discuss the potential for the transfer of
the microbial pesticide to drinking water. The discussion should
include, but not be limited to, information pertaining to the biology
of the microorganism, and indicating whether the pesticide is
persistent and/or mobile or has the potential for transport in air
(spray drift and volatility data). Are any States conducting water
monitoring programs for this strain? If so, data collected by the
States and all other relevant information should also be included.
b) Non-occupational Exposures
Discuss the potential for significant exposure to the pesticide of
children by routes other than dietary. Are there any
non-occupational, structural, or residential uses (e.g., pet, swimming
pool, lawn and garden, or topical insect repellent)? Is the pesticide
used in or around schools, parks, or recreation facilities? Provide
all available exposure data. If the pesticide demonstrates acute
effects, then discuss the endpoint used to perform the assessment,
including relevance to infants and children and the details of how the
residential exposure assessment was conducted and whether the
estimated risk is within the Agency's levels of concern.
c) Multiple Pathway Assessment
Discuss the chronic and/or acute risk of aggregate exposure via
multiple pathways for the general population, and for infants and
children. This should include a discussion of all assumptions used
and uncertainties. You should also identify, and include in the
discussion, any non-pesticidal uses of the chemical (e.g., industrial,
pharmaceutical, cosmetic, food additive).
Cumulative Effects
Discuss the mechanism and mode of action of this pesticide. Identify
other chemicals that may fall into this category (both pesticide and
non-pesticide chemicals). Provide information regarding common
mechanisms and modes of action with other chemical substances based on
structural similarity, same or similar endpoints, and other relevant
criteria. Provide any data and/or evidence illustrating similarities
at the cellular/molecular level.
Discuss the appropriateness of combining exposures in this particular
case. Where data are not available, discuss appropriateness of using
default assumptions and what defaults should be used.
Endocrine Effects(*4)
(*4) As indicated in section 408(p)(1) & (2), the Agency has 2
years to develop a screening method, with a total of 3 years to
implement such a program.
Discuss and provide any evidence relevant to the possibility that the
pesticide may have endocrine disrupter effects individually or in
combination with another chemical. Include the potential for
synergistic effects of your chemical in combination with other
chemicals.
Identify any instances of reported (proven or alleged) adverse
reproductive or developmental effects to domestic animals or wildlife
as a result of exposure to your chemical, or that occurred in an area
where the chemical is known to have been used. Provide all
information regarding the circumstances, estimated level of exposure,
and details of the effect.
Residue Chemistry
Information should include a discussion of compatibility with
established Codex Alimentarius Commission Maximum Residue Levels
(MRLs), submission of a practical analytical method with an
appropriate limit of detection, and a discussion of the potential need
for tolerances for processed foods. For tolerance exemption
petitions, indicate if the chemical is on the Food and Drug
Administration's Generally Recognized As Safe (GRAS) list. A summary
of all tolerances and exemptions from tolerance being proposed should
also be included.
Benefits Information (For Reregistration Actions Only)
If the information and data submitted indicate that an existing
tolerance, reviewed according to the requirements of the new legislation,
should be determined to be unsafe (that is, to exceed the "reasonable
certainty of no harm" standard), the new law allows EPA to consider
pesticide benefits information in certain instances. An "eligible
pesticide chemical residue" (for which an "eligible tolerance" may be
applicable) is defined as a chemical residue for which
1) EPA is unable to identify a level of exposure that will not cause
or contribute to a known or anticipated harm to human health (that is,
the effect is a non-threshold effect);
2) an appropriate quantitative risk assessment for the lifetime risk
of the non-threshold effect has been determined; and
3) if there are also threshold effects associated with the chemical,
EPA is able to identify a level at which the residue will not cause
any known or anticipated harm to human health and that the level of
aggregate exposure is safe.
Registrants who suspect that an existing tolerance for their chemical,
which has been classified by the Agency as exhibiting a non-threshold
effect, may exceed the new safety standard, and wish the Agency to consider
an eligible tolerance for residues of that pesticide, may need to submit
the following information:
Conditions Regarding the Use of the Pesticide
Information and/or data indicating that the use of the pesticide
chemical that produces the residue protects consumers from adverse
health effects that would pose a greater risk than the dietary risk
from the residue, OR
Information and/or data showing that the use of the pesticide chemical
that produces the residue is necessary to avoid a significant
disruption in the domestic production of an adequate, wholesome, and
economic food supply.
Conditions Regarding the Risk of a Pesticide
Evidence that the yearly risk associated with the nonthreshold effect
from aggregate exposure to the residue is not greater than ten times
the yearly risk allowed under the new safety standard, AND
Evidence that the tolerance is limited to ensure that the lifetime
risk associated with the nonthreshold effect from aggregate exposure
to the residue is not greater than twice the lifetime risk allowed
under the new safety standard.
It is important to note that the above information does not supersede
any existing benefits requirements under FIFRA, such as public health pests
and benefits data necessary for a public interest finding under FIFRA
section (3)(c)(7).
B. Non-Food Use Pesticides: Registration or Reregistration Actions
In the format described in Appendix C of this PR Notice, address each
of the following with respect to the pesticide and its use(s):
Potential for Exposure to Children
Describe the use pattern of your chemical. If you believe that its
use(s) would not potentially result in significant exposure to infants
and children, provide a discussion and rationale as to why this view
is held. For chemicals that appear not to result in a significant
exposure to infants and children, no additional information is needed.
If you believe that the use of your chemical may result in significant
children's exposure, the following factors may need to be addressed:
Special Sensitivities
Discuss and/or provide evidence as to whether or not infants and
children are more susceptible to the chemical than adults.
Discuss the potential for greater acute and/or chronic risk for
infants and children. If the pesticide demonstrates toxic effects,
then discuss the endpoint used to perform the assessment including
relevance to infants and children and the details as to how the
exposure assessment was conducted and whether the estimated risk is
within the Agency's levels of concern.
Aggregate Exposure
Discuss the potential for the transfer of residues of both the parent
chemical and any degradates or of the microbial pesticide to drinking
water. For chemical pesticides, the discussion should include, but
not be limited to, information indicating whether the pesticide is
persistent and/or mobile, the potential for transport in air (spray
drift and volatility data), and any available modeling data. For
microbial pesticides, the discussion should instead include
information pertaining to the biology of the microorganism and
indicate whether the pesticide is persistent and/or mobile.
Has the chemical or any of its degradates been detected in ground
water or surface water? Would this chemical or any of its degradates
likely pass through primary or secondary drinking water treatment into
finished water? Are any States conducting water monitoring programs
for this pesticide? If so, data collected by the States and all
relevant information should also be included.
Discuss the potential for significant exposure to the chemical of
children by non-dietary routes. Are there non-occupational,
structural, or residential uses (e.g., pet, swimming pool, lawn and
garden, or topical insect repellents)? Is the pesticide used in or
around schools, parks, or recreation facilities? Provide all
available exposure data.
Discuss the chronic and/or acute risk of aggregate exposure via
multiple pathways for the general population, infants and children
should include a discussion of all assumptions used and uncertainties.
Identify other non-pesticidal uses of the chemical (e.g., industrial,
pharmaceutical, cosmetic, food additive).
Cumulative Effects
Discuss the mechanism and mode of action of this pesticide. Identify
other chemicals that may fall into this category (both pesticide and
non-pesticide chemicals). Provide information regarding common
mechanisms and modes of action with other chemical substances based on
structural similarity, same or similar endpoints, and other relevant
criteria. Provide any data and/or evidence illustrating similarities
at the cellular/molecular level.
Discuss the appropriateness of combining exposures in this particular
case. Where data are not available, discuss appropriateness of using
default assumptions and what defaults should be used.
Endocrine Effects
Discuss and provide any evidence relevant to the possibility that the
chemical may have endocrine disrupter effects individually or in
combination with another chemical. Include the potential for
synergistic effects of your chemical in combination with other
chemicals and whether or not your chemical could act as a catalyst for
another hormone-disrupting chemical.
Identify any instances of reported (proven or otherwise) adverse
reproductive or developmental effects to domestic animals or wildlife
as a result of exposure to your chemical, or that occurred in an area
where the chemical is known to has been used. Provide all information
regarding the circumstances, estimated level of exposure, and details
of the effect.
|
