0277.20 Attachment D

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

Menu

Pesticide Registration

PRN 97-3: Guidelines for Expedited Review
of Conventional Pesticides under the
Reduced-Risk Initiative and for Biological
Pesticides
September 4, 1997
Notice To: Manufacturers, Producers, Formulators, 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
On This Page
I.
II.
III.
IV.
V.
VI.
VII.
VIII.
IX.
X.
XI.
XII.
XIII.

I.

Purpose
Applicability
Effective Date
Background On The Reduced-Risk Initiative
Characteristicis Of Acceptable And Unacceptable Submissions For The Reduced-Risk
Initiative
Procedures And Guidelines For Expedited Review of Conventional And Antimicrobal
Pesticides
Guidelines For Reduced Risk Rationales
Guidelines For FQPA Rationale For Reduced Risk Pesticides
Formatting And Submittal Procedures For Reduced-Risk Pesticides
Guidelines For Expedited Review Of Non-Fast-Track New Formulations For Currently
Registered Conventional Pesticides
Biological Pesticides
For Further Information
Appendix A

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

http://www2.epa.gov/pesticide-registration/prn...

Page 1 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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

http://www2.epa.gov/pesticide-registration/prn...

Page 2 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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 reducedrisk 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.

Characteristicis 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:

http://www2.epa.gov/pesticide-registration/prn...

Page 3 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

◦ 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), probablecarcinogens (B2s)]
◾ reduces exposure to mixers, loaders, applicators and reentry workers
◦ 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
◦ 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
◦ groundwater (GW)
◾ low potential for GW contamination
◾ low drift, runoff potential
◾ runoff mitigatable
◦ lower use rates than alternatives, fewer applications
◦ low pest resistance potential (i.e., new mode of action)
◦ highly compatible with IPM
◦ 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:
◦ 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
◦ non-target organism effects (birds and fish)
◾ toxic to birds
◾ toxic to fish
◾ risk reduction case inadequate when compared to alternatives
◦ potential GW problems
◦ unlikely to displace higher risk alternatives
http://www2.epa.gov/pesticide-registration/prn...

Page 4 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

◦ lack of efficacy data
◦ phytotoxicity.
VI.

Procedures And Guidelines For Expedited Review Of
Conventional And Antimicrobal 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

http://www2.epa.gov/pesticide-registration/prn...

Page 5 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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.
http://www2.epa.gov/pesticide-registration/prn...

Page 6 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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 reducedrisk 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

http://www2.epa.gov/pesticide-registration/prn...

Page 7 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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
http://www2.epa.gov/pesticide-registration/prn...

Page 8 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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

http://www2.epa.gov/pesticide-registration/prn...

Page 9 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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)
10. Mobility in Soil and Water
11. Transport in Air (Spray Drift and Volatility)
12. 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

http://www2.epa.gov/pesticide-registration/prn...

Page 10 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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.

http://www2.epa.gov/pesticide-registration/prn...

Page 11 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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 ReducedRisk 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

http://www2.epa.gov/pesticide-registration/prn...

Page 12 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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 nonfast-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.

http://www2.epa.gov/pesticide-registration/prn...

Page 13 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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.

http://www2.epa.gov/pesticide-registration/prn...

Page 14 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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 "biochemicallike" 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 nonpesticidal 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
http://www2.epa.gov/pesticide-registration/prn...

Page 15 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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
http://www2.epa.gov/pesticide-registration/prn...

Page 16 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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

XIII.

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); 20700122 (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.

http://www2.epa.gov/pesticide-registration/prn...

Page 17 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | 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.

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. Food Use Pesticides: Registration and Reregistration Actions, Experimental
Use Permits, Tolerance (or Exemption) Petitions and Reassessments
http://www2.epa.gov/pesticide-registration/prn...

Page 18 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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

http://www2.epa.gov/pesticide-registration/prn...

Page 19 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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).
http://www2.epa.gov/pesticide-registration/prn...

Page 20 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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 nonthreshold effect);
http://www2.epa.gov/pesticide-registration/prn...

Page 21 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

2. an appropriate quantitative risk assessment for the lifetime risk of the nonthreshold 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
http://www2.epa.gov/pesticide-registration/prn...

Page 22 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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 nondietary 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.
http://www2.epa.gov/pesticide-registration/prn...

Page 23 of 24

5/5/2015

PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesticides | Pesticide ...

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.

Last updated on April 14, 2015

http://www2.epa.gov/pesticide-registration/prn...

Page 24 of 24

5/5/2015