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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. Purpose

II. Applicability

III. Effective Date

IV. Background On The Reduced-Risk Initiative

V. Characteristicis Of Acceptable And Unacceptable Submissions For The Reduced-Risk 

Initiative

VI. Procedures And Guidelines For Expedited Review of Conventional And Antimicrobal 

Pesticides

VII. Guidelines For Reduced Risk Rationales

VIII. Guidelines For FQPA Rationale For Reduced Risk Pesticides

IX. Formatting And Submittal Procedures For Reduced-Risk Pesticides

X. Guidelines For Expedited Review Of Non-Fast-Track New Formulations For Currently 

Registered Conventional Pesticides

XI. Biological Pesticides

XII. For Further Information

XIII. Appendix A

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 

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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

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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:

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◦ 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

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◦ 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 

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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.

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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

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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 

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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

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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 

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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.

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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

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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.

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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.

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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 

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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 

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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); 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.

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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

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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

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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).

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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);

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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 

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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.

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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

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