OMB Control Number 2070-0060; EPA ICR Number 0277.15 

ICR ATTACHMENT C 

Pesticide Registration (PR) Notice 97-3: Guidelines for Expedited Review of Conventional 

Pesticides under the Reduced-Risk Initiative and for Biological Pesticides 
You are here: EPA Home Pesticides Regulating Pesticides Pesticide Registration (PR) 

Notices Pesticide Registration (PR) Notice 97-3 

Pesticide Registration (PR) Notice 97-3: 

Guidelines for Expedited Review of Conventional 

Pesticides under the Reduced-Risk Initiative and 

for Biological Pesticides 

Fax-On-Demand 

Telephone: (202) 401-0527 

Item: 6101 

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 

I. PURPOSE 

The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) as 

amended by the Food Quality Protection Act of 1996 (FQPA) requires the 

Environmental Protection Agency (EPA) to develop procedures and guidelines 

for expedited review of any pesticide. These procedures and guidelines 

must be in place within one year after the date of enactment of the FQPA 

(by August 3, 1997). EPA has already established a Reduced Risk Initiative 

for conventional pesticides, has formed the Biopesticides and Pollution 

Prevention Division to review biological pesticides and has established the 

Antimicrobial Division to review antimicrobial pesticides. The purpose of 

this PR Notice is to provide the process and criteria to guide applicants 

in developing their submissions to these programs. 

This PR Notice supersedes the reduced-risk criteria published in 

Federal Register Notices 57 FR 32140, July 20, 1992 and 58 FR 5854, January 

22, 1993 and PR Notice 93-9, July 21, 1993. In addition, it defines the 

types of pesticide products reviewed by the Biopesticides and Pollution 

Prevention Division and describes how an applicant can apply for 

biochemical pesticide classification. 

The goal of the Reduced-Risk Pesticide Initiative and the 

Biopesticides and Pollution Prevention Division is to encourage the 

development, registration and use of lower-risk pesticide products which 

would result in reduced risks to human health and the environment when 

Resources 

Pesticide Registration 

Notices 

Pesticides: Regulating Pesticides 

Last updated on Tuesday, September 11th, 2007.

http://www.epa.gov/PR_Notices/pr97-3.html

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compared to existing alternatives. The major incentive which EPA offers 

for these pesticides is expedited registration review. The major goal of 

the Antimicrobial Division is to provide expedited review of all types of 

antimicrobial registration actions. 

II. APPLICABILITY 

This notice applies to all applicants for initial registration and 

amended registration for conventional pesticides, as described more fully 

in Sections IV-X, and for biological pesticides, as described in Section 

XI. The term "conventional pesticides" as used in this notice includes all 

pesticides other than biological pesticides and antimicrobial pesticides 

(as defined in FQPA). Since certain pesticide products, such as wood 

preservatives and antimicrobials, are not defined as antimicrobial products 

in FQPA but are handled in the Antimicrobial Division, for the purposes of 

this notice they are considered conventional pesticides. 

III. EFFECTIVE DATE 

This PR Notice is effective immediately. 

IV. BACKGROUND ON THE REDUCED-RISK INITIATIVE 

In July 1992, the Office of Pesticide Programs (OPP) published a 

Federal Register notice announcing the need for incentives for the 

development and registration of reduced-risk pesticides. In a subsequent 

Federal Register notice (January 1993) OPP announced the initiation of the 

Reduced-Risk effort, and in July 1993 OPP published PR Notice 93-9 which 

provided interim reduced-risk criteria and guidance for submissions. 

Since July 1993, applicants have sent thirty-nine new chemical or new 

use submissions to OPP for consideration as reduced-risk pesticides. Of 

the thirty-nine, twenty-two have been accepted by OPP as reduced-risk 

candidates; and sixteen have been rejected. Of the twenty-two accepted 

reduced-risk submissions, fourteen have been registered. The following is 

a list of the registered pesticides by accepted common names (if available) 

and their trade name (in parenthesis): 

(1) Hexaflumuron (Recruit) - below ground bait station termiticide 

(2) Flumiclorac-pentyl (Resource) - post emergent herbicide on corn, 

soybeans 

(3) Methyl Anthranilate (Rejex-It) - bird repellent on cherries, 

grapes, blueberries, forestry 

(4) Tebufenozide (Confirm) - insecticide on walnuts 

(5) Hymexazol (Tachigaren) - fungicide seed treatment on sugar beets 

(6) Fludioxonil (Maxim) - fungicide seed treatment on corn, sorghum 

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(7) (Cadre) - herbicide on peanuts 

(8) (Mefenoxam) - fungicide on multiple crops 

(9) Spinosad (Spinosad) - insecticide on cotton 

(10) Azoxystrobin (Heritage) - fungicide on turf 

(11) Alpha-Metolachlor (CGA 77102) - herbicide on multiple crops. 

(12) Hexaflumuron (Recruit) - above ground bait station new use 

termiticide 

(13) Imazamox (Raptor) - herbicide on soybeans 

(14) Azoxystrobin (Heritage) - fungicide on grapes, bananas, peaches, 

tomatoes, pecans and peanuts 

The major advantage for reduced-risk pesticides is expedited 

registration review. For FY95 and FY96 (prior to the passage of FQPA in 

August 1996) the average total time required to register a new conventional 

pesticide was thirty-eight months. For reduced-risk pesticides the average 

total time for registration was only fourteen months. Since passage of 

FQPA three new AI, reduced-risk pesticides were registered in seventeen, 

eighteen and seventeen months, somewhat longer than the pre-FQPA average 

but still substantially shorter than the conventional pesticide times. The 

faster registration times reflect, in part, the expedited review status 

granted reduced-risk actions. Not only is the initial submission granted a 

high review priority but also any resubmission that may be necessary. 

If the applicant is simultaneously seeking registration in Canada, and 

if the application has been determined by Canada to be complete, the 

reduced-risk action can also qualify for work-sharing between the two 

countries. While this work-sharing program is still in the "pilot" stage, 

it could result in further reduced review times and greater harmonization. 

V. CHARACTERISTICS OF ACCEPTABLE AND UNACCEPTABLE SUBMISSIONS FOR THE 

REDUCED-RISK INITIATIVE 

OPP has assessed fourteen of the twenty-two reviews conducted by the 

Reduced Risk Committee of submissions that were determined to be 

reduced-risk. Those factors that most significantly contributed to EPA's 

decision 

to grant reduced risk status are summarized below in descending order: 

o human health effects 

- very low mammalian toxicity 

- toxicity generally lower than alternatives (10-100X) 

- displaces chemicals that pose potential human health 

concerns [e.g., organophosphates (OPs), probable 

carcinogens (B2s)] 

- reduces exposure to mixers, loaders, applicators and reentry 

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workers 

o non-target organism effects (birds) 

- very low toxicity to birds 

- very low toxicity to honeybees 

- significantly less toxicity/risk to birds than alternatives 

- not harmful to beneficial insects, highly selective pest 

impacts 

o non-target organism effects (fish) 

- very low toxicity to fish 

- less toxicity/risk to fish than alternatives 

- potential toxicity/risk to fish mitigatable 

- similar toxicity to fish as alternatives but significantly 

less exposure 

o groundwater (GW) 

- low potential for GW contamination 

- low drift, runoff potential 

- runoff mitigatable 

o lower use rates than alternatives, fewer applications 

o low pest resistance potential (i.e., new mode of action) 

o highly compatible with IPM 

o efficacy. 

OPP has also assessed eleven of the sixteen reviews conducted by the 

Reduced Risk Committee of submissions that were determined not to be 

reduced-risk. Those factors that most significantly contributed to an 

unacceptable decision by the committee are summarized below in descending 

order: 

o human health effects 

- inadequate/inappropriate comparisons with alternatives 

- inadequate documentation of effects 

- human health risk reduction case weak 

- risk reduction case inadequate when compared to alternatives 

o non-target organism effects (birds and fish) 

- toxic to birds 

- toxic to fish 

- risk reduction case inadequate when compared to alternatives 

o potential GW problems 

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o unlikely to displace higher risk alternatives 

o lack of efficacy data 

o phytotoxicity. 

This survey of past decisions should assist future applicants in 

preparing their submissions. 

VI. PROCEDURES AND GUIDELINES FOR EXPEDITED REVIEW OF 

CONVENTIONAL AND ANTIMICROBIAL PESTICIDES 

A. Background 

In general, FIFRA section 3(c)(3)(A) requires EPA after receipt of an 

application for registration of a pesticide "as expeditiously as possible" 

either to register it or to notify the applicant that the application does 

not comply with the Act. FIFRA also establishes expedited review 

procedures for a variety of Agency activities associated with the 

registration of pesticides, including expedited review for certain end-use 

pesticides that are identical or substantially similar to currently 

registered pesticides ("me too" registrations) as provided in FIFRA section 

3(c)(3)(B)(II), and for antimicrobial pesticides as provided for in FIFRA 

section 3(h)(2). EPA also has several programs to expedite the 

registration process for biological pesticides by the Biopesticides and 

Pollution Prevention Division, antimicrobial pesticides by the 

Antimicrobial Division and fast track procedures to expedite the 

registration of certain amendments to existing conventional pesticide 

registrations. As a result of these programs, EPA is already expediting 

many pesticide applications for registration. 

FIFRA section 3(c)(10) establishes an expedited review for 

applications for registration and amendments to registrations for 

pesticides that "may reasonably be expected to accomplish one or more of 

the following: 

(i) Reduce the risks of pesticides to human health. 

(ii) Reduce the risks of pesticides to nontarget organisms. 

(iii)Reduce the potential for contamination of groundwater, surface 

water or other valued environmental resources. 

(iv) Broaden the adoption of integrated pest management strategies, 

or make such strategies more available or more effective." 

The statute does not establish deadlines for review of registration 

applications or amendments that meet the above criteria. Section 3(c)(10), 

however, requires EPA to notify the applicant whether the application for 

expedited review is complete no later than 30 days after receipt of the 

application. 

B. Procedures 

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EPA intends to establish a two-step procedure for expedited review 

pursuant to FIFRA section 3(c)(10). 

1. Step One - Application. For step 1, the Agency will 

determine whether an application for registration or amended registration 

qualifies for expedited review based upon whether use of the pesticide 

proposed by the application may reasonably be expected to accomplish one or 

more of the criteria listed in Section VI.A. above. 

To initiate the process, the applicant must submit an application for 

expedited review demonstrating how the use of the pesticide may reasonably 

be expected to accomplish one or more of the criteria listed in section 

VI.A. above. The applicant also must submit a reduced-risk rationale 

pursuant to the guidelines and procedures specified in sections VII - IX of 

this notice. The step 1 rationale may be a sentence or a paragraph in the 

reduced-risk rationale summary as long as the claims are documented 

elsewhere in the reduced-risk rationale. 

Certain types of pesticide applications for registration and amended 

registration already receive expedited review pursuant to existing Agency 

programs. Because the Agency is already expediting review of these 

registrations, it is not necessary to include them in the review program 

established pursuant to FIFRA section 3(c)(10). Applications that already 

receive expedited review include applications for registration or amended 

registration for biological or antimicrobial pesticides, "me-too" 

applications for registration or amended registrations of end-use 

pesticides under FIFRA section 3(c)(3)(B)(I) that are identical or 

substantially similar to other EPA registered pesticide products, and 

applications for certain pesticides under FIFRA section 3(c)(3)(B)(II). 

The FQPA amendments require EPA to make expedited decisions on 

antimicrobial pesticides as defined in FIFRA section 2(mm). Specifically, 

FIFRA section 3(h)(2) establishes goals for the time periods during which 

EPA must review different types of applications for antimicrobials covered 

by the statutory definition and make decisions whether to approve or deny 

the applications. Generally, these review and decision deadlines are 30% 

to 60% shorter than historic Agency performance in processing such 

applications. 

While FIFRA antimicrobial review deadlines do not become legally 

binding until May 1998, as a matter of policy, the Agency has committed to 

and, in fact, is meeting the goals specified in FIFRA section 3(h)(2) as 

well as the expedited deadlines already mandated in FIFRA section 

3(c)(3)(B). For every application received by the Agency since November 1, 

1996, the Agency has made a registration decision within the review periods 

provided by the statute. EPA will continue to expedite review of 

applications for registrations and amendments to registrations for 

antimicrobial pesticides pursuant to its commitment. 

The Agency's improved performance in review of antimicrobials is the 

result of several new initiatives. First, EPA has established within the 

Office of Pesticide Programs a new Antimicrobials Division (AD) that is 

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responsible for all regulatory decisions relating to antimicrobial and 

related pesticides. In addition to regulatory staff, the new AD 

organization includes scientific personnel capable of performing most of 

the analyses needed to make a registration decision. Thus, AD is capable 

of providing "one-stop shopping" for registration decisions. Second, the 

new AD management team has instituted a number of process improvements, 

including a dedicated expedited review team of "me-too" applications, that 

have resulted in a significantly improved performance. 

Thus, because EPA's current organizational and resource allocations, 

and process improvements are providing expedited review for antimicrobials, 

all types of applications for antimicrobial pesticides (as defined in FQPA) 

will be outside the scope of this PR Notice. 

What types of applications for expedited review will the Agency 

accept? An application for expedited review may be submitted only for the 

following types of actions: 

(a) an application to register a conventional pesticide that contains 

an active ingredient not contained in any currently registered 

pesticide, provided the pesticide is not a biopesticide or an 

antimicrobial pesticide (as defined in FQPA). [See sections VII 

through IX for reduced-risk rationale guidelines]; or 

(b) an application to amend the registration of a currently 

registered conventional pesticide for an additional new use, 

provided the pesticide is not a biopesticide or an antimicrobial 

pesticide (as defined in FQPA). [See sections VII through IX for 

reduced-risk rationale guidelines]; or 

a non-fast-track application for registration of a new 

formulation provided the pesticide is not a biopesticide or an 

antimicrobial pesticide (as defined in FQPA). [See section X for 

expedited review rationale guidelines]. 

2. Step 2 - Reduced-Risk Determination If an application for 

expedited review qualifies under step 1, the Agency will expedite the 

review of the reduced-risk rationale presented by the applicant to 

determine whether the pesticide qualifies under the reduced- risk criteria 

described in sections VII and X below. The Agency's Reduced-Risk Committee 

will expedite the review of the reduced-risk rationale and complete its 

review within thirty days of receipt of a complete reduced-risk rationale. 

If the Agency decides that a pesticide qualifies for reduced-risk status, 

then it will further expedite review of the remainder of the application 

for registration or amended registration as described in section IV of this 

notice. 

If the Agency denies a submission reduced-risk status, applicants 

will be given only one opportunity to rebut this decision, and the 

applicant will have four weeks to resubmit their rebuttal. Due to limited 

program resources, the Agency can only allow one opportunity to rebut a 

decision. Pesticides that EPA determines do not qualify for reduced-risk 

status during step 2 will be processed in accordance with existing Agency 

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procedures. 

VII. GUIDELINES FOR REDUCED RISK RATIONALES 

While participation in the reduced-risk pesticides program is 

voluntary, those who elect to participate must fully address all of the 

following areas: (a) executive summary, (b) human health effects; (c) 

environmental fate and effects; (d) other hazards; (e) risk discussion (f) 

pest resistance and management (e.g., IPM); and (g) comparative 

performance, (h) other information and how application complies with FQPA. 

The Agency will consider all of these areas in determining the 

acceptability of these applications. However, these may not be the 

exclusive factors in all cases. If an applicant identifies additional 

criteria that substantiate the argument that their product is indeed a 

reduced-risk pesticide, then EPA invites the applicant to submit a 

rationale with any supporting data to verify such a claim. The Agency will 

consider this additional information. 

An applicant's documentation must contain both a discussion of the 

inherent reduced-risk properties of their product, as well as a comparison 

of those properties with the properties of the commonly-used alternatives 

where appropriate. Comparisons must be made to conventional chemical 

pesticides, antimicrobial pesticides, biological pesticides, and cultural 

practices currently being used for pest control at the same use site(s) and 

for the same pest(s). 

Please note that the Agency does not expect the applicant to perform 

any additional testing to derive the data necessary to develop rationales 

for the Reduced-Risk Program. The applicant must summarize all data in the 

applicant's possession or control or available through the open literature 

for the product being submitted to the Agency. If data addressing one of 

the stated factors has been developed, but is not required for registration 

of the pesticide in the United States, the applicant must provide a summary 

of these data as part of the Reduced-Risk Rationale. If any of the 

required information is not known, that fact must be noted in the 

rationale. 

If the rationale does not include a discussion of each of these 

factors or provide reasoning as to why the factor should not be considered 

in the Agency's decision, OPP will consider the rationale to be incomplete 

and not responsive to this PR Notice. However, if the applicant believes 

that the factor does not apply to the new pesticide, the registrant must 

provide a short rationale describing this reasoning. 

In situations where the Agency has already reviewed data on the active 

ingredient, the applicant should use the Agency's review to address the 

relevant factor(s). Applicants must also provide Master Record 

Identification (MRID) numbers for each study, where appropriate. 

A. Executive Summary. Provide an executive summary that addresses 

the following considerations: 

1. Chemical Name. 

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2. Chemical Abstracts Service Registry Number. 

3. Chemical Structure. 

4. Chemical Class or Family Name of the Active Ingredient. 

5. Mode/Mechanism of Pesticidal Action for the Active 

Ingredient (if known). 

6. Proposed Use Pattern (including site(s) of application and 

pest(s) controlled), Application Methods, Application Rates, 

Frequency of Application, and Product Formulation 

Percentages. Also indicate whether the new chemical will 

be used in combination with other registered pesticides. 

7. Brief Overview Summary of the Health, Ecological and 

Environmental Fate Effects. 

8. Tier 1 statement stating which of the four FQPA criteria are 

being met by this application. 

9. Reduced-Risk Statement, articulating the specific factors 

that lead the applicant to the conclusion that the active 

ingredient offers the opportunity for risk reduction. 

10. Data Matrix, providing tabular information on all data 

available for the active ingredient. The table should 

include the guideline reference number, the study title, 

MRID number (if available), outcome of the Agency's 

evaluation (i.e., in review, acceptable, supplemental, data 

waived, etc.), and date of the Agency's review (if 

applicable). 

B. Human Health. Clearly identify the portion of the rationale 

which addresses the potential effects of the active ingredient on human 

health. When specifying the dose levels used in the toxicity studies, 

present the no-observable-effects level (NOEL) and the 

lowest-observable-effects level (LOEL). Doses need to be specified in 

terms of mg/kg/day. Also, describe qualitatively and quantitatively the 

array of effects at all dose levels tested. In the format described in 

Part IX of this PR Notice, address each of the following aspects of the 

active ingredient and its use: 

1. Acute Toxicity of the active ingredient and the 

formulations. Provide the toxicity category for each of the 

acute toxicity studies conducted on the active ingredient 

and the formulated products. 

2. Reproductive, Developmental, Mutagenic and Neurotoxic 

Properties of the active ingredient. 

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3. Oncogenic and Other Subchronic and Chronic Effects of the 

active ingredient. 

4. Toxicity of Mammalian and Plant Metabolites. 

C. Environmental Fate and Effects. Clearly identify the portion of 

the rationale which addresses the potential ecological effects of the 

active ingredient and its environmental fate. The discussion should also 

address potential environmental degradates or metabolites of the active 

ingredient. Address each of the following aspects of the active 

ingredients and its use: 

1. Mammalian Acute Toxicity 

2. Avian Acute and Subacute Toxicity 

3. Avian Reproductive Toxicity 

4. Fish Acute and Chronic Toxicity 

5. Aquatic Invertebrate Toxicity 

6. Honeybee Acute Contact Toxicity 

7. Effects on Terrestrial Plant Growth 

8. Effects on Aquatic Plant Growth 

9. Potential Exposure to Non-target Organisms 

10. Environmental Persistence (Soil and Water) 

11. Mobility in Soil and Water 

12. Transport in Air (Spray Drift and Volatility) 

13. Bioaccumulation as Indicated by the Octanol/Water Partition 

Coefficient 

D. Other Hazards. Clearly identify the portion of the rationale 

which addresses other potential human health and environmental hazards 

produced by the following: 

1. Potential to Deplete Stratospheric Ozone thus increasing 

ultraviolet radiation. 

2. Potential to Present a Hazard through Storage, 

Transportation, Mixing, Use or Disposal based on its 

physical or chemical characteristics: 

a. stability 

b. flammability 

c. corrosion characteristics 

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d. explodability 

e. oxidizing or reducing action 

f. storage stability 

3. Potential to Affect Endangered and/or Threatened Plant and 

Animal Species as designated under the Endangered Species 

Act. 

E. Risk Discussion. Clearly identify the portion of the rationale 

which addresses the following items: 

1. Discuss the information which supports the claims that the 

active ingredient presents reduced toxicity, reduced 

exposure to humans or non-target organisms, and/or reduced 

environmental burden. When discussing the ecological levels 

of concern (LOCs), present the methods used to derive them 

and provide interpretations of what the LOCs mean. 

2. Where alternative, registered pesticides or pest control 

practices exist, make a quantitative and/or qualitative 

comparison between the risks posed by the active ingredient 

under consideration and all the other pesticides commonly 

used, and/or the other current pest control practices. 

3. The comparisons with alternative technology should also 

include biological pesticides as well as cultural and 

mechanical pest management practices. 

F. Pest Resistance and Management. Clearly identify the portion of 

the rationale which addresses the following items: 

1. Describe how the active ingredient addresses the development 

of pest resistance, either to the active ingredient itself 

or to existing pesticides registered for the same use. 

2. Discuss the suitability of the active ingredient for use in, 

or encouraging the adoption of, Integrated Pest Management 

(IPM) programs. This discussion should include information 

on the effects of the pesticide on natural predators, 

parasites and pathogens of each target pest, if such 

information is known. The degree of risk and/or usage 

reduction to be achieved by the IPM program must also be 

addressed. 

G. Comparative Performance Data (efficacy data). These data are 

important to assure that risk reduction has a reasonable opportunity to be 

accomplished by adoption of the new pesticide by growers. 

1. It is desirable to have summaries of comparative performance 

data in which the performance of the candidate pesticide is 

compared to that of alternative control measures under 

actual-use or simulated actual-use conditions. 

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2. Summaries of the available efficacy data if comparative 

performance data are not available. 

Summaries should include statistical analysis of significant 

differences between the new pesticide and the commonly used alternatives. 

Summaries should also include experimental methodologies such as 

application rates, application intervals, pest pressure, weather 

conditions, varieties of the crop used, etc. Unfavorable results must be 

included. Efficacy experiments performed under substantially different 

conditions should not be combined (examples include differences in pest 

pressure, geography, strain/race of pest and weather). Guidance for this 

requirement can be obtained from standardized published tests such 

"Fungicide and Nematicide Tests," "Insecticide and Acaricide Tests" and 

methods section sections of juried professional journals. 

H. Other Information. Submission of the following additional 

information will assist the Agency in making its decision on the active 

ingredient: 

1. A copy of the proposed product label(s). 

The Agency will consider all of these criteria using a 

weight-of-evidence approach. 

VIII. GUIDELINES FOR FQPA RATIONALE FOR REDUCED RISK PESTICIDES 

Reduced-risk submissions should also provide a rationale that 

explains how this registration action complies with the requirements of 

FQPA. Such rationale should follow guidance provided in Appendix A of PR 

Notice 97-1 (January 31, 1997). Such rationale should address at a minimum 

aggregate risk, special sensitivities, endocrine effects and potential 

common mechanisms of toxicity with other registered pesticides. Appendix A 

is provided as an attachment to this notice. 

IX. FORMATTING AND SUBMITTAL PROCEDURES FOR REDUCED-RISK PESTICIDES 

Formatting (A) and submittal (B) procedures for Reduced-Risk 

Rationales are provided below. These procedures will enable EPA to easily 

identify the application for priority consideration. Also, applicants 

should note that it is unlawful to falsify any portion of an application. 

FIFRA Sections 12(a) (2)(M), 12(a)(2)(R) and 18 U.S.C. Section 1001 make 

such actions unlawful and can result in civil or criminal penalties. The 

Agency will not consider an application under the Voluntary Reduced-Risk 

Pesticide Initiative if the applicant does not follow these procedures. 

A. Format. The reduced-risk rationale document must include the 

following elements in the order indicated: Title Page, Statement or 

Supplemental Statement of Data Confidentiality Claims, Cover Sheet to 

Confidential Attachment and Confidential Business Information (CBI) 

Reduced-Risk Attachment. Any supporting data must comply with PR Notice 

86-5 requirements. 

The Reduced-Risk Rationale must be bound as a separate entity and 

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consecutively paginated beginning with the title page as page 1. The total 

number of pages must be represented on the title page. Do not include CBI 

on the title page. On the title page, include titles and author(s). 

B. Submitting a Reduced-Risk Rationale Registration Application. The 

Reduced-Risk Rationale should accompany the registration application and 

supporting data packages. This PR Notice does not supersede established 

submittal procedures as addressed in PR Notice 91-5; rather, this PR Notice 

provides additional guidance for submitting the reduced-risk rationale. 

OPP uses distribution codes to facilitate the delivery of registration and 

other submissions within the program. When preparing your submission to 

mail or deliver to OPP, direct your submission to the Document Processing 

Desk and including the following distribution code: REDUCED-RISK APPL. 

The submission delivered via the U.S. Postal Service should be 

directed to OPP using the following address: 

Document Processing Desk (REDUCED-RISK APPL.) 

Office of Pesticide Programs (7504C) 

U.S. Environmental Protection Agency 

401 M Street, S.W. 

Washington, D.C. 20460-0001 

Submissions via personal or courier delivery should be directed to the 

Document Processing Desk between the hours of 8:00 a.m. and 4:00 p.m., 

Monday through Friday, excluding federal holidays. OPP's Document 

Processing Desk is located at the following address: 

Office of Pesticide Programs 

Document Processing Desk (REDUCED-RISK APPL.) 

Room 266A, Crystal Mall 2 

1921 Jefferson Davis Highway 

Arlington, VA 22202 

C. Rebuttals may be submitted to Rick Keigwin, Registration Division 

(7505C), U.S. Environmental Protection Agency, 401 M Street, S.W., 

Washington, DC 20460. 

X. GUIDELINES FOR EXPEDITED REVIEW OF NON-FAST-TRACK NEW FORMULATIONS 

FOR CURRENTLY REGISTERED CONVENTIONAL PESTICIDES 

Some new, non-fast-track, formulations and amendments to currently 

registered conventional pesticide products could result in reduced risk. 

To qualify, an application for expedited review under this section must 

first demonstrate that it meets one or more of the step 1 criteria listed 

in section VI.A of this notice. Secondly, the registrant must demonstrate 

that the new formulation, when compared with all of the existing 

formulation(s) for the active ingredient, results in significant risk 

reduction. Examples of risk reduction that would most likely qualify for 

expedited review include new formulations that result in (a) at least a 35% 

reduction in the amount of active ingredient applied, (b) at least a ten 

fold reduction in risks to mixers, loaders and applicators, (c) at least a 

50% reduction in the product's potential to leach into groundwater or run 

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off into surface water or (d) a significant reduction in risk to non-target 

species. Actions that are accepted will qualify for expedited review but 

will not be classified as reduced risk. 

The process for submission of a non-fast-track formulation or new 

end-use product differs from the new active ingredient/new uses procedures. 

For consideration of a non-fast-track new formulation/end-use product, the 

registrant shall make a submission to the Product Manager with documented 

rationale for consideration of expedited review. The Product Manager will 

review the request and determine if the submission qualifies for expedited 

review. Consultation with other Product Managers or Branch Chiefs in 

Registration Division may be necessary. The Product Manager will notify 

the applicant of the expedited review status within 30 days. If denied 

expedited review status, there will be one opportunity for rebuttal; the 

submitter has four weeks to resubmit their rebuttal to the PM. Finally, if 

the applicant holds the registrations for the old formulations that this 

new formulation will replace, a request for cancellation of the old 

formulations is also required. This cancellation request will not be 

processed until a registration is issued on the new formulation. 

XI. BIOLOGICAL PESTICIDES 

A. Background. In November, 1994, EPA established a pilot division, 

the Biopesticides and Pollution Prevention Division (BPPD), with part of 

its mission to expedite the registration and reregistration of biological 

pesticides (biopesticides). Biopesticides are any of the following: (1) 

naturally occurring or genetically altered microorganisms, (2) 

plant-pesticides (pesticidal substances produced in a plant and the genetic 

material necessary for the production of those substances), or (3) 

biochemical pesticides. In addition, BPPD does review the registration 

submissions for some other pesticidal substances which warrant a reduced 

data set as described below in Part C. 

BPPD is now a permanent part of the Office of Pesticide Programs. To 

date, BPPD has been successful at expediting the registration of biological 

pesticides. Since the Division was established in the fall of 1994, 37 new 

biological pesticides have been registered including the first 

plant-pesticide products. New biopesticide active ingredients are 

typically registered in less than 11 months which is substantially less 

time than the average review time for conventional pesticides. 

B. Priority for Review in BPPD. EPA believes that biological 

pesticides generally pose less risk than most conventional pesticides. 

Therefore, EPA established BPPD to provide an expedited review to all 

biological pesticide products. BPPD's priority of actions is based upon 

the order submissions are received rather than a comparison of risk among 

the biopesticides. When a particular pesticide registrant requests that a 

certain one of its submissions receives top priority amongst that company's 

other biological actions, BPPD honors the requests. Also, if a 

biopesticide would replace the use of a hazardous pesticide requested for 

an emergency exemption under FIFRA Section 18, BPPD would make a 

case-by-case determination on whether to further expedite the regulatory 

decision. 

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C. Characteristics of Biopesticides 

1. Microbial Pesticides. Microbial pesticides contain a 

bacterium, fungus, virus, protozoan or alga as the active ingredient. 

Approximately 50 microbial pesticide active ingredients are registered by 

EPA. The most widely known of these are varieties of the bacterium, 

Bacillus thuringensis or Bt, which can control certain moths, beetles, and 

mosquitoes. Data requirements for microbial pesticides are found in 40 CFR 

158.740. BPPD encourages potential registrants to contact the Division for 

a preregistration submission meeting to discuss these data requirements, 

and the scientific rationales for study waivers. 

2. Plant-Pesticides. In November of 1994, EPA published a 

proposed rule for regulation of plant-pesticides. In that document, EPA 

encouraged potential registrants to follow the proposed rule until the 

final rule is published. To date, seven plant-pesticide registrations have 

been issued. Once the final rule is published, EPA will propose guidelines 

for registration of plant-pesticides which will be incorporated into 40 CFR 

Part 158. The guidelines will be open to public comments and appropriate 

public meetings will be held prior to final guidelines being issued. In 

the meantime, potential registrants should work closely with BPPD to 

determine the data requirements for their products. 

3. Biochemical Pesticides. Biochemical pesticides are 

distinguished from conventional chemical pesticides by their nontoxic mode 

of action toward target organisms (usually species specific), e.g. growth 

regulation or mating disruption, and by the natural occurrence of the 

pesticidal substance. In contrast, conventional pesticides generally are 

toxic and may affect a wider range of target species. Biochemical 

pesticides generally fall into distinct biologically functional classes: 

Semiochemicals (chemicals emitted by a plant or animal that modify the 

behavior of receptor organisms of similar or different species), hormones, 

natural plant regulators, natural insect growth regulators, and enzymes. 

In many instances, biochemical pesticides may be synthesized rather than 

isolated from nature. In order for synthesized pesticides to be considered 

as biochemical pesticides, they must be demonstrated to be structurally 

similar and functionally identical to a naturally occurring biochemical 

pesticide. 

Although there are no strict criteria for the definition of 

biochemical pesticides, most biochemical pesticides are applied at very low 

rates, are highly volatile, or are applied in bait, trap, or "encapsulated" 

formulations, thus resulting in less exposure (and less likelihood of 

adverse effects to humans and the environment than from use of most 

conventional pesticides). In keeping with their unique properties, 

biochemical pesticides have been assigned a set of data requirements which 

are organized in a tiered testing scheme to ensure, to the greatest extent 

possible, that only the minimum data sufficient to make scientifically 

sound regulatory decisions will be required. The data requirements are 

outlined in 40 CFR Part 158.690. 

4. Pesticides Which Warrant Reduced Data Requirements. The 

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Agency recognizes that many naturally occurring pesticidal chemicals may be 

highly toxic to their target organisms and does not intend to include these 

as biochemical pesticides. BPPD has elected to review certain of these 

naturally occurring pesticides that may operate via a toxic mode of action 

toward target organisms, but which a priori also would be candidates for an 

initial tiered data set, as required for biochemical pesticides. These 

"biochemical-like" pesticides have not yet been formally classified into a 

subcategory of pesticides for nomenclature purposes. These pesticides 

usually have uncomplicated structures and are commonly present in the 

environment or the human diet at significant levels or have been widely 

used for non-pesticidal purposes. Thus, any clinical or nontarget effects 

are very likely to have been noticed and should be well documented. BPPD 

has found that potential registrants for these products generally follow 

the same data requirements as the biochemicals, but a preregistration 

meeting with the Division is highly recommended before extensive testing 

and before formal submission of an application. 

D. Guidelines for Classification as a Biochemical or a 

"Biochemical-like" Pesticide to be Reviewed by BPPD. On request, the 

Biopesticides and Pollution Prevention Division (BPPD) will evaluate 

products on an individual basis to classify them as biochemical pesticides, 

pesticides warranting reduced data requirements ("biochemical-like"), or 

conventional chemical pesticides. 

BPPD has formed a Biochemical Classification Committee to evaluate 

written requests for classifying products proposed for BPPD review as 

biochemicals and similar products. A classification request should include 

information to support the natural occurrence of the chemical and 

information bearing on its mode of action toward the target pest. 

Additional information to support low toxicity or low exposure levels may 

be useful if available. This could include GRAS (generally regarded as 

safe) status (please cite the listing number) or information on application 

rates and/or degradation rates. Published studies or private data should 

be attached if the supporting information is not commonly known or obvious. 

E. Evaluation Standards 

1. Natural Occurrence. Naturally occurring substances may be 

inorganic or organic. As noted above, if the chemical is not naturally 

occurring, information must be provided showing that it is structurally 

similar and functionally identical to a naturally occurring substance. The 

Biochemical Classification Committee recognizes that "natural occurrence" 

may technically include substances that occur at very low levels in the 

environment, but in such amounts or locations that humans and/or nontarget 

organisms have not been exposed to significant levels of these chemicals. 

The committee may decide that these substances are not biochemical 

pesticides if there is any indication that natural exposure levels are 

insufficient to indicate potential effects from the expected product 

exposure. 

2. Nontoxic Mode of Action. A nontoxic mode of action is one 

that does not kill the target pest. The most obvious are repellents and 

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attractants. The committee has also included in the nontoxic mode of 

action category, those chemicals that may be lethal to the target, but 

operate via a physical mode of action to control the target pest. For 

example, certain oils and/or sticky substances can kill insects by clogging 

their respiratory spiracles and trachea, but such substances are not likely 

to have adverse effects on non-target organisms or humans. Desiccants also 

are considered as acting via a nontoxic mode of action. Plant growth 

regulators are usually considered to have a nontoxic mode of action; 

however, some plant growth regulators may act as herbicides at higher 

application rates. Thus, higher application rates may result in additional 

data requirements (as required for conventional chemical herbicides) or 

reclassification as a conventional chemical pesticide. 

F. Formatting and Submittal of Request for Biochemical 

Classification. The classification request should be in the form of a 

letter and should be sent directly to the Biopesticides and Pollution 

Prevention Division (7511W), Office of Pesticide Programs, US Environmental 

Protection Agency, 401 M St SW, Washington, DC 20460. It should be labeled 

"Attn.: Biochemical Classification Committee." 

G. EPA Response to Request for Biochemical Classification. 

Submissions for classification are reviewed by a team of scientists from 

several divisions within OPP. The recommendations of the Committee are 

brought to management for approval. Decisions can include classification 

as a biochemical, classification as a "biochemical-like" substance that 

warrants reduced data requirements, but is not a biochemical, or 

classification as a conventional pesticide. The potential registrant is 

informed by letter of the decision. Because these are preapplication 

requests for classification, the information submitted and the results may, 

upon request, be treated as confidential business information. 

H. Rebuttals to Denials for Biochemical Classification. In some 

cases, inadequate information is supplied so that a Committee 

recommendation cannot be made. In these cases the potential registrant is 

asked to submit additional information. If a potential registrant 

disagrees with classification as a conventional pesticide (essentially a 

denial of classification as a biochemical), a rebuttal can be submitted to 

the Biochemical Classification Committee for reconsideration. 

XII. FOR FURTHER INFORMATION 

For further information on reduced-risk submissions for conventional 

pesticides, contact Peter Caulkins, Associate Director, Registration 

Division at (703)305-6550. For further information on antimicrobial 

pesticides, contact Bill Jordan, Associate Director, Antimicrobials 

Division at (703)308-6411. For further information on microbial and 

plant-pesticides, contact Phil Hutton, Chief, Microbial Pesticides Branch, 

BPPD at (703) 308-8260 and for biochemicals, contact Roy Sjoblad, Chief, 

Biochemical Pesticides Branch, BPPD at (703) 308-8269. 

Daniel M. Barolo, Director 

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Office of Pesticide Programs 

APPENDIX A 

CONTENT OF SUPPLEMENTAL INFORMATION 

As indicated at the beginning of the PR Notice, registrants, 

applicants and petitioners are not currently required to submit any 

additional information. Nevertheless, since the new statute requires the 

Agency to consider additional information in order to make the necessary 

decisions, EPA recognizes that many registrants, applicants and petitioners 

may wish to provide the supplemental information to the Agency even without 

a requirement to do so. For those registrants, applicants or petitioners 

who wish to supplement their original submissions with additional 

information, this Appendix describes what information the Agency would 

consider helpful additions for its review.(*1) 

(*1) An agency may not conduct or sponsor, and a person is not 

required to respond to, a collection of information unless it either 

displays a currently valid OMB control number or is imposed on the 

person by statute (5 CFR 1320.6(a) & (e)). The collection of 

information relating to the registration, reregistration, and 

tolerance programs have are approved under OMB Control Numbers 

2070-0024 (expires: 6/30/99); 2070-0032 (expires: 5/3/98); 2070-0040 

(expires: 11/30/99); 2070-0060 (expires: 5/31/98); 2070-0122 (expires: 

11/30/97); 2070-0107 (expires: 7/31/99). If you should have any 

comments on the collection activities, please send them to the 

Director, OPPE Regulatory Information Division, U.S. Environmental 

Protection Agency (Mailcode 2137), 401 M St., S.W., Washington, D.C. 

20460. Include the OMB control number in any correspondence. Note 

that this address is ONLY for comments on the collection activity. Do 

not submit your information to this address. 

All tolerances or tolerance exemptions and associated registration 

actions under FIFRA section 3 or reregistration actions under FIFRA section 

4, whether pending or future, will need to comply with the new safety 

standard of section 408(b)(2) of the Federal Food, Drug and Cosmetic Act. 

In addition, because EPA intends to apply a similar standard to actions 

involving non-food use pesticides that may pose significant non-dietary 

risks to infants and children, all registration and reregistration actions 

also will need to comply with this standard with respect to the Agency's 

consideration of infants and children exposure to the pesticide. 

In preparing a package to be submitted, those seeking a registration, 

reregistration, tolerance, or an exemption from the requirement of a 

tolerance for a food use pesticide, or a registration or reregistration of 

a non-food use pesticide that may result in significant exposure to 

children, may need to provide additional information and/or materials to 

address adequately the factors and specific questions contained here. 

Those who wish to submit additional information should keep in mind that 

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the Agency will consider each factor listed below (and perhaps others as 

Agency policies are developed) in addition to any data and information 

already required. In addition, it is important to note that the 

information identified here may not be definitive in all cases. Additional 

information or more detailed information may be needed in individual cases. 

If a registrant, applicant, or petitioner can identify additional 

information that would assist the Agency in addressing the FQPA provisions, 

EPA welcomes such information. Although the submission of this information 

is not currently required by the regulations, if such information is not 

submitted, the Agency must rely on previously submitted data, if 

applicable, or on broad or default assumptions when considering the factors 

listed. As a result, favorable action on an application, petition, or 

reregistration decision may be significantly delayed or precluded 

altogether. 

It would be helpful for any submitted documentation to contain a 

discussion of each of the following factors as it relates to the pesticide 

and proposed tolerance or tolerance exemption. If information on any 

factor is not known, that fact, along with an explanation, should be noted 

in the rationale. It is important to note that EPA does not expect the 

registrant, applicant, or petitioner at this time to perform any additional 

testing to derive the data necessary to develop its rationales. However, 

if it has in its possession data from preliminary reports of ongoing 

studies, articles from published literature, unpublished report 

information, previously unsubmitted studies, or supplemental data that are 

otherwise pertinent to the Agency's concerns, the party is encouraged to 

submit them. Likewise, if a registrant, applicant, or petitioner believes 

that a factor is not applicable to its product, a discussion as to why this 

view is held should also be included. The Agency will consider all 

relevant factors in determining an application's completeness and in 

setting priorities for review. 

Based on the new safety standard, EPA will need the following 

additional information in order to make appropriate regulatory decisions: 

(For details on each factor, please refer to the explanations below in 

parts A and B.) 

1. An informative summary of the petition or application, including a 

summary of the supporting data, information, accompanying rationales, 

and a statement providing permission to publish such summary, and 

2. Information and discussion pertaining to a specific safety 

determination for infants and children including their special 

susceptibilities and exposure patterns to the particular pesticide. 

A. Food Use Pesticides: Registration and Reregistration Actions, 

Experimental Use Permits, Tolerance (or Exemption) 

Petitions and Reassessments 

In the format described in Appendix C of this PR Notice, address each 

of the following with respect to the pesticide and its use(s): 

Special Sensitivities 

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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, 

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pharmaceutical, cosmetic, food additive). 

Cumulative Effects 

Discuss the mechanism and mode of action of this pesticide. Identify 

other chemicals that may fall into this category (both pesticide and 

non-pesticide chemicals). Provide information regarding common 

mechanisms and modes of action with other chemical substances based on 

structural similarity, same or similar endpoints, and other relevant 

criteria. Provide any data and/or evidence illustrating similarities 

at the cellular/molecular level. 

Discuss the appropriateness of combining exposures in this particular 

case. Where data are not available, discuss appropriateness of using 

default assumptions and what defaults should be used. 

Endocrine Effects(*4) 

(*4) As indicated in section 408(p)(1) & (2), the Agency has 2 

years to develop a screening method, with a total of 3 years to 

implement such a program. 

Discuss and provide any evidence relevant to the possibility that the 

pesticide may have endocrine disrupter effects individually or in 

combination with another chemical. Include the potential for 

synergistic effects of your chemical in combination with other 

chemicals. 

Identify any instances of reported (proven or alleged) adverse 

reproductive or developmental effects to domestic animals or wildlife 

as a result of exposure to your chemical, or that occurred in an area 

where the chemical is known to have been used. Provide all 

information regarding the circumstances, estimated level of exposure, 

and details of the effect. 

Residue Chemistry 

Information should include a discussion of compatibility with 

established Codex Alimentarius Commission Maximum Residue Levels 

(MRLs), submission of a practical analytical method with an 

appropriate limit of detection, and a discussion of the potential need 

for tolerances for processed foods. For tolerance exemption 

petitions, indicate if the chemical is on the Food and Drug 

Administration's Generally Recognized As Safe (GRAS) list. A summary 

of all tolerances and exemptions from tolerance being proposed should 

also be included. 

Benefits Information (For Reregistration Actions Only) 

If the information and data submitted indicate that an existing 

tolerance, reviewed according to the requirements of the new legislation, 

should be determined to be unsafe (that is, to exceed the "reasonable 

certainty of no harm" standard), the new law allows EPA to consider 

pesticide benefits information in certain instances. An "eligible 

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pesticide chemical residue" (for which an "eligible tolerance" may be 

applicable) is defined as a chemical residue for which 

1) EPA is unable to identify a level of exposure that will not cause 

or contribute to a known or anticipated harm to human health (that is, 

the effect is a non-threshold effect); 

2) an appropriate quantitative risk assessment for the lifetime risk 

of the non-threshold effect has been determined; and 

3) if there are also threshold effects associated with the chemical, 

EPA is able to identify a level at which the residue will not cause 

any known or anticipated harm to human health and that the level of 

aggregate exposure is safe. 

Registrants who suspect that an existing tolerance for their chemical, 

which has been classified by the Agency as exhibiting a non-threshold 

effect, may exceed the new safety standard, and wish the Agency to consider 

an eligible tolerance for residues of that pesticide, may need to submit 

the following information: 

Conditions Regarding the Use of the Pesticide 

Information and/or data indicating that the use of the pesticide 

chemical that produces the residue protects consumers from adverse 

health effects that would pose a greater risk than the dietary risk 

from the residue, OR 

Information and/or data showing that the use of the pesticide chemical 

that produces the residue is necessary to avoid a significant 

disruption in the domestic production of an adequate, wholesome, and 

economic food supply. 

Conditions Regarding the Risk of a Pesticide 

Evidence that the yearly risk associated with the nonthreshold effect 

from aggregate exposure to the residue is not greater than ten times 

the yearly risk allowed under the new safety standard, AND 

Evidence that the tolerance is limited to ensure that the lifetime 

risk associated with the nonthreshold effect from aggregate exposure 

to the residue is not greater than twice the lifetime risk allowed 

under the new safety standard. 

It is important to note that the above information does not supersede 

any existing benefits requirements under FIFRA, such as public health pests 

and benefits data necessary for a public interest finding under FIFRA 

section (3)(c)(7). 

B. Non-Food Use Pesticides: Registration or Reregistration Actions 

In the format described in Appendix C of this PR Notice, address each 

of the following with respect to the pesticide and its use(s): 

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Potential for Exposure to Children 

Describe the use pattern of your chemical. If you believe that its 

use(s) would not potentially result in significant exposure to infants 

and children, provide a discussion and rationale as to why this view 

is held. For chemicals that appear not to result in a significant 

exposure to infants and children, no additional information is needed. 

If you believe that the use of your chemical may result in significant 

children's exposure, the following factors may need to be addressed: 

Special Sensitivities 

Discuss and/or provide evidence as to whether or not infants and 

children are more susceptible to the chemical than adults. 

Discuss the potential for greater acute and/or chronic risk for 

infants and children. If the pesticide demonstrates toxic effects, 

then discuss the endpoint used to perform the assessment including 

relevance to infants and children and the details as to how the 

exposure assessment was conducted and whether the estimated risk is 

within the Agency's levels of concern. 

Aggregate Exposure 

Discuss the potential for the transfer of residues of both the parent 

chemical and any degradates or of the microbial pesticide to drinking 

water. For chemical pesticides, the discussion should include, but 

not be limited to, information indicating whether the pesticide is 

persistent and/or mobile, the potential for transport in air (spray 

drift and volatility data), and any available modeling data. For 

microbial pesticides, the discussion should instead include 

information pertaining to the biology of the microorganism and 

indicate whether the pesticide is persistent and/or mobile. 

Has the chemical or any of its degradates been detected in ground 

water or surface water? Would this chemical or any of its degradates 

likely pass through primary or secondary drinking water treatment into 

finished water? Are any States conducting water monitoring programs 

for this pesticide? If so, data collected by the States and all 

relevant information should also be included. 

Discuss the potential for significant exposure to the chemical of 

children by non-dietary routes. Are there non-occupational, 

structural, or residential uses (e.g., pet, swimming pool, lawn and 

garden, or topical insect repellents)? Is the pesticide used in or 

around schools, parks, or recreation facilities? Provide all 

available exposure data. 

Discuss the chronic and/or acute risk of aggregate exposure via 

multiple pathways for the general population, infants and children 

should include a discussion of all assumptions used and uncertainties. 

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Identify other non-pesticidal uses of the chemical (e.g., industrial, 

pharmaceutical, cosmetic, food additive). 

Cumulative Effects 

Discuss the mechanism and mode of action of this pesticide. Identify 

other chemicals that may fall into this category (both pesticide and 

non-pesticide chemicals). Provide information regarding common 

mechanisms and modes of action with other chemical substances based on 

structural similarity, same or similar endpoints, and other relevant 

criteria. Provide any data and/or evidence illustrating similarities 

at the cellular/molecular level. 

Discuss the appropriateness of combining exposures in this particular 

case. Where data are not available, discuss appropriateness of using 

default assumptions and what defaults should be used. 

Endocrine Effects 

Discuss and provide any evidence relevant to the possibility that the 

chemical may have endocrine disrupter effects individually or in 

combination with another chemical. Include the potential for 

synergistic effects of your chemical in combination with other 

chemicals and whether or not your chemical could act as a catalyst for 

another hormone-disrupting chemical. 

Identify any instances of reported (proven or otherwise) adverse 

reproductive or developmental effects to domestic animals or wildlife 

as a result of exposure to your chemical, or that occurred in an area 

where the chemical is known to has been used. Provide all information 

regarding the circumstances, estimated level of exposure, and details 

of the effect. 

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