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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 Regi stration of Pesticide Products Subject: Guidelines for Expedited Review of Conve ntional 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 Unaccep table Submissions For The Reduced-Risk Initiative VI. Procedures And Guidelines For Expedited Review of Conventi onal And Antimicrobal Pesticides VII. Guidelines For Reduced Risk Rationales VIII. Guidelines For FQPA Rationale For Reduced Risk Pesticides

IX. Formatting And Submittal Procedur es For Reduced-Risk Pesticides X. Guidelines For Expedited Revi ew 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, F ungicide, 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 expedi ted review of any pesticide. These procedures and guidelines must be in place within one year after the date PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 1 of 24 5/5/2015of enactment of the FQPA (by August 3, 1997) . EPA has already established a Reduced Risk Initiative for conventional pesticides , has formed the Biope sticides and Pollution Prevention Division to review biological pesticides and has established the Antimicrobial Division to review antimicrobial pesticides. Th e 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 cr iteria published in Fede ral 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 Divi sion and describes how an applicant can apply for biochemical pe sticide classification. The goal of the Reduced-Risk Pesticide Initiative and the Biopesticides and Pollution Prevention Division is to encourage the devel opment, 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 expedi ted review of all types of antimicrobial registration actions.

II. 

## Applicability
This notice applies to all applicants for in itial registration and am ended registration for conventional pesticides, as described more fully in Sections IV-X, and for biological pesticides, as described in Section XI. The term "conventional pesticid es" as used in this notice includes all pesticides other than biologi cal pesticides and anti microbial pesticides (as defined in FQPA). Since certain pesticide products, suchas wood preservatives and antimicrobials, are not defined as antimicrobi al products in FQPA but are handled in the Antimicrobial Division, for the purposes of th is 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 Program s (OPP) published a Federal Register notice announcing the need for incentives for the de velopment and registration of reduced-risk pesticides. In a subsequent Federal Regi ster 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 cr iteria and guidance for submissions. Since July 1993, applicants have sent thirty-n ine new chemical or new use submissions to OPP for consideration as redu ced-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, f ourteen have been registered. The following is a list of the registered pest icides by accepted common names (if available) and their trade name (in parenthesis): 1. Hexaflumuron (Recruit) - below ground bait station termiticide PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 2 of 24 5/5/20152. 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) - fungici de 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 (Heritag e) - 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) - fu ngicide on grapes, bananas, peaches, tomatoes, pecans and peanuts
The major advantage for reduced-risk pesticid es is expedited registration review. For FY95 and FY96 (prior to the passage of FQ PA in August 1996) the average total time required to register a new conventional pest icide 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 pe sticide 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 priori ty but also any resubmission that may be necessary. If the applicant is simultaneous ly seeking registration in Canada, and if the application has been determined by Canada to be comple te, the reduced-risk action can also qualify for work-sharing between the two countries. Wh ile this work-sharing program is still in the "pilot" stage, it could result in further reduced reviewtimes 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 determin ed to be reduced-risk. Those factors that most significantly contributed to EPA's d ecision to grant reduced risk status are summarized below in descending order: PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 3 of 24 5/5/2015◦ human health effects

◾ very low mammalian toxicity

◾ toxicity generally lower th an 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 insect s, 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 fishas alternatives but significantly less exposure

◦ groundwater (GW)

◾ low potential for GW contamination

◾ low drift, runoff potential

◾ runoff mitigatable

◦ lower use rates than altern atives, fewer applications

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

◦ highly compatible with IPM

◦ efficacy

OPP has also assessed eleven of the sixt een reviews conducted by the Reduced Risk Committee of submissions that were determ ined 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 PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 4 of 24 5/5/2015◦ 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) requi res 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 pesticid es, including expedited review for certain end-use pesticides that are identical or s ubstantially similar to currently registered pesticides ("me too" registrations) as pr ovided in FIFRA secti on 3(c)(3)(B)(II), and for antimicrobial pesticides as provided for in FIFRA sect ion 3(h)(2). EPA also has several programs to expedite the registra tion process for biological pesticides by the Biopesticides and Pollution Prevention Division, antimicrobialpesticides by the Antimicrobial Division and fast track pro cedures to expedite the registration of certain amendments to existi ng conventional pesticide registrations. As a result of these programs, EPA is al ready expediting many pest icide 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 whethe r 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 proc edure 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 amende d registration qualifies for expedited review based upon whether use of the pesticide proposed by the application PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 5 of 24 5/5/2015may reasonably be expected to accomplish one or more of the criteria listed in Section VI.A. above. To initiate the process, the applic ant must submit an application for expedited review demonstrating how th e 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 senten ce 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 applicat ions for registration and amended registration already receive expedited review pursuant to existing Agency programs. Because the Agency is al ready 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 appl ications for registration or amended registration for biological or antimicrobi al pesticides, "me- too" applications for registration or amended registrati ons of end-use pest icides under FIFRA section 3(c)(3)(B)(I) that are identical or substantia lly similar to other EPA registered pesticide products, and appl ications 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 inFIFRA section 2(mm). Specifically, FIFRA section 3(h)(2) establishes goals for the time periods during which EPA must review different types of a pplications for antimicrobials covered by the statutory definition and make d ecisions whether to approve or deny the applications. Generally, these revi ew and decision deadlines are 30% to 60% shorter than historic Agency performance in processing such applications. While FIFRA antimicrobial review de adlines 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 alre ady mandated in FIFRA s ection 3(c)(3)(B). For every application received by the Agency since November 1, 1996, the Agency has made a registration decisi on 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 re view of antimicrobials is the result of several new initiatives. First, EP A 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 cap able of providing "one-stop shopping" for registration decisions. Second, th e new AD management team has instituted a number of process im provements, including a dedicated expedited review team of "me-too" a pplications, that have resulted in a significantly improved performance. PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 6 of 24 5/5/2015Thus, because EPA's current organizational and resource allocations, and process improvements are providing expe dited review for antimicrobials, all types of applications for antimicrobial pesticides (as defi ned in FQPA) will be outside the scope of this PR Notice. What types of applications for expedi ted 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 conve ntional pesticide th at contains an active ingredient not contained in any currently registered pesticide, provided the pesticide is not a bi opesticide 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 regi stration of a currently registered conventional pesticide for an additional new use, provided the pesticide is not a biopesticide or an antimicrobial pest icide (as defined in FQPA). [See sections VII thr ough IX for reduced-risk rationale guidelines]; or
a non-fast-track application for re gistration of a new formulation provided the pesticide is not a bi opesticide or an antimicrobial pesticide (as defined in FQPA). [S ee 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 Comm ittee will expedite the review of the reduced-risk rationale and complete its review within thirty days of receipt of a complete reduced-risk rati onale. 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 PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 7 of 24 5/5/2015While participation in the reduced-risk pestic ides program is voluntary, those who elect to participate must fully address all of th e following areas: (a) executive summary, (b) human health effects; (c) environmental fate and effects; (d) other hazards; (e) risk discussion (f) pest resistance and mana gement (e.g., IPM); and (g) comparative performance, (h) other information and howapplication complies with FQPA. The Agency will consider all of these areas in determining the a cceptability of these applications. However, these may not be the ex clusive 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. Th e 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 comp arison of those properties with the properties of the commonly-used alternatives where a ppropriate. Comparisons must be made to conventional chemical pesticides, antimicrobi al pesticides, biolog ical pesticides, and cultural practices currently bei ng 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 de velop rationales for the Reduced-Risk Program. The applicant must summarize all data in the applicant's possession or control or available through the ope n literature for the product bei ng submitted to the Agency. If data addressing one of the st ated factors has been developed, but is not required for registration of the pesticide in the United St ates, the applicant must provide a summary of these data as part of the Re duced-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 res ponsive to this PR Notice. However, if the applicant believes that the factor does not appl y 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 Identifi cation (MRID) numbers for each study, where appropriate. A. Executive Summary. Provide an executiv e summary that addresses the following considerations:
1. Chemical Name.
2. Chemical Abstracts Se rvice 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, Appl ication Rates, Frequenc y of Application, and PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 8 of 24 5/5/2015Product Formulation Percentages. Also indicate whether the new chemical will be used in combination wi th other registered pesticides. 7. Brief Overview Summary of the Heal th, Ecological and Environmental Fate Effects. 8. Tier 1 statement stating which of th e 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 act ive ingredient offers the opportunity for risk reduction. 10. Data Matrix, providing tabular info rmation on all data available for the active ingredient. The table should in clude the guideline reference number, the study title, MRID number (if avai lable), 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 porti on of the rationale which addresses the potential effects of the active ingredie nt on human health. When specifying the dose levels used in the toxicity studies , present the no-observable-effects level (NOEL) and the lowest-obs ervable-effects level (LO EL). Doses need to be specified in terms of mg/kg/ day. Also, describe qualitativ ely and quantitatively the array of effects at all dose le vels 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 ingredie nt and the formulations. Provide the toxicity category for each of the ac ute toxicity studies conducted on the active ingredient and the formulated products. 2. Reproductive, Developmental, Mutage nic 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 eco logical effects of the ac tive ingredient and its environmental fate. The discussion should also address potential environmental degradates or metabolites of the active i ngredient. Address eachof the following aspects of the active ingredients and its use: 1. Mammalian Acute Toxicity 2. Avian Acute and Subacute Toxicity 3. Avian Reproductive Toxicity PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 9 of 24 5/5/20154. 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 Or ganisms 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 Part ition Coefficient

D. Other Hazards. Clearly identify the porti on of the rationale which addresses other potential human health and environmental hazards produced by the following: 1. Potential to Deplete Stratospheri c Ozone thus increasing ultraviolet radiation.
2. Potential to Present a Hazard thr ough Storage, Transportation, Mixing, Use or Disposal based on its physicalor 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 envir onmental burden. When discussing the ecological levels of concern (LOCs), present the methods used to derive them and provide interpretati ons of what the LOCs mean. 2. Where alternative, registered pesticides or pest control practices exist, make a quantitative and/or qualitative comp arison between the risks posed by the PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 10 of 24 5/5/2015active ingredient under consideration and all the other pesticides commonly used, and/or the other current pest control practices. 3. The comparisons with alternative te chnology should also include biological pesticides as well as cultural and m echanical pest management practices. F. Pest Resistance and Manage ment. Clearly identify th e 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 ingred ient itself or to existing pesticides registered for the same use. 2. Discuss the suitability of the active i ngredient for use in, or encouraging the adoption of, Integrated Pest Manageme nt (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 usag e 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 opportuni ty 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 pesticid e is compared to that of alternative control measures under ac tual-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 co mmonly used alternatives. Summaries should also include experimental method ologies 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 foll owing 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 thes e criteria using a weight-of-evidence approach. PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 11 of 24 5/5/2015VIII. 

## Guidelines For FQPA Rationale For Reduced Ris k Pesticides

Reduced-risk submissions shoul d also provide a rationale that explains how this registration action complies with the requireme nts 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, sp ecial sensitivities, endocrine effects and potential common mechanisms of toxicity with other registered pestic ides. 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 criminalpenalties. 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 docume nt must include the following elements in the order indicated: Title Page, Statem ent or Supplemental Statement of Data Confidentiality Claims, Cover Sheet to C onfidential Attachment and Confidential Business Information (CBI) Reduced-Ris k Attachment. Any supporting data must comply with PR Notice 86-5 requirements.
The Reduced-Risk Rationale mu st 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 in clude CBI on the title page. On the title page, include titles and author(s). B. Submitting a Reduced-Risk Rationale Re gistration Application. The Reduced-Risk Rationale should accompany the registration application and supporting data packages. This PR Notice does not supers ede established submittal procedures as addressed in PR Notice 91-5; rather, this PR Notice provides additional guidance for submitting the reduced-ris k rationale. OPP uses distri bution codes to facilitate the delivery of registration and other submissions within the program. When preparing your submission to mail or delive r to OPP, direct your submission to the Document Processing Desk and includi ng the following distribution code: REDUCED-RISK APPL.
The submission delivered via the U.S. Post al 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 PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 12 of 24 5/5/2015Submissions via personal or courier delive ry 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 Do cument 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 Ke igwin, Registration Division (7505C), U.S. Environmental Protecti on 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 inreduced risk. To qualify, an application for expedited review under this section must fi rst demonstrate that it meets one or more of the step 1 criteria listed in section VI.Aof this notice. Secondl y, the registrant must demonstrate that the new formulation, wh en compared with all of the existing formulation(s) for the active ingredient, resu lts in significant risk reduction. Examples of risk reduction that would most likely qua lify 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 risk s to mixers, loaders and applicators, (c) at least a 50% reduction in the product's potentialto leach into groundwater or run off into surface water or (d) a significant reduction in ri sk to non-target species. Actions that are accepted will qualify for expedi ted 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 i ngredient/new uses procedures . For consideration of a nonfast-track new formulation/end- use product, the registrant sh all make a submission to the Product Manager with documented rationale fo r 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. PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 13 of 24 5/5/2015XI. 

## Biological Pesticide s A. Background. In November, 1994, EPA es tablished a pilot division, the Biopesticides and Pollution Prevention Divisi on (BPPD), with part of its mission to expedite the registration and reregistration of biological pe sticides (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 fo r the production of those substances), or (3) biochemical pesticides. In additi on, BPPD does review the registration submissions for some other pe sticidal substances which warrant a reduced data set as described below in Part C. BPPD is now a permanent part of the Offi ce 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-pe sticide products. New biopesticide active ingredients are typically regi stered in less than 11 months which is substantially less time than the average reviewtime for conventional pesticides. B. Priority for Review in BPPD. EPA believ es that biological pe sticides generally pose less risk than most conventional pest icides. Therefore, EPA established BPPD to provide an expedited review to all bi ological pesticide produc ts. BPPD's priority of actions is based upon the order subm issions are received rather than a comparison of risk among the biopesticides. When a particular pe sticide registrant requests that a certain one of its submi ssions receives top priority amongst that company's other biologicalactions, BPPD honors the requests. Also, if a biopesticide would replace the use of a hazardous pesticide requested for an emergency exemption under FIFRA Secti on 18, BPPD would make a case-by-case determination on whether to furthe r expedite the regulatory decision. C. Characteristics of Biopesticides
1. Microbial Pesticides. Micr obial pesticides contain a bacterium, fungus, virus, protozoan or alga as the active i ngredient. Approximately 50 microbial pesticide active ingredients are regi stered by EPA. The most widely known of these are varieties of the bacterium, Bacillus thuringensis or Bt, which can control certain moths, beetles, a nd mosquitoes. Data requirements for microbial pesticides are found in 40 CFR 158.740. BPPD encourages potential registrants to contact the Di vision for a preregistration submission meeting to discuss these data requireme nts, 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 th e meantime, potential registrants should work closely with BPPD to determ ine the data requirements for their products. PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 14 of 24 5/5/20153. Biochemical Pesticides. Biochemical pesticides are distinguished from conventional chemical pesticides by their nontoxic mode of action toward target organisms (usually species spec ific), e.g. growth regulation or mating disruption, and by the natural occurrence of the pesticidal substance. In contrast, conventional pesticides genera lly are toxic and may affect a wider range of target species. Biochemical pe sticides generally fall into distinct biologically functional classes: Semi ochemicals (chemical s emitted by a plant or animal that modify the behavior of receptor organisms of similar or different species), hormones, natural pl ant regulators, natural insect growth regulators, and enzymes. In many inst ances, biochemical pesticides may be synthesized rather than isolated fro m nature. In order for synthesized pesticides to be considered as biochemical pesticides, they must be demonstrated to be structurally si milar 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 appl ied in bait, trap, or "en capsulated" formulations, thus resulting in less exposure (and less likelihood of adverse effects to humans and the environment than from us e of most conventional pesticides). In keeping with their unique properties, biochemical pesticides have been assigned a set of data requirements whic h are organized in a tiered testing scheme to ensure, to the greatest extent possible, that only the minimum data sufficient to make scientifically s ound 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 al so would be candidates for an initial tiered data set, as required for bioc hemical pesticides. These "biochemicallike" pesticides have not yet been form ally classified into a subcategory of pesticides for nomenclature purposes. These pesticides usually have uncomplicated structures and are comm only 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 we ll 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 Biochemi cal or a "Biochemical-like" Pesticide to be Reviewed by BPPD. On request, the Bi opesticides and Pollution Prevention Division (BPPD) will evaluate products on an individual ba sis to classify them as biochemical pesticides, pesticides warranting reduced data requirements ("biochemical-like"), or conve ntional chemical pesticides.
BPPD has formed a Biochemical Classi fication Committee to evaluate written requests for classifying products proposed for BPPD review as biochemicals and similar products. A classification request s hould include information to support the natural occurrence of the chemical and information bearing on its mode of action PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 15 of 24 5/5/2015toward the target pest. Additional inform ation to support low toxicity or low exposure levels may be useful if availabl e. This could include GRAS (generally regarded as safe) status (please cite the listing number) or information on application rates and/or degr adation rates. Published studies or private data should be attached if the supporting inform ation is not commonly known or obvious.
E. Evaluation Standards 1. Natural Occurrence. Naturally occurr ing substances may be inorganic or organic. As noted above, if the ch emical is not naturally occurring, information must be provided showing th at it is structurally similar and functionally identical to a naturally occurring substance. The Biochemical Classification Committe e 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 si gnificant levels of these chemicals. The committee may decide that thes e substances are not biochemical pesticides if there is any indicati on that natural exposure levels are insufficient to indicate potential effect s from the expected product exposure.
2. Nontoxic Mode of Action. A nontoxic m ode 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 nont oxic 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 th eir 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; how ever, some plant growth regulators may act as herbicides at higher application rate s. 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 Requestfor Biochemical Classification. The classification request should be in the form of a letter and should be sent directly to the Biopesticides and Pollution Preventi on Division (7511W), Office of Pesticide Programs, US Environmental Protecti on Agency, 401 M St SW, Washington, DC 20460. It should be labeled "Attn.: Bioc hemical Classification Committee." G. EPA Response to Request for Bioche mical Classificati on. Submissions for classification are reviewed by a team of scientists from several divisions within OPP. The recommendations of the Comm ittee are brought to management for approval. Decisions can include classification as a bioche mical, classification as a "biochemical-like" substance that warrants reduced data requirements, but is not a biochemical, or classifi cation as a conventional pesticide. The potential registrant is informed by letter of the decision. Becau se these are preappl ication requests for classification, the information submitte d and the results may, upon request, be treated as confidential business information.
H. Rebuttals to Denials for Biochemical Classifi cation. In some cases, inadequate information is supplied so that a Comm ittee recommendation cannot be made. In PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 16 of 24 5/5/2015these cases the potential registrant is as ked to submit additional information. If a potential registrant disagrees with cl assification as a conventional pesticide (essentially a denial of classification as a biochemical), a rebuttal can be submitted to the Biochemical Classificati on Committee for reconsideration.

XII. 

## For Further Information

For further information on reduced-risk submi ssions for conventional pesticides, contact Peter Caulkins, Associate Di rector, Registration Divisi on at (703)305-6550. For further information on antimicrobial pesticides, c ontact Bill Jordan, Associate Director, Antimicrobials Division at (703)308-6411. Fo r further information on microbial and plant-pesticides, contact Phil Hutton, Chief, Microbial Pesticides Br anch, BPPD at (703) 308-8260 and for biochemicals, contact Roy Sj oblad, 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 additiona l information. Nevertheless, since the new statute requires the Agency to consider a dditional information in order to make the necessary decisions, EPA recogni zes 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 peti tioners who wish to supplement their original submissions wi th additional information, this Appendix describes what information the Agency would consider helpful additions for its review. (*1) (*1) An agency may not conduct or s ponsor, 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 statut e (5 CFR 1320.6(a) & (e)). The collection of information relating to the registration, rere gistration, and tolerance programs have are approved under OMB Control Number s 2070-0024 (expires: 6/30/99); 2070-0032 (expires: 5/3/98); 2070-0040 (expires: 11/30/99); 2070-0060 (expi res: 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 se nd them to the Director, OPPE Regulatory Information Division, U.S. Environmenta l 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 FIFR A 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 EP A intends to apply a similar standard to actions involving non-food use pesticides thatmay pose significant non-dietary risks to infants and children, all regist ration and reregistration actions also will need to comply with this standard with respect to the Agen cy's consideration of infants and children exposure to the pesticide. PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 17 of 24 5/5/2015In preparing a package to be submitted, those seeking a registration, reregistration, tolerance, or an exemption from the requireme nt 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 a dditional 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 Ag ency 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 defini tive in all cases. Additional information or more detailed information may be needed in i ndividual cases. If a registrant, applicant, or petitioner can identify additional information that would assist the Agency in addressing the FQPA provisions, EPA welcomes such in formation. Although the submission of this information is not currently required by the regulations, if such information is not submitted, the Agency must rely on previouslysubmitted data, if a pplicable, or on broad or default assumptions when considering the factors listed. As a re sult, 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 st udies, articles from published literature, unpublished report information, previously uns ubmitted 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 th at 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 n eed 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 suscep tibilities 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: Regist ration and Reregistration Actions, Experimental Use Permits, Tolerance (or Exemption) Petitions and Reassessments PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

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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 pr ovide evidence as to whether or not infants and children are more susceptibl e 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 childr en is not necessary, provide evidence to support the additional safety fact or, if any, you believe to be more appropriate. Please bear in mind thatthe Agency may accept a different margin of safety only if, based on re liable 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 targ et pest. Does the toxicity testing indicate that the establishment of an Rf D 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-causi ng 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 ri sk from microbial pesticides, the Agency requires a battery of acute toxi city/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 diet ary risks for infants and children. Discuss and/or provide evidence as to whether or not infants and children are more susceptible to the microbial pe sticide than is the adult population.

b. Acute Endpoints
Discuss the potential for greater acute di etary risk for infants and children. If the chemical or biochemical pesticid e 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 PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 19 of 24 5/5/2015If the chemical or biochemical has be en determined to be a carcinogen and has a cancer potency factor (Q1*), discuss the aggregat e excess lifetime cancer risk resulting from exposure to the chemical fro m residues in food and drinking water (ground and surface wate r) and from residential and other non-occupational source(s). Aggregate Exposure

a. Water
For a chemical or biochemical pestic ide: Discuss the potential for the transfer of residues (of both the pare nt pesticide and any degradates) to drinking water. The discussion shoul d 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 degradat es 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 monitori ng programs for this pesticide? If so, data collected by the States and al l relevant information should also be included. For a microbial pesticide: Discuss the potential for the transfer of the microbial pesticide to drinking water. The discussi on 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 th is 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 expos ure 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 Agen cy'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 th e discussion, any non-pesticidal uses of the chemical (e.g., industrial, pharma ceutical, cosmetic, food additive). PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 20 of 24 5/5/2015Cumulative Effects Discuss the mechanism and mode of acti on of this pesticide. Identify other chemicals that may fall into this cat egory (both pesticide and non-pesticide chemicals). Provide inform ation regarding common me chanisms and modes of action with other chemical substances ba sed on structural similarity, same or similar endpoints, and other relevant crit eria. Provide any data and/or evidence illustrating similarities at the cellular/molecular level. Discuss the appropriateness of combining e xposures in this particular case. Where data are not available, di scuss appropriateness of usi ng 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 indivi dually or in combination with another chemical. Include the potential for syne rgistic effects of your chemical in combination with other chemicals. Identify any instances of reported (prove n or alleged) adverse reproductive or developmental effects to domes tic animals or wildlife as a result of exposure to your chemical, or that occurred in an ar ea where the chemical is known to have been used. Provide all information regardi ng 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 wi th an appropriate limit of detection, and a discussion of the potential need for tolerances fo r processed foods. For tolerance exemption petitions, indicate if the chemical is on the Food and Dr ug Administration's Generally Recognized As Safe (GRAS) li st. A summary of all tolerances and exemptions from tolerance being proposed should also be included. Benefits Information (For R eregistration Actions Only) If the information and data s ubmitted indicate that an existing tolerance, reviewed according to the requirements of the new le gislation, 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 bene fits 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 humanhealth (that is, the effect is a nonthreshold effect); PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 21 of 24 5/5/20152. an appropriate quantitative risk asse ssment for the lifetime risk of the nonthreshold effect has been determined; and
3. if there are also threshol d 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 exhibi ting 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 fr om adverse health effects that would pose a greater risk than the di etary risk from the residue, OR Information and/or data showing that th e use of the pesticide chemical that produces the residue is necessary to avoi d a significant disruption in the domestic production of an adequate, whol esome, and economic food supply. Conditions Regarding The Risk Of A Pesticide Evidence that the yearly risk associated with th e 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 expos ure 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: Registra tion Or Reregistration Actions
In the format described in Appendix C of this PR Notice, address each of the following with respect to th e 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 expos ure to infants and children, provide a discussion and rationale as to why this viewis 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 chemi cal may result in significant children's PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 22 of 24 5/5/2015exposure, the following factor s 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 effect s, 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 conduc ted 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 pest icide to drinking water. For chemical pesticides, the discussion should include , but not be limited to, information indicating whether the pesticide is persis tent and/or mobile, the potential for transport in air (spray drif t and volatility data), and any available modeling data. For microbial pesticides, the discussi on should instead include information pertaining to the biology of the microorganismand indicate whether the pesticide is persistent and/or mobile. Has the chemical or any of its degradates been detected in gr ound water or surface water? Would this chemical or any of its degradates likely pa ss through primary or secondary drinking water treatment into fi nished water? Are any States conducting water monitoring programs for this pesticid e? If so, data collected by the States and all relevant information should also be included. Discuss the potential for significant expos ure to the chemical of children by nondietary routes. Are there non-occupational, structural, or resident ial uses (e.g., pet, swimming pool, lawn and garde n, or topical insect repellents)? Is the pesticide used in or around schools, parks, or recreation facilities? Provide al l available exposure data. Discuss the chronic and/or acute risk of aggregate exposure via multiple pathways for the general population, infants and chil dren 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 acti on of this pesticide. Identify other chemicals that may fall into this cat egory (both pesticide and non-pesticide chemicals). Provide inform ation regarding common me chanisms and modes of action with other chemical substances ba sed on structural similarity, same or similar endpoints, and other relevant crit eria. Provide any data and/or evidence illustrating similarities at the cellular/molecular level. Discuss the appropriateness of combining e xposures in this particular case. Where data are not available, di scuss appropriateness of usi ng default assumptions and what defaults should be used. PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

http://www2.epa.gov/pesticide-registra tion/prn... Page 23 of 24 5/5/2015Endocrine Effects Discuss and provide any evidence relevant to the possibility that the chemical may have endocrine disrupter effects indivi dually or in combination with another chemical. Include the potential for syne rgistic effects of your chemical in combination with other chemicals and whether or not your chemical could act as a catalyst for another horm one-disrupting chemical. Identify any instances of reported (proven or otherwise) adverse reproductive or developmental effects to domes tic 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 PRN 97-3: Guidelines for Expedited Review of Conventional Pesticides under the Reduced-Risk Initiative and for Biological Pesti cides | Pesticide ...

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