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### Pyraflufen-ethyl Preliminary Work Plan – Table of Contents

OVERVIEW ...................................................................................................................... ............. 4

ANTICIPATED DATA NEEDS .................................................................................................... 5

STATUTORY AND REGULATORY AUTHORITY ................................................................... 6

CHEMICAL FACTS ................................................................................................................ ...... 6

USE AND USAGE INFORMATION ............................................................................................ 7

RECENT ACTIONS ................................................................................................................ ....... 9

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW ................................ 9

TIMELINE ...................................................................................................................... .............. 11

NEXT STEPS .................................................................................................................... ........... 11

Appendix – Additional Areas Considered in th e Pyraflufen-ethyl Re gistration Review ......... 12

References:

This Preliminary Work Plan summarizes the En vironmental Protection Agency's current position based on the following documents:

1. EFED Registration Review Problem Formulation for Pyraflufen-ethyl

. Housenger, Ruhman. June 3, 2014.

2. Pyraflufen-Ethyl. Human Health Assessment Scoping Document in Support of Registration

Review . Rury, Ottley, Dodd. April 16, 2014.

3. Revised: Pyraflufen-ethyl: Tier I Review of Human Incidents . Recore, Evans. February 18,

2014.

4. BEAD Chemical Profile (BCP) for Regist ration Review: Pyraflufen-ethyl (030090). Ratnayke, Alsadek, Lee. May 5, 20014.

5. Pyraflufen-ethyl (030090) Screening Level Usage Analysis (SLUA) . April 15, 2013.3 6. Environmental Fate and Effects Division Tabl e 1 Report, Pyraflufen-ethyl (030090). March 18, 2014

.

7. Health Effects Division Master Label Re port, Pyraflufen-ethyl (030090). March 18, 2014

.

8. Pyraflufen-ethyl: Focus Meeting with Nichino America Notes. May 5, 2014.

These and other supporting documents for the pyrafl ufen-ethyl registration review case may be found in the docket EPA-HQ-OPP-2014-0415 at http://www.regulations.gov

.4 OVERVIEW

The docket for pyraflufen-ethyl is now open, ini tiating the first public comment period for this registration review (docket number EPA-HQ-O PP-2014-0415). Pyraflufen-e thyl is a contact type herbicide registered for use as a defoliant in cotton, and as a desi ccant in potatoes to facilitate the harvesting of these crops. Pyraflufen -ethyl is also registered for use as a pre-plant burn-down, on plant before crop emergence, an d as a post-emergence treatment depending on the crop and stage of crop growth. This Prelim inary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about pyraflufen-ethyl, highligh ting anticipated data and assessment needs, identifying th e types of information that would be especially useful to the Agency in conducting the review, and providing an anticipated timeline for completing the registration review for pyraflufen-ethyl.

The registration review process was designed to include a publi c participation component to solicit input from interested stake holders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows abou t pyraflufen-ethyl and what types of new data or other information would be helpful for the Agen cy to receive as it moves toward a decision on pyraflufen-ethyl. The Agency encourages all in terested stakeholders to review the PWP and Appendix and to provide comments and addition al information that will help the Agency’s decision-making process for this chemical. In addition to general areas on which persons may wish to comment, there are some areas iden tified in the PWP and Appendix about which the Agency specifically seeks comments and informa tion. Interested stakeholders could include: environmental non-profit or interest groups; pe sticide manufacturers; agricultural labor or commodity groups; commercial, institutional, reside ntial, and other users of pesticides; or the public at large.

The Preliminary Work Plan begins by listing the anticipated data needs for pyraflufen-ethyl. Next, it discusses the statutory and regulatory authority for Registration Review. Then the document provides chemical facts, use and usage information, recent actions , the anticipated risk assessments, and a projected registration review timeline for pyraflufen-ethyl. Finally, the Appendix to this document includes identifica tion and discussion of some areas that are considered generally in Registra tion Review along with some a dditional chemical case-specific

information.5 ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipa ted data needs for pyraflufen-et hyl. For addi tional discussion of the anticipated data needs, see the EFED Registration Review Problem Formulation for Pyraflufen-ethyl and Pyraflufen-Ethyl. Human Health Assessment Scoping Document in Support of Registration Review

.

Table 1: Anticipated Data Needs for the Pyraflufen-ethyl Registration Review

Guideline

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated Data Needs for the Parent Pyraflufen-ethyl

850.6100 Environmental chemistry methods and associated independent laboratory validations for soil, sediment, and water TGAI 12

860.1650 Submittal of Analytical Reference Standards TGAI Currently

needed 2

860.1300 Nature of the Residue – Orange 3 TGAI 6
Anticipated Data Needs for the Degradates E1, E2, E3, and E-15

850.6100 Environmental chemistry methods and associated independent laboratory validations for soil, sediment, and water Degradate E1, E2, and E3 12

860.1650 Submittal of Analytical Reference Standards E-15

Metabolite Currently

needed 2

TGAI = technical grade active ingredie nt; TEP = typical end-use product;

1 On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850 – Ecological Effects Tests

– including renumbering and other designations or changes for some guideline studies. See “Final Test Guidelines; OCSPP 850 Series; Notice of Av ailability” 77 FR 38282 , June 27, 2012. http://www.regulations.gov/#!documen tDetail;D=EPA-HQ-OPPT-2009-0154-0028

2 Previous reference standards have expired and new ones are currently needed.

3 Information needs to be submitted on sample storage conditions and durations for samples analyzed in the orange plant metabolism study (MRID 47872706).6 STATUTORY AND REGULATORY AUTHORITY

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All pesticides distributed or sold in the United Stat es (U.S.) generally must be registered by the Environmental Protection Agency (EPA or the Ag ency), based on scientific data showing that they will not cause unreasonable ri sks to human health or the environment when used as directed on product labeling. The registration review program is intended to ma ke sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonabl e adverse effects to human health or the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review prog ram, the Agency periodically r eevaluates pesticides to make sure that as change occurs, products in the mark etplace can be used safely. Information on this program is provided on EPA’s website. 4

The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), a nd will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing regi stration review begin at 40 CFR 155.40. The Agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses

and data or information it believes are needed to make a registration review decision. After reviewing and responding to comments and data received in the docke t during this initial comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for the registration review of pyraflufen-ethyl.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for pyraflufen-ethyl.

Table 2: Chemical Facts for Pyraflufen-ethyl

PC code 030090

Case Number 7259

CAS Number 129630-19-9 Year first registered 2002 Pesticide Type Contact herbicide Chemical class Pyraflufen-e thyl is a phenyl pyrazole. 5
Reregistration Eligibility Decision (RED) Because it was registered afte r November 1984, pyraflufen-ethyl was not subject to reregistration.

Tolerance Reassessment Eligibility Decision (TRED) No TRED was done for pyraflufen- ethyl, tolerances were last reassessed through a 2008 registration action.

4 http://www.epa.gov/oppsrrd1/registration_review/

5 Pyraflufen-ethyl is also a light-dep endent peroxidizing herbic ides (LDPH) because it co ntains a light-dependent moiety. LDPH herbicides are known to have a photo-toxic mode of action in plants and possibly in fish. LDPHs may be more toxic when exposed to natural sunlight.7 Table 2: Chemical Facts for Pyraflufen-ethyl

Cumulative group Not applicable. Pyraflufen -ethyl has not been identified as a member of a cumulative group that shares a common mechanism of toxicity.

40 CFR Citation Tolerances for pyraflufen-et hyl are established in §180.585. Dual-use Pyraflufen-ethyl is registered for conventional pesticidal uses only and has no registered antimicr obial or biopesticidal uses. Non-pesticidal uses There are no identified non-pesticidal uses of pyraflufen-ethyl.

Pesticide Re-evaluation Division, Chemical Review Manager Steven Snyderman, snyderman.steven@epa.gov, 703-347-0249

Registration Division, Product Manager Kathryn Montague, monta gue.kathryn@epa.gov, 703-305-1243

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for pyraflufen-ethyl. Please see the BEAD Chemical Profile (BCP) for Registra tion Review: Pyraflu fen-ethyl (030090) in the registration

review docket for more details.

Table 3: Pyraflufen-ethyl Use and Usage Information

Summary of Use Pyraflufen-ethyl is a contact type herbicide regi stered for use as a defoliant in cotton and desiccant in potatoes to facilitate the harvesting of these crops as we ll as a pre-plant burn-down, on plant prior to crop emergence, a nd as a post-emergence treatment depending on the crop and stage of the crop growth. Use Sites The registered agricultural us e sites of pyraflufe n-ethyl include: bulb vegetables, tree nuts, grapes, po me fruits, stone fruits, dates, figs, feijoa, mangos, loquat, pe rsimmons, pomegranates, kiwi, chicory, ginger, turmeric, cucurb its, fruiting vegetables, leafy vegetables, cole crops, root crops , beans, peas, lentils, corn, barley, oats, rye, wheat, sugar cane, ginseng, flax, safflower, sunflower, canola, sugar beets, celery, cotton, mustard, olives, sorghum, peanuts, soybeans, pa stureland, conservation reserve program, and Christmas trees.

Registered non-agricultural use si tes of pyraflufen-ethyl include: ornamentals, grasses, ditch banks , uncultivated areas, vacant lots, airfields, rights-of-way, roadsi des, railroads, lumber yards, industrial sites, storage areas, fe ncerows, hedgerows, fences and

commercial areas. Summary of Usage Based on private ma rket usage data from 2003-2012, usage averaged approximately 2,000 pounds active ingredient (a.i.) applied annually on approximately 654,000 acres treated. The average application rate over this time period was 0.003 pounds8 Table 3: Pyraflufen-ethyl Use and Usage Information

a.i./acre. Total area treated (i n acres) of pyraflufen-ethyl has tripled since 2009 with major uses on cotton, grapes (for raisins and wine) and spring wheat. Formulation Type(s) Emulsifiab le and soluble concentrates. Application Method(s) Products can be applied by ground and aerial application equipment. Technical Registrant(s) Nichino America, Inc No. of Registrations 16 Section 3 products 6 and one Special Local Need in Arizona

Restricted Use No

Guidance for Commenters: Additional areas of use and usage related information requested for this registration review, and of part icular interest to EPA, are described below.

 Certain pyraflufen-ethyl labels are unclear with respect to a pplication parameters such as the number of applications and retreatment in tervals. Without further information, EPA expects to use conservative assumptions to approximate these parameters in order to conduct a quantitative risk assessment. Howe ver, the Agency will work with registrants to clarify information on pyraf lufen-ethyl product labels.

 Confirmation of the following label information: sites of application; formulations; application methods and equipment; maxi mum application rates; frequency of application, application intervals, and maxi mum number of applica tions per season; and geographic limitations on use.

 Use distribution ( e.g. , acreage and geographical distri bution of relevant use sites).

 Median and 90 th percentile reported use rates (lbs a i/A) from usage data – national, state, and county.

 Typical application timing (date of first applic ation and application in tervals) – national, state, and county.

 Usage/use information for non-agricultural uses.

 Typical application interval (days).

 State or local use restrictions.

 Foreign technical registrants not listed above who s upply technical pyrafl ufen-ethyl to the

US market.

 Information about the following use sites are needed to help improve future assessments by the Agency related to these specific uses and the importance of pyraflufen-ethyl use

therein:

o flax, Christmas trees, ornamentals, rights- of-way, roadsides, railroads, lumber yards, industrial sites, storage areas , fencerows, hedgerows, fences and

commercial areas.

6 Section 3 product labels can be obtained from th e Pesticide Product Label System (PPLS) website

(http://oaspub.epa.gov/pestlabl/ppls.home).9 RECENT ACTIONS

On May 5, 2014, the Agency’s pyraflufen-ethyl t eam, along with representatives from USDA, met with Nichino America, the sole technical regi strant for pyraflufen ethyl to discuss usage of pyraflufen-ethyl nationwide and to clarify several label uncertainties. Notes from this meeting can be found in the pyraflufen-et hyl registration review docket, Pyraflufen-ethyl: Focus Meeting

with Nichino America Notes

.

ANTICIPATED RISK ASSESSMENT S FOR REGISTRATION REVIEW

The most recent human health risk assessment for pyraflufen-ethyl was completed on October 1, 2012 for a new use request on hops and peanuts. The most recent ecological and environmental fate risk assessment was completed for the same purpose. It should be noted that both risk assessments relied upon information from the last comprehensive risk assessment conducted in 2002 in support of pyraflufen-ethy l’s initial registration. Findings and conclusions from these

risk assessments are summarized in the EFED Registration Review Problem Formulation for Pyraflufen-ethyl and Pyraflufen-Ethyl. Human Health Assessment Scoping Document in Support of Registration Review.

During registration review, the Agency antici pates the need to conduct a comprehensive ecological risk assessment, including an enda ngered species assessment, for all uses of pyraflufen-ethyl. For human health, EPA antic ipates the need to conduct revised dietary, residential, aggregate, and occupational ri sk assessments during registration review. If toxicological endpoints or points of departure are revised based on th e data that are anticipated to be required for registration review, they will be considered in the new assessments, as well as any changes to the standard operating pro cedures or default exposure assumptions.

Table 4 below summarizes the anticipated regi stration review risk assessments based on the

EFED Problem Formulation and HED Scoping Document.10 Table 4: Anticipated Risk Assessments for the Pyraflufen-ethyl Registration Review

Type of Risk Assessment Conduct? Notes

Ecological and Environmental Fate Comprehensive ecological (species to be assessed include terrestrial and aquatic organisms), including endangered species Y Chronic estimated drinki ng water concentrations (EDWCs) will be determined by modeling the total toxic residues of parent and the E-1, E-2, and E-3 degradates, noting that exposure will be mainly associated with E-3 as it is the most persistent degradate.

Incidents Will check for updates For a discussion of reporte d ecological incidents for pyraflufen-ethyl, see page 25 of the Problem

Formulation.

Human Health Dietary Food Y A new dietary exposure and risk assessment may be needed during Registration Review to incorporate updated EDWCs into the chronic and cancer dietary
exposure assessments. Drinking water Y

Occupational Handlers (mixers, loaders, applicators) Y Occupational uses are expected to result in both shortand intermediate-term exposures. An updated occupational assessment may be needed to account for changes in occupationa l assessment policies (e.g. unit exposures and transfer coefficients) and to evaluate the maximum regist ered single application

rate for each use site. Post-application Y

Residential Handlers Y The agency will be considering volatilization exposure, as well as the potential for exposure from spray drift as part of th e residential assessment. Post-application Y

Other Aggregate Y Evaluates the combined risk from dietary and residential exposures. Cumulative N/A Pyraflufen-ethyl is not a member of a cumulative

group. Tolerances Y The Agency anticipat es updating tolerances to include parent and metabolites E-1 and E-9 for livestock

commodities.

Incidents Will check for updates Due to low frequency and severity of incident cases reported for pyraflufen-ethyl, there does not appear to

be a concern at this time that would warrant further investigation. For furthe r discussion of reported human incidents for pyraflufe n-ethyl, see page 10 of the Scoping Document and the Revised: Pyraflufenethyl: Tier I Review of Human Incidents

.11 Guidance for Commenters: Additional ecological information requested for this registration review, and of particular interest to EPA, is described below.

 Further toxicity data on the de gradation products of pyraflufe n-ethyl would be useful in reducing the uncertainties associated w ith ECOSAR analysis if available.

 Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not alr eady reported to the Agency.

 Water quality monitoring data (s ee Appendix for further details).

TIMELINE

EPA has created the following estimated timelin e for the completion of the pyraflufen-ethyl registration review in Table 5 below.

Table 5: Projected Pyraflufen-eth yl Registration Review Timeline

Activities Estimated Date
Opening the Docket
Open Docket and 60-day Public Comment Period 2014 – June
Close Public Comment 2014 – August
Case Development

Final Work Plan 2014 – November

Issue DCI 2015 Jan. - March

Data Submission 2016 Jan. - March
60-day Public Comment Period for Draft Risk

Assessments [1] 2017 July – Sept.

Registration Review Decision
60-day Public Comment Period for Proposed
Registration Review Decision 2018 April - June

Registration Review Decisi on and Begin Post-Decision
Follow-up 2019

Total (years) 5

NEXT STEPS

After the 60-day public comment period closes , the Agency will review and respond to any comments received in a timely manner and then i ssue a Final Work Plan for the registration review of pyraflufen-ethyl.

[1] The regulations governing Registration Review generally require the Agency to provide a public comment period

of at least 30 calendar days for draft risk assessments; see 40 CFR Part 155.53(c). For conventional pesticides, the Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.12 

### Appendix – Additional Areas Considered in the Pyraflufen-ethyl Registration

Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest to the Agency where your comments, data submi ssions, or reference to sources of additional information could be of particular use.

Trade Irritants:

Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, take steps toward facilitating irritant resolution. The Agency will work to harmonize tolerances and international maximum residue limits (MRLs) and may modify tolerance levels to do so, when possible. Growers and other stakeholders are asked to

comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and MRLs in key export markets, provi ding as much specificity as possible regarding

the nature of the concern.

Water Quality:

Pyraflufen-ethyl is not identifie d as a cause of impairment fo r any water bodies listed as impaired under section 303(d) of the Clean Water Act. 7 In addition, no Total Maximum Daily Loads (TMDL) have been developed for pyraflufen-ethyl. 8 More information on impaired water bodies and TMDLs can be found at the Agency’s website. 9 The Agency invites submission of water quality data for this pesticide. To the extent possible, submissions should include the key data elements noted in the OPP Guidance for Submission of St ate and Tribal Water Quality Monitoring Data 10 in order to ensure they can be used quantitatively or qualitatively in pesticide

risk assessments.

Environmental Justice:

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to pyraflufe n-ethyl compared to the general population. Please comment if you are aware of any sub- populations that may have atypical, unusually high exposure compared to the general population.

7 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

8 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl _pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES

9 http://www.epa.gov/owow/tmdl/

10 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm13 ENDANGERED SPECIES:

A risk assessment that supports a complete endangered species determination has not been conducted for pyraflufen-ethyl. The ecologica l risk assessment planned during registration review will allow the Agency to determine whet her use of pyraflufen-ethyl has “no effect” or “may affect” federally listed threatened or endang ered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use “may affect” a listed species or its designated critical habitat, the Ag ency will consult with the U.S. Fish and Wildlife

Service and/or National Marine Fisheries Se rvice (the Services), as appropriate.

ENDOCRINE DISRUPTOR SCREENING PROGRAM:

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its most rece nt registration decisi on for pyraflufen-ethyl, EPA

reviewed these data and select ed the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), pyraflufen-ethyl is subject to th e endocrine screening part of th e Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her certain substances (including pesticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily required

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pest icide active ingredient s and 9 inert ingredients. A second list

of chemicals identified for EDSP sc reening was published on June 14, 2013 11 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists

should be construed as a list of know n or likely endocri ne disruptors.

11 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of

chemicals.14 For further information on the status of the ED SP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening batt ery, please visit our

website. 12

HUMAN STUDIES:

Occupational and Residential

Past pyraflufen-ethyl risk assessments rely in part on data from studies in which adult human subjects were intentionally exposed to a pest icide to determine their dermal and inhalation exposure. Many such studies, i nvolving exposure to many different pesticides, comprise generic pesticide exposure databases such as the Pest icide Handlers Exposure Database (PHED), the Agricultural Reentry Task Force (ARTF) Databa se, and the Outdoor Residential Exposure Task Force (ORETF) Database. EPA has reviewed all the studies supporting these multi-pesticide generic exposure databases, and has found no cl ear and convincing evidence that the conduct of any of them was either fundamentally unethical or significantly deficient relative to the ethical standards prevailing at the time the research wa s conducted. All applicab le requirements of EPA’s Rule for the Protection of Human Subject s of Research (40 CFR Part 26) have been satisfied, and there is no regulatory barri er to continued reliance on these studies.

12 http://www.epa.gov/endo/