2 

### Fluopicolide Preliminary Work Plan

– Table of Contents

Overview 3

Anticipated Data Needs 3

Statutory and Regulatory Authority 4

Chemical Facts 5

Use and Usage Information 5

Recent Actions 7

Anticipated Risk Assessment s for Registration Review 7

Timeline 10

Next Steps 10

Appendix

– Additional Areas Considered in Fluopicolide’s Registration Review 11

References:

This Preliminary Work Plan summarize s the Environmental Protection Agency's current position based on the following documents:

1. Registration Review: Problem Formulation for the Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments for Fluopicolide

. M. Lowit, E. Odenkirchen . March 14, 2013

.

2. Fluopicolide Human Health Risk Assessment Scoping Document In Support of Registration

Review

. D. Drew, A.LaMay, J. Liccione

. Feb. 10, 2013

.

3. BEAD Chemical Profile for Registration Review: Fluopicolide (027412)

. C. Chen, J. Alsadek, S. Smearman

. November 1, 2012

.

4. Fluopicolide: Review of Human Incidents

. S. Recore

. October 16, 2012

.

These and other supporting documents for the Fluopicolide registration review case may be

found in the docket EPA

- HQ

- OPP

- 2013

- 0037 at http://www.regulations.gov

.3 OVERVIEW

The docket for fluopicolide is now open , initiating the first public comment period for this registration review (docket number EPA

- HQ

- OPP

- 2013

- 0037

. This case includes the active ingredient fluopicolide

. Fluopicolide is a mesosystemic, benzamide fungicide registered for use to control plant diseases including downy mildew and Phytophthora blight on cucurbit vegetables, Phytophthora diseases on peppers, and downy mildew on lettuce and onion. Fluopicolide is also registered for use on turf grass to control Pythium diseases, an d on ornamentals to control Pythium diseases, downy mildew, and Phytophthora diseases. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs

knows about f luopicolide

, highlighting anticipated data and assessment needs, identifying the types of information that would be especially useful to the Agency in conducting the review , and providing an anticipated timeline for completing the Agency’s review of fluopicolide ’s review.

The registration review process was designed to include a public participation component to solicit input from interested stakeholders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows about f luopicolide and what types of new data or

other informat ion would be helpful for the Agency to receive as it moves toward a decision on

f luopicolide . The Agency encourages all interested stakeholders to review the PWP and Appendix and to provide comments and additional information that will help the Agency’s

d ecision

- making process for this chemical. In addition to general areas on which persons may wish to comment, there are some areas identified in the PWP and Appendix about which the Agency specifically seeks comments and information. Interested stakeholde rs could include:

environmental non

- profit or interest groups; pesticide manufacturers; agricultural labor or commodity groups; commercial, institutional, residential, and other users of pesticides; or the public at large.

The Preliminary Work Plan begin s by listing the anticipated data needs for f luopicolide

. Next, it discusses the statutory and regulatory authority for R egistration R eview. Then the document provides fluopicolide ’s chemical facts, use and usage information, recent actions, the anticipated risk assessments, and a projected registration review timeline. Finally, the Appendix to this document includes identification and discussion of some areas that are considered generally in

R egistration R eview along with some additional chemica l case

- specific information.

ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for f luopicolide . For additional discussion of the anticipated data needs, see the support documents: Registration Review: Problem Formulation for the E nvironmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments for Fluopicolide and Fluopicolide Human Health Risk Assessment Scoping Document In Support of Registration Review

.4 Table 1: Anticipated Data Needs for Fluopicolide ’s Registration Review

Guideline

Number Study Title Test Material 1 Estimated

Timeframe

(Months from receipt of DCI)

850.2100 Avian acute oral toxicity test (passerine) TGAI 12

850.1400 Estuarine/marine fish

– early life stage test 2 TGAI 12

850.1350 Estuarine/marine invertebrate life cycle test TGAI 12

850.4100 Seedling emergence 3 TEP 12

850.4150 Vegetative vigor 3 TEP 12

850.4500 Aquatic plant growth on freshwater diatom and

marine diatom 3 TGAI 12

860.1380 Storage stability on Brassica , celery, and spinach TEP 48

860.1520 Processed food and feed for

• A spirated grain fractions TEP 24

860.1900 Field accumulation in rotational crops 4

• Small grain

• Soybean

• Corn

• Rice

• Oilseed TEP 36

870.7800 Immunotoxicity TGAI 12

875.2100 Turf transferable residue TEP 12

1 : TGAI = technical grade active ingredient; TEP = typical end

- use product;

2 : Alternative to this study is submission of an acute toxicity test (850.1075) with fathead minnow. IF that study is acceptabl e and yields a definiti ve toxicity endpoint then an acute

- to

- chronic ratio (ACR) may be used to estimate chronic toxicity to

estuarine/marine fish.

3 : On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850

– Ecological Effects Tests

– including

renu mbering and other designations or changes for some guideline studies. See “Final Test Guidelines; OCSPP 850 Series; Notice of Availability” 77 FR 38282, June 27, 2012. http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0154

- 0028

4 : These data are only being noted here. These data were previously required in connection with the registration action to ad d certain crops to fluopicolide use, (EPA memo date Apr il 20, 2011) and are required to be submitted to the Agency by April 25, 2013).

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 States (U.S.) generally must be registered by the Environmental Protection Agency (EPA or the Agency), based on scientific data showing that they will not cause unreasonable risks to human health or the envi ronment when used as directed on product labeling. The registration review program is intended to make 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 unreasonable 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 program, the Agency periodically reevaluates pesticides to make5 s ure that as change occurs, products in the marketplace can be used safely. Informatio n on this program is provided on EPA’s website 1

.

The Agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)

, and will review each registered pesticide every 15 years to determine whether it continues to meet the FIFRA standard for registration. The regulations governing registration review begin at 40 CFR 155.40

. T he Agen cy 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 wha t 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 docket during this initial comment period, the Agency will develop a F ina l W ork P lan (FWP) and anticipated schedule for the registration review of f luopicolide

.

Table 2 provides a summary of th e current regulatory status of fluopicolide

. Table 2: Fluopicolide CHEMICAL FACTS

PC code 027412

Case Number 7055

CAS Number 239110

- 15

- 7

Year first registered 2007 Pesticide Type Fungicide

Chemical class Benzamide

R eregistration Eligibility Decision (R E D) Because fluopicolide was registered after November 1984, it was not subject to reregistration.

Tolerance Reassessment Eligibility Decision (TRED) Not applicable

Cumulative group Not applicable

40 CFR Citation Tolerances for f luopicolide are established in 180.627

Dual

- use Conventional pesticide uses only

Non

- pesticidal uses No non

- pesticidal uses of fluopicolide

Pesticide Re

- evaluation Division, Chemical Review Manager Rusty Wasem, wasem.russell@epa.gov , 703

- 305

- 6979

Registration Division

, Product Manager Tony Kish, kish.tony@epa.gov , 703

- 308

- 9443

USE AND USAGE INFORMATION Table 3 summarizes the use and usage information for fluopicolide

. Please see the BEAD Chemical Profile for Registration Review: Fluopicolide in the registration review docket for

more details

.

1 http://www.epa.gov/oppsrrd1/registration_review/6 Table 3: USE AND USAGE INFORMATION

Summary of Use Fluopicolide is a mesosystemic, benzamide fungicide registered for

use to control plant diseases including downy mildew and Phytophthora blight on cucurbit vegetables, Phytophthora diseases on peppers, and downy mildew on lettuce and onion. Fluopicolide is also registered for use on turf grass to control Pythium diseases,

an d on ornamentals to control Pythium diseases, downy mildew, and Phytophthora diseases.

Use Sites • Agricultural Use Sites : currants, grapes, huckleberries, nut trees, pome fruits, flavoring and spice crops, cucurbits, eggplant, tomatoes and other fruiting vegetables, leafy and stem vegetables, root crop vegetables, okra, onions, sugar beets and turnips.

• Non

- Agricultural Use Sites : forest trees, herbaceous plants, ornamental plants, ornamental lawns and turf, ornamental woody shrubs and vines, ornamental tr ees, recreational areas, parks, athletic fields, commercial and industrial

areas. Summary of Usage From 2008

- 2010, the annual total agricultural usage averaged approximately 4,000 pounds active ingredient (a.i.) for 36,000

treated acres with an average application rate of 0.1lbs. a.i. per acre.

During this time frame, the crops with the most use in terms of total pounds of active ingredient were cucumbers (57%), and squash (16%). The crops with the most use in terms of total area treated

were also c ucumbers (59%), and squash (17%).

EPA has no data on the non

- agricultural uses of fluopicolide

. Formulation Type(s) Suspension concentrate Application Method(s) Fluopicolide products may be applied by ground or aerial equipment, depending on the crop. Application methods include broadcast, chemigation, spray, soil drench treatment, band treatment, and containerized plant treatment. Technical Registrant (s) Valent U.S.A. Corporation No. of Registrations Five FIFRA Section 3 products 2

Restricted Use No

Guidance for Commente rs: Additi onal areas of use and usage related information requested for this registration r eview , and of particular interest to EPA, are described below.

• A dditional information on non

- agricultural usage, including application rates and the number of applications per year.

2 FIFRA Section 3 product labels can be obtained from the Pesticide Produ ct Label System (PPLS) website

( http://oaspub.epa.gov/pestlabl/ppls.home ).7 • C onfirmation of the following label information : sites of application ; formulations ; application methods and equipment ; maximum application rates ; frequency of application, application intervals, and maximum numbe r of applications per season ; and geographic limitations on use

.

• U se distribution ( e.g. , acreage and geographical distribution of relevant use sites )

• M edian and 90 th percentile reported use rates (lbs a

. i

. / A ) from usage data

– national, state, and county

.

• A pplication timing (date of first application and application intervals)

– national, state, and county

.

• Usage/use information for non

- agricultural uses

.

• Typical application interval (days)

.

• S tate or local use restrictions

.

• F oreign technical registrants not listed above who supply technical f luopicolide to the US

market

.

RECENT ACTIONS

New uses and tolerances were granted in 2011 that granted fluopicolide tolerances in food, feed,

and livestock commodities. Please see Federal Register Fluopicolide; Pesticide Tolerances (76 FR 22045) at https://federalregister.gov/a/2011

- 9435

.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for f luopicolide was completed in

2010 in preparation for a new use request. T he most recent ecological and environmental fate risk assessment was completed 2010 for the same purpose . Findings an d conclusions from these

risk assessments are summarized in the Registration Review: Problem Formulation for the Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments for Fluopicolide and Fluopicolide Human Health Risk Assessment Scoping Document In Support of Registration Review.

During registration review, t he Agency anticipates the need to conduct a comprehensive ecological risk assessment, including an endangered species assessment and an updated drinking

wate r assessment that incorporates recently available fate data for the degradate BAM

. For human health, EPA anticipates the need to conduct revised dietary, residential

, and occupational

risk assessment s that reflect both fluopicolide and the degradate BAM during registration review

. If toxicological endpoints or points of departure are revised , or if there are changes to the standard operating procedures or to default exposure assumptions, then these changes will be

considered in the new assessments.

Tabl e 4 below summarizes the anticipated registration review risk assessments based on the

EFED Problem Formulation and the HED Scoping Document

.8 Table 4: Anticipated Risk Assessments for Fluopicolide Registration Review

Type of Risk Assessment Conduct ? Notes

Eco logical and Environmental Fate Comprehensive ecological (species to be assessed include terrestrial and aquatic organisms ), including endangered species Y Will incorporate recently received information on the degradate BAM.

Incidents Y For a discussion of fluopicolide reported ecological incidents, see page 17 of the Problem Formulation.

Human Health Dietary

Food Y Updated dietary exposure assessments for fluopicolide and BAM may be necessary under registration review if the toxicological endpoints or point of departure(s) ( PODs ), or FQPA safety factors change, percent crop treated estimates increase significantly

. Drinking water Y Updated drinking water assessment for fluopicolide and BAM may be warranted based upon changes in the estimated drinking water concentrations

. Residential

Handlers Y An updated residential exposure assessment for fluopicolide may be warranted during registration

review as a result of the 2012 revisions to HED’s Residential Exposure Standard Operating Procedures (SOPs ). In addition, revised residential assessments may be needed if toxicological PODs change or other new data are received by the Agency that impact exposure estimates.

Post

- application Y The dermal post

- application assessment for fluopicolide and BAM may be revised during registration review. Post application inhalation may be assessed for both residential and occupational exposure scenarios

. Occupational Handlers (m ixer s, loader s, applicators ) Y An updated occupational handler assessment for fluopicolide may be required under registration review if warranted by any significant changes in exposure assessment methodology, toxicological

PODs or uncertainty factors.9 Post

- application Y An updated occupational post

- application assessment or fluopicolide and BAM may be required under registration review if warranted by any significant changes in exposure assessment methodology, toxicological endpoints or points of departure

, or uncertainty fa ctors.

Other Aggregate N Currently , there are no aggregate ( food, drinking water, and residential exposures ) risks of concern for fluopicolide or for BAM. If significant changes are made to the previous fluopicolide or BAM residential or dietary risk assessments, revised aggregate risk assessments may be performed under registration

review.

Cumulative N Not Applicable

Tolerances N The Codex and U.S. residue definitions are harmonized and both express determination of parent fluopicolide. The Codex m aximum residue levels (MRLs) and U.S. tolerance levels for grapes and cucurbit vegetables are harmonized. The residue levels are not harmonized for brassica vegetables, bulb vegetables, fruiting vegetables or leafy vegetables. Much of this discrepancy is because of differences in commodity definitions (e.g. U.S. tolerances are established at 5.0 ppm on Brassica, head and stem, subgroup 5A whereas Codex MRLs are established at 2 ppm on Flowerhead brassicas (includes broccoli

, Chinese broccoli and cauliflow er), 7 ppm on cabbages, head, and 0.2 ppm on brussel sprouts). Canada also has MRLs established for residues of fluopicolide on several commodities, many which are harmonized with U.S. tolerances, and

a few which have lower values.

Incidents For a discussion of fluopicolide’s reported human incidents, see page 12 of the Scoping Document.10 TIMELINE

EPA has created the following estimated timeline for the completion of fluopicolide registration

review in Table 5 below

.

Projected Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and 60

- day Public Comment Period 2013

- March

Close Public Comment 2013

- May Case Development

Final Work Plan 2013

- August

Issue DCI 2014

– April

- June

Data Submission 201 8

– April

- June

60

- day Public Comment Period for Draft Risk Assessments 201 9

– Oct.

– Dec. Registration Review Decision

60

- day Public Comment Period for Proposed Registration Review

Decision 20 20

– April

- June

Registration Review Decision and Begin Post

- Decision Follow

- up 20 21 Total (years) 8

NEXT STEPS

After the 6 0

- day public comment period closes, the Agency will review and respond to any comments received in a timely manner and then issue a Final Work Plan for the registration

review of f luopicolide

.11 

### Appendix

– Additional Areas Considered in Fluopicolide’s Registration

Review

PUBLIC COMMENTS AND FEEDBACK :

Guidance for C ommenters: The areas below highlight topics of special interest to the Agency where your comments, data submissions, or reference to sou rces of additional information c ould be of particular use.

Trade Irritants:

Through the registration review process, the Agency intends to solicit information on trade irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency

will work to harmonize tolerances and international maximum residue limits (MRL s ) 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, providing as much specificity as possible regarding

the nature of the concern.

Water Quality:

Fluopicolide is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act 3

. In addition, n o Total Maximum Daily Load s (TMDL) has been developed for f luopicolide 4 . More information on impaired water bodies and

TMDLs can be found at the Agency’s website 5

. The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 6 in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

Environmental Justice:

EPA seeks to a chieve environmental justice, the fair treatment and meaningful involvement of all people, regardless of race, color, national origin, or income, in the development, implementation, and enforcement of environmental laws, regulations, 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 their location, cultural practices, or other factors, may have atypical, unusually high exposure to f luopicolide c ompared 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.

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

4 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name =PESTICIDES

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

6 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm12 ENDANGERED SPECIES :

A risk assessment that supports a complete endangered species determination has not been

conducted for f luopicolide

. The ecological risk assessment planned during registration review will allow the Agency to determine whether fluopicolide’s use has “no ef fect” or “may affect” federally listed threatened or endangered 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 Agenc y will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Service (the Services), as appropriate.

On January 19, 2011, the Center for Biological Diversity and the Pesticide Action Network

North America filed a lawsuit in the United States District Court for the Northern District of California, against the Environmental Protection Agency (EPA) for allegedly failing to undergo

consultation with the United States Fish and Wildlife Service and the National Marine Fisheries

Service regarding the effects of over 350 pesticides, including f luopicolide , on over 200 endangered and threatened species throughout the United States (Center for Biological Diversity, et al. v. EPA, et al., No. C 11

- 00293 (N.D.Cal.)

.

ENDOCRINE DISRUPTOR SCREE NING PROGRAM :

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxici ty, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturati on, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision for f luopicolide

, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p),

f luop icolide is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether 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 other such endocrine effects as the Administrator may designate.” The EDSP employs a two

- tiered approach to making the 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 estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and

establish a dose

- response relationship between the dose and the E, A, or T effect.13 Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/da ta call

- ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Fluopicolide is not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly , as part of registration review, EPA will issue future EDSP orders/data call

ins, requiring the submission of EDSP screening assays for f luopicolide

. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals , future lists, the test guidelines and the Tier 1 screening battery, please visit our website 7

.

HUMAN STUDIES :

Occupationa l and Residentia l

Past f luopicolide risk assessments rely in part on data from studies in which adult human subjects were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. Many such studies, involving exposure to many different pesticides, comprise gen eric pesticide exposure databases such as the Pesticide Ha ndlers Exposure Database (PHED), the Agricultural Reentry Task Force (ARTF) Database , and the Outdoor Residential Exposure Task Force (ORETF) Database

. EPA has reviewed all the studies supporting t hese multi

- pesticide generic exposure databases, and has found no clear 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 resea rch was conducted. A ll applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been

satisfied , and t here is no regulatory barrier to continued reliance on these studies

.

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