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 Assessments for Registration Review 7

Timeline 10

Next Steps 10

Appendix – Additional Areas Considered in Fluopicolide’s Registration Review 11

References:

This Preliminary Work Plan summarizes 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, and 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 fluopicolide, 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 fluopicolide and what types of new data or 

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

fluopicolide. 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 

decision-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 stakeholders 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 begins by listing the anticipated data needs for fluopicolide. Next, it 

discusses the statutory and regulatory authority for Registration Review. 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 

Registration Review along with some additional chemical case-specific information.

ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for fluopicolide. For additional discussion of 

the anticipated data needs, see the support documents: 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.
4

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

Guideline 

Number Study Title Test Material1

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 test2 TGAI 12

850.1350 Estuarine/marine invertebrate life cycle test TGAI 12

850.4100 Seedling emergence3 TEP 12

850.4150 Vegetative vigor3 TEP 12

850.4500 Aquatic plant growth on freshwater diatom and 

marine diatom3 TGAI 12

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

860.1520 Processed food and feed for 

• Aspirated grain fractions TEP 24

860.1900

Field accumulation in rotational crops4

• 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 acceptable 

and yields a definitive 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 

renumbering 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 add 

certain crops to fluopicolide use, (EPA memo date April 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 environment 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 make 
5

sure that as change occurs, products in the marketplace can be used safely. Information on this 

program is provided on EPA’s website1.

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. 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 docket during this initial 

comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for 

the registration review of fluopicolide.

Table 2 provides a summary of the 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

Reregistration Eligibility 

Decision (RED)

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 fluopicolide 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, 

and 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 trees, 

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 cucumbers (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 products2

Restricted Use No

Guidance for Commenters: Additional areas of use and usage related information

requested for this registration review, and of particular interest to EPA, are described below.

• Additional 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 Product Label System (PPLS) website 

(http://oaspub.epa.gov/pestlabl/ppls.home).
7

• Confirmation of the following label information: sites of application; formulations;

application methods and equipment; maximum application rates; frequency of 

application, application intervals, and maximum number of applications per season; and 

geographic limitations on use.

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

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

state, and county.

• Application timing (date of first application and application intervals) – 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 supply technical fluopicolide 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 fluopicolide was completed in 

2010 in preparation for a new use request. The most recent ecological and environmental fate 

risk assessment was completed 2010 for the same purpose. Findings and 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, the Agency anticipates the need to conduct a comprehensive

ecological risk assessment, including an endangered species assessment and an updated drinking 

water 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 assessments 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.

Table 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

Ecological 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 (mixers, loaders, 

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 factors.

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 maximum 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 cauliflower), 

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 2018 – April - June

60-day Public Comment Period for Draft Risk Assessments 2019 – Oct. –Dec.

Registration Review Decision

60-day Public Comment Period for Proposed Registration Review 

Decision

2020 – April - June

Registration Review Decision and Begin Post-Decision Follow-up 2021

Total (years) 8

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 issue a Final Work Plan for the registration 

review of fluopicolide.
11

Appendix – Additional Areas Considered in Fluopicolide’s Registration 

Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest to the Agency 

where your comments, data submissions, or reference to sources of additional information could 

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 (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, 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 Act3

. In addition, no Total Maximum Daily Loads 

(TMDL) has been developed for fluopicolide4

. More information on impaired water bodies and

TMDLs can be found at the Agency’s website5

. 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 Process6 in order to ensure they can be used quantitatively or qualitatively in 

pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve 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 fluopicolide 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.

 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.htm
12

ENDANGERED SPECIES:

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

conducted for fluopicolide. The ecological risk assessment planned during registration review 

will allow the Agency to determine whether fluopicolide’s use has “no effect” 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 Agency 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 fluopicolide, 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 SCREENING 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, neurotoxicity, 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 maturation, 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 fluopicolide, 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), 

fluopicolide 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/data 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 callins, requiring the submission of EDSP screening assays for fluopicolide. 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 website7.

HUMAN STUDIES:

Occupational and Residential

Past fluopicolide 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 generic 

pesticide exposure databases such as the Pesticide Handlers 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 these 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 research was conducted. All applicable requirements of 

EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been 

satisfied, and there is no regulatory barrier to continued reliance on these studies.

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