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INTRODUCTION

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan (FWP) for 

the registration review of fluopicolide. This work plan addresses public comments received 

concerning the Preliminary Work Plan (PWP), which was posted in the fluopicolide registration 

review docket (EPA-HQ-OPP-2013-0037). 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.

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. Changes in science, public policy, and pesticide use practices occur over time. 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. 

The public phase of registration review begins when the initial docket is opened for each case. 

Information on this program is provided on the Agency’s website.

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The FWP begins with any updates since the PWP was issued. Next is a summary of substantive 

comments received during the public comment period for the PWP concerning anticipated data 

needs, expected risk assessments, or the estimated timeline identified in the PWP, and a 

summary of the Agency’s responses to those comments. This section is followed by registration 

review planned data needs, risk assessments expected to be conducted, and the projected

registration review timeline for fluopicolide. Lastly, there is a discussion of next steps.

UPDATES SINCE THE PWP WAS ISSUED

During the comment period, the technical registrant, Valent USA Corporation (Valent) informed 

the Agency that two of the potential data needs listed in the PWP were previously required as 

conditions of registration, and have already been submitted. Specifically, Valent has already 

submitted an immunotoxicity study (GLN 870.7800) and a storage stability study (GLN 

860.1380) on Brassica, celery, and spinach. In addition to the immunotoxity study and the 

storage stability study submitted as a condition of registration, the Agency determined that the 

field accumulation in rotational crops (GLN 860.1900) for small grain, soybean, corn, rice, and 

oilseed data requirement which was listed in the PWP as a potential data need has already been 

required as condition of registration. Therefore, the Agency will not issue a DCI for the 

immunotoxicity study, a storage stability study (for the commodities listed above), and field 

accumulation in rotational crops (for the commodities listed above) to support the registration 

review of fluopicolide.

 1 http://www.epa.gov/oppsrrd1/registration_review/
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SUMMARY OF COMMENTS AND AGENCY RESPONSES

During the 60-day public comment period on the Fluopicolide Preliminary Work Plan, which 

opened on March 27, 2013 and closed on May 28, 2013, the Agency received comments from 

the technical registrant Valent and the FIFRA Endangered Species Task Force (FESTF). The 

comments question the timeline described in the PWP, the planned ecological and human health 

risk assessments and the data requirements. In the PWP, EPA also solicited comments on the 

specific topics of environmental justice, water quality concerns, and trade irritants, and of these 

topics EPA only received one comment on trade irritants.

This section does not capture every comment made in response to the PWP nor all of the 

Agency’s responses. Summarized below are public comments that resulted in changes to the 

anticipated registration review data needs, risk assessments, or timeline, or are of a broader 

regulatory nature. Public comments and EPA responses in their entirety are located in the docket, 

EPA-HQ-OPP-2013-0037. Summarized public comments and Agency responses related to the 

anticipated ecological risk assessment or data needs are in the Response to Public Comments on 

the Fluopicolide Registration-Review Problem Formulation (D412196) while those relevant to 

the anticipated human health risk assessment or data needs are in the Fluopicolide HED 

Response to Comments Submitted on the Human Health Assessment Scoping Document in 

Support of Registration Review (D412203). 

• Comments submitted by FIFRA Endangered Species Task Force (FESTF) in EPAHQ-OPP-2013-0037-0008.

1. Comment: FESTF submitted a comment that the fluopicolide technical registrant, Valent, is 

a member of the FESTF task force and is entitled to rely on data submitted by FESTF.

Response: The Agency thanks FESTF for its comment and will consider this information as it 

conducts the registration review process and makes its registration review decision.

• Comments submitted by Valent in EPA-HQ-OPP-2013-0037-0009.

2. Comment: Valent questioned why fluopicolide, which was first registered in January 2008, is 

now undergoing registration review only 5 years after registration.

Response: Fluopicolide was first registered in 20082 and while the registration review program 

dictates a 15 year review cycle for all registered pesticides, EPA is required to complete the first 

registration review process in 2022. Fluopicolide has been included among the first set of 

chemicals statutorily required to go through registration review by the 2022 initial completion 

date.

3. Comment: Valent informed the Agency that it will provide time and location specific 

fluopicolide usage data as it becomes available to assist with human health and ecological risk 

assessment refinement.

 2 In the Fluopicolide PWP and the BEAD Chemical Profile for Registration Review: Fluopicolide, the data of first 

registration was incorrectly listed as 2007. The correct date for fluopicolide’s first registration is January 2008.
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Response: The Agency appreciates Valent’s offer for more specific usage data.

4. Comment: The Agency requested that the registrant provide additional label information 

where necessary to clarify label use directions. Valent commits to work with the Agency to 

clarify label inconsistencies or ambiguities before the Registration Review Risk Assessment is 

completed. For example, Valent specifically noted that the drench rate for container grown

ornamental plants is 5 to 10 quarts per 10 square foot for container grown plants, including 

non-bearing fruit and nut trees. The rate is not intended to be extrapolated to a whole acre of 

land at 27.133 lb./acre applied 2x/year. 

Response: The Agency appreciates Valent’s offer to clarify their labels with regards to use rates. 

5. Comment: Valent noted that an immunotoxicity study (MRID 48809201) was submitted on 

October 5, 2012

Response: The immunotoxicity study (MRID 48809201) has been received by the Agency and a 

data evaluation review is in the process of being finalized. This data gap has been fulfilled and 

will not be included as a data requirement in the data call-in (DCI) to support the registration 

review of fluopicolide. This data requirement will be removed from the work plan for 

fluopicolide

6. Comment: Valent noted that the following storage stability data (Brassica head and stem, 

bulb, and root vegetable and leafy vegetable) were submitted on January 31, 2013 (MRIDs 

49054401, 49054402, 49054403, 49054404). 

Response: The submitted storage stability studies will be evaluated during the registration 

review of fluopicolide to determine if those studies fulfill the 860.1380 data requirements. This 

data requirement will be removed from the work plan for fluopicolide.

7. Comment: Valent indicated that it will submit a waiver for the 860.1520 guideline 

requirement (Processed Food and Feed – aspirated grain fractions). 

Response: When a waiver rationale is provided, the Agency will review the waiver rationale and 

provide a timely response.

8. Comment: Valent informed the Agency it intends to request a waiver for GLN 850.4100 

(Seedling Emergence) since according to existing data, there does not seem to be a statistical 

significance in any of the 10 plant species tested, and the data indicate that the NOAEC for both 

monocots and dicots is 0.121 lb a.i./A, the highest dose tested.

Response: EPA believes that risk to terrestrial plants cannot be precluded because effects were 

noted in the available Tier 1 Seedling Emergence studies which tested applications rates below 

currently labeled rates for some uses (e.g. turf). Therefore, additional testing (seedling 

emergence and vegetative vigor) is needed on all ten plant species. Tier 1 testing could be 

conducted at the maximum labeled application rate in lieu of Tier 2 testing; however, Tier 2 

would be required for any species showing effects in a Tier 1 study (conducted at the maximum 

labeled application rate). As an alternative, the available Tier 1 studies could be used for risk 
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assessment if all labeled application rates are lowered to the tested rate (0.121 lb ai/A). In that 

case, Tier II testing would be needed only for the species that showed effects in the currently 

available Tier I studies (buckwheat – seedling emergence* and ryegrass – vegetative vigor).

9. Comment: Valent noted that the Agency indentifed GLN 835.4300 (Aerobic Aquatic 

Metabolism) as a data gap, but that it did not to require these data; and, instead will assume 

stability. Valent commented that it will provide the data for this data gap.

Response: The Agency appreciates Valent’s efforts to support the risk assessment with available 

data.

10. Comment: Valent commented that because of fluopicolide’s low solubility in test solutions 

and low toxicity of TGAI to Daphnia magna, it proposes to use the EC50 of 5.3 mg a.i./L, 

(calculated from EC50 of 11 mg formulation/L of the study with TEP) as a definitive acute 

endpoint for Daphnia magna with which to predict (via an Acute to Chronic Ratio) chronic 

toxicity to estuarine/marine invertebrate.

Response: EPA notes that TEP data should not be used to in an acute-to-chronic ratio (ACR) as 

data developed with a TEP would result in additional uncertainty because the formulation may 

reduce or enhance the toxicity of fluopicolide. An ACR based on TEP to TGAI may differ from 

that of the TGAI to TGAI. An ACR may be calculated in lieu of conducting 850.1350 if a 

definitive acute toxicity endpoint is available from an acceptable study testing the TGAI on 

Daphnia magna. Otherwise, a study on chronic toxicity to marine/estuarine invertebrates 

(850.1350) is needed to address risk

11. Comment: Valent alerted the Agency to several trade irritants. Specifically, lettuce and 

spinach gaps with the EU, and cantaloupe, carrot and watermelon with Japan.

Response: The Agency appreciates Valent providing this information. Where possible, the 

Agency will work to resolve issues of trade irritants during the registration review process.
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PLANNED DATA NEEDS

Table 1 below summarizes the planned data needs for fluopicolide based on the Response to 

Public Comments on the Fluopicolide Registration-Review Problem Formulation (D412196),

and Fluopicolide HED Response to Comments Submitted on the Human Health Assessment 

Scoping Document in Support of Registration Review (D412203). The table has been updated 

since the PWP to reflect public comments which resulted in changes to the data needs. 

Table 1: 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

860.1520 Processed food and feed for 

• Aspirated grain fractions TEP 24

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.

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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

RISK ASSESSMENTS FOR REGISTRATION REVIEW

During registration review, the Agency will 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 major degradate 2,6-dichlorobenzamide (BAM). 

For human health, EPA will 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 2 below summarizes the planned registration review risk assessments based on the EFED 

Problem Formulation and HED Scoping Document. The planned assessments have not changed 

from what was included in the PWP.
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Table 2: 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 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 An 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 An updated drinking water assessment for 

fluopicolide and BAM may be required under 

registration review if warranted by 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 OPP’s 

Residential Exposure Standard Operating Procedures 

(SOPs). In addition, revised residential assessments 

may be needed if toxicological PODs change or 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. The Agency will determine 

whether a post application inhalation assessment is 

needed 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.
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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 i.e., both express determination of parent 

fluopicolide. However, not all tolerance and MRL

values are harmonized. 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.
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TIMELINE

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

registration review in Table 3 below. The projected timeline has been updated to reflect impacts 

of public comments received that changed to the planned data needs.

Table 3. Registration Review Timeline for Fluopicolide

Activities Estimated Date

Opening the Docket

Open Docket and 60-day Public Comment Period 2013 – Mar.

Close Public Comment 2013 – May

Case Development

Final Work Plan 2013 – Sept.

Issue DCI 2014 – Apr. – June

Data Submission 2016 – Apr. - June

60-day Public Comment Period for Draft Risk Assessments 2017 – Oct. –Dec.

Registration Review Decision

60-day Public Comment Period for Proposed Registration Review 

Decision

2018 – Apr. – June

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

Total (years) 6

NEXT STEPS

As noted previously, the Agency plans to require several environmental fate, ecological effects, 

and human health studies for fluopicolide through a Data Call-In Notice, expected to be issued in 

2014.