2 I NTRODUCTION

This is the Environm ental 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

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. Fluopicolide is a mesosystemic, benzamide fungicide registered for use t o 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 ea ch 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 t hat, 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.

Informatio n 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 response s to th o se 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 potenti al data needs listed in the PWP were previously required as conditions of registration , and have already been submitted

. Specifically, V alent has already

submitted an i mmunotoxicity study (GLN 870.7800 ) and a storage stability study (GLN 860.1380) on Brass ica

, 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, t he Agency will not issue a DCI for the

i mmunotoxicity study, a storage stability study (for the comm odities 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/3 SUMMARY OF COMMENTS AND AGENCY RESPONSES

During the 60

- day public comment period on the Fluopicolid e 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 P WP, 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 recei ved 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

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- 0037 . Summarized public comments and Agency responses relat ed 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 a re 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 EPA

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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 infor mation as it conducts the registration review process and makes its registration review decision.

• Comments submitted by Valent in EPA

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. Comment: Valent question ed why f luopicolide, which wa s first registered in January 2008

, is now undergoing registration review only 5 years after registration.

Response: F luopicolide was first registered in 200 8 2 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 i nformed 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 2008.4 Response: The Agency appreciates Valent’s offer for more specific usa ge data

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4

. Comment: The Agency request ed 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 Registr ation 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 ap preciates 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 b y 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 requirem ent will be removed from the work plan for fluopicolide

6. Comment: Valent noted that t he following storage stability data (Brassica head and stem, bulb, and root vegetable and leafy vegetable) were submitted on January 31, 2013 (MRIDs
49054401, 4905440 2, 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, t he Agency will re view 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 i n 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 t esting 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 ava ilable Tier 1 studies could be used for risk5 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 indentif ed 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 fluop icolide’s low solubility in test solutions and low toxicity of TGAI to Daphnia magna

, it proposes to use the EC 50 of 5.3 mg a.i./L, (calculated from EC 50 of 11 mg formulation/L of the study with TEP) as a definitive acute endpoint for Daphnia magna with wh ich 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 w ould 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 seve ral trade irritants. Specifically, lettuce and spinach gaps with the EU, and cantaloupe, carrot and watermelon with Japan.

Response: The Agency appreciates Va lent providing this information. Where possible, the Agency will work to resolve issues of trade irritants during the registration review process.6 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 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

860.1520 Processed food and feed for

• A spirated 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.

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 Av ailability” 77 FR 38282, June 27, 2012. http://www.regulations.gov/#!documentDetail;D=EPA

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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

- d ichlorobenzamide (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 ar e 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 th e EFED

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

from what was included in the PWP

.7 Table 2 : 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 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 u pdated 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 u pdated drinking water assessment for fluopicolide and BAM may be required under registration review if warranted b y changes in the

estimated drinki ng water concentrations

. Residential

Handlers Y An u pdated 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 revise d during registration review. The Agency will determine whether a p ost application inhalation assessment is

needed for both residential and occupational exposure

scenarios

. Occupational Handlers (mixers, loaders, applicators) Y An u pdated occupational ha ndler assessment for fluopicolide may be required under registration review if warranted by any significant changes in exposure assessment methodology, toxicological

PODs or uncertainty factors.8 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

asses sments 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 (inclu des 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.9 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 change d 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.

– Jun e Data Submission 201 6

– 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 20 18

– Apr.

– June

Registration Review Decision and Begin Post

- Decision Follow

- up 20 19 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 D ata C all

- I n Notice , expected to be issued in

2014

.