Docket Number EPA-HQ-OPP-2012-0859 

www.regulations.gov 

Folpet Final Work Plan 

Registration Review 

Case Number 0630 

June 2013 

Approved by: ~p ~)? Richard P. Keigw~' ' 

Date: 

Director 

Pesticide Re-evaluation Division 

and 

Susan Lewis 

Acting Director 

Antimicrobials Division 
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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 folpet. This work plan addresses public comments received concerning 

the Preliminary Work Plan (PWP), which was posted in the folpet registration review docket 

(EPA-HQ-OPP-2012-0859). Folpet (Folpan®) is a dicarboximide fungicide. Folpet is 

formulated as water-dispersible granules or wettable powder and is registered for use as a foliar

treatment on avocados in Florida to manage scab and on hops to manage downy mildew. It is 

also registered for several additional food uses in countries outside the U.S. Because foods 

treated with folpet are imported into the U.S., EPA has established several import tolerances with 

no U.S. registrations. In addition, there are seven antimicrobial end-use products that contain 

folpet, some of which are registered for residential use. One product is a wood preservative and 

six products are materials preservatives. The wood preservative product is formulated as a readyto-use liquid that is applied using brush, roller, or airless sprayer. The material preservative 

products are formulated as liquid concentrates, wettable powders, and water-dispersible granules 

that are added during the manufacturing process. The wood preservative product contains

another active ingredient, 3-iodo-2-propynl butyl carbamate (IPBC), registration review case 

2725, docket number EPA-HQ-OPP-2011-0420. The material preservative products do not 

contain any other active ingredients.

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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This 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 planned 

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

timeline for the folpet registration review. Last, there is a discussion of next steps.

UPDATES SINCE THE PWP WAS ISSUED

The PWP for folpet identified changes needed to clarify the label for Folpan®80WG (EPA Reg. 

No. 66222-48) to ensure that the directions for use are consistent with the folpet Reregistration 

Eligibility Decision (RED) and conditions of registration for hops. The Agency is working with 

Makhtesthim-Agan of North America (MANA) to amend the labels for Folpan®80WG as 

described in the PWP. 

 

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http://www.epa.gov/oppsrrd1/registration_review/
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Subsequent to the issuance of the PWP, the Agency has clarified some of the anticipated data 

requirements for the folpet registration review. Some of the anticipated antimicrobial data 

requirements were incorrectly listed in the PWP as 835 guideline series studies; these studies are now 

correctly listed as 850 guideline series studies, in accordance with the recently promulgated rule, Data 

Requirements for Antimicrobial Pesticides in 40 CFR § 158(W) (see 78 FR 26978)2. In some cases the 

incorrect test compound was inadvertently listed. Last, the time frame was corrected for certain studies to 

allow for the necessary protocol review.

On February 12, 2013, MANA submitted comments to EPA regarding the anticipated 

registration review data needs listed in the PWP and technical support documents. MANA cited 

existing studies that they believed would address several data needs, including the hydrolysis 

and adsorption/desorption of the folpet degradate phthalimide (PI). As a result of this comment, 

EPA no longer expects to require new hydrolysis or adsorption/desorption studies (Guidelines 

835.2120 and 835.1240, respectively)

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for PI for the folpet registration review. MANA also 

mentioned several studies to be submitted to address the anticipated data needs for the folpet 

registration review. These studies were received by EPA on May 9, 2013, and will be reviewed 

to determine if they address the planned data needs for folpet.

SUMMARY OF COMMENTS AND AGENCY RESPONSES

During the 60-day public comment period on the Folpet PWP, which opened on December 14, 

2012 and closed on February 12, 2013, the Agency received comments from seven individuals 

and/or companies. Comments were submitted by the US Hop Industry Plant Protection 

Committee, a few entomology managers for farms and/or greenhouse operations in Mexico, an 

avocado farmer from Columbia, Ashland Corporation, and MANA. The comments do not 

address the timeline described in the PWP, but they do address the anticipated ecological and 

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

on the specific topics of environmental justice, water quality concerns, and trade irritants. EPA 

received comments on the need to maintain US tolerances for folpet, especially those for 

imported commodities, but received no comments or other information on environmental justice 

or water quality concerns.

This section summarizes public comments that resulted in changes to the anticipated registration 

review data needs, risk assessments, or timeline, or are of a broader regulatory nature. This 

section does not capture every comment or all of EPA’s responses. However, public comments 

and EPA responses in their entirety are located in the docket, EPA-HQ-OPP-2012-0859. EPA’s 

response to comments related to the anticipated ecological risk assessment or data needs are in

the documents Response to Public Comments on the Folpet Registration-Review Problem 

Formulation, and Responses to the 60-day Public Comments on the Folpet Registration Review 

Preliminary Work Plan, while those comments relevant to the anticipated human health risk 

assessment or data needs are addressed in the document, Folpet: HED’s Response to Comments 

on the Folpet Preliminary Work Plan (PWP).

 

2

This rule was promulgated on May 8, 2013, with an effective date of July 8, 2013.

3 This study was listed as an anticipated data requirement in the folpet problem formulation document, but 

inadvertently omitted from the Preliminary Work Plan. 
4

Comments submitted by Ann E. George, U.S. Hop Industry Plant Protection Committee in 

EPA-HQ-OPP-2012-0859-0008 and 0009. 

Comment: It is critically important to maintain the US MRL for folpet on hops (120 ppm), as 

it is harmonized with both the European Union (150 ppm) and Japan (120 ppm), two major 

US hop trading partners. The loss of this MRL would be detrimental to European hop 

growers who ship to the United States and would create a trade irritant with European 

countries that produce hops.

Response: EPA notes the US Hop Industry support of the folpet tolerance on hops and its 

importance to trade with European countries that produce hops. The Agency will work to 

avoid the creation of trade irritants whenever possible during the registration review process. 

3. Comment: The Agency’s proposed changes to the folpet application rate on hops (from 3 lbs 

to 2.5 lbs 80WG per application) and the proposed REI of 48 hours for retraining hop vines

are acceptable to the US hops industry.

Response: EPA appreciates the comment and will be working with the folpet registrants to 

amend labels to reflect these changes. 

Comment: Ashland expects to provide additional use and usage information to the Agency if 

requested in the folpet Data Call-In.

Response: Although EPA will not be including requirements for use and usage information 

in the folpet Data Call-In, such information would be extremely helpful to the Agency as it 

develops the risk assessments to support the folpet registration review. 

Comments submitted by Robert Everich Ph.D., Senior Scientist, Makhteshim-Agan of 

North America, Inc. (MANA) in EPA-HQ-OPP-2012-0859-0015

Comment: MANA disagrees with the requirement for an adsorption/desorption studyi

(835.1240) for phthalimide (PI), the major aerobic soil metabolite of folpet. The adsorption 

and desorption properties of phthalimide were studied in five European soils in accordance 

with OECD guidelines (MRID 45784609). The soils were representative of a wide a range of 

properties, except for pH. Due to the instability of phthalimide in neutral to alkaline 

conditions the soils were selected with pH 6 to enable the study to be carried out. The 

characteristics of the soils used are described in detail in the study and should meet EPA’s 

requirements.

Response: EPA will incorporate the cited study into the risk assessment at the time of 

registration review. A new adsorption/desorption study (835.1240) with PI is no longer 

expected to be required for this registration review. 

Comment: MANA believes that the behavior of phthalimide (PI) in the environment can be 

explained and described by the existing hydrolysis studies ... the rate of hydrolysis as a 

function of pH and temperature has been determined and the products of hydrolysis and their 

future degradations identified using [C14]folpet. 
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Response: The studies referenced by MANA, along with information from the European 

Food Safety Authority, indicate that PI is stable to hydrolysis. Therefore, EPA will assume 

that PI is stable for modeling purposes. A new hydrolysis study (Guideline 835.2120) with 

PI is no longer needed for the folpet registration review. 

PLANNED DATA NEEDS

Table 1 below summarizes the planned data needs for folpet based on the December 4, 2012

document, Registration Review: Preliminary Problem Formulation for Environmental Fate, 

Ecological Risk, Endangered Species, and Drinking Water Exposures for Folpet, and the 

November 28, 2012 document, Folpet: Human Health Risk Scoping Document in Support of 

Registration Review and the response to comments documents previously cited. As previously 

mentioned, EPA clarified some of the anticipated data requirements for the folpet registration 

review subsequent to the issuance of the PWP, including the guideline numbers and test 

compound. EPA has also determined that the hydrolysis and adsorption/desorption studies for 

the PI degradate are no longer needed. Last, EPA has extended the time frame to conduct the 

worker exposure monitoring study. Please see Table 1 below for the corrected list of planned 

data requirements for the registration review of captan. 

Table 1: Planned Data Needs for the Folpet Registration Review

Guideline 

Number Study Title1

Test Material2

Estimated 

Timeframe

(Months from 

receipt of DCI)

835.2410 Soil Photolysis TGAI 12

835.4100 Aerobic Soil Metabolism3 TGAI and PI 24

835.4300 Aerobic Aquatic Metabolism TGAI 24

835.4400 Anaerobic Aquatic Metabolism TGAI 24

850.1300 Aquatic invertebrate life cycle (freshwater) PI 12

850.1400 Fish early life stage (freshwater) PI 12

850.2100 Avian oral toxicity (passerine species)4 TGAI 12

850.2300 Avian Reproduction (upland game & waterfowl spp) TGAI 24

Non-GDLN

(Special Study) Avian Inhalation Toxicity4 TGAI 12

850.3030 Honeybee toxicity of residues on foliage4,5 TGAI 12

835.31106 Ready Biodegradability7PI 12

835.32206Porous Pot Test7PI 12

835.32406 Simulation Test – Aerobic Sewage Treatment: A. 

Activated Sludge Units7 PI 12

835.32806 Simulation Test to Assess the Biodegradability of 

Chemicals Discharged to Wastewater7 PI 12

850.3300 Activated Sludge Respiration Inhibition (ASRI) PI and PAI812

850.4100 Seedling Emergence and Seedling Growth TEP 12

850.4150 Vegetative Vigor TEP 12

850.4500 Algal toxicity9PI 12
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Table 1: Planned Data Needs for the Folpet Registration Review

Guideline 

Number Study Title1

Test Material2

Estimated 

Timeframe

(Months from 

receipt of DCI)

850.6100 Environmental Chemistry Methods/Independent 

Laboratory Validation for soil and water TGAI 12

870.3465 90-day Inhalation TGAI 12

870.7800 Immunotoxicity TGAI 12

875.1200 Dermal Exposure, Indoor10, 11 TEP 36

875.1400 Inhalation Exposure, Indoor10, 11 TEP 36

875.2300 Indoor Surface Residues12 TEP or treated 

article 24

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

– including renumbering and other designations or changes for some guideline studies. See “Final Test Guidelines; 

OCSPP 850 Series; Notice of Availability” 77 FR 38282, June 27, 2012. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0028. In addition, EPA promulgated 

the Final Rule establishing Data Requirements for Antimicrobial Pesticides on May 8, 2013; these requirements 

become effective on July 8, 2013. 

2

PI = phthalimide degradate; PAI = phthalamic acid; TGAI = technical grade active ingredient; TEP = typical enduse product

3 The anticipated DCI will require testing of folpet TGAI on 3 soil types and PI on 4 soils. 

4 The anticipated DCI will require the submission of a protocol prior to study initiation.

5 Expected to be required for residues of folpet on treated wood to support paint, stain, and wood preservative uses. .

6 The guideline number was erroneously listed as 850 (rather than 835) series in the PWP. 

7 EPA expects that the results of the Activated Sludge Respiration Inhibition (ASRI) study (Guideline 850.3300/ 

850.6800) will determine which biodegradation study is needed. See http://regulations.gov docket item number 

EPA-HQ-OPPT-2009-0154-0021 for the final study guideline. 

8The test substance was erroneously listed as TGAI in the PWP.

9 Expected to be required for the species showing the greatest sensitivity to folpet (i.e., Navicula pelliculosa).

10 Expected to be required for handlers applying paints and stains containing folpet using brushes, rollers, or airless 

sprayers.

11 EPA’s Human Studies Review Board and/or the Institutional Review Board may need to review the protocols for 

these studies as well as the study data to ensure compliance with 40 CFR Part 26. The study timeframe has been 

adjusted accordingly. 

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For dermal & incidental oral exposure to children from transferable folpet residues from treated carpet and treated

decks.

RISK ASSESSMENTS FOR REGISTRATION REVIEW

During registration review, the Agency will conduct a comprehensive ecological risk assessment, 

including an endangered species assessment, for all uses of folpet. For human health, EPA will 

conduct revised residential and occupational risk assessments during registration review. If 

toxicological endpoints or points of departure are revised based on the data that are required for 

registration review, they will be considered in the new assessments, as well as any changes to the

standard operating procedures or default exposure assumptions.

Table 2 summarizes the planned registration review risk assessments based on the EFED 

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

changed from what was included in the PWP.
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Table 2: Planned Risk Assessments for the Folpet 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 

Yes The anticipated ecological risk assessment will support a 

complete endangered species determination for folpet. 

Incidents Will check 

for updates

For a discussion of reported ecological incidents for folpet, 

see page 20 of the Problem Formulation.

Human Health

Dietary

Food No EPA expects to rely on previous assessments, which showed 

that folpet dietary risks were not of concern.1

Drinking water No EPA does not expect significant dietary exposure to folpet 

residues in drinking water. 

Occupational

Handlers (mixers, loaders, 

applicators)

Yes EPA anticipates conducting an occupational handler 

assessment for use of folpet as a material preservative and for 

use in paints, stains, and wood preservatives. EPA also 

anticipates updating the assessment for agricultural uses. 

Post-application Yes EPA anticipates conducting an assessment for postapplication inhalation and dermal exposures to folpet.

Residential

Handlers Yes EPA anticipates conducting a residential handler assessment 

for use of folpet in paints, stains, and wood preservatives. 

Post-application Yes EPA anticipates conducting a residential post-application 

assessment to evaluate dermal & incidental oral exposure to 

children from transferable folpet residues from treated carpet 

and treated decks.

Other

Aggregate Yes Evaluates the combined risk from dietary and residential 

exposures. EPA anticipates conducting an aggregate cancer 

assessment for oral exposure to the thiophosgene metabolite 

of both folpet and captan. 

Cumulative No Although folpet and captan share the common metabolite 

thiophosgene, this compound is transient and not easily 

measured. Thus, the role of thiophosgene in folpet’s toxicity 

has not been determined and EPA has not assumed that 

folpet has a common mechanism of toxicity with captan or 

any other substances. 

Tolerances Yes The folpet tolerances are expected to be updated to reflect 

current policy, to harmonize with international tolerances

where possible, and to align more closely with the available 

residue chemistry data. 

Incidents Will check 

for updates

For a discussion of reported human incidents for folpet, see 

page 14 of the Scoping Document.

1 New acute and chronic dietary risk assessments may be needed if there are changes to the folpet toxicological 

points of departure or uncertainty factors.
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TIMELINE

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

review in Table 3 below. The projected timeline has changed since the PWP; an additional year 

has been added to allow for review of protocols for studies involving intentional human 

exposure. 

Table 3: Registration Review for Folpet – Projected Timeline

Activities Estimated Date

Opening the Docket

Open Docket and 60-day Public Comment Period 2012 – December

Close Public Comment 2013 – February

Case Development

Final Work Plan 2013 – May

Issue DCI 2014 – Jan - March

Data Submission 2017 – Jan - March

60-Day Public Comment Period for Draft Risk Assessments12018 – July -Sept.

Registration Review Decision

60-Day Public Comment Period for Proposed Registration Review Decision 2019 – Jan - March

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

Total (years) 7

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

of at least 30 calendar days for draft risk assessments; see 40 CFR Part 155.53(c). For conventional pesticides, the 

Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.

NEXT STEPS

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

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

2014.