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 Division2

I NTRODUCTION

This is the Environm ental 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 fu ngicide

. Folpet is

formulated as water

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

treatment on avocado s 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, t here are seven anti microbial 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 ready

to

- use liquid that is applied using brush, roller

, or airless spray er . 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 con tain s

an other active ingredient

, 3

- iodo

- 2

- propynl butyl carb a mate (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 re gistration 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.

Informatio n on this program is provided on the Agency’s website

. 1

Th is FWP begins with any updates since the PWP was issued. Nex t 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 com ments

. 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 ISS UED

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 R eregistration

E ligibility D ecision (RED) and conditions of registration for hops. The Agency is working with

Mak h testhim

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

described in the PWP.

1 http://www.epa.gov/oppsrrd1/registration_review/3

Subsequent to the issuance of the PWP, the Agency has clarified some of the antic ipated 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 s tudies to allow for the necessary protocol review

.

On February 12, 2013, MANA submitted comment s to EPA regarding the anticipated registration review data needs listed in the PWP and technical support documents. MANA cited existing studies that they bel ieved 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 requir e new hydrolysis or adsorption/desorption stud ies ( Guideline s 835.2120 and 8 3 5.1240 , respectively ) 3 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 P WP, 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 Colum bia, 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 re ceived no comments or other information on environmental justice or water quality concerns

.

This section s ummarize s public comments that resulted in changes to the anticipated registration review data needs, risk assessments, or timeline, or are of a broa der regulatory nature. This section does not capture every comment or all of EPA’s responses. However, p ublic 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 anticip ated 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: I

t 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 tr ading 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.

R esponse : EPA notes the US Hop Industry support of the folpet tol erance on hops and its importance to trade with European countries that produce hops

. The Agency will work to

avoid the creation of trade irritants when e ver 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 vine s 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 Cal l

- 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.

Comment s submitted by Robert Everich Ph.D., Senior Scientist, Makh teshim

- Agan of North America, Inc. (MANA) in EPA

- HQ

- OPP

- 2012

- 0859

- 0015

Comment : MANA disagrees with the requirement for an adsorption/desorption study i
(835.1240) for phthalimide (PI), the major aerobic soil metabolite of folpet. T he 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 (8 35 .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 e nvironment 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 [C 14 ]folpet.5

Resp onse: 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: Prelim inary 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 r espon se to c omments 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 stud ies 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 lis t of planned data requirements for the registration review of captan.

Table 1: Planned Data Needs for the Folpet Registration Review

Guideline

Number Study Title 1 Test Material 2 Estimated

Timeframe

(Months from receipt of DCI)

835.2410 Soil Photolysis TGAI 12

835.4100 Aerobic Soil Metabolism 3 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 Toxicity 4 TGAI 12

850.3030 Honeybee toxicity of residues on foliage 4 ,5 TGAI 12

8 35 .3110 6 Ready Biodegradability 7 PI 12

8 35 .3220 6 Porous Pot Test 7 PI 12

8 35 .3240 6 Simulation Test

– Aerobic Sewage Treatment : A.

Activated Sludge Units 7 PI 12

8 35 .3280 6 Simulation Test to Assess the Biodegradability of

Chemicals Discharged to Wastewater 7 PI 12

850. 3300 Activated Sludge Respiration Inhibition (ASRI) PI and PAI 8 12

850.4100 Seedling E mergence and Seedling Growth TEP 12

850.4150 Vegetative Vigor TEP 12

850. 45 00 Algal toxicity 9 PI 126 Table 1: Planned Data Needs for the Folpet Registration Review

Guideline

Number Study Title 1 Test Material 2 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, Indoor 10 , 11 TEP 36

875.1400 Inhalation Exposure, Indoor 10 , 11 TEP 36

875.2300 Indoor Surface Residues 12 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 A vailability ” 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 end

use 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 r e quired 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 d e term ine which biodegradation study is needed

. See http://regulations.gov docket item number

EPA

- HQ

- OPPT

- 2009

- 0154

- 0021 for the final study guideline.

8 T he t est substance was erroneously listed as TGAI in the PWP.

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

. 10 Expected to be required f or 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 wit h 40 CFR Part 26. The study timeframe has been adjusted accordingly.

1 2 For dermal & incidental oral exposure to children from transferable folpet re s i d ues 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 re gistration 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 p rocedures or de fault exposure assumptions

.

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

Problem Formulation and HED Scoping Document

. T he planned risk assessments have not changed from what was included in the PWP

.7 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 post

application 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 c hemistry 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 toxicologica l points of departure or uncertainty factors

.8

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 201 7

– Jan

- March

60

- D ay Public Comment Period for Draft Risk Assessments 1 201 8

– July

- Sept. Registration Review Decision

60

- D ay Public Comment Period for Proposed Registration Review Decision 201 9

– Jan

- March Registration Review Decision and Begin Post

- Decision Follow

- up 201 9 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 comme nt 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 D ata C all

- I n Notice , expected to be issued in early

2014

.