2 

### Folpet Preliminary Work Plan

– Table of Contents

Overview 3

Anticipated Data Needs 3

Statutory and Regulatory Authority 5

Chemical Facts 6

Use and Usage Information 6

Recent Actions 7

Anticipated Risk Assessment s for Registration Review 8

Timeline 10

Next Steps 10

Appendix

– Additional Areas Considered in Folpet’s Registration Review 11

References:

This Preliminary Work Plan summarize s the Environmental Protection Agency's current position based on the following documents:

1. Registration Review: Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposures for Folpet. Lowit et

al. December 4 , 2012

.

2. Folpet: Human Health Risk Scoping Document in Support of Registration Review. Kidwell, et al. November 28, 2012.

3. Folpet: Review of Human Incidents. Recore. July 31, 2012

4. BEAD Chemical Pro

file for Registration Review: Folpet

. Yourman et al. June 21, 2012.

5. PRD Label Data Report: Food/Feed & Non

- Food/Non

- Feed Uses Considered in Registration Review Work Planning for Folpet. June 25, 2012.

These and other supporting documents for the folpet registration review case may be found in the

docket EPA

- HQ

- OPP

- 2012

- 0859 at http://www.regulations.gov

.3

OVERVIEW

The docket for folpet is now open , initiating the first public comment period for this registration

review (docket number EPA

- HQ

- OPP

- 2012

- 0 859). 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 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. There are seven end use antimicrobial

p roducts 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 brus h, roller or airless spray. The material preservative products are formulated as liquid concentrates, wettable powders and

water

- dispersible granules that are added during material manufacture. The wood preservative product contain s an other active ingredie nt

, 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. T his Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about folpet

, 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 comp leting folpet’s review

.

The registration review process was designed to include a public participation component to solicit input from interested stakeholders. The Agency intends, b y sharing this information in the docket, to inform the public of what i t knows about folpet and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on folpet

. The Agency encourages all interested stakeholders to review the PWP and Appendix and to provide commen ts 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 specific ally

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 pesticide s; or the public at large.

The Preliminary Work Plan begins by listing the anticipated data needs for folpet

. Next, it discusses the statutory and regulatory authority for R egistration R eview. Then the document provides folpet’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

R egistration R e view along with some additional chemical case

- specific information.

ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for folpet

. EPA anticipates issuing a data call

in for these data during registration review. For additional discussion of the anticipated data needs, see the December 4, 2012 document

, Registration Review: Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water4

Exposures for Folpet, and the November 28, 20 12 document, Folpet: Human Health Risk Scoping Document in Support of Registration Review

.

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

Guideline

Number Study Title Test Material Estimated

Timeframe

(Months from receipt of DCI)

835. 2120 Hydrolysis PI degradate 1 12

835. 2 410 Soil Photolysis TGAI 2 12

835.4100 Aerobic Soil Metabolism 3 TGAI and PI 1 24

835.4 3 00 Aerobic Aquatic Metabolism TGAI 24

835.4 4 00 Anaerobic Aquatic Metabolism TGAI 24

850.1300 Aquatic invertebrate life cycle (freshwater) 4 PI 12

850.1400 Fish early life stage (freshwater) 4 PI 12

850.2100 Avian oral toxicity (passerine species) TGAI 12

850.2300 Avian Reproduction (upland game & waterfowl

species) TGAI 24

Non

- GDLN Avian Inhalation Toxicity 5 TGAI 12

850.3030 Honeybee toxicity of residues on foliage 6 TGAI 12

850.31 10 7 Ready Biodegradability PI 12

850.32 2 0 7 Porous Pot Test PI 12

850.3240 7 Simulation Test

– Aerobic Sewage Treatment PI 12

850.3280 7 Simulation Test

– Wastewater PI 12

850.3300 8 Activated Sludge Respiration Inhibition TGAI 12

850.4100 S eedling emergence and seedling growth TEP 12

850.4150 V egetative V igor TEP 12

850.4500 9 A lgal toxicity PI 12

850.6100 10 Environmental Chemistry Methods (ECM) and

Associated Independent Laboratory Validation (ILV) for soil and water TGAI 12

870.346 5 90

- day Inhalation TGAI 12

870.7800 Immunotoxicity TGAI 12

875.1200 Dermal Exposure, Indoor 11 TEP 24

875.1400 Inhalation Exposure, Indoor 11 TEP 24

875.2300 Indoor Surface Residues 12 TEP 24

1 Data are anticipated to be required for the phthalimide (PI) degradate.

2 TGAI = technical grade active ingredient; TEP = typical end

- use product

3 Data are anticipated to be required on 4 soil types; the study submitted to EPA (MRID 42122022) test ed only one soil type.

4 The anticipated DCI will require this study to be conducted on the same species that was tested in the acute study (i.e., fish

- rainbow trout or bluegill sunfish; invertebrates

– Daphnia ). Alternatively, for fish testing, if the test species is different from that used in the freshwater acute toxicity tests, then a 96

- hour acute LC50 value on that species would need to be provided. See 40 CFR §158.630, table footnote 13.

5 The anticipated DCI will require the submission and EPA approval of a protocol prior to study initiation.5 6 Anticipated to be r equired for residues of folpet on treated wood to support wood preservative uses

. .

7 EPA has published final guidelines for these four biodegradation studies: Ready Biodegradability Test at http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0152

- 0017 , Porous Pot at http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0152

- 0024 , Simulation Test

-- Activated Sludge Units at http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0152

- 0034 , and Biodegradability of Chemicals Discharged to Wastewater at http://www.regulations.gov/#!documentDetail;D=EPA

HQ

- OPPT

- 2009

- 0152

- 0036 . One biodegradation study is anticipated as required; the biodegradation study anticipated as required is based on results of the A ctivated Sludge Respiration Inhibition test. The Agency anticipates codifying these studies in 40 CFR 158W in the near future.

8 EPA has a published final guideline for this study at http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

OPPT

- 2009

- 0152

- 0003 . The Agency anticipates codifying this study in 40 CFR 158W in the near future. OECD

Test Guideline 209 can also be used as guidance for this study, available online at http://www.oecd

ilibrary.org/content/book/9789264070080

- en

. 9 The DCI anticipated to be issued is expected to require testing be done on the species showing the greatest sensitivity to folpet (i.e., Navicula pelliculosa)

1 0 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

1 1 F or handlers applying paints and stains containing folpet using brushes, rollers, or airless sprayers

1 2 For dermal & incidental oral exposure to children from transferable folpet re s i d ues from treated carpet and treated

decks.

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 cau se 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 p esticides 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 Age ncy periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Informatio n on this program is provided on EPA’s website 1

.

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

. T he 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 F inal W ork P lan (FWP) and anticipated schedule for the registration review of folpet

.

1 http://www.epa.gov/oppsrrd1/registration_review/6

Table 2 provides a summary of the current regulatory status of folpet.

Table 2: F o lpet Chemical Facts

PC code 081601

Case Number 0630

CAS Number 133

- 07

- 03

Year first registered 1948 Pesticide Type Fungicide, Antimicrobial

Chemical class Thiophthalimide

R eregistration Eligibility Decision (R E D) 1999

Tolerance Reassessment Eligibility Decision (TRED) Folpet tolerances were reassessed through the 1999 RED.

Cumulative group Folpet is not a member of a cumulative group.

40 CFR Citation Tolerances for folpet are established in 40 CFR §180.191

. Dual

- use Yes. Folpet is registered for both conventional and antimicrobial uses.

Non

- pesticidal uses No n on

- pesticidal uses for folpet.

Pesticide Re

- evaluation Division, Chemical Review Manager Christina Scheltema

, schelt e ma.christina@epa.gov

, (703)308

- 2201

Antimicrobial Division, Chemical Review Manager Wanda Henson

, henson.wanda@epa.gov , (703) 308

- 6435

Registration Division

, Product Manager Tony Kish, kish.tony@epa.gov , (703) 308

- 9443

Antimicrobial Division, Product Manager Marshal Swindell, Swindell.marshal@epa.gov , (703) 308

- 6341

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for f olpet

. Please see the June 21, 2012 document, BEAD Chemical Profile for Registration Review: Folpet

, in the registration review

docket for more details

.

Table 3: U se and Usage Information for Folpet Summary of Use Registered for f oliar treatment of scab & mildew in avocados and hops. Also registered for use as a f ungicide in paints & coatings and a fungicide/mildewcide in adhesives & sealants.

Use Sites Avocado, hops, paints, coatings, wood structures & furniture, industrial

materials

, adhesive s , caulks, coatings, paints, plastics, stains, wood composites, surface treatments, and polymer compounds. Summary of Usage There is no available information on folpet usage in agriculture. In 2004/2005, an estimated 630,000 lbs of folpet were used in pa ints and coatings and 70,000 lbs were used in adhesives and sealants. Formulation Type(s) Water

- dispersible granules, wettable powders, liquid concentrates, and ready

- to

- use liquids. Co

- formulated with 3

- iodo

- 2

- propynl butyl carbamate (IPBC) for wood p reservative uses. Application Method(s) Ground and aerial for avocados & hops; brush, roller, spray, or dip for paints, stains, coatings, & wood preservatives; mixed or blended at manufacturing facilities for all material preservative uses.7

Table 3: U se and Usage Information for Folpet

Technical Re gistrant (s) Ma kh teshim

- Agan North America (MANA), Mak h teshim Chemical

Works No. of Registrations 12

Restricted Use No

Guidance for Commente rs: Additi onal areas of use and usage related information requested for this registration r eview , and of particular interest to EPA, are described below.

C onfirmation 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

. Usage information for Florida avocados and for hops Information on nonagricultural use sites, including outdoor domestic dwellings, wood and wood structure protection, indust rial preservatives, and surface treatments for tile, outdoor furniture, plaster, paint, finished wood, and wood surfaces

U se distribution ( e.g. , acreage and geographical distribution of relevant use sites )

M edian and 90 th percentile reported use rates (lbs ai/ A ) from usage data

– national, state, and county

A pplication timing (date of first application and application intervals)

– national, state, and county Usage/use information for both agricultural and non

- agricultural uses Typical application interval (days)

S tate or local use restrictions

F oreign technical registrants not listed above who supply technical folpet to the U

. S

. market

RECENT ACTIONS

EPA published a final rule codifying the tolerances fo r folpet in 40 CFR §180.191 on August 1,

2007. The tolerance for avocados was codified as a tolerance with a regional registration for use

in Florida only. Import only tolerances were established for apple, cranberry, cucumber, grape, raisin, lettuce, me lon, onion (dry bulb), strawberry, and tomatoes because there were no US registrations for the use of folpet on these commodities. (See 72 FR41923).

In 2004, EPA approved a new food use registration for domestic use on hops. See 69 FR 52192

for detail s. However, EPA believes label amendments are needed to clarify the directions for use for one product, FOLPAN 80 WDG (EPA Registration Number 66222

- 48) : (1) revise the maximum rate of application on hops to be 2 lb ai/A/application; (2) revise t he PHI f or avocados to 7 days; (3) a t the application rate currently on the FOLPAN 80 WDG label, add a 48 hour reentry interval ( REI ) to reach an acceptable MOE for training hop vines. The Agency will work with the registrant to amend this label prior to the registration review assessment for folpet.

A NTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW8

The most recent comprehensive human health risk assessment for folpet was completed in 2004 to support a petition for domestic use of folpet on hops and registration of a new formulation for folpet on avocados in Florida. T he most recent ecological and environmental fate risk assessment was completed in 2003 to support a petition for re gistration of folpet use on hops and registration of a new formulation on avocados

. Findings and conclusions from these risk

assessments are summarized in the December 4, 2012 document, Registration Review: Preliminary Problem Formulation for Environment al Fate, Ecological Risk, Endangered Species, and Drinking Water Exposures for Folpet, and in the November 28, 2012 document, Folpet: Human Health Risk Scoping Document in Support of Registration Review

.

During registration review, t he Agency anticipates the need to conduct a comprehensive ecological risk assessment, including an endangered species assessment, for all uses of folpet

. For human health, EPA anticipates the need to conduct revised residential and occupational risk

assessment s dur ing registration review

. If toxicological endpoints or points of departure are

revised based on the data that are anticipated to be required for registration review

, they will be

considered in the new assessment s
, as well as any changes to the standard op erating p rocedures or default exposure assumptions

.

Table 4 summarizes the anticipated registration review risk assessments based on the EFED

Problem Formulation and HED Scoping Document

.

Table 4: Anticipated Risk Assessments for Folpet’s 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 es The anticipated ecological risk assessment will support a complete endangered species determination for folpet

.

Incidents Y es For a discussion of folpet’s reported ecological incidents, see

page 20 of the Problem Formulation.

Human Health Dietary

Food N o EPA expects to rely on previous assessments, which showed that folpet dietary risks were not of concern. 1
Drinking water N o EPA does not expect significant dietary exposure to folpet residues in drinking water. Occupational Handlers (m ixer s, loader s, applicators ) Y es EPA anticipate s 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

.9

Post

- application Yes EPA anticipates conducting a residential post

- application assessment to evaluate dermal & incidental oral exposure to children from transferable folpet re s i d ues 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, its role in folpet’s and captan’s toxicity has not been determined because thiophosgene is transient and not easily measurable. Therefore, the EPA has not assumed that folpet has a common mechanism of toxicity with captan o r any other substances.

Tolerances Yes The folpet tolerances are expected to be updated to reflect current policy, to harmonize with international tolerances, and to align more closely with the available residue chemistry data.

Incidents Yes For a discussion of folpet’s reported human incidents, 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

.

TIMELI NE

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

review in Table 5

.

Table 5: Registration Review for Folpet

– Projected Registration Review 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 2016

-- Jan

-- March

30

- D ay Public Comment Period for Draft Risk Assessments 201 7

– J uly

– Sept. Registration Review Decision

60

- D ay Public Comment Period for Proposed Registration Review Decision 2018

– Jan

– March Registration Review Decision and Begin Post

- Decision Follow

- up 2018 Total (years) 6

NEXT STEPS

After the 6 0

- 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 folpet

.10



### Appendix

– Additional Areas Considered in Folpet’s Registration Review

PUBLIC COMMENTS AND FEEDBACK :

Guidance for C ommenters: The areas below highlight topics of special interest to the Agency where your comments, data submissions, or reference to sou rces of additional information c ould 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 an d international maximum residue limits (MRL s ) 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

. Folpet is registered for avocado and hops in the US, and EPA has established tolerances for these and several commodities (without US registrations) so that these commodities can be imported into the US.

Water Quality:

Folpet is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act 2

. In addition, n o Total Maximum Daily Load s (TMD L) have been developed for folpet 3 . More information on impaired water bodies and TMDLs can be

found at the Agency’s website 4

. 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 Process 5 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 popula tion who, as a result of their location, cultural practices, or other factors, may have atypical, unusually high exposure to folpet compared to the general population. Please comment if you are aware of any sub

- populations that may have atypical, unusuall y high exposure compared to the general population.

2 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

3 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES

4 http://www.epa.gov/owow/tmdl/

5 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm11

ENDANGERED SPECIES :

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

conducted for folpet

. The ecological risk assessment planned during registration review will allow the Agency to determine whether folpet’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 folpet, 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, neurotoxici ty, 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 maturati on, 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 reregistration eligibility decision for folpet, 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), folpet 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 wildlif e 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.12

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. Folpet was included on

that list and was subject to a Tier 1 test order issued on January 7, 2012

. Once all required Tier 1

and Tier 2 data h ave been received and reviewed, the endpoints and safety factors used for risk assessment purposes will be examined and a new risk assessment performed if necessary. 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

website 6

.

HUMAN STUDIES :

Occupational

Past folpet 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 Ha ndlers Exposure Database (PHED) and the Agr icultural Reentry Task Force (ARTF) 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 o r significantly deficient relative to the ethical standards prevailing at the time the research was conducted. A ll applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied , and t here is no regulatory barrier to continued reliance on

these studies

.

STRUCTURE ACTIVITY RELATIONSHIPS

EPA must rely upon information of appropriate quality and reliability for each decision made by the Agency. In the Office of Pesticide Programs (OPP), the evaluat ion process for a pesticide chemical traditionally begins with the applicant’s submission of a set of studies conducted with the specific pesticide chemical of interest. The use of the results of such testing (measured data) is a logical, scientifically ri gorous process that identifies the physical, chemical, and environmental fate properties of the pesticide, as well as the dose and endpoints at which an adverse effect can occur in various animal species.

Today, there is significant interest in alternativ e techniques, i.e., techniques other than data generation that could significantly inform the Agency’s decision

- making process. Recently, OPP has made increasing use of structure activity relationship (SAR) as part of its regulatory

decision

- making process . In the SAR process, a chemical's molecular structure is compared to

that of other chemicals for which data are available. These structural similarities are then used to make predictive judgments about a chemical’s physical, chemical, and biological prope rties. Thus, the chemical’s physical, chemical, and biological properties are a function of (or directly related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To

6 http://www.epa.gov /endo/13

develop a QSAR, a selected set of measured data on a single physical, chemical, or biological property is used to derive a model (an equation) to predict the value of that property.

Because SAR assessments and QSAR modeling are another set of tools that are available to Agency scientists, OPP has begun a process shift that envisions shifting from the current study

by

- study approach to an approach in which the use of predicted data, generated using validated models, is considered along with information from open literature and studies specifically generated under P art 161 requirements. All relevant information would be considered as part of a weight

- of

- the

- evidence evaluation.

At this time, EPA believes that for certain endpoints, especially physical/chemical and fate properties, that SAR and QSAR might be effectiv ely utilized to fulfill some of the data requirements for many antimicrobial pesticide chemicals. When considering biological properties, at this time, EPA believes that SAR and QSAR can be most effectively utilized in the

evaluation of chemicals that exhi bit lower toxicity for human health and/or ecotoxicity parameters. This is appropriate because the risk assessment for lower toxicity chemicals can be

stream

- lined, i.e., a screening

- level assessment procedure rather than multiple tiers of

assessments with progressively more data requirements.

If stakeholders believe that submission of predicted data can fulfill one of the data needs for the folpet registration review case, then the Agency invites submission of this information. The

submitter would be expected to supply a rationale describing the utility of the information and provide documentation on the scientific validity of the information. The determination that the predicted data fulfills the data requirement would be at the sole discretion of the Agency. Pre

submission consultation with the Agency is encouraged.