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 Assessments for Registration Review 8

Timeline 10

Next Steps 10

Appendix – Additional Areas Considered in Folpet’s Registration Review 11

References:

This Preliminary Work Plan summarizes 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 Profile 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-2012-0859). 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. There are seven end use antimicrobial 

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. 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 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. This 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 completing folpet’s review.

The registration review process was designed to include a public participation component to 

solicit input from interested stakeholders. The Agency intends, by sharing this information in the 

docket, to inform the public of what it 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 comments 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 specifically 

seeks comments and information. Interested stakeholders could include: environmental nonprofit or interest groups; pesticide manufacturers; agricultural labor or commodity groups; 

commercial, institutional, residential, and other users of pesticides; 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 Registration Review. 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 

Registration Review 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 callin 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 Water 
4

Exposures for Folpet, and the November 28, 2012 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 degradate112

835.2410 Soil Photolysis TGAI212

835.4100 Aerobic Soil Metabolism3 TGAI and PI124

835.4300 Aerobic Aquatic Metabolism TGAI 24

835.4400 Anaerobic Aquatic Metabolism TGAI 24

850.1300 Aquatic invertebrate life cycle (freshwater)4PI 12

850.1400 Fish early life stage (freshwater)4PI 12

850.2100 Avian oral toxicity (passerine species) TGAI 12

850.2300 Avian Reproduction (upland game & waterfowl 

species) TGAI 24

Non-GDLN Avian Inhalation Toxicity5 TGAI 12

850.3030 Honeybee toxicity of residues on foliage6 TGAI 12

850.31107 Ready Biodegradability PI 12

850.3220

7

Porous Pot Test PI 12

850.32407Simulation Test – Aerobic Sewage Treatment PI 12

850.32807Simulation Test – Wastewater PI 12

850.33008 Activated Sludge Respiration Inhibition TGAI 12

850.4100 Seedling emergence and seedling growth TEP 12

850.4150 Vegetative Vigor TEP 12

850.45009 Algal toxicity PI 12

850.610010

Environmental Chemistry Methods (ECM) and 

Associated Independent Laboratory Validation 

(ILV) for soil and water

TGAI 12

870.3465 90-day Inhalation TGAI 12

870.7800 Immunotoxicity TGAI 12

875.1200 Dermal Exposure, Indoor11 TEP 24

875.1400 Inhalation Exposure, Indoor11 TEP 24

875.2300 Indoor Surface Residues12 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) tested 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 required 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=EPAHQ-OPPT-2009-0152-0036. One biodegradation study is anticipated as required; the biodegradation study 

anticipated as required is based on results of the Activated 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-HQOPPT-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.oecdilibrary.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)

10 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

11

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

12

For dermal & incidental oral exposure to children from transferable folpet residues 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 cause 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 pesticides 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 Agency periodically reevaluates pesticides to make 

sure that as change occurs, products in the marketplace can be used safely. Information on this 

program is provided on EPA’s website1.

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. The 

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 Final Work Plan (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: Folpet Chemical Facts

PC code 081601

Case Number 0630

CAS Number 133-07-03

Year first registered 1948

Pesticide Type Fungicide, Antimicrobial

Chemical class Thiophthalimide

Reregistration Eligibility 

Decision (RED)

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 non-pesticidal uses for folpet. 

Pesticide Re-evaluation 

Division, Chemical Review 

Manager

Christina Scheltema, scheltema.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 folpet. Please see the June 21, 2012 

document, BEAD Chemical Profile for Registration Review: Folpet, in the registration review 

docket for more details.

Table 3: Use and Usage Information for Folpet

Summary of Use Registered for foliar treatment of scab & mildew in avocados and hops. 

Also registered for use as a fungicide in paints & coatings and a 

fungicide/mildewcide in adhesives & sealants.

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

materials, adhesives, 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 paints 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 preservative 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: Use and Usage Information for Folpet

Technical Registrant(s) Makhteshim-Agan North America (MANA), Makhteshim Chemical 

Works

No. of Registrations 12

Restricted Use No

Guidance for Commenters: Additional areas of use and usage related information

requested for this registration review, and of particular interest to EPA, are described below.

Confirmation 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, industrial preservatives, and surface treatments for tile, 

outdoor furniture, plaster, paint, finished wood, and wood surfaces

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

Median and 90th percentile reported use rates (lbs ai/A) from usage data – national, state, 

and county

Application 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)

State or local use restrictions

Foreign technical registrants not listed above who supply technical folpet to the U.S.

market

RECENT ACTIONS

EPA published a final rule codifying the tolerances for 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, melon, 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 details. 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 the PHI for avocados 

to 7 days; (3) at 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. 

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW
8

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. The most recent ecological and environmental fate risk 

assessment was completed in 2003 to support a petition for registration 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 Environmental 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, the 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 

assessments during 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 assessments, as well as any changes to the standard operating procedures 

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 

Yes The anticipated ecological risk assessment will support a 

complete endangered species determination for folpet. 

Incidents Yes For a discussion of folpet’s reported ecological incidents, 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. 
9

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, 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 or 

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.

TIMELINE

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-Day Public Comment Period for Draft Risk Assessments 2017 – July – Sept.

Registration Review Decision

60-Day 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 60-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 Commenters: The areas below highlight topics of special interest to the Agency 

where your comments, data submissions, or reference to sources of additional information could 

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 and international maximum residue limits (MRLs) 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 Act2. In addition, no Total Maximum Daily Loads (TMDL) 

have been developed for folpet3. More information on impaired water bodies and TMDLs can be 

found at the Agency’s website4. 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 Process5in 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 

population 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, unusually 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.htm
11

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, neurotoxicity, 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 maturation, 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 wildlife 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 have 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 

website6.

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 Handlers Exposure Database (PHED) and the 

Agricultural 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 or significantly 

deficient relative to the ethical standards prevailing at the time the research was conducted. All 

applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 

CFR Part 26) have been satisfied, and there 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 evaluation 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 rigorous 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 alternative 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 properties. 

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 studyby-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 Part 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 effectively 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 exhibit 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. Presubmission consultation with the Agency is encouraged.