2



### Fenamidone Preliminary Work Plan

– Table of Contents

OVERVIEW

................................ ................................ ................................ ................................ ... 3

ANTICIPATED DATA NEEDS

................................ ................................ ................................ .... 3

STATUTORY AND REGULATORY AUTHORITY

................................ ................................ ... 4

CHEMICAL FACTS

................................ ................................ ................................ ...................... 4

USE AND USAGE INFORMATION

................................ ................................ ............................ 5

RECENT ACTIONS

................................ ................................ ................................ ....................... 6

ANTICIPATED RISK A SSESSMENTS FOR REGISTRATION REVIEW

................................ 6

TIMELINE

................................ ................................ ................................ ................................ ...... 8

NEXT STEPS

................................ ................................ ................................ ................................ . 8 Appendix

– Additional Areas Considered in the Fenamidone Registration Review

.................. 9

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 the Ecological Risk Assessment and Drinking Water Exposure Assessment to be Conducted for Fenamidone. Wolf and Stebbins. February 6, 2014.

2. Fenamidone: Human Health Risk Assessment Scoping Docume nt in Support of Registration Review. Britton et al. February 28 , 2014.

3. Fenamidone: T

ier I Review of Human Incidents. E. Evans and S. Recore. November 20,

2013

.

4. BEAD Chemical Profile (BCP) for Registration Review: Fenamidone

. Yourman et al. September 18, 2013.

5. Fenamidone Screening Level Use Analysis (SLUA )

. March 23, 2013.

6. EFED Table 1 Report. September 6, 2013.

7. HED Master Label Report. September 6, 2013.

These and other supporting documents for the fenamidone registr ation review case may be found

in the docket EPA

- HQ

- OPP

- 2014

- 0048 at http://www.regulations.gov

.3

OVERVIEW

The docket for fenamidone is now open , initiating the first public comment period for this registration review (docket number EPA

- HQ

- OPP

- 2014

- 0048 )

. Fenamidone is an imidazoline fungicide registered for use to control downy mildew and Pythium species and to manage Alternaria species, rust, early and late blight, and several other pathogens. It is currently registered for use on leafy vegetables (both Brassica and non Brassica); turnip greens; carrots; cotton; cucurbits; grapes; potatoes, various bulb/root/tuberous/corm vegetables; tomatoes, peppers and other fruiting vegetables; sunflower; tobacco; and comm ercial greenhouse ornamentals. Fenamidone is also registered for use as a seed treatment of sunflower and cotton. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs

knows about fenamidone

, 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 the registration review for fenamidone

.

The registration review p rocess 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 it knows about fenamidone and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on fenamidone

. The Agency encourages all interested stakeholders to review the PWP and Appendix and to provide comments and additional informat ion 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 in formation. Interested stakeholders could include:

environmental non

- profit 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 fenamidone

. Next, it discusses the statutory and regulatory authority for R egistration R eview. Then the document provides chemical facts, use and usage information, recent actio ns, the anticipated risk assessments, and a projected registration review timeline for fenamidone

. Finally, the Appendix

to this document includes identification and discussion of some areas that are considered generally in R egistration R eview along with some additional chemical case

- specific information.

ANTICIPATED DATA NEEDS

Table 1 summarizes anticipated data needs for fenamidone . For additional discussion of the anticipated data needs, see the documents, Registration Review

– Preliminary Problem

Fo rmulation for the Ecological Risk Assessment & Drinking Water Exposure Assessment to be

Conducted for Fenamidone and Fenamidone: Human Health Risk Assessment Scoping Document in Support of Registration Review

.4 Table 1: Anticipated Data Needs for the Fenamidone Registration Review

Guideline

Number Study Title Test Material Estimated

Timeframe

(Months from receipt of DCI)

850.6100 Environmental chemistry methods & associated

independent laboratory validations for water TGAI 12

850.1075 Freshwater fish toxicity (fathead minnow) TGAI 12

850.4150 Vegetative vigor TEP 12
TGAI = technical grade active ingredient; TEP = typical end

- use product

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 i n 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 fenamidone

.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for fenamidone

.

Table 2: Chemical Facts for Fenamidone

PC code 046679

Case Number 7033

1 http://www.epa.gov/oppsrrd1/registration_review/5 Table 2: Chemical Facts for Fenamidone

CAS Number 161326

- 34

- 7

Year first registered 2002 Pesticide Type Fungicide

Chemical class Imidazolinone (quinone outside inhibitors)

R eregistration Eligibility Decision (R E D) Not applicable. Because fenamidone was first registered in 2002, it was not subject to reregistration.

Tolerance Reassessment Eligibility Decision (TRED) Not applicable. Because fenamidone was first registered in 2002, it was not subject to tolerance reassessment. Cumulative group Fenamidone has not been identified as a member of a cumulative group that shares a common mechanism of toxicity.

40 CFR Citation Tolerances for fenamidone are established in 40 CFR § 180.579

. Dual

- use Fenamidone is registered for conventional pesticidal uses only

. Non

- pesticidal uses There are no identified non

- pesticidal uses of fenamidone.

Pesticide Re

- evaluation Division, Chemical Review Manager Christina Scheltema, Scheltema.christina@epa.gov , (703)308

- 2201

Registration Division , Product Manager Tony Kish, kish.tony@epa.gov

, (703) 308

- 9443

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for fenamidone

. Please see the BEAD Chemical Profile (BCP) for Registration Review: Fenamidone in the registration review docket

for more details

.

Table 3: Fen amidone Use and Usage Information

Summary of U s e F ungicide registered for use to control and manage a variety of pathogens, including mildew, Pythium

, Alternaria , rust, and early and late blight.

Use Sites Leafy vegetables; turnip greens; carrots; cotton; cucurbits; grapes; potatoes; various bulb, root, and tuberous vegetables; tomatoes; peppers; sunflower; tobacco; and commercial greenhouse ornamentals. Also registered for use as seed treatment for sunflower and cotton. Summary of Usage Between 2005 and 2011, approximately 23,000 lbs of fenamidone were applied annually to 106,000 acres, at an average application rate of 0.2 lbs

ai/A. Formulation Type(s) E mulsifiable concentrate. Application Method(s) Foliar spray, in

- furrow treatment

, chemigation, and aerial application. Technical Registrant (s) Bayer CropScience No. of Registrations One technical and two end

- use products.

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.

 Certain fenamidone labels are unclear with respect to application parameters such as

minimum retreatment intervals and maximum seasonal or annual application rates (e.g., the number of applications of fenamidone that can be applied per calendar year on a6

given field is not explicitly stated on current labels)

. Without further information, EPA

expects to use conservative assumptions to approximate these paramet ers in order to conduct a quantitative risk assessment. However, t he Agency will work with registrants to clarify information on fenamidone product labels

.

 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

per year ; and geographic limitations on use

.

 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

.

 Typical a pplication timing (date of first application and application intervals)

– national, state, and county

.

 Efficacy data for crops where fenamidone may be particularly effective and used preferentially rather than other registered fungicides.

 Usage/use information seed treatment and any use on non

- agricultural uses

.

 Typical application interval (days)

.

 S tate o r local use restrictions

.

 F oreign technical registrants not listed above who supply technical fenamidone to the US

market

.

RECENT ACTIONS

EPA establish ed n ew tolerances for residues of fenamidone in/ on ginseng , onions, and other

crops in March 2014

. The Agency anticipates amending fenamidone registrations to allow these

uses in the near future. The Agency has recently completed risk assessments as part of its review

of th e tolerance petition and application to amend the fenamidone registration ; these assessments may be found in the regulatory docket (EPA

- HQ

- OPP

- 2013

- 0161)

.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

Other than the assessments mentioned above, t he most recent comprehensive human health risk

assessment for fenamidone was completed in July 2011 and t he most recent ecological and

environmental fate risk assessment was completed i n 2009. Findings and conclusions from these

risk assessments are summarized in the Registration Review

– Preliminary Problem Formula tion for the Ecological Risk Assessment and Drinking Water Exposure Assessment to be Conducted for Fenamidone and Fenamidone: Human Health Risk Assessment Scoping Document in Support of Registration Review

.

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

fenamidone

. For human health, EPA does not anticipate the need to conduct revised dietary,

residential

, and occupational risk assessment s during registration review with the possible exception of a residential bystander assessment

. However, i f toxicological endpoints or points of departure are revised , or if there are changes to the standard operating p rocedures or default7

exposure assumptions , then EPA anticipate s evaluating the need to conduct revised human health

risk assessments.

T able 4 summarizes the anticipated registration review risk assessments based on the EFED

Problem Formulation and HED Scoping Document

.

Table 4: Anticipated Risk Assessments for the Fenamidone Registration Review

Type of Risk Assessment Conduct ? Notes

Ecological and Environmental Fate Comprehensive ecological

assessment (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 fenamidone. The anticipated risk assessment will be conducted on the parent compound.

Incidents Will check for updates For a discussion of reported ecological incidents for

fenamidone , see page s 19 and 20 of the Problem

Formulation.

Human Health Dietary

Food No EPA does not anticipate conducting a dietary risk assessment unless the toxicology points of departure, uncertainty factors, or estimated drinking water concentrations change. Drinking water No

Occupational Handlers (mixers, loaders, applicators) No EPA does not anticipate conducting an occupational risk assessment unless the toxicology points of departure or uncertainty factors for dermal and/or inhalation exposure change. Post

- application No

Residential

Handlers No Fenamidone is not registered for residential use. However,

EPA may need to conduct a residential bystander assessment. Post

- application Yes

Other Aggregate No Evaluates the combined risk from dietary and residential

exposures. Cumulative No Fenamidone is not a member of a cumulative group.

Tolerances Yes EPA anticipates updating fenamidone t olerances

, established in 40 CFR §180.579 , to align with new crop groups and, where possible, to harm o nize with international MRLs.

Incidents Will check for updates At present, EPA is aware of only one reported human

incident for fenamidone. For details, see Fenamidone: Tier I Review of Human Incidents

.

Guidance for Commente rs: Additional ecological i nformation r equested for this registration r eview , and of particular interest to EPA, is described below.

 Ec ological incidents (non

- target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency

.

 Water quality m onitoring data (see Appendix fo r further details)

.

 Number of crop cycles per year for crops that may have multiple growing seasons

.8

TIMELINE

EPA has created the following estimated timeline for the completion of the fenamidone registration review in Table 5

.

Table 5: Projected Fenamidone Registration Review Timeline

Activities Estimated Date
Opening the Docket

Open Docket and 60

- day Public Comment Period 2014

– March

Close Public Comment 2014

– May
Case Development

Final Work Plan 2014

– August

Issue DCI 2014 Oct.

– Dec.

Data Submission 201 5 Oct.

– Dec.

60

- day Public Comment Period for Draft Risk Assessments 2 201 7 April

– June
Registration Review Decision

60

- day Public Comment Period for Proposed Registration

Review Decision 201 8 Jan.

– March

Registration Review Decision and Begin Post

- Decision

Follow

- up 20 19

Total (years) 5

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 fenamidone

.

2 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 conven tional pesticides, the Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.9



### Appendix

– Additional Areas Considered in the Fenamidone 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 and international maximum r esidue 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.

Water Quality:

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

. 3 In addition, n o Total Maximum Daily Load s (TMDL) have been developed for fenamidone

. 4 More information on impaired water bodies and

TMDLs can be found at the Agency’s website

. 5 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

Wa ter Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 6 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 poli cies. 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 fenamidone 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.

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

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

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

6 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm10

ENDANGERED SPECIES :

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

conducted for fen a midone

. The ecological risk assessment planned during registration review will allow the Agency to determine whether use of fenamidone 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 Ser vice and/or National Marine Fisheries Service (the Services), as appropriate.

ENDOCRINE DISRUPTOR SCREENING PROGRAM :

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collective ly, 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 t ests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision for fenamidone, 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),

fenamidone is subject to the endocrine screening part of the Endocrin e 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 e strogen, 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

chem ical 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 relationshi p between the dose and the E, A, or T effect.

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. A second list of chemicals identified for EDSP screening was published on June 14, 2013 7 and includes some

7 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.11

pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our

website. 8

HUMAN STUDIES :

Occupational

Past fenamidone 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 gen eric pesticide exposure databases such as the Pesticide Ha ndlers 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. A ll applicable requirements of EPA’s Rule f or 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

.

8 http://www.epa.gov/endo/