2 

### Famoxadone	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 the Famoxadone Registration Review ............... 11

References:

This Preliminary Work Plan summarizes the En vironmental Protection Agency's current position based on the following documents:

1. Registration Review Problem Formulation fo r the Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Assessment for Famoxadone

. F. Jewett and CM Koper. March 3, 2015.

2. Famoxadone. Human Health Assessment Scopi ng Document in Support of Registration

Review. I. Negron-Encarnacion, S. Daps on, and K. King. March 4, 2015.

3. Famoxadone: Tier I Revi ew of Human Incidents. S. Recore and E. Evans. October 28,
2014.



### 4. BEAD Chemical Profile for Registration Review: Famoxadone. T. Chandgoyal. October 12, 2014.



### 5. Famoxadone Screening Level Usage Analysis . June 17, 2014.

These and other supporting documents for the famoxadone registration review case may be found in docket EPA-HQ-OPP-2015-0094 at http://www.regulations.gov

.3 OVERVIEW

The docket for famoxadone is now open, initiatin g the first public comment period for this registration review (docket number EPA-HQ- OPP-2015-0094). Famoxadone is a fungicide registered for use to control and/or manage a variety of fungal and ba cterial diseases on caneberries ( subgroup 13-07A ); cilantro leaves; cucurbit vege tables; grapes (East of the Rocky Mountains); hops; bulb onion ( subgroup 3-07A ); green onion ( subgroup 3-07B ); potato; pepper; tomato; and leafy vegetables except Brassica ( group 4 ). Famoxadone is not currently registered for residential use. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about famoxadone, hi ghlighting 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 antici pated timeline for completing the registration
review for famoxadone.

The registration review process was designed to include a publi c participation component to solicit input from interested stake holders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows abou t famoxadone and what types of new data or other information would be helpful for the Agen cy to receive as it moves toward a decision on famoxadone. The Agency encourages all intere sted stakeholders to review the PWP and Appendix and to provide comments and addition al 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 iden tified in the PWP and Appendix about which the Agency specifically seeks comments and informa tion. Interested stakeholders could include: environmental non-profit or interest groups; pe sticide manufacturers; agricultural labor or commodity groups; commercial, institutional, reside ntial, and other users of pesticides; or the public at large.

The Preliminary Work Plan begins by listing the anticipated data needs for famoxadone. Next, it discusses the statutory and regul atory authority for Registration Review. Then the document provides chemical facts, use and usage info rmation, recent actions, the anticipated risk assessments, and a projected registration review timeline for famoxadone. Finally, the Appendix
to this document includes identification and di scussion of some areas that are considered generally in Registration Review along with some additional chem ical case-specific information.

ANTICIPATED DATA NEEDS

Table 1 summarizes anticipated data needs for famoxadone. For additional discussion of the anticipated data needs, see the Registration Review Problem Formulation for the Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Assessment for Famoxadone
and the Famoxadone Human Health Assessment Scopi ng Document in Support of Registration

Review.4 Table 1: Anticipated Data Needs fo r the Famoxadone Registration Review

Guideline

Number 1 Study Title Test 2

Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated Data Needs for the Parent Famoxadone
835.4200 Anaerobic Soil Metabolism (3 additional soils) TGAI 24

835.4300 Aerobic Aquatic Metabolism (1 additional sediment-water system) TGAI 24

835.4400 Anaerobic Aquatic Metabolism (2 additional sediment-water systems) TGAI 24

850.6100 Environmental Chemistry Methods and Independent Laboratory Validation in Soil TGAI 12

850.3040 Field Testing for Pollinators TEP 24

850.2100 Avian Acute Oral Toxicity – Passerine Species TGAI 12

860.1340 3 Livestock Enforcement Method and Independent Laboratory Validation TGAI 12

860.1380 Storage Stability in Soil and Water TGAI 12 Non-guideline Pollinator Acute Oral Toxicity, Adult TGAI 12 Non-guideline Pollinator Acute Oral Toxicity, Larvae TGAI 12 Non-guideline Pollinator Chronic Oral Toxicity, Adult TGAI 24 Non-guideline Pollinator Chronic Oral Toxicity, Larvae TGAI 24

Non-guideline Pollinator Tier II Semi-field toxicity Testing (tunnel/enclosure studies) TEP 24

Non-guideline Pollinator Tier II Semi-field toxicity Testing (feeding studies) TEP 24

Non-guideline Residues in Pollen and Nectar (Higher Tier Testing Under Semi-Field or Field Conditions) TEP 24

NonGuideline 4 Whole sediment: Chronic Invertebrates Freshwater and Marine (using Chironomus
dilutus

, Hyalella azteca and/or Leptocheirus plumulosus ) TGAI 24

870.3465 90-day Inhalation Toxicity – Rat TGAI 12 875.2100 Dislodgeable Foliar Residue TEP 24

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

– including renumbering and other designations or changes for some guideline studies. See “Final Test Guidelines; OCSPP 850 Series; Notice of Av ailability” 77 FR 38282 , June 27, 2012. http://www.regulations.gov/#!documen tDetail;D=EPA-HQ-OPPT-2009-0154-0028

2 TGAI = technical grade active ingredie nt; TEP = typical end-use product.

3 If the registrant proposes DuPont Method 1452 for livestock tolerance enforcement, an independent laboratory validation is not anticipated to be required.

4 ORD Study Methods 600/R-099-064 for Chironomus and Hyalella and 600/R-099-020 for Leptocheirus.5 Table 1: Anticipated Data Needs fo r the Famoxadone Registration Review

Guideline

Number 1 Study Title Test 2

Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated Data Needs for the Famoxad one Degradates IN-KZ007, IN-MN467, IN-MN968, IN-MN468-0, IN-KF015, and IN-H3310
850.1010 Acute toxicity, freshwater invertebrates (Daphnia magna) 5 DEGR 12

Outstanding Data Requirement from Conditional Registration(s) 6

850.1735 Whole Sediment: Acute Freshwater Invertebrates ( Chironomus dilutus ) 7 TGAI Due
6/30/2015

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 Stat es (U.S.) generally must be registered by the Environmental Protection Agency (EPA or the Ag ency), based on scientific data showing that they will not cause unreasonable ri sks to human health or the environment when used as directed on product labeling. The registration review program is intended to ma ke 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 unreasonabl e 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 prog ram, the Agency periodically r eevaluates pesticides to make sure that as change occurs, products in the mark etplace can be used safely. Information on this program is provided on EPA’s website. 8

The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), a nd will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing regi stration 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 docke t during this initial comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for the registration review of famoxadone.

5 Although data for famoxadone degradates IN-MN468-0, IN-KF015, and IN-H3310 have been submitted and are in review, this is considered a data gap until the review is complete and the studies are found to be acceptable.

6 The study listed in this section was previously required as a condition of registration in July 2003 and is still

outstanding. This study is not anticipated to be required in the anticipated Registration Review DCI because it is already required as a condition of registration.

7 The required 28-day study must use OECD Method 218 (modified).

8 http://www.epa.gov/oppsrrd1/registration_review/6 CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for famoxadone.

Table 2: Chemical Facts for Famoxadone

PC code 113202

Case Number 7038

CAS Number 131807-57-3 Year first registered 2003 Pesticide Type Fungicide Chemical class Quinone Outside Inhibitor (QoI) Reregistration Eligibility Decision (RED) Not applicable. Because famoxadone was registered after November 1984, it was not subject to reregistration.

Tolerance Reassessment Not applicable. Because famoxadone was registered after the passage of FQPA, it was not subject to tolerance

reassessment. Cumulative group Not applicable. Famoxadone has not been identified as a member of a cumulative group that shares a common mechanism of toxicity.

40 CFR Citation Tolerances for famoxadone are established in 40 CFR §180.587. Dual-use Famoxadone is registered for conventional pesticidal uses only and has no registered antimicrobial or biopesticidal

uses. Non-pesticidal uses There are no identif ied non-pesticidal uses of famoxadone. 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 informa tion for famoxadone. Please see the October 12,
2014 BEAD Chemical Profile for Re gistration Review: Famoxadone and June 17, 2014 Famoxadone Screening Level Usage Analysis in the registration review do cket for more details.

Table 3: Famoxadone Use and Usage Information

Summary of Use Famoxadone is a fungicide regi stered for use to control and/or manage bacterial and fungal disease. Famoxadone is always co-formulated with cymoxanil for resistance management. Famoxadone must also be tank mixed with a contact fungicide that has a different mode of action. Use Sites Famoxadone is registered for use on caneberries ( subgroup 13-07A ); cilantro leaves; cucurbit vegetables; grapes (East of the Rocky Mountains); hops; bulb onion ( subgroup 3-07A ); green onion ( subgroup 3-07B ); potato; pepper; tomato; and leafy vegetables except Brassica ( group 4 ). Not currently registered for residential use.7 Table 3: Famoxadone Use and Usage Information

Summary of Usage Between 2008 and 2012, ~ 41,000 pounds of famoxadone were used to treat an average of 352,000 acres acr oss the US. The average application rate was 0.12 pounds active ingredient per acre. The major uses in terms of percent crop treated are cucumbers (25%); cranberries (15%); and onions, peppers, potatoes, and pumpkin (10% for each). In terms of pounds applied, major uses are potatoes, cucumbers, tomatoes, and

peppers. Formulation Type(s) Water-dispers ible granules (dry flowable) Application Method(s) Ground, air, and chemigation

Technical Registrant DuPont No. of Registrations Two

Restricted Use No

Guidance for Commenters: Additional areas of use and usage related information requested for this registration review, and of particul ar interest to EPA, are described below.

 The famoxadone (Tanos®) product label (E PA Reg. No. 352-604) is unclear with respect to the number of cropping cycles per season a nd per year, retreatment intervals, or maximum annual application rates. Without further information, EPA expects to use conservative assumptions to approximate these parameters in order to conduct a quantitative risk assessment. However, the Agency anticipates working with the registrant to clarify this inform ation on the famoxadone product label, and to
amend the label as needed.

 Confirmation of the following label information: sites of application; formulations; application methods and equipment; maxi mum application rates; frequency of application, application intervals, and ma ximum number of applications per season; and geographic limitations on use.

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

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

 Typical application timing (date of first application and applic ation intervals) – national, state, and county.

 Typical application interval (days).

 State or local use restrictions.

 Foreign technical registrant s not listed above who supply technical famoxadone to the
US market.

RECENT ACTIONS

There are no recent actions for famoxadone. New food uses for leafy greens (crop subgroup 4A ), bulb vegetables ( group 3 ), cilantro, caneberry ( subgroup 13A ), and leaf petioles ( subgroup 4B ) 9

9 The famoxadone registrations were amended in 2011 to delete use on leaf petioles ( subgroup 4B ).8 were registered in April 2009; associated tole rances were establishe d in March 2009 (74 FR 9358).

ANTICIPATED RISK ASSESSMENT S FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for famoxadone was completed in 2008 to support a petition to regist er new food uses of famoxadone in or on leafy greens (crop subgroup 4A ), bulb vegetables ( group 3 ), cilantro, caneberry ( subgroup 13A ), and leaf petioles ( subgroup 4B ) and to establish associated tolera nces. The most recent ecological and environmental fate risk assessment was completed in 2008 for the same purpose. Findings and
conclusions from these risk assessments are summarized in the Famoxadone Registration Review Problem Formulation for the Environmental Fate, Ecologica l Risk, Endangered Species, and Drinking Water Assessment for Famoxadone and the Famoxadone Human Health Assessment Scoping Document in Support of Registration Review.

During registration review, the Agency antici pates the need to conduct a comprehensive ecological risk assessment, including an enda ngered species assessment, for all uses of famoxadone. For human health, EPA anticipates the need to conduct revised dietary and occupational risk assessments during registration re view. If toxicologica l endpoints or points of departure are revised based on the data that are an ticipated 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 registrati on review risk assessments based on the EFED Problem Formulation and HED Scoping Document.9 Table 4: Anticipated Risk Assessments for the Famoxadone 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 risk assessment will include an updated drinking water assessment using the total toxic residues approach.

Incidents Will check for updates One ecological incident has been reported for famoxadone. See page 18 of the Problem Formulation for details.

Human Health Dietary

Food Yes Drinking water Yes The anticipated asse ssment will consider famoxadone and degradates using the total toxic residue approach. Occupational Handlers (mixers, loaders, applicators) Yes Anticipated to be conduc ted for intermediate term

exposure. Post-application Yes

Residential Handlers No Famoxadone is not registered for residential use. Post-application Yes EPA anticipates eval uating the need for spray drift and
volatilization assessments.

Other Aggregate Yes The anticipated assess ment will evaluate only the dietary risk from food and drinking water.

Cumulative No Famoxadone has not been identified as a member of a cumulative group that shares a common mechanism of toxicity. Tolerances Yes The tolerance expressi on for famoxadone will be evaluated during registration review to ensure that it appropriately
covers the metabolites and de gradates of famoxadone and that it specifies the residues to be measured for each commodity.

Incidents Will check for updates For a discussion of reported human incidents for famoxadone, see the October 28, 2014 document, Famoxadone: Tier I Review of Human Incidents.

Guidance for Commenters: Additional ecological information requested for this registration review, and of particular interest to EPA, is described below.

 Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not alr eady reported to the Agency.

 Water quality monitoring data (s ee Appendix for further details).10 Guidance for Commenters: Additional human health information requested for this registration review, and of particular interest to EPA, is described below.

 Information to better characterize the eye catar acts, to resolve the uncertainties related to the microscopic findings in the eye obser ved in the chronic dog feeding study, to
elucidate the mechanism of action of famoxa done in the eyes, and to evaluate whether this is a species-specific effect. See page 6 of the Scoping Document for further details.

TIMELINE

EPA has created the following estimated timeline for the completion of the famoxadone registration review in Table 5 below.

Table 5: Projected Famoxadone Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and 60-day Public Comment Period 2015 – March Close Public Comment 2015 – May Case Development Final Work Plan 2015 – August

Issue DCI 2015 – Oct.-Dec.

Data Submission 2017 – Oct.-Dec. 60-day Public Comment Period for Draft Risk

Assessments 10 2019 – April-June

Registration Review Decision 60-day Public Comment Period for Proposed Registration Review Decision 2020 – Jan.-March

Registration Review D ecision and Begin PostDecision Follow-up 2021

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 i ssue a Final Work Plan for the registration
review of famoxadone.

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

of at least 30 calendar days for draft risk assessments; see 40 CFR Part 155.53(c). For conventional pesticides, the Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.11 

### Appendix – Additional Areas Considere d in the Famoxadone Registration
Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest to the Agency where your comments, data submi ssions, or reference to sources of additional information could be of particular use.

Trade Irritants:

Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, 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, provi ding as much specificity as possible regarding
the nature of the concern.

Water Quality:

Famoxadone is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. 11 In addition, no Tota l Maximum Daily Loads (TMDL) have been developed for famoxadone. 12 More information on impaired water bodies and TMDLs can be found at the Agency’s website. 13

The Agency invites submission of wa ter quality data for this pesticide. To the extent possible, data should conform to the qua lity 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 14 in order to ensure they can be used quantitatively or qualitati vely in pesticide risk assessments.

Aquatic benchmarks have been establis hed for famoxadone and are available at http://www.epa.gov/oppefed 1/ecoris k_ders/aquatic_life_benchmark.htm . Any data submitted or otherwise located as part of th e registration review process may be used to update aquatic life benchmarks, if applicable.

Environmental Justice:

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation,

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

12 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl _pollutant_detail?p_pollutant_group_id=885&p_pollutant

_group_name=PESTICIDES

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

14 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm12 and enforcement of environmental laws, regulati ons, 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 thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to fam oxadone 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.

ENDANGERED SPECIES:

A risk assessment that supports a complete endangered species determination has not been conducted for famoxadone. The ecological risk assessment anticipated to be conducted during registration review will allow the Agency to determine whether use of famoxadone 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 Fisher ies Service (the Services), as appropriate.

ENDOCRINE DISRUPTOR SCREENING PROGRAM:

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its most re cent registration de cision for famoxadone, EPA
reviewed these data and select ed the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), famoxadone is subject to the e ndocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e 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 estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects caused by the substance, and establish a dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between13 October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pest icide active ingredient s and 9 inert ingredients. A second list
of chemicals identified for EDSP sc reening was published on June 14, 2013 15 and includes some 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 policie s and procedures, the lis ts of chemicals, future lists, the test guidelines and the Tier 1 screeni ng battery, please visit our website. 16

HUMAN STUDIES:

Past famoxadone risk assessments rely in part on data from studies in which adult human subjects were intentionally exposed to a pest icide to determine their dermal and inhalation exposure. Many such studies, i nvolving exposure to many different pesticides, comprise generic pesticide exposure databases such as the Pestic ide Handlers Exposure Database (PHED) and the Agricultural Reentry Task Force (ARTF) Databa se. EPA has reviewed all the studies supporting these multi-pesticide generic exposure databa ses, 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 prevai ling 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.

15 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of

chemicals.

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