2



### Fenbuconazole Preliminary Work Plan

– Table of Contents

OVERVIEW ................................

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

ANTICIPATED DATA NEEDS ................................................................

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

STATUTORY AND REGULATORY AUTHORITY ................................

................................ ... 7

CHEMICAL FACTS ................................

................................................................ ...................... 7

USE AND USAGE INFORMATION ................................................................

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

RECENT ACTIONS ................................

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

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW ................................ 9

TIMELINE ................................

................................ ................................................................ .... 13

NEXT STEPS ................................

................................................................ ............................... 13

Appendix

– Additional Areas Considered in the Fenbuconazole Registration Review ........... 14

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 Human Health Drinking Water Exposure Assessments for Fenbuconazole

. Wendel, Christina and Lin, James. December 2, 2015.

2. Fenbuconazole. Human Health Assessment Scoping Document in Support of Registration

Review. Hansen, Linnea. December 14, 2015

.

3. Fenbuconazole: Tier 1 (Scoping) Review of Human Incidents and Epidemiology . Evans, Elizabeth and Recore, Shanna. September 1, 2015.

4. BEAD Chemical Profile (BCP) for Registration Review: Fenbuconazole (129011). Chandgoyal, Tara; Prieto, Rafael A.; Lee, Andrew. December 3, 2015.

5. Fenbuconazole (129011) Screening level Usage Analysis (SLUA) . April 28, 2015.3

6. EFED Table 1 Repo rt

. March 18, 2015

.

7. HED Master Label Report. March 18, 2015

.

These and other supporting documents for the Fenbuconazole registration review case may be

found in the docket EPA

- HQ

- OPP

- 2015

- 0716 at http://www.regulations.gov

.4

OVERVIEW

The docket for f

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

- HQ

- OPP

- 2015

- 0716 )

. Fenbuconazole is a broad

spectrum systemic fungicide of the triazole (conazole) chemical class. It is currently registered for use on the following food/feed crops: almonds, apples, bananas, blueberries , citrus fruits (group 10), cranberries, pecans, peanuts, peppers, stone fruits (group 12), sugar beets and wheat. At present there are no registered residential uses. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about f enbuconazole

, 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 f enbuconazole

.

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 it knows about f enbuconazole and what types of new data or other information would be helpf ul for the Agency to receive as it moves toward a decision on f enbuconazole

. 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 pr ocess 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 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 f enbuconazole

. Next, it discusses the statutory and regulatory authority for R egistration R eview. Then the document provides chemical facts, use and usage information, recent actions, the anticipated risk assessments, and a pro

jected registration review timeline for f enbuconazole

. 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.5

ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for f enbuconazole . For additional discussion of the anticipated data needs, see the Registration Review: Preliminary Problem Formulation for Environmental Fate, Ecolog ical Risk, Endangered Species, and Human Health Drinking Water Exposure Assessments for Fenbuconazole and Fenbuconazole. Human Health Assessment Scoping Document in Support of Registration Review

.

Table 1: Anticipated Data Needs for the Fenbuconazole Re gistration Review

Guideline

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Non

G uideline Chronic Freshwater Sediment Testing

( Hyale l la azteca ) TGAI 24

Non

Guideline Chronic Freshwater Sediment Testing

( Chironomus dilutus ) TGAI 24

Non

Guideline Chronic Estuarine/Marine Sediment Testing

( Leptocheirus plumulosus ) TGAI 24

850. 2100 A vian A cute Oral Toxicity with passerine

species TGAI 12

Non

Guideline (OECD TG 213) Adult honey bee acute oral toxicity TGAI 12

Non

Guideline Adult honey bee chronic oral toxicity TGAI 12

Non

Guideline (OECD TG 237) Larval honey bee acute oral toxicity TGAI 12

Non

Guideline Larval honey bee chronic oral toxicity TGAI 12

Non

guideline 2 Field trial mea suring residues in pollen and

nectar 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 A vailability” 77 FR 38282, June 27, 2012. http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0154

- 0028

2 These studies are anticipated to be included in t he DCI. However the need for the data will be determined by EPA based upon the results of the Tier 1 honey bee laboratory studies.6

Table 1: Anticipated Data Needs for the Fenbuconazole Re gistration Review

Guideline

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Non

Guideline

OECD

TG 75 2 Semi

- field test ing for pollinators (Tier II) TEP 24

OSCPP

850.3040 2 Field testing for pollinators (Tier III) TEP 24

875.2100 Dislodgeable Foliar Residue 3 TEP 24

Outstanding Data Requirements from Conditional Registration(s) 4

850.4100 Terrestrial plant seedling emergence toxicity,

cabbage only 5 TEP 12

TGAI = technical grade active ingredient; TEP = typical end

- use product ;

3 A dislodgeable foliar residue (DFR) study (EPA MRID 45250601) has been submitted to the Agency but has not yet been re viewed. Until the study has been reviewed and found to be acceptable, this will remain as an anticipated data requirement.

4 The studies listed in this section were previously required as a condition of registration in July 2013 and are still

outstandi ng. These studies will not be included in the anticipated Registration Review DCI because they are already required as a condition of registration.

5 A terrestrial plant seedling emergence toxicity study (EPA MRID 49760701) has been submitted to the Agenc y but has not yet been reviewed. Until the study has been reviewed and found to be acceptable, this will remain as an outstanding conditional data requirement7

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 scienti fic 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 t he registration review program, the Agency 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

. 6

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 dock et 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 f enbuconazole

.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for f enbuconazole

.

Table 2: Chemical Facts for Fenbuconazole

PC code 129011

Case Number 7012

CAS Number 114369

- 43

- 6

Year first registered 1995 Pesticide Type Fungicide

Chemical class Triazole

R eregistration Eligibility Decision (R E D) Because it was r egistered after November 1984, f enbuconazole was not subject to reregistration.

Tolerance Reassessment Eligibility Decision (TRED) Not Applicable

6 http://www2.epa.gov/pesticide

- reevaluation8 Table 2: Chemical Facts for Fenbuconazole

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

40 CFR Citation Tolerances for f enbuconazole are established in § 180.480

. Dual

- use Fenbuconazole is registered for conventional pesticidal uses only and has no registered antimicrobial or biopesticidal uses

. Non

- pesticidal uses There are no identified n on

- pesticidal uses of f enbuconazole

. Pesticide Re

- evaluation Division, Chemical Review Manager Na than Sell, sell.nathan@epa.gov , (703) 347

- 8020

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 f enbuconazole

. Please see the BEAD Chemical Profile (BCP) for Registration Review: Fenbuconazole (129011) in the registration
review docket for more details

.

Table 3 : Fenbuconazole Use and Usage Information

Summary of Use Broad

- spectrum systemic fungicide of the triazole (conazole) chemical class. Fenbuconazole inhibits sterol demethylation in fungi , causing fungal cell wall collapse and inhibition of hyphal growth. These antifungal properties r esult in fungal disease control on various crops.

Use Sites Agricultural : Citrus fruit ( crop group 10 ) , stone fruit (crop group 12 ) , almond, apple, banana, blueberry, cranberry, peanuts, pecan, pepper, sugar beet, and wheat.

Not registered for non

- agricultural uses. Summary of Usage Based on private market usage data from 2004

- 2008, fenbuconazole annual usage averaged 28,000 pounds of active ingredient (A.I.) treating an annual average of 300,000 acres, and an average application rate of 0.093 pounds A. I. per acre.

For years 2009

- 2013, fenbuconazole annual usage averaged 36,000 pounds of A.I. treating an annual average of 350,000 acres, and an overall average application rate of 0.103 pounds A. I. per acre.

The use of fenbuconazole, both in terms of pounds A. I. and total area treated (TAT), has been increasing since 200 6

. Formulation Type(s) Flowable concentrate, and wettable powder in water soluble packets9 Table 3 : Fenbuconazole Use and Usage Information

Application Method(s) Applied by ground or aerial methods. Technical Registrant (s) Dow Agrosciences

No. of Registrations 4 Section 3 products 7 , 13 section 24 ( c ) 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.

 Information for its declining use on pecans since 2008 and increasing use on oranges. And information on its use specific to the following commodities: banana, pepper, blueberries, grapes and stone fruit.

 C onfirmation of the following label information : sites of application ; formulations ; application m ethods and equipment ; maximum application rates ; frequency of application, application intervals, and maximum number of applications per season ; and geographic limitations on use

.

 U se distribution ( e.g. , acreage and geographical distribution of relevant us e 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

.

 Usage/use information for non

- agricultural uses.

 Typical application interval (days).

 S tate or local use restrictions

.

 F oreign technical registrants not listed above who supply technical f enbuconazole to the
US market

.

RECENT ACTIONS

T here are no recent actions for f enbuconazole.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for f enbuconazole was completed on January 31, 2013. T he most recent ecological and environmental fate risk assessment was completed on April 2 9, 2008 . Findings and conclusions from these risk assessments are

summarized in the Registration Review: Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered Species, and Human Health Drinking Water Exposure Assessments for Fenbuconazole and Fenbuconazole. Human Health Assessment 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

7 Section 3 product labels can be obtained from the Pesticide Produ ct Label System (PPLS) website ( http://oaspub.epa.gov/pestlabl/ppls.home ).10

f enbuconazole

. For human health, EPA anticipates the need to conduct revised dietary (food and drinking water) and occupational risk assessment s during registration review

. If toxic ological 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 operating p rocedures or default expo sure assumptions

.

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

EFED Problem Formulation and HED Scoping Document

.11

Table 4: Anticipated Risk Assessments for the Fenbuconazole Registration Review

Type of Risk Assessment Conduct ? Notes

Eco logical and Environmental Fate Comprehensive ecological (species to be assessed include terrestrial and aquatic organisms ), including endangered species

. Yes

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

f enbuconazole

, see page 61 of the Problem

Formulation.

Human Health Dietary

Food Y es The need for an updated dietary assessment for fenbuconazole will be considered during registration
review and may be needed if new data are identified which impact dietary exposure estimates including those from drinking water; toxicological endpoints or points of departure are revised; and if there are any changes to the standard operating procedures or

default e xposure assumptions.

It should be noted, that the Agency has previously assessed dietary risk from triazole

- derived metabolites, 1

- 2,4

- traizole and its conjugates triazolylanine and triazolyacetic acid, resulting from exposure to conazole fungicides (inc luding fenbuconazole) as a group. The need for an updated dietary triazole assessment will be determined at the time of registration review. Drinking water Yes It’s anticipated that an updated drinking water

assessment for fenbuconazole will be needed.

It is also anticipated that an updated drinking water
assessment will be needed for triazole

- derived metabolites, 1

- 2,4

- traizole and its conjugates triazolylanine and triazolyacetic acid. Occupational Handlers (m ixer s, loader s, applicators ) Yes U pdated occupational handler exposure assessments are anticipated as being needed to reflect current policies , current data, and any updates to the toxicity

database

.12

Post

- application Yes Updated post

- application exposure assessments are anticipated as being needed to reflect current policies, current data, and any updates to the toxicity

database.

Residential

Handlers No Residential handler and post

- application exposure assessments are not anticipated as being needed because there are currently no registered uses that
allow for residential use or would result in residential

exposer.

However, the Agency will examine the n eed for spray drift and volatilization assessments based on potential exposure to bystanders from agricultural applications. Post

- application

Other Aggregate Y Evaluates the combined risk from food and drinking

water.

It’s anticipated that an updated aggregate assessment will be needed if a new dietary exposure assessment is conducted, and /or if there are changes in estimated drinking water concentration s

.

It should be noted, that the Agency has previously assessed dietary risk from triazole

- d erived metabolites, 1

- 2,4

- traizole and its conjugates triazolylanine and triazolyacetic acid, resulting from exposure to conazole fungicides (including fenbuconazole) as a group. The need for an updated
aggregate triazole assessment will be determine d at the time of registration review.

Cumulative No Fenbuconazole has not been identified as a member of a cumulative group that shares a common mechanism of toxicity.

T here i s currently no evidence to demonstr ate that

conazoles share common mechanisms of toxicity

. Tolerances Yes The Agency anticipates it will re

- evaluate U.S.
tolerances and will harmonize them with Codex

M aximum R esidue L evels (MRL s ) to the extent possible.

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

f enbuconazole , see page 11 of the Scoping

Document and the Fenbuconazole: Tier 1 (Scoping) Review of Human Incidents and Epidemiology

.13

Guidance for Commente rs: Additional ecological i nformation r equested for this registration

r eview , and of particul ar 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 for further details)

.

TIMELINE

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

.

Table 5 : Projected Fenbuconazole Registration Review Timeline

Activities Estimated Dat e Opening the Docket Open Docket and 60

- day Public Comment Period 2015

- December

Close Public Comment 2016

- February Case Development

Final Work Plan 2016

- May

Issue DCI 2016

- July

- September

Data Submission 2018

– July

- September

6 0

- day Public Comment Period for Draft Risk

Assessments 8 2020

– January

- March

Registration Review Decision

60

- day Public Comment Period for Proposed Registration Review Decision 2020

– September

- November

Registration Review Decision and Begin Post

- Decision
Follow

- up 2021

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 f

enbuconazole

.

8 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, t he Agency plans to provide a 60 calendar day public comment period generally for draft risk assessm ent s

.14



### Appendix

– Additional Areas Considered in the Fenbuconazole 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 in formation 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 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.

Water Quality:

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

. 9 In addition, n o Total Maximum Daily Load s (TMDL) have been developed for f enbuconazole

. 10 More information on impaired water bodies

a nd TMDLs can be found at the Agency’s website

. 11 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 o f Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 12 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 f enbuconazole 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.

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

10 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant _group_name=PESTICIDES

11 http://water.epa.gov/lawsregs/lawsguidance/cwa/tmdl/index.cfm

12 http://archive.epa.gov/pesticides/ppdc/web/pdf/sess ion1

- sop.pdf15

ENDANGERED SPECIES :

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

conducted for f

enbuconazole

. The ecological risk assessment planned during registration review will allow the Agency to determine whether use of f enbuconazole 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 W ildlife Service 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. 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 evalua tes acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision for fenbuconazole

, EPA reviewed these data and selected the most sensitive endpo ints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p),

fenbuconazole 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 Administra tor 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 T ier 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.

Under FFDC A 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 13 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 endo crine disruptors.

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

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of
chemicals.16

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. 14

HUMAN STUDIES :

Occupational

Past f enbuconazole 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 Agricultural Reentry Task Force (ARTF) Database

. EPA has reviewed all the studies supporting

these multi

- pesticide generic exposure databases, an d 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 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

.

14 http://www.epa.gov/endocrine

- disruption