2 

### Ethofumesate Preliminary Work Plan – Table of Contents

OVERVIEW ...................................................................................................................... ............. 4

ANTICIPATED DATA NEEDS .................................................................................................... 5

STATUTORY AND REGULATORY AUTHORITY ................................................................... 6

CHEMICAL FACTS ................................................................................................................ ...... 7

USE AND USAGE INFORMATION ............................................................................................ 7

RECENT ACTIONS ................................................................................................................ ....... 9

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

TIMELINE ...................................................................................................................... .............. 11

NEXT STEPS .................................................................................................................... ........... 12

Appendix – Additional Areas Considered in the Ethofumesate Registration Review ............. 13

References:

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

1. Ethofumesate: Registration Review: Prelimi nary Problem Formulati on for Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments. Ryan Mroz and Faruque Khan, Ph.D. February 18, 2016.

2. Ethofumesate. Human Health Assessment Sc oping Document in Support of Registration

Review. William Irwin, Ph.D., Peter Savoia, and Kelly M. Lowe. February 22, 2016.

3. Ethofumesate: Tier I (Scoping) Review of Human Incidents and Epidemiology. Elizabeth Evans and Shanna Recore. December 8, 2015.

4. BEAD Chemical Profile for Registration Re view: Ethofumesate: (PC Code: 110601). Sunil Ratnayake Ph.D., Jihad Alsadek, Ph.D ., and Stephen Smearman. March 14, 2016.

5. Ethofumesate (110601) Screening Level Usage Analysis (SLUA). July 20, 2015.3 6. Environmental Fate and Effects Divisi on Label Data Report. PC Code 110601. July 20,

2015.

7. Health Effects Division Master Label Report Spreadsheet: Ethofumes ate PC Code 110601. July 20, 2015.

These and other supporting documents for the et hofumesate registrati on review case may be found in the docket EPA-HQ-OPP-2015-0406 at http://www.regulations.gov

.4 OVERVIEW

The docket for ethofumesate is now open, initiati ng the first public comment period for this registration review (docket number EPA-HQ-O PP-2015-0406). Ethofumesate is a pre- and postemergence herbicide used to control annual gras ses and broadleaf weeds. The major use of ethofumesate is for sugar beets with other food uses including onions, carrots, and garlic. Nonfood uses include treatments for seed crops, turf, and sod farms. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about ethofumesate, highlighting anticipated data and assessment need s, 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 ethofumesate.

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 ethofumesate 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 ethofumesate. The Agency encourages all inte rested 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 ethofumesate. Next, it discusses the statutory and re gulatory authority for registrati on review. Then the document provides chemical facts, use and usage info rmation, recent actions, the anticipated risk assessments, and a projected registration revi ew timeline for ethofumesate. Finally, the Appendix to this document includes identifica tion and discussion of some areas that are considered generally in registration review al ong with some additional chemical case-specific

information.5 ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for ethofumesate. For additional discussion of the anticipated data needs, see the Ethofumesate: Registration R eview: Preliminary Problem Formulation for Environmental Fate, Ecologica l Risk, Endangered Speci es, and Drinking Water Exposure Assessments and Ethofumesate. Human Health Assessment Scoping Document in Support of Registration Review

.

Table 1: Anticipated Data Needs for the Ethofumesate Registration Review

Guideline

Number 1 Study Title Test Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated Data Needs for the Parent Ethofumesate

835.4100 Aerobic soil metabolism TGAI or

PAIRA 24

835.4200 Anaerobic soil metabolism TGAI or

PAIRA 24

835.4300 Aerobic aquatic metabolism TGAI or

PAIRA 24

835.4400 Anaerobic aquatic metabolism TGAI or

PAIRA 24

850.1010 Freshwater invertebrate acute toxicity TGAI 12

850.1350 Estuarine/marine invertebrate life cycle; mysid shrimp ( Mysidopsis bahia ) TGAI 12

850.2100 Avian oral toxicity; passerine species TGAI 12 850.3040 Tier III field testing for pollinators 2 TEP 24 850.4500 Algal toxicity (freshwater and marine diatom) TGAI 12 850.4550 Cyanobacteria ( Anabaena flos-aquae ) toxicity TGAI 12

860.1340 Residue analytical method (livestock) TGAI and degradates 3 24

875.2100 Dislodgeable foliar residue and turf transferable

residues TEP 24

Nonguideline Tier I honeybee adult chronic oral toxicity TGAI 12

Nonguideline/

OECD 237 Tier I honeybee larval acute oral toxicity TGAI 12

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 The need for Tier II and Tier III pollinator data is contingent upon the results of lower tier testing.

3 Degradates of concern are NC 8493, NC 9607, and NC 206456 Table 1: Anticipated Data Needs for the Ethofumesate Registration Review

Guideline

Number 1 Study Title Test Material Estimated

Timeframe

(Months from receipt of DCI)

Nonguideline Tier I honeybee larval chronic oral toxicity TGAI 12

Nonguideline Tier II residues in pollen and nectar 2 TEP 24

Nonguideline Tier II semi-field testing for pollinators (tunnel and colony feeding studies) 2 TEP 24

Anticipated Data Needs for the Degradate NC 8493

850.2200 Avian dietary toxicity; bobwhite quail or mallard

duck Degradate 12

PAIRA = pure active ingredient radio-labeled; TGAI = technical grade active ingred ient; 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 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. 4

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 ethofumesate.

4 http://www2.epa.gov/pesticide-reevaluation7 CHEMICAL FACTS

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

Table 2: Chemical Facts for Ethofumesate

PC code 110601

Case Number 2265

CAS Number 26225-79-6 Year first registered 1977 Pesticide Type Herbicide

Chemical class Benzofuranes Reregistration Eligibility Decision (RED) Issued 2005; revised 2007

Tolerance Reassessment Eligibility Decision (TRED) Not applicable. Tolerance reassessment included in RED.

Cumulative group No cumulative risk assess ment is required at this time as the Agency has not made a determin ation regarding a common mode

of action.

40 CFR Citation Tolerances for ethofumes ate are established in 40 CFR § 180.345. Dual-use Ethofumesate is registered for conventional pesticidal uses only and has no registered antimicr obial or biopesticidal uses. Non-pesticidal uses There are no identifi ed non-pesticidal uses of ethofumesate.

Pesticide Re-evaluation Division, Chemical Review Manager Jordan Page; page.jordan@epa.gov ; 703.347.0467

Registration Division, Product Manager Heather Garvie; garvie.heather@epa.gov ; 703.308.0034

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage info rmation for ethofumesate. Please see the BEAD Chemical Profile for Registration Re view: Ethofumesate: (PC Code: 110601) in the registration

review docket for more details.

Table 3: Ethofumesate Use and Usage Information

Summary of Use Selective herbicide applied as pre-plant, pre-emergence, and postemergence treatments to control broadleaf and grassy weeds. Ethofumesate acts as a seedling shoot inhibitor, affecting developing leaves at growing points. Use Sites Agricultural use sites include sugar beets, garden beets, table beets, carrots, shallots, garlic, and onions. Non-agricultural use sites include grasses grown for s eed, ornamental lawns, turf, and

ornamental sod farms.8 Table 3: Ethofumesate Use and Usage Information

Summary of Usage Based on market data from 2009-2013, usage averaged approximately 35,000 pounds a.i. applied annually on 104,000 acres at 0.34 pounds a.i./acre. Formulation Type(s) Flowable liquid concen trate, emulsifiable concentrate, soluble concentrate/liquid Application Method(s) banded, broadcast, so il band treatment, soil band broadcast treatment, soil incorporated tr eatment, spray, impregnated dry

bulk fertilizer treatment Technical Registrant(s) Bayer Cropscien ce LP, Etho Tech, Willowood Ethofumesate,

LLC No. of Registrations 16 Section 3 products 5

Restricted Use No

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

 Certain ethofumesate labels ar e unclear with respect to appl ication parameters such as maximum annual application rate s, applications allowed per year and single application rates in terms of lbs a.i./A (see Ethofumesate: Registration R eview: Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments) . Without further information, EPA expects to use conservative assumptions to approximate these parameters in order to conduct a quantitative risk assessment. However, the Ag ency will work with registrants to clarify information on ethofumesate product labels.

o There is no annual maximum applica tion rate stated or the maximum application use rate is stated in terms of crop growing season rather than the annual rate for the following Registration #s: 264-612, 264-613, 264-615, 70506-106, 70506-107, 70506-283, 87290-1, 87290-2

o Labels are not clear on number of applications allowed per year for registration #s: 264-612, 264-613, 264- 615, 70506-106 and 87290-1. In the absence of yearly information, multip le seasons or crop cycles may be assumed for some crops when performing the risk assessment.

o Single application rates are listed on th e label in terms of volume of product instead of lbs a.i./A for registration #s: 264-612, 264-613, 264-615, 70506- 106, 70506-107, 70506-283, 87290-1 and 87290-2.

o The Agency recommends stating a ll single, seasonal, and/or annual application rates in terms of lbs a.i./A.

 Data on pounds a.i. applied and percen t crop treated on registered crops.

 Usage/use information for non-agricultural uses.

 Foreign technical registrants not listed above who supply te chnical ethofumesate to the
US market.

5 Section 3 product labels can be obtained from th e Pesticide Product Label System (PPLS) website

(http://oaspub.epa.gov/pestlabl/ppls.home).9 RECENT ACTIONS

There are no current or pending regi stration actions for ethofumesate.

ANTICIPATED RISK ASSESSMENT S FOR REGISTRATION REVIEW

The most recent ecological and environmental fate risk assessment for ethofumesate was completed in 2004 in preparation for the Reregist ration Eligibility Decision. The most recent comprehensive human health risk assessment was completed in 2006 for the same purpose. Findings and conclusions from these ri sk assessments are summarized in the Ethofumesate: Preliminary Problem Formula tion for Environmental Fate , Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments and Ethofumesate. 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 ethofumesate. For human health, EPA anticipates the need to conduct re vised residential postapplication, aggregate, and occupational risk assessments during registration review to incorporate updated exposure and residue data, and updated toxicological endpoints or points of departure, if revised based on the data that are anticipated to be require d for registration review.

Table 4 below summarizes the anticipated regi stration review risk assessments based on the

EFED Problem Formulation and HED Scoping Document.10 Table 4: Anticipated Risk Assessments for the Ethofumesate Registration Review

Type of Risk Assessment Conduct? Notes

Ecological and Environmental Fate Comprehensive ecological (species to be assessed include terrestrial and aquatic organisms), including endangered species Y The Agency will conduct a comprehensive ecological risk assessment including an endangered species assessment during registration review.

Incidents Will check for updates For a discussion of reported ecological incidents for ethofumesate, see page 16 of the Problem

Formulation.

Human Health Dietary Food N Not unless anticipated residues on food or revised estimated drinking water concentrations are significantly greater than those used in the most

recent assessment. Drinking water N

Occupational Handlers (mixers, loaders, applicators) Y Updated assessments will be conducted to reflect current occupational reside ntial exposure policies, the revised dermal absorption factor, and/or updated toxicological inhalation poi nts of departure (POD). Post-application Y

Residential Handlers N The Agency assumes that applications by residential handlers are made with handheld equipment only. Ethofumesate labels proh ibit the use of handheld equipment and therefore residential handler exposures are not anticipated. Post-application Y A revised residential post-application assessment may be necessary using the revised 2012 Residential SOPs, the revised dermal ab sorption factor, new turf transferable data, and any potential changes to the toxicological PODs. The need for spray drift and

volatilization risk assessments for ethofumesate will

be considered.

Other Aggregate Y An updated aggregate assessment will be performed to reflect any updates to the dietary and non-dietary assessments, as well as a ny potential updates to the toxicity PODs and uncertainty factors.

Cumulative N EPA has not made a common mechanism of toxicity finding for ethofumesate and any other substances.11 Tolerances N The current toleran ce for ethofumesate on sugar beet tops should be revoked as this commodity is no longer a significant livestock feed item or a recognized human food item. There are no Codex or Mexican maximum residue limits (MRLs) for

residues of ethofumesate. Canadian MRLs for ethofumesate have been established, and they are

harmonized with U.S. tolerance levels.

Incidents Will check for updates For a discussion of reported human incidents for ethofumesate, see page 9 of the Scoping Document

and Ethofumesate: Tier I (Scoping) Review of Human Incidents and Epidemiology

.

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).

TIMELINE

EPA has created the following estimated time line for the completion of the ethofumesate registration review in Table 5 below.

Table 5: Projected Ethofumesate Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and 60-day Public Comment Period March 2016 Close Public Comment May 2016 Case Development Final Work Plan August 2016

Issue DCI October-December 2016

Data Submission October-December 2018 60-day Public Comment Period for Draft Risk

Assessments 6 April-June 2020

Registration Review Decision 60-day Public Comment Period for Proposed Registration Review Decision January-March 2021

Registration Review Decisi on and Begin Post-Decision Follow-up 2021

6 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.12 Table 5: Projected Ethofumesate Registration Review Timeline

Activities Estimated Date 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 ethofumesate.13 

### Appendix – Additional Areas Considere d in the Ethofumesate 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 internatio nal maximum residue limits (MRLs) as needed and may modify tolerance levels to do so, when possible. Growers and other stakeholders are

asked to comment on any trade irritant i ssues resulting from lack of MRLs or disparities between U.S. tolerances and MRLs in key expor t markets, providing as much specificity as possible regarding the natu re of the concern.

Water Quality:

Ethofumesate is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. 7 In addition, no Tota l Maximum Daily Loads (TMDL) have been developed for ethofumesate. 8 More information on impaired water bodies and TMDLs can be found at the Agency’s website. 9 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 Procedur e: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Regist ration Review Risk Assessment and Management Process 10 in order to ensure they can be us ed quantitatively or qualitatively in pesticide risk assessments.

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, 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 ethofum esate 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.

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

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

group_name=PESTICIDES

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

10 http://www2.epa.gov/pesticide-reevaluation/opp-guidance- submission-state-and-tribal-water-quality-monitoringdata14 ENDANGERED SPECIES:

A risk assessment that supports a complete endangered species determination has not been conducted for ethofumesate. The ecological risk assessment planned during registration review will allow the Agency to determine whether use of ethofumesate has “no effect” or “may affect” federally listed threatened or endangered specie s (listed species) or their designated critical habitats. When an assessment concludes that a pe sticide’s use “may affect” a listed species or its designated critical habitat, the Agency will c onsult with the U.S. Fish and Wildlife Service

and/or National Marine Fisheries Service (the Se rvices), 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 re registration decision for ethofumesate, EPA reviewed these data and selected the most sensitive endpoints fo r relevant risk assessment scenarios from the existing hazard database. However, as requi red by FFDCA section 408 (p), ethofumesate is subject to the endocrine screeni ng part of the Endocrine Disrup tor 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. Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticide ac tive ingredients and 9 inert ingredients. 11 A second list

of chemicals identified for EDSP sc reening was published on June 14, 2013 12 and includes some pesticides scheduled for registration review and chemicals found in water

. Ethofumesate does

11 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2004-0109-0080 for the final initial list of

chemicals.

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

chemicals.15 not appear on either of the lists. Neither of thes e lists should be construed as a list of known or likely endocrine disruptors.

For further information on the status of the ED SP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening ba ttery, please visit our

website. 13

HUMAN STUDIES:

Occupational and Residential

Past ethofumesate risk assessments rely in pa rt 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 Pest icide Handlers Exposure Database (PHED), the Agricultural Reentry Task Force (ARTF) Databa se, and the Outdoor Residential Exposure Task Force (ORETF) Database. EPA has reviewed all the studies supporting these multi-pesticide generic exposure databases, and has found no cl ear 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 wa s conducted. All applicab le requirements of EPA’s Rule for the Protection of Human Subject s of Research (40 CFR Part 26) have been satisfied, and there is no re gulatory barrier to continue d reliance on these studies.

13 http://www2.epa.gov/endocrine-disruption