2 

### Cycloate Preliminary Work Plan

– Table of Contents

OVERVIEW

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

ANTICIPATED DATA NEEDS

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

STATUT ORY AND REGULATORY AUTHORITY

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

CHEMICAL FACTS

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

USE AND USAGE INFORMATION

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

RECENT ACTIONS

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

ANTICIPATED RI SK ASSESSMENTS FOR REGISTRATION REVIEW

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

TIMELINE

................................ ................................ ................................ ................................ .... 10

NEXT STEPS

................................ ................................ ................................ ............................... 10 Appendix

– Additional Areas Considered in the Cycloate Registration Review

..................... 12

References:

This Preliminary Work Plan summarize s the Environmental Protection Agency's current position based on the following documents:

1. Registration Review

– Preliminary Problem Form ulation for Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Cycloate

. Hartless, Christine; Lin, James

. June 5, 2015

.

2. Cycloate. Human Health Scoping D ocument in Support of Registration Review. O’Keefe, Barry; Negussie, Meheret; Ottley

, Myron S. May 20, 2015

.

3. Cycloate: Tier I Review of Human Incidents . Evans, Elizabeth; Recore, Shanna. March 31,

2015.

4. BEAD Chemical Profile (BCP) for Registration Review: Cycloate (041301)

. Ratnayake, Sunil; Haddad, Sepehr; Smearman, Stephen. December 2, 2014

.

5. Cycloate (041301) S creening Level Usage Analysis (SLU ). July 18, 2014.

6. Cycloate (041301) EFED Table 1 Report

. November 24, 2014.

7. Cycloate (041301) HED Master Label Report. November 24, 2014.

These and other supporting documents for the cycloate registration review case may be found in

the docket EPA

- HQ

- OPP

- 2015

- 0288 at http://www.regulations.gov

.3

OVERVIE W

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

- HQ

- OPP

- 2015

- 0288 )

. Cycloate belongs to the

thiocarbamate family of herbicide s. It is a systemic, b road

- spectrum, and pre

- emergent herbicide registered for control of certain grasses and broadleaf weeds in table beets, spinach, and sugar beets. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about cycloat e , 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 cycloate

.

The registration review process was designed to include a public participation component to solicit input from interested stakeholders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows about cycloate an d what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on cycloate . The Agency encourages all interested stakeholders to review the PWP and Appendix and to provide comments and additional inf ormation 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 a nd 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 l arge.

The Preliminary Work Plan begins by listing the anticipated data needs for cycloate

. 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 projected registration review timeline for cycloate

. Finally, the Appendix to this document includes identification and discussion of some areas that are considered generally

in R egistration R eview along wi th some additional chemical case

- specific information.4

ANTICIPATED DATA NEEDS

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

– Preliminary Problem Formulation for Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Cycloate and Cycloate: Human Health Scoping Document in Support of Registration Review

.

Table 1: Anticipated Data Needs for the C ycloate Regis tration Review

Guideline

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipated D ata Needs for the Parent C ycloate

850.2100 Avian acute oral toxicity test , one passerine

species TGAI 12

Non

guideline Avian inhalation, one species. TGAI 12

Non

guideline Acute oral toxicity to adult honey bees TGAI 12

Non

guideline Acute oral toxicity to larval honey bees TGAI 12

Non

guideline Chronic oral toxicity to larval honey bees TGAI 12

Non

guideline Chronic oral toxicity to adult honey bees TGAI 12

Non

guideline Field trial of residues in pollen and nectar 2 TGAI 24

Non

guideline Se mi

- field testing for pollinator 2 TGAI 24

Non

guideline Field testing for pollinators 2 TGAI 24

850.4500 Algal toxicity test, three species TGAI 12

850.4550 Cyanobacteria toxicity test TGAI 12

835.2410 Photodegradation on soil TGAI 12

835.4100 Aerobic soil metabolism (with 3 additional

soils) (835.4100) TGAI 24

835.4400 Aerobic aquatic metabolism (with 2 systems) TGAI 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 Availability” 77 FR 38282, June 27, 2012. http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0154

- 0028

2 The need for t his anticipated data requirement is contingent on results of the tier 1 bee studies (including acute oral toxicity to adult honey bees, acute oral toxicity to larval honey bees, chronic oral toxicity to adult honey bees, and chronic oral toxicity to larval honey bees).5 Table 1: Anticipated Data Needs for the C ycloate Regis tration Review

Guideline

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Outstanding Data Requirements from GDCI

- 041301

- 26252

835.6100 (835.6100) ECM and ILV for Terrestrial

Field Dissipation Study TEP 12

850.4100 Seedling emergence toxicity test, 10 species TEP 12

850.4150 Vegetative vigor toxicity test, 10 species TEP 12

850.4400 Aquatic plant toxicity test using Lemna spp. TGAI 12

850.1035 Mysid acute toxicity test TGAI 12

850.1350 Freshwater invertebrate life

- cycle test TGAI 12

850.1075 Fish acute toxicity test, marine TGAI 12

850.1400 Freshwater fish early

- life stage test TGAI 12

850.2300 Avian reproduction toxicity test, two species TGAI 24

860.1900 Field Accumulation in Rotational Crops TEP 12

870.6300 Developmental Neurotoxicity Study TGAI 24

TGAI = technical grade active ingredient; TEP = typical end

- use product ; The need for this anticipated data requirement is contingent on results of the tier 1 bee studies (including acute oral toxicity to adult honey bees, acute oral toxicity to larval honey bees, chronic oral toxicity to adult honey bees, and

chronic oral tox icity to larval honey bees).6

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

En vironmental Protection Agency (EPA or the Agency), based on scientific data showing that they will not cause unreasonable risks to human health or the environment when used as directed on product labeling. The registration review program is intended to 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 unreasonable adverse effects to human health or the

environment. Changes in science, public p olicy, and pesticide use practices will occur over time. Through the registration review program, the Agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Informatio n on this

progr am is provided on EPA’s website

. 2

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 a nd data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses

and data or information it believes are needed to make a registration review decision. After reviewing and responding to comments and data received in the docket during this initial comment period, the Agency will develop a F inal W ork P lan (FWP) and anticipated sched ule for the registration review of cycloate

.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for cycloate

.

Table 2: Chemical Facts for C ycloate

PC code 0 41301

Case Number 2125

CAS Number 1134

- 23

- 2 Year first registered 1967 Pesticide Type Herbicide

Chemical class Thiocarbamate

R eregistration Eligibility Decision (R E D) The RED was completed in 2004

.

Tolerance

Reassessment Eligibility Decision (TRED) Not applicable

2 http://www.epa.gov/oppsrrd1/registration_review/7 Table 2: Chemical Facts for C ycloate

Cumulative group Unlike other pesticides for whi ch EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding with cycloate

. Cycloate does not appear to produce a toxic metabolite produced by

other substances.

40 CFR Cita tion Tolerances for cycloate are established in 40 CFR §180.212

. Dual

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

Non

- pesticidal uses There are no identified non

- pesticidal u ses of cycloate.

Pesticide Re

- evaluation Division, Chemical Review Manager Matthew Manupella, manupella.matthew@epa.gov, (703) 347

- 0411

Registration Division

, Product Manager Reuben Baris, baris.reuben@epa.gov

, (703 ) 305

- 7356

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for cycloate

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

details

.

Table 3: C ycloate Use and Usage Information

Summary of Use Cycloate is a systemic, broad

- spectrum, and pre

- emergent herbicide registered for control of certain grasses and broadleaf weeds in table beets, spinach, and sugar beets.

Use Sites Cycloate registered agricultural use sites are table beets, spinach, and sugar beets Summary of Usage Based on private market usa ge data from 1998

- 2012, average annual usage was approximately 220,000 pounds active ingredient (a.i.) on 100,000 acres treate d. The average a.i. rate

over this time period was pounds 2.2 lbs a.i./acre. Formulation Type(s) Cycloate is formulated as an emul sifiable concentrate liquid. Application Method(s) As pre

- plant or at plant treatments, cycloate is applied as a

g round broadcast or band application with mechan ical or sprinkler incorporation, soil injection, or i mpregnation onto dry bulk fertilizer followed by soil incorporation Technical Registrant (s) Helm Agro, Tri

- Ag No. of Registrations 2 Section 3 products 3 and 11 S ection 24c Products

Restricted Use No

3 Section 3 product labels can be obtained from the Pesticide Produ ct Label System (PPLS) website ( http://oaspub.epa.gov/pestlabl/ppls.home ).8

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.

 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 geographic limitations on use

.

 Use and usage information of cycloate on table beets may be needed for risk assessments.

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

market

.

RECENT ACTIONS

There are no recent actions for cycloate.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent human health risk assessment for cycloate was in 2004 for the Reregistration Eligibility Decision (RED) for use on spinach, garden beets, and sugar beets

. T he most recent ecological and environmental fate risk assessment was completed in 2004 for the same purpose

. Findings and conclusions from these risk assessments are summarized in the Registration Review

– Preliminary Problem Formulation for Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Cycloate and Cycloate: Human Health 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 cycloate

. For human health, EPA anticipates the need to conduct revised dietary

, and occupational risk

assessment s during registration review

. If toxicological endpoi nts 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 exposure assumptions

.

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

EFED Problem Formulation and HED Scoping Document

.9

Table 4: Anticipated Risk Assessments for the C ycloate 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 The most recent comprehensive risk assessment was completed in 2004 for uses on table beets, sugar beets, and spinach.

Incidents Will check for updates A review of the Ecological Incident Information

System (EIIS, version 2.1) and the Avian Monitoring Information System (AIMS) was completed on August 7, 2014, an d no ecological incidents involving cycloate or cycloate sulfate were identified. Incident databases will be reviewed again at the time of the

risk assessment.

Human Health Dietary

Food Yes Since the acute and chronic dietary assessments and

the drinking water estimations were conducted several years ago, they will need to be updated during Registration Review to reflect current methods, models and data inputs. Drinking water Yes

Occupational Handlers (mixers, loaders, applicators) Yes There is sufficient information available to assess occupational handler application exposures. During Registration Review a new assessment of occupational handler exposures will be needed

because the most recent assessment was conducted several years ago , and policies and data inputs and assumptions have changed. Also, there were risks of concern for some dermal and all inhalation exposures with varying levels of personal protective equipment ( PPE ) . HED has since updated its policy on body weights and u pdated unit exposure values, and other inputs for determining these risk estimates. Post

- application No

Residential

Handlers Yes New occupational handler and post

- application exposure and risk assessments will be needed during Registration Review, because the most recent assessment was conducted several years ago, and policies and data inputs and assumptions have changed. HED has since updated its policy on body weights and updated unit exposures values, and other inputs for determining these risk estimates. Post

- application/ bystander Yes

Other10

Aggregate Yes A new aggregate assessment will be needed during Registration Review, since the chronic dietary assessment and the drinking water estimations were conducted several years ago and they will need to be updated.

Cumulative No Unlike other pesticides for which EPA has followed a

cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding with cycloate. Cycloate does not appear to produce a toxic metabolite produced by other substances.

Tolerances No Tolerances for cycloate are established in 40 CFR §180.212

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

cycloate , see page 9 of the Scoping Document and the Cycloate: Tier I Review of Human Incidents

TIMELINE

EPA has created the following estimated timeline for the completion of the c ycloate registration

review in Table 5 below

.

Table 5: Projected C ycloate Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and 60

- day Public Comment Period June 2015

Close Public Comment August 2015 Case Development

Final Work Plan November 2015

Issue DCI January

- March 2016

Data Submission January

- March 2018

6 0

- day Public Comment Period for Draft Risk

Assessments 4 July

- September 2019

Registration Review Decision

60

- day Public Comment Period for Proposed Registration Review Decision October

– December 2020

Registration Review Decision and Begin Post

- Decision

Follow

- up 2021

Total (years) 6

NEXT STEPS

4 The regulations governing Registration Review g enerally 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 assessment s

.11

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 cycloate

.12



### Appendix

– Additional Areas Considered in the C ycloate 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 market s, providing as much specificity as possible regarding

the nature of the concern.

Water Quality:

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

. 5 In addition, no Total Maximum Daily Loads (TMDL) have been developed for cycloate

. 6 More information on impaired water bodies and TMDLs can be found at the Agency’s website

. 7 The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the quality standards in Appendix

A of the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 8 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 policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the popula tion who, as a result of their location, cultural practices, or other factors, may have atypical, unusually high exposure to cycloate compared to the general population. Please comment if you are aware of any sub

- populations that may have atypical, unusua lly high exposure compared to the general population.

ENDANGERED SPECIES :

5 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause _group_id=885

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

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

8 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm13

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

conducted for cycloate

. The ecological risk assessment planned during registration review will

allow the Agency to determine whether use of cycloate 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 c onsult with the U.S. Fish and Wildlife 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

outcom es 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 endpoi nts which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of Reregistration Eligibility Decision (RED)

, EPA reviewed these

data and selected the mos t sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), cycloate is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP ).

EPA ha s 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 th e Administrator may designate.” The EDSP employs a two

- tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will determine which, if a ny, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and

establish a dose

- response relationship between the dose and the E, A, or T effect.

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 ingr edients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 9 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.

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

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.14

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. 10

HUMAN STUDIES :

Occupational

Past cycloate 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 differe nt 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 exposur e 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 r equirements 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

.

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