2

Cycloate Preliminary Work Plan – Table of Contents

OVERVIEW ................................................................................................................................... 3

ANTICIPATED DATA NEEDS .................................................................................................... 4

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

CHEMICAL FACTS ...................................................................................................................... 6

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

RECENT ACTIONS....................................................................................................................... 8

ANTICIPATED RISK 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 summarizes the Environmental Protection Agency's current position 

based on the following documents:

1. Registration Review –Preliminary Problem Formulation 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 Document 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) Screening 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

OVERVIEW

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 herbicides. It 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. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide 

Programs knows about cycloate, 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 and 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 information that will help the Agency’s decisionmaking process for this chemical. In addition to general areas on which persons may wish to 

comment, there are some areas identified in the PWP and Appendix about which the Agency 

specifically seeks comments and 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 cycloate. Next, it 

discusses the statutory and regulatory authority for Registration Review. 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 Registration Review along with 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 Cycloate Registration Review

Guideline 

Number1 Study Title1

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

Anticipated Data Needs for the Parent Cycloate

850.2100 Avian acute oral toxicity test, one passerine 

species TGAI 12

Nonguideline

Avian inhalation, one species. TGAI 12

Nonguideline

Acute oral toxicity to adult honey bees TGAI 12

Nonguideline

Acute oral toxicity to larval honey bees TGAI 12

Nonguideline

Chronic oral toxicity to larval honey bees TGAI 12

Nonguideline

Chronic oral toxicity to adult honey bees TGAI 12

Nonguideline

Field trial of residues in pollen and nectar2

TGAI 24

Nonguideline

Semi-field testing for pollinator2

TGAI 24

Nonguideline

Field testing for pollinators2

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 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 toxicity to larval honey bees).
5

Table 1: Anticipated Data Needs for the Cycloate Registration Review

Guideline 

Number1 Study Title1

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 toxicity 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 

Environmental 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 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 the registration review program, the Agency periodically reevaluates pesticides to make 

sure that as change occurs, products in the marketplace can be used safely. Information on this 

program 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. 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 docket during this initial 

comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for 

the registration review of cycloate.

CHEMICAL FACTS

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

Table 2: Chemical Facts for Cycloate

PC code 041301

Case Number 2125

CAS Number 1134-23-2

Year first registered 1967

Pesticide Type Herbicide

Chemical class Thiocarbamate 

Reregistration 

Eligibility Decision 

(RED)

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 Cycloate

Cumulative group 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.

40 CFR Citation 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 uses 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: Cycloate 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 usage data from 1998-2012, average 

annual usage was approximately 220,000 pounds active 

ingredient (a.i.) on 100,000 acres treated. 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 emulsifiable concentrate liquid. 

Application Method(s) As pre-plant or at plant treatments, cycloate is applied as a 

ground broadcast or band application with mechanical or 

sprinkler incorporation, soil injection, or impregnation onto dry 

bulk fertilizer followed by soil incorporation

Technical Registrant(s) Helm Agro, Tri-Ag

No. of Registrations 2 Section 3 products3and 11 Section 24c Products

Restricted Use No

 

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

(http://oaspub.epa.gov/pestlabl/ppls.home).
8

Guidance for Commenters: Additional areas of use and usage related information

requested for this registration review, and of particular interest to EPA, are described below.

 Confirmation 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.

 Foreign 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. The 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, the 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 

assessments during registration review. If toxicological 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 assessments, as well as any changes to the standard operating procedures 

or default exposure assumptions.

Table 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 Cycloate 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 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, and 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 updated 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

Other
10

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 cycloate registration

review in Table 5 below.

Table 5: Projected Cycloate 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

60-day Public Comment Period for Draft Risk 

Assessments4

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 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

After the 60-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 Cycloate Registration Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest to the Agency 

where your comments, data submissions, or reference to sources of additional information could 

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 (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, providing as much specificity as possible regarding 

the nature of the concern. 

Water Quality:

Cycloate 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 Process8in 

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 

population 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, unusually 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

6http://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.htm
13

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 consult 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 

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 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 most 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 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 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 any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response 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 ingredients. A second list 

of chemicals identified for EDSP screening was published on June 14, 20139and 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 different pesticides, comprise generic pesticide 

exposure databases such as the Pesticide Handlers Exposure Database (PHED) and the 

Agricultural Reentry Task Force (ARTF) Database. EPA has reviewed all the studies supporting 

these multi-pesticide generic exposure databases, and has found no clear and convincing 

evidence that the conduct of any of them was either fundamentally unethical or significantly 

deficient relative to the ethical standards prevailing at the time the research was conducted. 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.

 

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