Docket Number EPA-HQ-OPP-2011-0153 

www.regulations.gov

Cyclanilide 

Summary Document 

Registration Review: Initial Docket 

March 2011 

 

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TABLE OF CONTENTS 

 

I. Preliminary Work Plan (PWP) 4 

II. Fact Sheet 12 

 

This Preliminary Work Plan and Fact Sheet summarize the Environmental Protection Agency’s 

current position based on the following documents: 

1. EFED Registration Review Problem Formulation for Cyclanilide. March 3, 2011. 

2. Cyclanilide. Human Health Assessment Scoping Document in Support of Registration Review. 

January 18, 2011. 

3. Cyclanilide: Review of Human Incidents. November 30, 2010. 

4. BEAD Chemical Profile for Registration Review: Cyclanilide. December 20, 2010. 

5. Cyclanilide California Department of Pesticide Regulation Usage Data. May 26, 2010. 

6. Cyclanilide Screening Level Usage Analysis (SLUA). June 22, 2010. 

7. PRD Appendix A: Food/Feed & Non-Food/Non-Feed Uses Considered in Registration 

Review Work Planning. Cyclanilide (026201). March 26, 2010. 

Supporting documents for the registration review of cyclanilide are located in docket EPA-HQOPP-2011-0153 at www.regulations.gov. 
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I. PRELIMINARY WORK PLAN 

Introduction

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 at: http://www.epa.gov/oppsrrd1/registration_review/ . 

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 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 and commit to a final work plan and 

schedule for the registration review of cyclanilide. 

Cyclanilide is a plant growth regulator and defoliant. It is currently registered for use as a 

synergist or co-active ingredient on cotton as a harvest aid and for use to increase branching of 

trees, shrubs, and cut flowers in plant production facilities and outdoor nurseries; it is not 

registered for use in greenhouses. Cyclanilide products registered for use on cotton contain 

cyclanilide mixed with one other active ingredient, either ethephon or mepiquat chloride. Nonagricultural ornamental use sites include shade trees, herbaceous plants, non-flowering plants, 

and woody shrubs. Outdoor nursery use sites include nursery stock of apple, cherry, pear, and 

plum. There are no residential uses. Cyclanilide was first registered in the United States in 

1997; therefore, it was not subject to the reregistration requirements of FIFRA. 

Anticipated Risk Assessment and Data Needs

The Agency anticipates conducting a comprehensive human health and ecological risk 

assessment, including an endangered species risk assessment, for all uses of cyclanilide. The 

Agency anticipates needing data to conduct these assessments. The Agency also intends to 

require additional toxicological data and to update and revise the human health risk assessment 
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for cyclanilide. Below is a summary of the issues relevant to the registration review of 

cyclanilide and the anticipated data requirements. 

Ecological Risk: 

• The most recent ecological risk assessments for cyclanilide were conducted in 1996 in 

support of the first registration of this chemical and in 2006 in support of the proposed 

new use of cyclanilide on ornamentals, cut flower crops, and non-bearing fruit trees. 

• The Agency anticipates conducting an updated environmental fate and ecological risk 

assessment for cyclanilide, including an endangered species assessment, during 

registration review. 

• The Agency has not conducted a risk assessment that supports a complete endangered 

species determination for cyclanilide. The ecological risk assessment planned during 

registration review will allow the Agency to determine whether cyclanilide’s use 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 (USFWS) and/or National Marine Fisheries 

Service (NMFS) (the Services), as appropriate. 

• On January 19, 2011, the Center for Biological Diversity and the Pesticide Action 

Network North America filed a lawsuit in the United States District Court for the 

Northern District of California, against the Environmental Protection Agency (EPA) for 

allegedly failing to undergo consultation with the USFWS and the NMFS regarding the 

effects of over 350 pesticides, including cyclanilide, on over 200 endangered and 

threatened species throughout the United States (Center for Biological Diversity, et al. v. 

EPA, et al., No. C 11-00293 (N.D.Cal.). 

• The Agency anticipates needing the following data in order to conduct a complete 

ecological risk assessment, including an endangered species assessment, for cyclanilide:

Environmental Fate

o Guideline No. 835.4100 – Aerobic Soil Metabolism 

o Guideline No. 835.6100 (footnote 7) – Terrestrial Field Dissipation (the 

environmental chemistry method and associated independent laboratory validation 

(ILV) of the submitted analytical method are expected to be required) 

o Guideline No. 835.6200 (footnote 7) – Aquatic Field Dissipation (the environmental 

chemistry method and an associated independent laboratory validation (ILV) of the 

submitted analytical method are expected to be required) 
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Ecological Toxicity

o Guideline No. 850.1350 – Aquatic Invertebrate Life-cycle (saltwater) 

o Guideline No. 850.1400 – Fish Early Life Stage (saltwater) 

o Guideline No. 850.2100 – Avian Acute Oral Toxicity (passerine species) 

o Guideline No. 850.4150 - Nontarget Area Phytotoxicity Tier II, Vegetative Vigor1

 

• Please refer to EFED Registration Review Problem Formulation for Cyclanilide, dated 

March 3, 2011, located in docket EPA-HQ-OPP-2011-0153 at www.regulations.gov, for 

a more detailed discussion of the anticipated ecological risk assessment and data needs.

Human Health Risk: 

• The most recent human health risk assessment was conducted in 2007 in support of the 

use of cyclanilide on ornamentals, cut flowers, and non-bearing fruit trees. 

• During registration review, the endpoints, and safety factors used in the most recent 

human health risk assessment will be revisited based on current Agency policy, as well as 

any new data received. 

• The cyclanilide tolerance expression will be reviewed during registration review to 

ensure that it appropriately covers the metabolites and degradates of cyclanilide and that 

it specifies the residues to be measured for each commodity. 

• The current 40 CFR §180.506 listing for sheep, meat is incorrectly given as 0.20 ppm. 

This tolerance should be the same as that for the meat of cattle, goat, hog, and horse, at 

0.02 ppm. The Agency anticipates correcting this listed tolerance in advance of the draft 

risk assessment. 

• The Agency anticipates conducting updated dietary, aggregate, and occupational 

exposure risk assessments to include any changes in toxicological endpoints, doses, and 

procedures for dermal and inhalation risk assessment. 

 

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 A Tier II study is expected to be required. The DCI expected to be issued will provide that a Tier I plant study 

may be conducted in lieu of a Tier II study with the understanding that any adverse effects observed by the Tier I 

study would necessitate conduct and submission of a Tier II study as well. The purpose of a Tier II study is to 

establish both a definitive No Observed Adverse Effect Concentration (NOAEC), or alternatively, a concentration at 

which there is a 5% observed inhibition effect (IC05) to be used in a risk assessment and effects determination for 

endangered or threatened species (listed species), and a definitive IC25 (concentration at which there is a 25% 

observed inhibition effect) for assessing risk to non-listed nontarget plants. If any adverse effects are observed in a 

Tier I study and neither a definitive NOAEC nor a definitive IC05 value is available, then the Agency may have to 

presume in its effects determination, that cyclanilide "may affect" and is “likely to adversely affect” listed plant 

species. 
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• During registration review, the endpoints, doses, and safety factors used in the most 

recent human health risk assessment will be revisited based on current policy as well as 

to incorporate any new data received and determined to be adequate. 

• During registration review, the Agency anticipates conducting an updated dietary 

exposure risk assessment to reflect current methodologies. 

• Based on current registered use patterns of cyclanilide and the current toxicological 

points of departure, the Agency does not anticipate conducting an updated drinking water 

exposure risk assessment at this time. If, in the future, any new uses are requested or if 

there is any reason for re-evaluation of the points of departure, a revised dietary (food + 

water) risk assessment may be needed. 

• Currently, there are no registered uses for cyclanilide that would result in residential 

exposure. As such, risks from residential exposures have not been considered in previous 

assessments nor would they be considered at this time. However, residential bystander 

inhalation exposures resulting from off-site transport (e.g., spray drift or volatilization) 

may occur as a result of applications of cyclanilide. The Agency is in the process of 

examining its policies and refining the methods used to complete residential exposure 

assessments. Therefore, the potential need for a bystander inhalation risk assessment for 

cyclanilide will be examined during registration review. 

 

• During registration review, the Agency anticipates conducting updated occupational and 

postapplication assessments based on updated doses, endpoints, and procedures for 

dermal and inhalation risk assessment. The Agency anticipates including additional and 

more detailed review of the handler and postapplication exposure scenarios. 

• The toxicity database for cyclanilide is complete except for the following studies, which 

the Agency anticipates requiring in order to conduct an updated human health risk 

assessment: 

o Guideline No. 870.3465 – 28-Day Inhalation Toxicity 

o Guideline No. 870.7800 – Immunotoxicity 

• Please refer to Cyclanilide. Human Health Assessment Scoping Document in Support of 

Registration Review, dated January 18, 2011, available in docket EPA-HQ-OPP-2011-0153 at 

www.regulations.gov, for a detailed discussion of the anticipated human health risk assessment 

and data needs. 
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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 its most recent cyclanilide registration decision, 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), cyclanilide 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. Cyclanilide is 

not among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for cyclanilide. For further information 

on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the 

test guidelines and the Tier 1 screening battery, please visit our website: 

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

Timeline

 

The projected timeline for the completion of the cyclanilide registration review is presented in 

Table 1. 
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Table 1. Projected Cyclanilide Registration Review Timeline 

Activity Estimated Date 

Opening the Docket 

Open Docket and Open Public Comment Period 2011 – March 

Close Public Comment Period 2011 – May 

Case Development 

Develop Final Work Plan (FWP) 2011 – August 

Issue Data Call-In (DCI) 2012 – April - June 

Data Submission 2014 – April - June 

Develop Preliminary Risk Assessments and Open Public Comment 2015 – Oct. - Dec. 

Close Public Comment Period 2016 – Jan. - March 

Registration Review Decision 

Develop Proposed Registration Review Decision and Open Public 

Comment Period 

2016 – April - June 

Close Public Comment Period 2016 – July - Sept. 

Issue Registration Review Decision and Begin Post-Decision Follow-up 2017 

Total (years) 6 

Guidance for Commenters

The public is invited to comment on EPA’s preliminary work plan and rationales. The Agency 

will carefully consider all comments, as well as any additional information or data provided in a 

timely manner, prior to issuing a final work plan for the cyclanilide case. 

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. Growers and 

other stakeholders are asked to comment on any trade irritant issues resulting from lack of 

Maximum Residue Limits (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. 

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 cyclanilide 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. 
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Water Quality

Cyclanilide is not identified as a cause of impairment for any water bodies listed as impaired 

under section 303(d) of the Clean Water Act2

. In addition, no Total Maximum Daily Loads 

(TMDL) have been developed for cyclanilide3

. More information on impaired water bodies and 

TMDLs can be found at the Agency’s website4. 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 

Process5 in order to ensure they can be used quantitatively or qualitatively in pesticide risk 

assessments. 

Other Information

Stakeholders are also specifically asked to provide information and data that will assist the 

Agency in refining risk assessments, including any species-specific ecological effects 

determinations, for cyclanilide. The Agency is interested in receiving the following information: 

1. Confirmation on the following label information. 

a. sites of application 

b. formulations 

c. application methods and equipment 

d. maximum application rates 

e. frequency of application, application intervals, and maximum number of 

applications per season and per year 

f. geographic limitations on use 

2. Use or potential use distribution (e.g. geographical distribution of relevant uses). 

3. Use history. 

4. Median and 90th percentile reported use rates (lbs ai/A, lbs ai/1000 sq. ft.) from usage 

data – national, state and county. 

5. Application timing (date of first application and application intervals) by use – national, 

state, and county. 

6. Usage/use information for non-agricultural uses on ornamental use sites including shade 

trees, herbaceous plants, non-flowering plants, and woody shrubs, and on outdoor nursery 

use sites including nursery stock of apple, cherry, pear, and plum; and information on 

effective alternatives. 

7. Directly acquired county-level usage data (not derived from state level data). 

a. maximum reported use rate from usage data – county 

b. median and 90th percentile number of applications – county 

c. total pounds per year – county 

 

2 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885 3 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_group_name=PESTICIDES 4 http://www.epa.gov/owow/tmdl/

5 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
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d. the year the pesticide was last used in the county/sub-county area 

e. the years in which the pesticide was applied in the county/sub-county area 

8. Typical application interval (days). 

9. State or local use restrictions. 

10. Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian, 

mammalian mortalities, and bee or beneficial insect mortalities) not already reported to 

the Agency. 

11. Comparative efficacy information of cyclanilide to similar products registered for similar 

uses in cotton. 

12. Information on growers’ selection criteria for growth regulator at each crop stage where 

cyclanilide may be used. 

13. For agricultural uses, worker activities that occur in treated fields at the typical time of 

cyclanilide applications. 

14. Comparative costs of cyclanilide versus other growth regulators and defoliants in 

identified use sites. 

Next Steps

After the 60-day comment period closes, the Agency will review and respond to any comments 

received in a timely manner. The Agency expects to issue a Final Work Plan for cyclanilide in 

August 2011. 
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II. FACT SHEET 

Background Information

• Cyclanilide Registration Review Case Number: 7018. 

• Cyclanilide Pesticide Chemical (PC) Code: 026201. 

• Cyclanilide Chemical Abstracts Service (CAS) Number: 113136-77-9. 

• Cyclanilide was first registered in the U.S. in 1997. 

• Currently, the technical registrant for cyclanilide is Bayer Crop Sciences LP. 

• Cyclanilide was not subject to reregistration; therefore, there is no Reregistration 

Eligibility Decision (RED) for cyclanilide. 

• U.S. tolerances for cyclanilide currently range from 0.02 ppm to 25.0 ppm [40 CFR 

180.506]. There are established tolerances for residues of cyclanilide in cottonseed, 

cotton gin byproducts, milk, and the fat, meat, kidney, and meat byproducts (except 

kidney), of cattle, goats, horses, hogs, and sheep. 

• Currently, there are seven Section 3 registrations for cyclanilide, including one technical 

and six end-use products. 

• Pesticide Re-evaluation Division (PRD) Contact: Katherine St. Clair 

(stclair.katherine@epa.gov). 

• Registration Division (RD) Contacts: Shaja Joyner (joyner.shaja@epa.gov); CynthiaGiles Parker (parker.cynthia@epa.gov). 

Use and Usage Information

For additional details, please refer to BEAD Chemical Profile for Registration Review: 

Cyclanilide, dated December 20, 2010; Cyclanilide California Department of Pesticide 

Regulation Usage Data, dated May 26, 2010; Cyclanilide Screening Level Usage Analysis 

(SLUA), dated June 22, 2010; and PRD Appendix A: Food/Feed & Non-Food/Non-Feed Uses 

Considered in Registration Review Work Planning. Cyclanilide (026201), dated March 26, 2010; 

located in docket EPA-HQ-OPP-2011-0153 at www.regulations.gov. 

• Cyclanilide is a plant growth regulator and defoliant. Cyclanilide’s mode of action is 

inhibition of auxin activity, especially in meristematic plant tissue. 
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• Cyclanilide is currently registered for use as a synergist or co-active ingredient on cotton 

as a harvest aid and for use to increase branching of trees, shrubs, and cut flowers in plant 

production facilities and outdoor nurseries; it is not registered for use in greenhouses. 

• Cyclanilide products registered for use on cotton contain cyclanilide mixed with one 

other active ingredient, either ethephon or mepiquat chloride. 

• Non-agricultural ornamental use sites for cyclanilide include shade trees, herbaceous 

plants, non-flowering plants, and woody shrubs. Outdoor nursery use sites for 

cyclanilide include nursery stock of apple, cherry, pear, and plum. 

• There are no registered uses of cyclanilide that would result in residential exposure; a 

residential exposure assessment was not conducted. 

• Cyclanilide formulation types include liquid and emulsifiable liquid. 

• Cyclanilide application methods include groundboom and aerial equipment, and 

backpack and low-pressure handwand sprayers. 

• Cyclanilide usage is mainly on cotton and it fluctuates from year to year. According to 

June 2010 screening level estimates of the agricultural uses of cyclanilide in the U.S., 

approximately 150,000 pounds of active ingredient are used annually. The largest and 

only agricultural use is on cotton, with an average of 10 percent of the crop treated and a 

maximum of 20 percent of the crop treated. According to private market research data 

from 1998-2008, the average agricultural usage of cyclanilide in the U.S. is 

approximately 156,000 pounds of active ingredient on approximately 1.5 million acres 

per year.

Recent and Pending Actions

• There are no recent or pending actions for cyclanilide. 

Ecological Risk Assessment Status

The following are key findings from the most recent ecological risk assessments regarding the 

environmental fate, ecological effects and risks of cyclanilide. Please refer to EFED 

Registration Review Problem Formulation for Cyclanilide, dated March 3, 2010 located in 

docket EPA-HQ-OPP-2011-0153 at www.regulations.gov, for a detailed discussion. 

• The most recent ecological risk assessments for cyclanilide were conducted in 1996 in 

support of the first registration of this chemical and in 2006 in support of the proposed 

new use of cyclanilide on ornamentals, cut flower crops, and non-bearing fruit trees. 
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Ecological Effects: 

• Previous ecological risk assessments concluded that the use of cyclanilide exceeded 

acute Levels of Concern (LOCs) for listed birds that feed on insects and for small-tointermediate-sized mammals that feed on short grass. 

• Previous ecological risk assessments concluded that the use of cyclanilide exceeded 

chronic LOCs for listed and non-listed mammals. 

• Previous ecological risk assessments concluded that the use of cyclanilide exceeded 

LOCs for listed and non-listed species of terrestrial plants (dicots). Potential risk to listed 

and non-listed terrestrial plants was not quantitatively assessed in the most recent 2006 

risk assessment because the previously-submitted vegetative vigor study was classified as 

invalid. 

Human Health Risk Assessment Status

The following are key findings from the human health risk assessments conducted for cyclanilide 

registered uses. Please refer to Cyclanilide. Human Health Assessment Scoping Document in 

Support of Registration Review, dated January 18, 2011, located in docket EPA-HQ-OPP-2011-

0153 at www.regulations.gov, for a detailed discussion of the human health risk assessment 

status. 

• The most recent human health risk assessment was conducted in 2007, in support of the 

use of cyclanilide on ornamentals, cut flowers, and non-bearing fruit trees. 

Hazard Characterization – Cyclanilide: 

• The acute toxicity of technical grade cyclanilide is severe by the oral route (toxicity 

category II), but has moderate to mild dermal and inhalation acute toxicity (categories III 

and IV, respectively). It is a severe eye irritant (toxicity category II), but not a skin 

irritant (toxicity category IV). It is not a skin sensitizer. 

• Cyclanilide has been classified as “not likely to be carcinogenic in humans.” There is no 

mutagenicity concern for cyclanilide based on the available data. 

• A 3X uncertainty factor was retained for the chronic dietary risk assessment to account 

for the extrapolation of the lowest observed adverse effect level (LOAEL) to the no 

observed adverse effect level (NOAEL) in the rat reproductive study selected for chronic 

dietary risk assessment. 

Summary of Risks – Cyclanilide: 
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Dietary (Food and Drinking Water)

• Acute and chronic dietary risk estimates for cyclanilide were below the Agency’s level of 

concern for the general U.S. population and all sub-populations. Cyclanilide was 

classified as “not likely to be carcinogenic to humans.” Therefore, a cancer dietary risk 

assessment was not conducted for cyclanilide. 

• In the acute dietary risk assessment, the Agency found that cyclanilide exposure for the 

general U.S. population resulted in an estimated risk equivalent to less than 1% of the 

acute population adjusted dose (aPAD). Infants less than one year old was the most 

highly exposed population subgroup, which used 1% of the aPAD. 

• In the chronic dietary risk assessment, the Agency found that cyclanilide exposure for the 

general U.S. population resulted in an estimated risk equivalent to 6.3% of the chronic 

population adjusted dose (cPAD). Children one to two years old was the most highly 

exposed subpopulation, which used 25% of the cPAD. 

Residential 

• Cyclanilide is not registered for use in residential settings and there is currently no risk 

concern for residential exposure. 

Aggregate

• Since a residential risk assessment was not conducted for cyclanilide, acute and chronic 

aggregate risks were equivalent to acute and chronic dietary risks and were below the 

Agency’s level of concern. 

Occupational

• Occupational handler and postapplication dermal and inhalation exposures were assessed 

qualitatively in 1997 for use of cyclanilide as a harvest aid on cotton. In 2007, a 

quantitative handler (dermal and inhalation) and postapplication (dermal) exposure 

assessment was performed for use of cyclanilide as a plant growth regulator for 

ornamentals, non-bearing fruit trees, and cut flowers. 

• In those assessments, occupational handler scenarios resulted in dermal and inhalation 

exposure risk estimates below the Agency’s level of concern based on use of the 

personal protective equipment (PPE) required by the product label. Occupational 

postapplication scenarios also resulted in exposure risk estimates below the Agency’s 

level of concern. 

Cumulative
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• The Agency has not determined whether cyclanilide shares a common mechanism of 

toxicity with other chemical substances. If, in the future, EPA obtains new data 

suggesting that cyclanilide shares a common mechanism of toxicity with other chemical 

substances, the Agency will revisit the need for a cumulative risk assessment. 

Human Studies

• Past cyclanilide 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 (40 CFR Part 26) have been satisfied, and 

there is no regulatory barrier to continued reliance on these studies. 

Incidents

Ecological Incidents: 

• In September 2010, the Agency reviewed the Ecological Incident Information System 

(EIIS), which is maintained by the EPA Office of Pesticide Programs, and the Avian 

Monitoring System (AIMS), which is maintained by the American Bird Conservancy, for 

ecological incident reports associated with the use of cyclanilide in the U.S. There were 

no reported ecological incidents associated with the use of cyclanilide. A review of the 

EFED Aggregate Incident Report database also yielded no ecological incident reports for 

cyclanilide. 

• Although no incidents have been reported to the Agency, the absence of reported 

incidents should not be construed as the absence of incidents. 

Human Health Incidents: 

• In November 2010, the Agency reviewed the OPP Incident Data System (IDS) for human 

health pesticide incident data associated with the use of cyclanilide in the U.S. to identify 

potential patterns on the frequency of health effects attributed to cyclanilide exposure. 

The IDS aggregate summaries from January 1, 2002 to May 27, 2010 include four cases 

reported for cyclanilide. This aggregate report does not provide details about the 

incidents, and single chemical incidents are not distinguished from multiple chemical 
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incidents. A review of the main IDS from January 1, 2002 to October 7, 2010 found no 

cases reported in the database for the single chemical cyclanilide only. 

• Based on the low frequency of incident cases reported in the OPP IDS, there does not 

appear to be a concern at this time that would warrant further investigation of cyclanilide 

human health incidents in the preliminary risk assessment phase of registration review. 

However, the Agency anticipates continuing to monitor the incident information and 

including additional analysis in the registration review risk assessment if a concern is 

triggered. 

Tolerances and International Harmonization

• A table listing the differences between U.S. tolerances and Canadian, Mexican, and 

CODEX Maximum Residue Limits (MRL) for cyclanilide is included in the Cyclanilide. 

Human Health Assessment Scoping Document in Support of Registration Review, dated 

January 18, 2011, available in docket EPA-HQ-OPP-2011-0153 at www.regulations.gov. 

Currently, there are no harmonization issues with Canada, CODEX, or Mexico. During 

registration review, if any Codex MRLs have been established, the Agency anticipates 

harmonizing the U.S. tolerances with the Codex MRLs when the data warrant 

harmonization. 

• U.S. tolerances for cyclanilide are established for residues of cyclanilide in or on the crop 

and livestock commodities listed in 40 CFR §180.506. Tolerances are established in 

terms of the parent compound [1-(2,4-dichlorophenylaminocarbonyl)-cyclopropane 

carboxylic acid] only. Currently, residues are determined as 2,4-dicloroaniline and 

calculated as cyclanilide. 

• During registration review, the Agency anticipates revising the tolerance expression so 

that it addresses both coverage and measurement. 

Existing Data Call-Ins

• There are currently no outstanding data requirements for cyclanilide. 

Labels 

• Active Section 3 labels for cyclanilide can be obtained from the Pesticide Product Label 

System (PPLS) website: http://oaspub.epa.gov/pestlabl/ppls.home.