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Docket Number EPA-HQ-OPP-2012-0167

www.regulations.gov

Cypermethrin

Summary Document

Registration Review: Initial Docket

March 2012

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TABLE OF CONTENTS

 

I. Preliminary Work Plan (PWP) 4

II. Fact Sheet 14

III. Summary of Data Gaps 22

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

current position based on the following documents:

1. Problem Formulation for the Environmental Fate and Ecological Risk, Endangered 

Species, and Drinking Water Assessments in Support of the Registration Review of 

Racemic Cypermethrin and Zeta-Cypermethrin. March 1, 2012.

2. Cypermethrin and Zeta-Cypermethrin. Human Health Risk Scoping Document in Support of 

Registration Review. March 1, 2012.

3. Cypermethrin and Zeta-Cypermethrin: Review of Human Incidents. January 12, 2012.

4. BEAD Case Level Chemical Profile for Registration Review: Cypermethrin (109702) and 

Zeta-Cypermethrin (129064). December 8, 2011.

5. Cypermethrin Appendix A. October 12, 2011.

6. Cypermethrin (109702) Screening Level Usage Analysis (SLUA). October 31, 2011.

7. Zeta-Cypermethrin Appendix A. May 24, 2011.

8. Zeta-cypermethrin (129064) Screening Level Usage Analysis (SLUA). October 31, 2011.

Supporting documents for the registration review of cypermethrin are located in docket EPAHQ-OPP-2012-0167 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 occur, 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 cypermethrin.

The cypermethrin case includes two active ingredients: racemic cypermethrin (hereafter referred 

to as cypermethrin) and zeta-cypermethrin. Cypermethrin is a combination of 8 stereoisomers 

and zeta-cypermethrin is an enriched enantiomer of cypermethrin. Collectively, cypermethrin 

and zeta-cypermethrin are referred to as “the cypermethrins.” 

The cypermethrins are synthetic pyrethroids that act through modulation of nerve axon sodium 

channels, causing neurotoxity in insects and mammals. Products containing the cypermethrins

are broad spectrum insecticides registered for agricultural use as a foliar application on food and 

feed crops including cotton, pecans, peanuts, and broccoli and other Brassicas. The 

cypermethrins can be applied to livestock in eartags, and to horses. The cypermethrins are also 

registered for use on industrial, commercial, and residential sites. They are registered for 

outdoor use as a soil residual termiticide and to control insect pests such as ants in and on 

structures, impervious surfaces (in perimeter and crack and crevice treatments) and lawns. The 

cypermethrins can also be applied indoors to control ants, cockroaches, fleas, and other insects.
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Cypermethrin was first conditionally registered in 1984 by FMC Corporation, which

subsequently registered zeta-cypermethrin in 1992. The Reregistration Eligibility Decision for 

Cypermethrin was completed in 2006. Zeta-cypermethrin was not subject to reregistration since 

it was registered after 1984.

Anticipated Risk Assessment and Data Needs

The Agency anticipates requiring data for use in updating and refining the ecological risk 

assessment (including an endangered species risk assessment) and the human health risk 

assessment for all uses of the cypermethrins. Below is a summary of the issues relevant to the 

registration review of the cypermethrins and the data the Agency anticipates requiring.

Ecological Risk:

• The most recent ecological risk assessment for cypermethrin is reflected in the “Revised 

Cypermethrin RED Chapter After 30-Day “Error Only” Comment Period” dated October 

25, 2005. Since the RED, multiple Section 3 New Use Risk Assessments have been 

completed for zeta-cypermethrin. Risks identified in these assessments were similar to 

those identified in the RED. 

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

species determination for the cypermethrins. The ecological risk assessment planned 

during registration review will allow the Agency to determine whether the 

cypermethrins’ 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 United States Fish and Wildlife Service 

and the National Marine Fisheries Service regarding the effects of over 350 pesticides, 

including the cypermethrins, 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.).

• Data gaps exist in the environmental fate and ecological toxicity database for the 

cypermethrins. Since both cypermethrin and zeta-cypermethrin have similar 

toxicological profiles, either compound may be used to address the data gaps. The 
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Agency anticipates needing the following data for use in conducting a complete 

ecological risk assessment, including an endangered species assessment, for the 

cypermethrins:

Environmental Fate Data Gaps

o GLN 835.4100 Aerobic Soil Metabolism

o GLN 835.4300 Aerobic Aquatic Metabolism

o GLN 835.4400 Anaerobic Aquatic Metabolism

o GLN 835.6100 Analytical method and associated independent laboratory 

validations in soil

o Non GLN Study of Fate in Publicly-Owned Treatment Works (POTW) (Special 

Study)

Ecological Toxicity Data Gaps

o Non GLN Acute Freshwater Invertebrate Toxicity (Hyalella azteca) – water 

column (Special Study)

o Non GLN Fish Acute Toxicity Test (freshwater) (Special Study)

o Non GLN Whole Sediment Invertebrate Toxicity (Hyalella azteca) (Special 

Study)

o Non GLN Whole Sediment Chronic Invertebrate Toxicity, freshwater 

(Chironomus dilutes) (Special Study)

o Non GLN Whole Sediment Chronic Invertebrate Toxicity, marine/estuarine 

(Leptocherirus plumulosus) (Special Study)

o GLN 850.2100 Avian Acute Oral Toxicity, Passerine

o GLN 850.2300 Avian Reproduction Test, Quail/Duck1

o GLN 850.4150 Seedling Emergence, Tier II

o GLN 850.4250 Vegetative Vigor, Tier II

o GLN 850.4400 Aquatic Plant Growth (aquatic vascular plant toxicity), Tier II

o GLN 850.5400 Aquatic Plant Grown (algal plant toxicity), Tier II

• Please refer to the Problem Formulation for the Environmental Fate and Ecological Risk, 

Endangered Species, and Drinking Water Assessments in Support of the Registration 

Review of Racemic Cypermethrin and Zeta-Cypermethrin, March 1, 2012, located in 

docket EPA-HQ-OPP-2012-0167 at www.regulations.gov, for a more detailed discussion 

of the anticipated ecological risk assessment and data needs for the cypermethrins.

 1 Tests are expected to be recommended to be conducted with the technical product with waterfowl and an upland 

game bird species.
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Human Health Risk:

• The most recent comprehensive human health risk assessment for cypermethrin was 

conducted in support of the 2006 Reregistration Eligibility Decision (RED) and is dated 

April 6, 2006. Since the RED, an additional human health assessment for the use of zetacypermethrin on citrus, oilseeds, safflower, wild rice and okra was completed in 2007.

• The Agency does not anticipate requiring any data for use in conducting the human 

health risk assessment for the cypermethrins.

• The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative 

risks of chemicals sharing a common mechanism of toxicity. Cypermethrin and zetacypermethrin are members of the pyrethroid/pyrethrins common mechanism group 

(http://www.regulations.gov; EPA-HQ-OPP-2008-0489-0006). The members of this 

group share the ability to interact with voltage-gated sodium channels ultimately leading 

to neurotoxicity. The cumulative risk assessment for the pyrethroids/pyrethrins was 

published on Nov. 9, 2011 and is available at http://www.regulations.gov; EPA-HQ-OPP2011-0746. No cumulative risks of concern were identified, allowing the Agency to 

consider new uses for pyrethroid actives. For information regarding EPA’s efforts to 

evaluate the risk of exposure to pyrethroids, refer to 

http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html.

• Under FQPA, the Agency is required to apply a 10X Safety Factor (SF) to be protective 

of infants and children unless there are data to support a reduction or removal. Based on 

the weight of the evidence and overall completeness of the database, the Agency reduced 

the FQPA SF to 1X for cypermethrin during reregistration. 

• The Agency reevaluated the FQPA SF for human health risk assessments for pyrethroid 

pesticides in 2011. Based on information available in the database of pyrethroid

guideline studies and in the open literature, the Agency reduced the safety factor to 1X 

for adults, including pregnant woman. However, the Agency retained a 3X factor for 

children <6 years of age. The 3X factor is based on age-dependent-pharmacokinetics and 

is further supported by physiologically-based pharmacokinetic (PK) model predictions of 

a 3-fold increase of pyrethroid concentration in juvenile target tissue compared to adults. 

A more complete description of the Agency’s reasoning behind a 3X FQPA SF for 

children can be found at www.regulations.gov; EPA-HQ-OPP-2011-0746-0011.

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

recent human health risk assessments may be revisited based on current policy as well as 

to incorporate any new data received and determined to be adequate. The re-evaluation 

of the FQPA safety factor may be conducted following a final determination of the 
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potential for increased susceptibility of infants and children to pyrethroid pesticides based 

on the review of all available data.

• The Agency anticipates conducting updated dietary (food and water), aggregate, 

residential, and occupational exposure risk assessments to include any changes in 

toxicological endpoints, doses, and procedures for risk assessment during the registration 

review timeframe. 

• The Agency will review the need for an updated drinking water exposure risk assessment 

during registration review.

• The tolerance expressions for cypermethrin in 40 CFR §180.418(1)(1) and zetacypermethrin §180.418(a)(2) will be reviewed during registration review to ensure that 

they appropriately cover the respective metabolites and degradates and that they specify

the residues to be measured in each commodity.

• The Agency will modify tolerance levels as needed, and work to harmonize 

tolerances/maximum residue limits (MRLs), where possible, in key export markets 

during registration review.

• Please refer to Cypermethrin and Zeta-Cypermethrin. Human Health Assessment Scoping 

Document in Support of Registration Review dated March 1, 2012, available in docket EPA-HQOPP-2012-0167 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 registration decision for the cypermethrins, 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),

the cypermethrins are 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. The 

cypermethrins are 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 call-ins, requiring the submission of EDSP screening assays for the 

cypermethrins. 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/.

 

The projected timeline for the completion of the cypermethrins registration review is presented

below in Table 1.

Timeline
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Table 1. Projected the Cypermethrins Registration Review Timeline2

Activities Estimated Date

Opening the Docket

Open Docket and Public Comment Period 2012 – March

Close Public Comment 2012 – May

Case Development

Final Work Plan 2012 – August

Issue DCI 2013 – April – June

Data Submission 2015 – April – June

Open Public Comment Period for Draft Risk Assessments 2016 – Oct. – Dec.

Close Public Comment Period 2017 – Jan. – March

Registration Review Decision

Open Public Comment Period for Proposed Registration Review Decision 2017 – April – June

Close Public Comment Period 2017 – July – Sept.

Registration Review Decision and Begin Post-Decision Follow-up 2018

Total (years) 6

Guidance for Commenters

The public is invited to comment on EPA’s preliminary work plan and rationale. 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 cypermethrins 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 the cypermethrins compared to the general population. 

 2 Any changes in the cumulative risk from the pyrethroid class of insecticides may impact this time estimate.
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Please comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure, compared to the general population.

Water Quality

On October 11, 2011, EPA approved California's 2008 - 2010 list of impaired water bodies that 

require total maximum daily loads (TMDLs) pursuant to the Clean Water Act, section 303(d), 

and 40 CFR 130.7(d)(2). This list includes 11 water body impairments due to pyrethroid 

pesticides as a group, and three water body impairments with the pyrethroids bifenthrin, lambda 

cyhalothrin, esfenvalerate/fenvalerate, and permethrin identified as the cause of impairment. The 

cypermethrins are not included in this list. More information on California’s additional impaired 

water body listings can be found at EPA’s website3. 

No water bodies have been designated as impaired specifically for the cypermethris, nor have 

any TMDLs been developed for this active ingredient4. More information on impaired water 

bodies and TMDLs can be found at the Agency’s website5. 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 Process6 in order to ensure they can be used quantitatively or qualitatively in 

pesticide risk assessments.

On October 28, 2011, the California Department of Pesticide Regulation (DPR) announced 

proposed restrictions to 17 pyrethroid pesticides, including cypermethrin, used by pest control 

applicators and maintenance gardeners in urban areas to protect water quality. Restrictions 

would include: 1) prohibiting applications during rain events and when puddles are present; 2) 

prohibiting use over drains or natural drainage areas; and 3) restricting application methods 

around structures. More information about the proposed regulations is available on DPR’s 

website7.

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 

 3 http://www.epa.gov/region9/water/tmdl/california.html 4

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

group_name=PESTICIDES

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

6 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm 7 http://www.cdpr.ca.gov/docs/legbills/rulepkgs/11-004/11-004.htm
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determinations for the cypermethrins. The Agency is interested in receiving the following 

information:

1. Usage data such as pounds active ingredient (a.i.) applied, area treated, typical use rates, 

and typical number of applications on the following sites: industrial sites, livestock, milk, 

and meat

2. Usage data for the agricultural crops that are not covered in the usage section of this 

document

3. Usage data (pounds a.i. applied and area treated) for indoor/outdoor consumer use, use in 

food handling establishments/food processing establishments, and use in and around 

commercial and institutional facilities

4. 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

5. Use or potential use distribution (e.g., acreage and geographical distribution of relevant 

uses/use sites)

6. Use history

7. Median and 90th

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

state, and county

percentile reported use rates (lbs active ingredient(a.i.)/acre, lbs a.i./1000 

sq. ft.) from usage data – national, state and county

9. Sub-county use site location data

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

a. maximum reported use rate (lbs a.i./acre) from usage data – county

b. median and 90th

c. total pounds per year – county

percentile number of applications – county

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

11. Typical application interval (days)

12. State or local use restrictions

13. 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

14. Monitoring data
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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 issue a Final Work Plan for the registration 

review of the cypermethrins.
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II. FACT SHEET

Background Information

• Registration Review Case Number: 2130

• Pesticide Chemical (PC) Codes: Cypermethrin: 109702; Zeta-Cypermethrin: 120964

• Chemical Abstracts Service (CAS) Numbers: Cypermethrin: 52315-07-8; ZetaCypermethrin: 137497-61-1; 139203-31-9; 142443-95-6; 146909-55-9; 159940-28-0; 

186554-45-0; 52315-07-8; 69865-47-0; 71697-59-1; 86752-99-0; 86753-92-6; 88161-75-

5; 97955-44-7

• Cypermethrin was first conditionally registered in 1984, and zeta-cypermethrin was registered in 

1992.

• The Reregistration Eligibility Decision for cypermethrin was completed in June 2006. 

The RED and its supporting risk assessments are available in docket EPA-HQ-OPP2005-0293 at www.regulations.gov.

• Cypermethrin technical registrants: Syngenta Crop Protection; FMC Corporation; Control 

Solutions, Inc.; United Phosphorous, Inc.; Valent Biosciences Corporation

Zeta-cypermethrin technical registrant: FMC Corporation 

• Active cypermethrin registrations as of March 2012:

o 63 Section 3 registrations

Active zeta-cypermethrin registrations as of March 2012:

o 49 Section 3 registrations

o 41 Section 24(c) registrations (Special Local Need)

• U.S. tolerances for cypermethrin range from 0.05 ppm to 14 ppm [40 CFR §180.418(a)(1)] 

and 0.05 ppm to 40ppm [40 CFR §180.418(a)(2)] for zeta-cypermethrin.

• Pesticide Re-evaluation Division (PRD) Contact: Dana L. Friedman

(friedman.dana@epa.gov)

• Registration Division (RD) Contact: Richard Gebken (gebken.richard@epa.gov)

Use and Usage Information
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For additional details, please refer to BEAD Case Level Chemical Profile for Registration 

Review: Cypermethrin (109702) and Zeta-Cypermethrin (129064), Cypermethrin Appendix A, 

Cypermethrin (109702) Screening Level Usage Analysis (SLUA), Zeta-Cypermethrin Appendix 

A, and Zeta-cypermethrin (129064) Screening Level Usage Analysis (SLUA), located in docket 

EPA-HQ-OPP-2012-0167 at www.regulations.gov.

• The cypermethrins are registered for agricultural use as a foliar application on food and 

feed crops including cotton, pecans, peanuts, broccoli and other Brassicas, and sweet 

corn. The primary agricultural pests controlled by the cypermethrins include aphids, 

armyworms, stinkbugs, leafhoopers, loopers, thrips, and cornearworms. The 

cypermethrins can also be applied to livestock in eartags, and to horses. 

• The cypermethrins are also registered for use on industrial, commercial, and residential 

sites. It is registered for outdoor use as a soil residual termiticide and to control insect 

pests such as ants in and on structures, impervious surfaces (in perimeter and crack and 

crevice treatments) and lawns. 

Cypermethrin can be applied indoors to control ants, cockroaches, fleas, and other 

insects.

• Cypermethrin is formulated as a pressurized liquid, wettable powder, emulsifiable

concentrate and ready-to-use solution. Zeta-cypermethrin is formulated in many granular 

forms, as emulsifiable, flowable and soluble concentrates, and ready-to-use solution. 

They are compatible with a number of insecticides and fungicides, and have been 

formulated in products with two or more active ingredients. 

• Applications to agricultural crops can be made with aircraft, chemigation, groundboom, 

and air blast equipment. Applications at industrial, commercial, and residential sites can 

be made using handheld equipment such as low-pressure handwand sprayers, backpack 

sprayers, hose-end sprayers, handgun sprayers, paintbrushes, and termiticide injectors, in 

addition to ready-to-use (RTU) aerosol cans, indoor foggers, pump-trigger sprayers, 

impregnated wipes and eartags.

• Based on private market pesticide usage data from 1998-2010, agricultural usage for 

cypermethrin averaged approximately 100,000 pounds active ingredient for 1.6 million 

acres treated. Agricultural usage for zeta-cypermethrin averaged approximately 90,000 

pounds a.i. for 3.7 million acres. In terms of non-agricultural usage, generally, over the 

reported years (2000 through 2008), the majority of cypermethrin use was by pest control 

operators, using more than 500,000 pounds a.i. in 2000, and more than 400,000 pounds 

a.i. in 2003.

Recent and Pending Actions
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• Product mitigation specified in the 2006 Cypermethrin RED is still being implemented, 

as such, not all cypermethrin labels reflect the most up-to-date label language.

• The Agency issued the pyrethrins/pyrethroid cumulative risk assessment in November 

2011. Because there is sufficient room in the pyrethroid cumulative risk cup to support 

consideration of new uses, EPA is finalizing the evaluation of pending pyrethroid 

registration actions and new requests for registration, including the cypermethrins. 

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 the cypermethrins. Please refer to the 

Problem Formulation for the Environmental Fate and Ecological Risk, Endangered Species, and 

Drinking Water Assessments in Support of the Registration Review of Racemic Cypermethrin 

and Zeta-Cypermethrin, March 1, 2012, located in docket EPA-HQ-OPP-2012-0167 at 

www.regulations.gov, for a detailed discussion.

• The most recent comprehensive ecological risk assessment for cypermthrins is contained 

in the “Revised EFED Risk Assessment for the Reregistration Eligibility Decision (RED)

on Cypermethrin After 30-Day “Error Only” Comment Period,” dated October 25, 2005.

• In addition to the RED, there have been multiple Section 3 New Use Risk Assessments 

completed for zeta-cypermethrin. Risks identified in these assessments were similar to 

those identified in the RED. 

Ecological Effects:

• Based upon toxicity data and other information, acute and chronic risk estimates did not 

exceed the level of concern (LOC) for listed or non-listed mammalian and avian species, 

except for small birds and mammals feeding primarily on short grass (cotton use only).

• The review indicated acute risk concerns to fish and aquatic invertebrates (freshwater and 

estuarine/ marine). LOCs were exceeded for freshwater and estuarine/marine 

invertebrates and freshwater fish, depending on the crop scenario. The chronic LOC was 

not exceeded for marine/estuarine fish.

• On an acute basis, cypermthrins are highly toxic to honey bees.

Human Health Risk Assessment Status
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The following are key findings from the most recent human health risk assessments conducted 

for the registered uses of the cypermethrins. Please refer to Cypermethrin and ZetaCypermethrin. Human Health Assessment Scoping Document in Support of Registration Review, 

located in docket EPA-HQ-OPP-2012-0167 at www.regulations.gov, for a detailed discussion of 

the human health risk assessment status.

• The most recent comprehensive human health risk assessment was conducted in support 

of the 2006 Cypermethrin Reregistration Eligibility Decision (RED) and is dated April 6, 

2005. In addition, a 2007 assessment was conducted for the use of zeta-cypermethrin on 

citrus, oilseeds, safflower, wild rice and okra.

Human Studies:

• Past cypermethrins 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), the Agricultural Reentry Task Force (ARTF) Database, the 

Agricultural Handlers Exposure Task Force (AHETF), 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 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.

Hazard Characterization:

• As with the other pyrethroids, the cypermethrins cause neurotoxicity in insects and 

mammals by the modulation of nerve axon sodium channels. Pyrethroids interfere with 

the ability of the nervous system to relay nerve transmissions, and in mammals, can cause 

tremors, convulsions, salivation, and other clinical effects. 

• Cypermethrin has been classified as a possible human carcinogen, based on an increased 

incidence of lung adenomas and combined adenomas and carcinomas in female mice. 

However, the chronic toxicity endpoints selected for risk assessment are considered 

protective of any cancer risks. 

• In the most recent human health risk assessment for the cypermethrins, points-ofdeparture (PODs) for oral and inhalation exposure are based on both neurotoxic and 
18

systemic endpoints. Dermal risks were only assessed for children, by extrapolation from 

an oral study. 

• During phase 3 of reregistration, an FQPA safety factor of 10x was retained due to 

uncertainty regarding the susceptibility of cypermethrin to children. The developmental 

neurotoxicity study was submitted and reviewed during reregistration, and since there 

were adequate developmental toxicity studies in rats and rabbits, an adequate twogeneration reproduction study in rats, and no residual uncertainties that indicate the need 

for retaining an additional factor, the FQPA safety factor was reduced to 1X. 

Summary of Risks:

Dietary

• The dietary assessment (food and water) did not indicate risk estimates of concern.

Residential 

• Adult residential homeowners may experience dermal and inhalation exposure to 

cypermethrin and zeta-cypermethrin during application of the chemical. Adults and 

children may experience dermal, inhalation, and incidental oral (children only) exposure

to both active ingredients from contacting treated areas.

• Residential inhalation risks were below EPA’s level of concern (i.e., MOE > 100) for all 

non-occupational handler scenarios. Post-application inhalation risks to both adults and 

toddlers were below the Agency’s level of concern (i.e., MOE > 100). Risks from shortterm incidental oral exposures were also below EPA’s level of concern for all indoor and 

outdoor scenarios.

Aggregate

• The most recent risk assessment included aggregate assessments for combined 

cypermethrin and zeta-cypermethrin exposures and it considered exposure from food, 

drinking water, and residential uses. Acute aggregate exposures assessments for the 

cypermethins showed no risk estimates of concern. 

• A long-term aggregate risk assessment was not conducted since long-term exposures are

not expected from residential uses of cypermethrin and zeta-cypermethrin.

Occupational
19

• Occupational handler exposures were evaluated for all registered uses of cypermethrin

and zeta-cypermethrin. There are no occupational handler risks of concern for any route 

or duration. 

• Occupational postapplication risks to agricultural workers following treatments to 

agricultural crops were not assessed, since no short- or intermediate-term dermal 

endpoints of concern were identified and long-term dermal exposures are not expected 

for tasks involving any of the registered crop use patterns.

Cumulative

• The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative 

risks of chemicals sharing a common mechanism of toxicity. The cypermethrins are a 

member of the pyrethroid/pyrethrins common mechanism group 

(http://www.regulations.gov; EPA-HQ-OPP-2008-0489-0006). The members of this 

group share the ability to interact with voltage-gated sodium channels ultimately leading 

to neurotoxicity. The cumulative risk assessment for the pyrethroids/pyrethrins was 

published on Nov. 9, 2011 and is available at http://www.regulations.gov; EPA-HQ-OPP2011-0746. No cumulative risks of concern were identified, allowing the Agency to 

consider new uses for pyrethroid actives. For information regarding EPA’s efforts to 

evaluate the risk of exposure to pyrethroids, refer to 

http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html.

Incidents

Ecological Incidents:

• The Agency reviewed the Ecological Incident Information System (EIIS), which is 

maintained by the EPA Office of Pesticide Programs (OPP), and the Avian Monitoring 

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

incident reports associated with the use of the cypermethrins in the U.S. 

• The EIIS database contained 22 major incidents involving the cypermethrins. The reports 

included 15 fish incidents, 2 avian incidents, 3 mammalian incidents, and 2 terrestrial 

invertebrate incidents. With respect to the likelihood that the cypermethrins caused the 

reported incidents, the certainty ranged from unlikely to highly probable. Four of the 

incidents resulted from registered uses, seven were misuses and the remaining use

patterns are unknown. The AIMS database contains 2 avian incidents involving the 

cypermethrins, both of which are included in the EIIS database.
20

• For the cypermethrins, the registrants have reported 21 minor fish and wildlife incidents, 

4 minor plant incidents, and 1 “other-non-target” incident. All reported incidents 

occurred between 1995 and 2010 and involved currently registered products.

Human Health Incidents:

• The Agency reviewed the OPP Incident Data System (IDS) for human health pesticide 

incident data associated with the active ingredient cypermethrin in the U.S. to identify 

potential patterns on the frequency and severity of health effects attributed to 

cypermethrin exposure. The IDS aggregate summaries from January 1, 2006 to 

November 2, 2011 include 4,285 minor, unknown, or no effects outcomes reported for 

cypermethrin (67 of the exposures are classified as an unknown/no effects outcome, 

4,218 of the exposures are classified as resulting in a minor outcome). For the Main IDS,

from January 1, 2006 to November 2, 2011, there were 280 exposures reported for single 

chemical only in the database, and 304 additional exposures that involved more than one 

chemical.

• In Aggregate IDS, from January 1, 2006 to November 2, 2011, there are 57 incidents 

involving zeta-cypermethrin. In the main IDS, from January 1, 2006 to November 2, 

2011, there are 11 incidents reported for the single chemical only, and 10 additional zetacypermethrin exposures that involved more than one chemical.

• In general, a relatively high frequency of incidents was reported involving cypermethrin. 

Although most of these incidents were of low severity, it appears exposures to 

cypermethrin have the potential to result in high severity outcomes. Consequently, based 

on the frequency of exposures and the potential for exposures to result in high severity 

outcomes, these incident data warrant further analysis in the preliminary risk assessment 

phase of this registration review.

Tolerances and International Harmonization

• U.S. tolerances for the cypermethrins are located at 40 CFR §180.418(a)(1) and for zetacypermethrin at 40 CFR §180.418(a)(2).

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

CODEX Maximum Residue Limits (MRLs) for the cypermethrins is included in the

Cypermethrin and Zeta Cypermethrin. Human Health Risk Scoping Document in 

Support of Registration Review ̧ dated March 1, 2012, available in docket EPA-HQ-OPP2012-0167 at www.regulations.gov. 
21

• Codex has established MRLs for cypermethrin. For both cypermethrin and zetacypermethrin, Mexico adopts U.S. tolerances and/or Codex MRLs for its export 

purposes. Canada has established MRLs for cypermethrin only. During registration 

review, the Agency will harmonize the U.S. tolerances with the Codex MRLs to the 

extent possible.

Data Call-Ins

• The following data were required as part of the January 2010 DCI for cypermethrin 

(GDCI-109702-28852). To date, EPA has not received studies to satisfy the following 

requirements:

o GLN 835.6100 Terrestrial field dissipation

o GLN 835.6200 Aquatic field dissipation

Labels

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

Label System (PPLS) website: http://oaspub.epa.gov/pestlabl/ppls.home.
22

III. SUMMARY OF DATA GAPS

A summary of the anticipated data needs for cypermethrin registration review is presented in 

Table 2.

Table 2. Summary of Anticipated Data Needs for the Cypermethrins

Guideline Number Anticipated Data Requirement Test 

Material8

Estimated 

Timeframe

(Measured 

in Months 

from DCI 

Receipt)

835.4100 Aerobic Soil Metabolism TGAI 24

835.4300 Aerobic Aquatic Metabolism TGAI 24

835.4400 Anaerobic Aquatic Metabolism TGAI 24

835.6100 Terrestrial Field Dissipation TGAI 24

835.6200 Aquatic Field Dissipation TGAI 24

850.1020 Acute Freshwater Invertebrate Toxicity (Hyalella azteca) –

water column

TEP 12

850.1075 Fish Acute Toxicity Test (Freshwater) TEP 12

Non-GDLN

[850.1760 (in prep)]

Whole Sediment Invertebrate Toxicity, freshwater (Hyalella 

azteca)

TGAI

12

Non-GDLN

[850.1770 (in prep)]

Whole Sediment Chronic Invertabrate Toxicity, freshwater 

(Chironomus dilutus)

TGAI

12

Non-GDLN

[850.1780 (in prep)]

Whole Sediment Chronic Invertabrate Toxicity, 

marine/estuarine (Leptocheirus plumulosus)

TGAI

12

850.2100 Acute Avian Oral, Passerine TGAI 12

850.2300 Avian Reproduction TGAI 24

850.4150 Seedling Emergence, Tier II TEP 12

850.4250 Vegetative Vigor, Tier II TEP 12

850.4400 Aquatic Plant Growth (aquatic vascular plant toxicity), Tier 

II

TEP or 

TGAI

12

850.5400 Aquatic Plant Growth (algal plant toxicity), Tier II TEP or 

TGAI

12

Non-GDLN Study of fate in Publicly-Owned Treatment Works (POTW) TGAI 24

 8 Since both cypermethrin and zeta-cypermethrin have similar toxicological profiles, either compound may be used 

to address the data gaps.