Introduction

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan

(FWP) for the registration review of cyphenothrin. The Final Work Plan includes the expected 

registration review timeline. The FWP also addresses public comments received concerning the 

Preliminary Work Plan (PWP) in the Summary Document which was posted in the cyphenothrin 

registration review docket (EPA-HQ-OPP-2009-0842) and any other comments concerning the 

initial docket postings. The Summary Document provided information on what EPA knows 

about the pesticide and what additional risk analyses and data or information the Agency 

believes are needed to make a registration review decision. 

The Agency is implementing the registration review program and will review each 

registered pesticide every 15 years to determine whether it continues to meet the Federal 

Insecticide, Fungicide, and Rodenticide Act (FIFRA) standard for registration. Changes in 

science, public policy, and pesticide use practices occur over time. 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 that statutory standard. The public 

phase of registration review begins when the initial docket is opened for each case. Information 

on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/. 

Cyphenothrin is a systemic pyrethroid ester insecticide used indoors in household/ 

domestic dwellings, storage areas, pet living quarters, ships, processing plants, on horses and 

dogs; and outdoors on external doorways, window cracks and under porches. Cyphenothrin is 

registered as a liquid, squeeze-on product for insect control on dogs and horses; as a total release 

aerosol and fogger for insect control in indoor residential and commercial settings; and as an 

aerosol spray for crack and crevice spot treatments around doorways, windows and under 

porches. Target pests include spiders, ticks, fleas, beetles, ants, flies, midges, yellow jackets, 

small flying insects, cockroaches; and other pests in domestic, public health and industrial 

situations. Cyphenothrin was first registered in 1991 and therefore, it was not subject to a 

Reregistration Eligibility Decision (RED). 

Comments Received on Preliminary Work Plan

 

 On December 16, 2009, EPA opened a 60-day public comment period for the registration 

review of cyphenothrin. The Agency received comments from five parties, which included 

public interest groups, a technical advisory committee, counties and a water quality control 

board. 

 

 The County Sanitation Districts of Los Angeles County; the County of Sacramento; the 

League of California Cities, the California Association of Sanitation Agencies and the California 

Water Environment Association Technical Advisory Committee (TriTAC); and the California 

Regional Water Quality Control Board requested EPA to evaluate potential impacts from 

cyphenothrin in both Publicly Owned Treatment Works (POTW) effluent and biosolids in its 

registration review assessment. The commenters’ claim that the Agency’s down-the drain 

assessments in reregistration did not fully analyze the potential impacts to aquatic organisms 

from the indoor cyphenothrin uses. The commenters also urge the Agency to address the 

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environmental impacts of the cross media transfers of pesticides from waste water to biosolids. 

In addition, the commenters stated that acute and chronic toxicity data for freshwater and 

estuarine/marine fish and invertebrates are essential to perform an adequate down the drain 

assessment. The commenters also urged EPA to evaluate the cumulative risks to cyphenothrin 

with other pyrethroids. 

 BioSpotVictims.org commented on assumptions and application rates in the Agency’s 

human health residential exposure risk assessment. BioSpotVictims.org claimed that several of 

the Agency’s assumptions in a 2005 residential exposure assessment were deeply flawed. In 

addition, BioSpotVictims.org identified a registered cyphenothrin application rate that had not 

been previously assessed. BioSpotVictims.org also commented that the adverse incidents 

associated with cyphenothrin should be viewed as an environmental justice issue. 

 Physician’s Committee for Responsible Medicine’s (PCRM) comments strongly support 

the use of existing DNT studies for cyphenothrin. PCRM also recommends that the Agency 

request the submission of Quantitative Structure-Activity Relationship [(Q)SAR] data for 

applicable ecological or mammalian toxicology endpoints. 

 After reviewing these comments, the Agency has altered the work plan as follows: 

(1) The Agency is adding a chronic whole sediment toxicity data requirement to address soil 

metabolism uncertainties. The Agency recommends that the whole sediment studies be 

performed with the amphipod Hyalella azteca because it appears to be more sensitive to 

pyrethroids than Chironomus tentans; (2) The Agency is investigating how to modify its downthe-drain model to more accurately reflect environmental exposure from indoor pesticides. It is 

anticipated that a bench scale study (publically owned treatment works (POTW) treatability 

study (TEP)) of waste water treatment will be required to assess the percentage removed in the 

biosolids by the treatment, the amount that would degrade, and the amount that would remain in 

the waste water. This data would be used to inform removal percentages by waste water 

treatment, which is an input to the Exposure, Fate Assessment Screening Tool (E-FAST) down 

the drain model; and (3) Prior to the release of the risk assessment in 2016, the Agency is 

working with the registrant to develop data and, if needed, implement mitigation measures to 

ensure that the registered cyphenothrin products do not pose risks. These changes have not 

affected the time-line established in the PWP. Further, this document makes final the work plan 

for the cyphenothrin registration review process. 

 

 A more detailed description of the comments received and the Agency’s response to 

these comments are available in the separate response memoranda from the Agency’s 

Environmental Fate and Effects Division (EFED) and Health Effects Division (HED) located in 

the cyphenothrin registration review docket (EPA-HQ-OPP-2009-0842). 

Risk Assessment and Data Needs

The Agency anticipates conducting a comprehensive ecological risk assessment, 

including an endangered species risk assessment, for all uses of cyphenothrin. The Agency also 

anticipates reviewing toxicological studies that are anticipated as being required per registration 

review and reevaluating the cyphenothrin endpoints selected for human health risk assessment as 

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necessary. An updated occupational exposure risk assessment may be necessary if toxicological 

endpoints are revised for inhalation and dermal toxicity. In addition, the Agency anticipates 

performing a quantitative residential exposure assessment for all registered uses. Additional data 

that the Agency anticipates needing to complete these assessments are included below. 

 

Ecological Risk: 

• The Agency has not previously conducted an ecological risk assessment for cyphenothrin 

because its use was considered limited to the indoors. However, Agency policy has 

changed since the last cyphenothrin registration was granted. Current Agency policy 

dictates an assessment of potential ecological pesticide exposure from washoff of treated 

pets and runoff from outdoor spot treatments. Therefore, a complete ecological risk 

assessment for all cyphenothrin uses is planned during registration review. 

• The ecological risk assessment planned during registration review will allow the Agency 

to examine whether cyphenothrin’s current 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 FWS and/or 

National Marine Fisheries Service (the Services), as appropriate. 

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

ecological risk assessment, including an endangered species assessment, for 

cyphenothrin:

o GDLN 850.1300 – Aquatic Invertebrate Life Cycle (freshwater) 

o GDLN 850.1400 – Fish Early Life-Stage (freshwater) 

o GDLN 850.1735 – Whole Sediment: Acute Freshwater Invertebrates 

o GDLN 850.2100 – Avian Acute Oral Toxicity 

o GDLN 850.2300 – Avian Reproduction 

o GDLN 850.3020 – Honeybee Acute Contact Toxicity 

o GDLN 850.4100 – Seedling Emergence 

o GDLN 850.4150 – Vegetative Vigor 

o GDLNs 850.4400 & 5400 – Aquatic Plant Growth (algal and aquatic vascular plant 

toxicity) 

o GDLN 850.1730 – Fish Accumulation Study 

o GDLN 835.2120 – Hydrolysis 

o GDLN 835.2240 – Photodegradation in Water 

o GDLN 835.4100 – Aerobic Soil Metabolism 

o GDLNs 835.1230 and 835.1240 – Leaching and Adsorption/Desorption 

o Non-GDLN – Whole Sediment: Chronic Invertebrates (freshwater) (Hyalella 

azteca) 

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o Non-GDLN – Publically Owned Treatment Works (POTW) Treatability Study 

(TEP) 

- The Agency is anticipating requiring a bench scale study of waste water 

treatment, to assess the percentage removed in the biosolids by the 

treatment, the amount that would degrade and the amount that would remain 

in the waste water. This data would be used to inform removal percentages 

by waste water treatment, which is an input to the EFAST down the drain 

model. 

• For a detailed discussion of the anticipated ecological risk assessment and data needs 

refer to the Registration Review – Preliminary Problem Formulation for Ecological Risk 

and Environmental Fate, Endangered Species, and Drinking water Assessments for 

Cyphenothrin, dated December 15, 2009; the Addendum to the Cyphenothrin Registration 

Review Problem Formulation Data Requirments, dated June 23, 2010; and the Response 

to Comments on the Registration Review – Preliminary Problem Formulation for 

Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water 

Assessments for Cyphenothrin document, dated June 10, 2010. These documents are 

available in the docket. 

Human Health Risk: 

• The most recent human health risk assessment for cyphenothrin was completed in 2006 

to support the following new use: squeeze-on spot treatment for dogs. 

• The cyphenothrin toxicity database is not complete. EPA anticipates requiring the 

following guideline studies to reevaluate toxicological endpoints for cyphenothrin: 

o GDLN 870.3250 – 90-Day Dermal Toxicity Study in Rats 

o GDLN 870.3700 – Developmental Toxicity Study in Rats 

o GDLN 870.3700 – Developmental Toxicity Study in Rabbits 

o GDLN 870.6200 – Acute Neurotoxicity Study 

o GDLN 870.6200 – Subchronic Neurotoxicity Study 

o GDLN 870.6300 – Developmental Neurotoxicity Study 

o GDLN 870.7800 – Immunotoxicity Study 

• The Agency is investigating the need for additional experimentation, specific to the mode 

of action and pharmacokinetic characteristics of pyrethroids, to evaluate the potential for 

increased susceptibility of young organisms. A meeting of the FIFRA Scientific 

Advisory Panel (SAP) is planned for July 2010. For more information on the pyrethroid 

developmental neurotoxicity (DNT) requirement, see 

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

• EPA has recently determined that, as an alternative to the generation and submission of a 

new Developmental Neurotoxicity (DNT) study, registrants may instead choose to cite 

the six previously submitted DNT studies for pyrethroid pesticides. A decision regarding 

the need for an FQPA or other database uncertainty/safety factor required to assure 

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protection of infants and children will be made following receipt of remaining required 

toxicity data, and following a final determination of the potential for increased 

susceptibility of these subpopulations to pyrethroid pesticides based on the results of all 

available data. The cyphenothrin risk assessment may need to be revised to incorporate 

these decisions. 

• Based upon the limited nature of the registered outdoor uses of cyphenothrin, the Agency 

does not anticipate conducting a drinking water assessment for cyphenothrin. 

• The Agency has no plans to conduct a dietary assessment because there are no registered 

food uses and dietary exposure is not expected. 

• The Agency is currently revising the Residential Standard Operating Procedures (SOPs) 

for treated pets and indoor settings. The Agency anticipates conducting a new 

quantitative residential exposure assessment, which incorporates the revised SOPs and all 

cyphenothrin uses. 

• The Agency does not anticipate conducting an aggregate assessment because dietary 

exposure from food and water is not expected. 

• Cyphenothrin belongs to the pyrethroid class of insecticides. This class also includes 

permethrin, cypermethrin, cyfluthrin, deltamethrin, tau-fluvalinate, and lambdacyhalothrin, among others. EPA developed a draft science policy document on the 

proposed common mechanism of toxicity for naturally-occurring pyrethrins and synthetic 

pyrethroids (Proposed common mechanism grouping for the pyrethrins and pyrethroids, 

draft, May 19, 2009 

http://www.regulations.gov/search/Regs/home.html#documentDetail?R=09000064809a62df). 

This document was supported by the FIFRA SAP and is available in the docket. See

http://www.regulations.gov/search/Regs/home.html#documentDetail?R=0900006480a1f

8d7. EPA will finalize the policy document on the pyrethroid common mechanism of 

toxicity taking into account the SAP comments. Pesticides with a common mechanism of 

toxicity are subject to cumulative risk assessment under the FQPA. Research is on-going 

by EPA’s Office of Research and Development (ORD) to make improvements to the 

Stochastic Human Exposure and Dose Simulation (SHEDS) probabilistic exposure 

model, which are important for the cumulative risk assessment. EPA ORD is also 

developing physiologically-based pharmacokinetic models for several pyrethroids. The 

status of both of these research modeling efforts will be reviewed by the FIFRA SAP in 

July, 2010. For information regarding EPA’s efforts to evaluate the risk to pyrethroids, 

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

• The Agency does not anticipate conducting an occupational health risk assessment unless 

endpoints are updated for dermal and inhalation toxicity. 

• For a detailed discussion of the anticipated human health risk assessment and data needs 

for cyphenothrin please refer to the Cyphenothrin. Human Health Assessment Scoping 

Document in Support of Registration Review, dated August 20, 2009; and the 

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Cyphenothrin. Response to Registrant Comments on the Registration Review Human 

Health Scoping Document and Preliminary Workplan, dated June 17, 2010. These 

documents are available in the cyphenothrin docket. 

Other Data Needs:

• GDLN 830.750 UV/Visible Light Absorption – this study is a new data requirement 

under 40 CFR part 158 (Product Chemistry Data Requirements) for registration of a 

pesticide (food and non-food uses). The Agency anticipates requiring this study to obtain 

basic information about the compound’s identity/composition and the wavelengths at 

which the compound may be susceptible to photochemical degradation.

Timeline

 

The Agency has created the following estimated timeline for the completion of the 

cyphenothrin registration review. 

Registration Review for Cyphenothrin 

Projected Registration Review Timeline 

Activities Estimated 

Year/Month 

Opening the Docket 

Open Docket and Public Comment Period December 2009 

Close Public Comment February 2010 

Case Development 

Issue Final Work Plan (FWP) June 2010 

Issue Data Call-in (DCI) January – March 2011 

Data Submission1 January – March 2015 

Open Public Comment Period for Preliminary Risk Assessments July – September 2016

Close Public Comment Period October - December 

2016 

Registration Review Decision 

Open Public Comment Period for Proposed Registration Review 

Decision January – March 2017 

Close Public Comment Period April - June 2017 

Final Registration Review Decision & Begin Post-Decision Followup 2017 

Total (years)2 8 

1 If the registrants choose to cite the six previously submitted DNT studies for pyrethroid pesticides, as explained above, rather 

than conducting a DNT study with cyphenothrin, this time estimate will likely be shortened by approximately two years. 

2 An assessment of potential cumulative risk from the pyrethroid class of insecticides may impact this time estimate. 

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Next Steps

As noted previously, the Agency anticipates requiring several ecological effects and 

human health studies through a Data Call-In (DCI) Notice, expected to be issued in 2011. This 

new information will be used to conduct the risk assessments outlined in this FWP for all 

cyphenothrin uses. 

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