1 Docket Number EPA

- HQ

- OPP

- 2012

- 0167 www.regulations.gov



## Cypermethrin Summary Document Registration Review: Initial Docket March 20123 TABLE OF CONTENTS

I. Preliminary Work Plan (PWP) 4

II. Fact Sheet 1 4

III. Summary of Data Gaps 2 2

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, Endangere d 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. Octob er 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

.

S upporting documents for the registration review of cypermethrin are located in docket EPA

HQ

- OPP

- 2012

- 0167 at www.regulations.gov.4 I. PRELIMINARY WORK PLAN

Introduction

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review prog ram. 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 th e 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 st andard 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 F IFRA 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 comme nt period, the Agency will develop and commit to a final work plan and schedule for the registration review of cypermethrin

. The cypermethrin case i ncludes two active ingredients: racemic cypermethrin (hereafter referred to as cypermethrin) and zeta

- cyper methrin. Cypermethrin is a combination of 8 stereoisomers and z eta

- cypermethrin is an enri ched 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 fe ed 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, comme rcial, and residential sites. They a re 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 con trol ants, cockroaches, fleas, and other insects.5 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 3 0

- Day “Error Only” C omment 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 suppor t s 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 consul t 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 Ser vice 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. The6 Agency anticipates needing the following data for use in conduct ing 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 F ate in Publicly

- Owned Treatment Works (POTW) (Special Study)

Ecological To xicity 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/Duck 1

o GLN 850.4 15 0 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

- 201 2

- 0 167 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

.7 Human Health Risk:

**•** The most recent comprehensive human health risk ass essment for cypermethrin was conducted in support of the 2006 Reregistration Eligibility Decision (RED) and is dated April 6 , 2006. Since the RED, an add itional human health assessment for the use of zeta

cypermethrin 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 zeta

cypermethrin are member s 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

- OPP

2011

- 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/pyrethroi ds

- pyrethrins.html

.

**•** Under FQPA, the Agency is required to apply a 10X S afety 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

- pharmacokinetic s 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 FQP A 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

- evalu ation of the FQPA safety factor may be conducted following a final determination of the8 potential for increased susceptibility of infants and children to pyrethroid pesticides based on the review of all available data.

**•** The Agency anticipates conducting up dated 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 re view the need for an updated drinking water exposure risk assessment during registration review.

**•** The tolerance expression s for cypermethrin in 40 CFR § 180. 418(1)(1) and zeta

cypermethrin §180. 418(a)(2) will be reviewed during registration review to ensure that they appropriately cover the respective metabolites and degradates and that they specif y the residues to be measured in each commodity.

**•** The Agency will modify tolerance levels as needed, and work to harmonize tolerances/maximum residue limits (MRL s ), 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

- HQ

OPP

- 2012

- 0167 at www.regulations.gov, for a detailed discussion of the anticipated human health risk assessment and data needs

.9 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, neurotoxici ty, 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 maturat ion, 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 cypermethrin s , 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 est rogen, 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 whic h, 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 in ert 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 submi ssion 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. Timeline10 Table 1. Projected t he Cypermethrins Registration Review Timeline 2
Activities Estimated Date Opening the D ocket 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 D ecision 2017

– April

– June Close Public C omment P eriod 2017

– July

– Sept. Registration Review D ecision and Begin P ost

- D ecision F ollow

- 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 Age ncy 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 poli cies. 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.11 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 impairm ents due to pyrethroid pesticides as a group, and t hree w ater body impairments with the pyrethroids bifenthrin, lambda cyhalothrin, esfenvalerate/fenvalera te, 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 website 3

.

N o water bodies have been designated as impaired specifically for the cypermethris, nor have any TMDLs been developed for this active ingredient 4 . More information on impaired water bodies an d TMDLs can be found at the Agency’s website 5

. The Agency invites submission of water quality data for th is pesticide. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 6 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 pyre throid pesticides, including cypermethrin

, used by pest control applicators and maintenance gardeners in urban ar eas to protect water quality . Restrictions would include : 1) prohibit ing 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 regulation s is available o n DPR’s website 7

.

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_poll utant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES
5 http://www.epa.gov/owow/tmdl/
6 http://www.epa.gov/opp srrd1/registration_review/water_quality_sop.htm
7 http://www.cdpr.ca.gov/docs/legbills/rulepkgs/11

- 004/11

- 004.htm12 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 applicati on 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. Us e history 7. Median and 90 th

8. Application timing (date of first application and application intervals) by us e

– national,
state , and county percentile reported use rates (lbs a ctive ingredient(a

. i

. ) /acre , lbs a

. i

. /1000 sq. ft.) from usage da ta

– 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 90 th

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. Typi cal application interval (days) 12. State or local use restriction s 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 data13 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

.14 II. FACT SHEET

Background Information

**•** Registration Review Case Number: 2130

**•** Pesticide Chemical (PC) Co de s : Cypermethrin: 109702; Zeta

- Cypermethrin: 120964

**•** Chemical Abstracts Service (CAS) Number s : Cypermethrin: 52315

- 07

- 8 ; Zeta

Cypermethrin: 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 RE D and its supporting risk assessments are available in docket EPA

- HQ

- OPP

2005

- 0293 at www.regulations.gov

.

**•** Cypermethrin technical registrants: Syngenta Crop Protection; FMC Corporation; Control Solutions, Inc.; United Phosphorous, Inc.; Valent Biosciences Corporation

Zeta

- cypermethrin t echnical registrant: FMC Corporation

**•** Active cypermethrin registrations as of March 2012 :

o 6 3 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 40 ppm [ 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 Information15 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 livesto ck 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 f

ormulated 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 ha ndheld 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 wip es 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 u sage for zeta

- cypermethrin averaged appro ximately 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 wa s 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 Actions16 **•** Product mitigation specified in the 2006 Cypermethrin RED is still being implemented, as such, not all cypermethrin label s 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 regist ration 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

- 201 2

- 0 167 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 E ligibility 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 exceede d for freshwater and estuarine/ marine invertebrates and freshwater fish, depending on the crop scenario. T he chronic LOC was not exceeded for marine/estuarine fish.

**•** On an acute basis, cypermth rins a re highly toxic to honey bees

.

Human Health Risk Assessment Status17 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 Zeta

Cypermethrin. Human Health Assessment Scoping Document in Support of R egistration 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 p esticide 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) Databas e.

**•** 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 rela y nerve transmissions, and in mammals, can cause tremors, convulsions, salivation, and other clinical effects.

**•** C ypermethrin 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

- of

departure (PODs) for oral and inhalation exposure are based on both neurotoxic and18 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 two

generation 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

**•** A dult residential homeowners may experience dermal and inhalation exposure to cypermethrin and zeta

- cypermethrin dur ing application of the chemical. Adults and children may experience dermal, inhalation, and incidental oral (children only) expo sure to both active ingredients from contacting tre ated areas.

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

non

- occupational handler scenarios. Post

- application i nhalation risks to both adults and toddlers were below the Agency’s level of concern (i.e., MOE > 100). R isks from short

term incidental oral exposures were also below EPA’s level of concern for all indoor and outdoor sce narios.

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 cypermeth ins showed no risk estimates of con cern.

**•** A long

- term aggregate risk assessment was not conducted since long

- term exposure s are not expected from residential uses of cypermethrin and zeta

- cypermethrin.

Occupational19 **•** 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.

**•** O ccupational 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 conside r 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

- OPP

2011

- 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:

**•** T he 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 ra nged from unlikely to highly probable. Four of the incidents resulted from registered uses, seven were misuses and the remaining use pattern s are unknown. The AIMS d atabase 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 inciden t s, 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
cyperm ethrin exposure. The IDS aggregate summaries from January 1, 2006 to November 2 , 2011 include 4,285 minor , un known, or no effects outcomes reported for cypermethr i n ( 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 , 201 1 , there we re 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 zeta

cypermethrin exposures that involved more than one chemical.

**•** In general, a relatively high frequency of incidents was reported involving cyperme thrin

. Although most of these incidents were of low severity, it appears exposures to cypermeth rin have the potential to result in high severity outcomes. Consequently, based on the frequency of exposu res 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 r egistration r eview.

Tolerances and International Harmonization

**•** U.S. tolerances for th e cypermethrins are located at 40 CFR §180. 418(a)(1) and for zeta

cypermethrin at 40 CFR §180. 418(a)(2 )

.

**•** A table listing the differences between U.S. tolerances and Canadian, Mexican, and CODEX Maximum Residue Limits (MRL s ) 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

- OPP

2012

- 0167 at www.regulations.gov.21 **•** Codex has established MRLs for cypermethrin. For both cypermethrin and zeta

cypermethrin , 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 harmoniz e the U.S. toleran ces 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 835.61 00 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 t he C ypermethrins

Guideline Number Anticipated Data Requirement Test Material 8 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.