Docket Number: EPA

- HQ

- OPP

- 2 0 1 1

- 0039 www.regulations.gov



## Permethrin S ummary Document Registration Review : Initial Docket June 20 1 13 

### TABLE OF CONTENTS

Page

I. Preliminary Work Plan (PWP) 4

II. Fact Sheet 1 3

III. Summary of Data Gaps 2 2

________________________________________
Please Note

This Preliminary Work Plan and Fact Sheet summarize the Environmental Protection Agency's c urrent position bas ed on the following documents:

1. Registration Review

– Preliminary Problem Formulation for the Environmental Fate, Ecological Risk, and Endangered Species and Drinking W ater Assessments for Permethrin

, June 20 , 2011.

2. Permethrin : Registrat ion Review Scoping Document for Human Health Assessments

. June 1 5 , 2011.

3. Permethrin : R eview of Human Incidents

. March 1, 2011.

4. Permethrin Screening Level Usage Analysis (SLUA)

, August 24, 2010.

5. BEAD Chemical Profile for R egistration Review: Permethrin

. May 11, 2011.

6. Appendix A: Food/Feed & Non

- Food/Non

- Feed Uses Considered in Registration Review Work Planning, September 29, 2010.

Additional sup porting documents for permethrin may be found in the registration review docket EPA

- HQ

- OPP

- 2011

- 0039 located on the internet at www.regulations.gov

.4 I. PRELIMINARY WORK PLAN

– Permethrin

Introduction:

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program

. All pesticides sold or distri buted in the United States generally must be registered by the E nvironmental P rotection A gency (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 directe d
on p roduct 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 effect s to human health or the environment

. Changes in science, public policy, and pesticide use practices will occur over time. Through the r egistration review program, the Agency periodically reevaluates pesticides to make sure that as change occurs, product s 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, Fungic ide, 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 pub lic 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 permeth rin

.

Permethrin is a broad spectrum, non

- systemic, synthetic pyrethroid insecticide that targets adults and larvae of many diverse species of biting, chewing, scaling, soil, and flying invertebrates

. Permethrin is registered for use on numerous food/feed crops, livestock and livestock housing, modes of transportation, structures, buildings, Public Health Mosquito abatement programs, numerous indoor and outdoor residential spaces, pets, and clothing. It is also regulated by the F ood and D rug A dministratio n (FDA) as a pediculicide for the treatment of head lice and scabies. Permethrin was first registered on February 25 , 19 79 and

, therefore

, was subject to the reregistration requirements of FIFRA. A Reregistration Eligibility Decision (RED) was completed in April 2006. As a result of the Agency’s review of public comments, t he 2006 RED was amended in December 2007 to reflect changes to certain mitigation measures

. The Agency conducted a new occupational and residential (ORE) exposure assessment in April 2009

. Subsequently the permethrin RED was revised again in May 2009 to incorporate changes to the residential and occupational mitigation measures , resulting from the revised ORE assessment. Documents related to the reregistration of p ermethrin can be f ound i n docket EPA

- OPP

- HQ

2004

- 0385 at www.regulations.gov

.5 Anticipated Risk Assessment and Data Needs:

The Agency anticipates requir ing data to conduct a comprehensive ecological risk assessment, including a n endangered species risk assessment, for all uses of permethrin

. The Agency also anticipates requir ing additional toxicity data to reevaluate the toxicological endpoints and safety / uncertainty factors. Revised human health exposure and risk assessments may be needed if new data are identified which impact exposure estimates, toxicological endpoints change, new points of departure are selected, the FQPA safety factor is revised, or other parameters are modified (e.g., changes to standard operating proced ures or default exposure assessment assumptions)

. Below is a summary of the issues relevant to the registration review of permethrin

.

E cological Risk :

**•** The most recent comprehensive national

- level ecological risk assessment for permethrin was completed i n support of the permethrin RED in April 2006.

**•** The Agency completed endangered species assessments evaluating the potential effects of permethrin on the Valley Elderberry Longhorn Beetle ( Desmocerus californicus dimorphus ) (VELB) consistent with the follo wing court orders and settlements: Center for Biological Diversity v. EPA, No. 07

- 2794 (N.D. Cal., May 20, 2007) [addressing 11 federally threatened or endangered species in the greater San Francisco Bay area], and Center for Biological Diversity v. Johnso n, et al. , No. 02

- 1580 (N.D. Cal., October 20, 2006) [addressing the California red

- legged frog (CRLF)]. The Agency will consider any prudent measures or risk assessment considerations that may be included in the U.S. Fish and Wildlife Service’s future re sponses to the Agency’s requests for consultation on the CRLF.

**•** The Agency has not conducted a risk assessment that supports a complete endangered species determination for permethrin

. The ecological risk assessment planned during registration review will allow the Agency to determine whether permethrin ’ s use has “no effect” or “may affect” federally listed threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use “may affe ct” a listed species or its designated critical habitat, the Agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Service (the Services), as appropriate.

**•** 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 Services regard ing the effects of over 350 pesticides, including permethrin, on over 200 endangered and threatened species throughout the United States (Center for Biological Diversity, et al. v. EPA, et al., No. C 11

- 00293 (N.D.Cal.).

**•** The Agency anticipates requiring t he following data for permethrin in order to conduct a complete ecological risk assessment, including an endangered species assessment :6 **•** GDLN 835.1230

– Adso r p tion/Desorption

**•** GDLN 835.2240

– Photodegradation in Water

**•** GDLN 835.4100

– Aerobic Soil Metabolism (three additional soils)

**•** GDLN 835.4200

– Anaerobic Soil Metabolism (three additional soils)

**•** GDLN 835.4300

– Aerobic Aquatic Metabolism (two additional soil systems)

**•** GDLN 835.4400

– Anaerobic Aquatic Metabolism (two additional soil systems)

**•** GDLN 835.6100

– Environmental Chemistry Analytical Methods (ECM) and Independent Laboratory Validation (ILV) for Soil

**•** GDLN 835.6200

– Environmental Chemistry Analytical Methods (ECM) and ILV for Water

**•** GDLN 850.1010

– A cute Toxicity Freshwater Invertebrates (TEP)

**•** G DLN 850.102 0

– A cute Toxicity Freshwater Invertebrates [ TEPs using co

formulated products with the highest ratio of the synergist piperonyl butoxide (PBO) to permethrin and the highest ratio of the synergist MGK

- 264 to permethrin (Hyalella azteca ) ]

**•** GDLN 850.10 25

– Acute Toxicity Estuarine/Marine Organisms ( oyster shell deposition)

**•** GDLN 850.1075

– Acute F reshwater Fish Toxicity (TEPs using co

formulated products with the highest ratio of the synergist PBO to permethrin and the highest ratio of the synergist MGK

- 264 to permethrin )

**•** GDLN 850.1350

– Aquatic Invertebrate Life

- Cycle Toxicity Test (saltwater)

**•** GDLN 850.2100

– Avian Oral Toxicity Test ( p asserine species)

**•** GDLN 850.4100

– Seedling Emergence , Tier II

**•** GDLN 850. 4150

– Vegetative Vigor , Tier II

**•** GDLN 850.4400

– Aquatic Plant Growth, ( vascular plants ) (Tier II)

**•** GDLN 850.5400

– Aquatic Plant Growth ( algal plants ) ( Tier II )

**•** NON

- GDLN

– ( Special Study ) Leachability from Treated Wood

**•** NON

- GDLN

– (Special Study) P ublicall y Owned Treatment Works (P OTW ) Treatability St udy

o 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. These data would be used to inform removal percentages by waste water treatment, which is an input to the Exposure and Fate Assessment Screening Tool (E

- FAST) down

- the

drain model.

**•** NON

- GDLN

– ( Special Study) Test Method 100.4: Hyalella azteca 42

- d Test for Measuring the E ffects of Sediment

- associated Contaminants on Survival, Growth, and Reproduction in USEPA 2000 Methods for Measuring the Toxicity and Bioaccumulation of Sediment

- associated Contaminants with Freshwater Invertebrates EPA 600/R

- 99/064

**•** NON

- GDLN

– (Special St udy) Test Method 100.5: Life

- cycle Test for Measuring the Effects of Sediment

- associated Contaminants on Chironomus7 dilutus (formerly known as C. tentans) in USEPA 2000 Methods for Measuring the Toxicity and Bioaccumulation of Sediment

- associated Contamina nts with Freshwater Invertebrates EPA 6001R

- 99/064

**•** NON

- GDLN

– (Special Study) Leptocheirus plumulosus in USEPA 2001 Method for Assessing the Chronic Toxicity of Marine and Estuarine Sediment

- associated Contaminants with the Amphipod Leptocheirus plumulosu s EPA 600/R

- 01/020

**•** Please refer t o Environmental Fate and Ecological Risk Assessment Preliminary Problem Formulation in Support of Registration Review of Permethrin

, June 20 , 2011

, located in the docket

, for a detailed discussion of the anticipated risk a ssessment and data needs.

Human Health Risk :

**•** The most recent comprehensive human health risk assessment for permethrin w as compl eted in February 2006 in support of the reregistration of permethrin. The occupational and residential risk assessment for pe rmethrin was updated in April 2009 in support of the 2009 Revised Permethrin RED.

**•** Permethrin is a member of the pyrethroid class of insecticides. This class also includes cypermethrin, cyfluthrin, tau

- fluvalinate, bifenthrin, fenpropathrin, and lambda

cy halothrin, 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=09000064809a6 2df ). This document was supported by the FIFRA Scientific Ad visory Panel (SAP) and is available in the docket ( http://www.regulations.gov/search/Regs/home.html#documentDetail?R=0900006480a1f 8d7 ). EPA will finalize t he 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 Resea rch 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 pharmacokine tic models for several pyrethroids. The status of both of these research modeling efforts was reviewed by the FIFRA SAP in July, 2010 and meeting materials are available in the docket ( http://www.regulations.gov/search/Regs/home.html#docketDetail?R=EPA

- HQ

- OPP

2010

- 0378 http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids

- pyrethrins.html. ). For information regarding EPA’s efforts to evaluate the risk to pyrethroids,

see

**•** The Agency anticipates requiring the following data for permethrin in order to re

evaluate toxicological endpoints and update the human health toxicity profile :

**•** GDLN 870.7800

– Immunotoxicity8 **•** After the immunotoxicity study that is expected to be requir ed is submitted and reviewed, EPA will re

- evaluate endpoints and safety/uncert ainty factors for permethrin.

**•** The uncertainty factor is currently 100X (1 X FQP A safety factor, 10X for inter

- species variation

, 10X for intra

- speci es variation). However, th e FQP A safety factor will be re

evaluated for permethrin following a f in al determination of the potential for increased susceptibility of infants and children to pyrethroid pesticides based on the review of all available data

.

**•** D uring registration review, the Agency may revise the dietary risk assessment if drinking water concentrations

, food residues, points of departure, or uncertainty factors are revised. Should review of the USDA Pesticide Data Program (PDP) and percent crop treated information show th at exposure may be increasing, revised anticipated residues may need to be generated and incorporated into acute and chronic dietary risk
assessments.

**•** The residential and occupational exposure databases are adequate ; and t herefore, the Agency does not ant icipate at this time that further residential and occupational exposure data will be needed in support of registration review.

**•** There are various indoor and outdoor uses of pe r methrin that could result in residential handler and post

- application (adult s and children) exposure. A n updated residential
exposure risk assessment may be required under registration review based upon revisio ns to the Agency ’ s Residential Standard Operating Procedures (SOPs)

, and if new data are identified which impact exposure estimates, new points of departure are selected

, the FQPA safety factor is revised , or revisions to exposure policies and procedures a re made. Furthermore, based upon the final determination for permethrin uncertainty factors, the residential assessment of permethrin will be reviewed to ensure that exposure/risk estimates do not exceed levels of concern

.

**•** During registration review, t he Agency anticipates updating the aggregate assessment if dietary or residential exposure estimates are updated, and if new data are identified which impact the permethrin points of departure, the FQPA safety factor, or if revisions are made to any exposu re and/or risk assessment policies and procedures.

**•** EPA expects to reevaluate all occupational dermal and inhalation exposure assessmen t s using standards and policies that are in place at the time of registration review. Revised

occ u pational handler and postapplication assessments may be needed if toxicological endpoints change, o t her new data are received, or other parameters are modified, such as changes to d efault exposure assessment assumptions.

**•** The permethrin tolerance expression in 40 CFR §180.378 will be reviewed during registration review to ensure that it appropriately covers the metabolites and degradates of perm e thrin and that it specifies the residues to be measured for each commodity. The Agency anticipates updating the current tolerance ex pression to reflect current EPA9 policies. Any permethrin toleran c es reassessed during the registration review process will be considered for pos si ble harmonization with international maximum residue limits (MRLs) should they be established.

**•** Permethrin i s among several agricultural chemicals included in the Agricultural Health Study (AHS). The AHS began in 1993 and is a collaboration of the National Institute of Environmental Health Sci ences (NIEHS), the National Cancer Institute (NCI), the EPA, and the National Institute for Occupational Safety and Health (NIOSH). Designed as a large long

- term epidemiological study, the AHS collects and analyzes data on the health and work practices of nearly 90,000 farmers and their families in Iowa and North Carolina who enrolled in the study before any disease developed. The study focuses particularly on farmers' exposure to 50 chemicals including many of the most widely used pesticides. As data are collected over a period of years, scientists can compare overall he alth outcomes for people who differ in whether they have had exposure to various chemicals. While these comparisons cannot conclusively demonstrate how exposure affects health, they can show some statistical associations. More information on the AHS can be found at: http://aghealth.nci.nih.gov . EPA is monitoring the results of the AHS and will consider this study in the registration review of permethrin as appropriate.

**•** P lease refer to Permethrin : Registration Review Scoping Document for Human Health

, June 1 5

, 2011

, located in the docket, for a detailed discussion of the anticipated risk assessment and data needs

. Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studi es 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 t oxicity. 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 se x 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 reregistration decision , EPA reviewed these d ata and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), permethrin is subject to the endocrine screening part of the Endocrine Disruptor Screenin g 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 suc h 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 in teract 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 to10 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 a nd 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 ing redients and 9 inert ingredients. Permethrin was included on that list and has been issued an order to conduct the Tier 1 testing. Once all required Tier 1 and Tier 2 data have been received and reviewed, the endpoints and safety factors used for risk as sessment purposes will be examined and a new risk assessment performed if
necessary. 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 batte ry, please visit our website: http://www.epa.gov/endo/

.

Timeline:

EPA has created the following estimated timeline for the completion of the permethrin registration review

.
Registration Review for Permethrin

– Pr ojected Registration Review Timeline
Activities Estimated Date Opening the Docket Open Docket and Public Comment Period 2011

– June Close Public Comment 2011

– August Case Development Final Work Plan 2011

– November Issue DCI 2012

– July

– Sept. Data Submission 2014

– July

– Sept. Open Public Comment Period for Draft Risk Assessments 2016

– Jan.

– March Close Public Comment Period 2016

– April

– June Registration Review Decision Open Public Comment Period for Proposed Registration Review D ecision 2016

– July

– Sept.

Close Public C omment P eriod 2016

– Oct.

– Dec. Registration Review D ecision and Begin P ost

- D ecision F ollow

- up 2017 Total ( years ) 1 6

1 An assessment of the potential cumulative risk from the pyrethroid class of insect icides may impact this time estimate

.

Guidance for Comment e rs :

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 ti mely manner

, prior to issuing a Final Work P lan for permethrin

.11 Trade Irritants:

Through the registration review process, the Agency intends to solicit information on trad e irritants and, to the extent feasible, take steps toward facilitating irritant re solution. Growers and other stakeholders are asked to comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the nature of the concern.

Water Quality:

Permethrin is not individually identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act 1

. However, the pyrethroids as a group have been identified as a cause for impairment for three water bodies in Central Valley, California: Del Puerto Creek, Ingram Creek Site (from confluence with Hospital Creek to Highway 33 crossing) and second Ingram Creek Site (from confluence with San Joaquin River to confluence with Hospi tal Creek). At the present time, additional bodies of water are being evaluated to be included into the list of impaired bodies of water; however, they have not been finalized. 2 No Total Maximum Daily Load s (TMDL) have been developed specifically for
per methrin 3 . More information on impaired water bodies and TMDLs can be found at the Agency’s website 4

. 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 5 in order to ensure they can be used quantitatively or qualitatively in pesticide r isk assessments.

Environmental Justice:

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all people, regardless of race, color, national origin, or income, in the development, implementation, and enforcement of environmental laws, regulations, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of their location, cultural practices, or other factors, ma y have atypical, unusually high exposure to permethrin

, compared to the general population. Please comment if you are aware of any sub

- populations that may have atypical, unusually high exposure compared to the general population.

1 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

2 http://www.waterboards.ca.gov/water_issues/programs/tmdl/integrated2010.shtml

,,

http://www.swrcb.ca.gov/rwqcb5/water_issues/tmdl/impaired_wat ers_list/303d_list.shtml
3 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutan t_group_id=885&p_pollutant_group_name=PESTICIDES

4 http://www.epa.gov/owow/tmdl/
5 http://www.epa.gov/oppsrrd1/registration_revi ew/water_quality_sop.htm12 Additional Informa tion: Stakeholders are also specifically asked to provide information and data that will assist the Agency in refining its risk assessments, including any species

- specific ecological effects determinations. The Agency is interested in receiving the follow ing information:

1. confirmation on the following label information

a. sites of application b. formulations

c. application methods and equipment d. maximum application rates in units related to mass per unit area of treatment

zone

e. frequency of application, application intervals and maximum number of applications per season f. geographic limitations on use 2. use or potential use distribution (e.g., acreage and geographical distribution of relevant crops) 3. use history 4. median and 90 th

5. application timing (date of first application and application intervals) by crop

– national, state and county percentile reported use rates (lbs. a.i./acr e) from usage data

– national, state, and county

6. sub

- county crop location data 7. directly acquired county

- level usage data (not derived from state l evel data)

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

– county b. percent crop treated

– county

c. median and 90 th
d. total pounds per year

– county percentile number of applications

– county

e. the year the pesticide was last used in the county/sub

- co unty area f. the years in which the pesticide was applied in the county/sub

- county area 8. typical interval (days) 9. state or local use restrictions 10. ecological incidents (non

- target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency 11. m onitoring data, including existing or ongoing Publically Owned Treatment Works (POTWs) effluent monitoring data for the pyrethroids be submitted to the Agency 12. updated usage information on the use of permethrin in non

- agricul tural areas 13. information on the exposure and effects to pollinators from permethrin use

Next Steps:

After the 6 0

- day comment period closes, the Agency will review and respond to any comments received in a timely manner , and expects to issue a Final Work P lan for permethrin.13 II. FACT SHEET

Background Information:

**•** Permethrin re gistration review case number : 2510

.

**•** Permethrin PC code : 109701

.

**•** The first permethrin

- containing pesticide was registered in the U.S. in 19 79.

**•** A Reregistration Eligibility Decisio n (RED) for permethrin was completed in April 2006,

an Amended RED was completed in December 2007, and a Revised RED was completed in May 2009.

**•** There are approximately 650 FIFRA Section 3 registrations for permethrin, including 21 technical registrations

. There are 19 Section 24 (c) Special Local Need registrations.

**•** Technical registrants for permethrin include : FMC Corp. Agricultural Products Group ; Bayer Environmental Science ; Amvac Chemical Corporation ; Clarke Mosquito Control Products, Inc. ; Gharda Ch emicals

, Ltd .; United Phosphorus, Inc. ; Meghani Organics Limited ; LG Life Sciences, Ltd. ; and Valent Biosciences Corporation

.

**•** Tolerance s for residues of permethrin, including its metabolites and degradates, in/on a variety of food and feed crops exist unde r 40 CFR § 180. 378

.

**•** Pesticide Re

- evaluation Division (PRD) Chemical Review Manager (CRM) : Kaitlin Keller, keller.kaitlin@epa.gov

**•** Registration Division (RD) Product Manager (PM): Richard Gebken

, gebken.richard @epa.gov

Use & Usage Information: For additional details, p lease refer to Appendix A: Food/Feed & Non

- Food/Non

- Feed Uses Considered in Registration Review Work Planning

, September 29

, 2010 ; Permethrin Scree ning Level Usage Analysis (SLUA)

, August 24 , 2010 ; and BEAD Ch emical Profile for Re gistration Review: Permethrin ( PC Code: 1 09701 )

, May 11, 2011

.

**•** Permethrin is part of the pyrethroid class of pesticides. It is a broad spectrum, non

systemic, Type I synthetic pyrethroid . It is a neurotoxic insecticide with contact and stomach action, h av ing a slight repellent effect. Permethrin is registered for use on numerous food/feed crops, livestock and livestock housing, modes of transportation, structures, buildings, Public Health Mosquito abatement programs, numerous indoor and outdoor resident ial spaces, pets, and clothing. It is also regulated by the F ood and D rug A dministration (FDA) as a pediculicide for the treatment of head lice and scabies. The majority of use is on non

- agricultural outdoor sites , including mosquito abatement control. Permethrin is the most widely used mosquito adulticide in the United States. The majority of agricultural use is on corn, lettuce, and pistachios.

**•** Permethrin is the only pesticide registered to pre

- treat clothing and fabrics to repel mosquitoes, ticks, a nd other public health pests. It is also the only pesticide registered for use in conjunction with “4 Poster” deer treatment bait stations for control of ticks which vector Lyme disease.14 **•** Permethrin is formulated as emulsifiable concentrate, liquid, we ttable powder, liquid

ready to use, granules, dust, pressurized gas, pressurized liquid, and water dispersable granule (dry flowable)

.

**•** Application methods include direct spray, surface treatment, soil broadcast , spot treatment, chemigation, soil injecti on , and Ultra Low Volume (ULV) applications for mosquito control

.

**•** According to the most recent usage data, a pproximately 400,000 pounds of permethrin active ingredient (A.I.) is used per year for agricultural p urposes applied to 3 million

acres . P istachi o s, lettuce, corn, and potatoes account for the highest agricultural usage (in pounds) of permethrin . Approximately half of all agricultural usage of permethrin occurs in California

. The majority of non

- agricultural usage is by consumers for outdoor use. Consumers use approximately 1.75 million pounds A.I. for outdoor use. Pest control operators use approximately 450,000 pounds A.I. Additionally, approximately 100,000 pounds A.I. is used for mosquito abatement and 12,000 pounds A.I. is used in nurserie s/greenhouses annually.

Recent Actions:

**•** A revised occupational and residential (ORE) risk assessment was completed in April 2009 using a decreased dermal absorption factor and a new draft approach for refining indoor cancer assessments developed by the A gency

. Subsequently, a Revised RED was completed in May 2009 to incorporate changes to the ORE mitigation measures, as a result of the updated ORE assessment. Documents related to the reregistration of permethrin can be found i n the docket EPA

- OPP

- HQ

- 200 4

- 0385 at : www.regulations.gov

.

**•** Permethrin p roduct labels are currently being revised as part of product reregistration to incorporate mitigation measures specified in the 2009 Revised Permethrin RED (e.g., mand atory label language for canine spot

- on products and pre

- construction termiticide application , and revised spray drift language for agricultural products).

Ecological Risk Assessment Status :

The following are key finding s of the most recent ecological risk assessment s for permethrin

. For a detailed discussion of the ecological risk assessment status please refer to the Environmental Fate and Ecological Risk Assessment Preliminary Problem Formulation in Support of Registration Review of Permethrin

, June 20 , 2011

, located in the registration review docket EPA

- HQ

- OPP

- 2011

- 0039

.

**•** The most recent comprehensive national

- level ecological risk assessment for permethrin was completed in support of the permethrin RED in April 2006. Acute and chronic risks were i dentified for listed and non

- listed aquatic organisms (fish and water

column / sediment

- dwelling invertebrates) that exceeded the Agency’s Level of Concern (LOC). Chronic risks exceeding the Agency’s LOC were identified for mammalian15 species . Acute risk to mammalian species and acute and chronic risk to avian species di d not exceed the Agency’s LOC. Risks were not quantified for terrestrial invertebrates. The 2006 Permethrin RED specified several risk reduction measures for products labeled for wide area mosquito abatement to reduce potential freshwater and estuarine invertebrate risks of concern. Mitigation measures included reductions in single and seasonal applications rates and buffer zones for agricultural uses of permethrin.

**•** In the 2006 risk asses sment, potential risk was not quantified for terrestrial invertebrates

. However, the Agency noted that a number of studies demonstrated that applications of formulations of permethrin were likely to reduce the numbers and possibly eliminate populations of beneficial insects. It was also concluded that toxicity data were not available for terrestrial plants and the potential for risk to plants remains an uncertainty.

**•** The 2006 risk assessment also indicated that there is potential for permethrin runoff fro m residential areas, and that applications

, such as perimeter treatments in and around buildings

, could potentially result in residues being transported to adjacent aquatic areas. Additionally, residues of permethrin have been found in aquatic areas that receive runoff from suburban developments.

**•** In October 2008, the Agency conducted a listed species

- specific risk assessment to assess the potential risk of permethrin to the federally

- listed California red

- legged frog (CRLF)

, California clapper rail, Salt marsh harvest mouse, San Francisco garter snake, and Bay checkerspot butterfly. The Agency made a “ May Affect ” and “ Likely to Adversely Affect ” determination for all of the abovementioned species from the labeled uses of permethrin. This was based on the potential for direct and indirect effects due to potential decreases in aquatic and terrestrial prey items. T he Agency also determined that there is potential for modification of designated critical habitat of the CRLF from the labeled uses of permethrin

. In October 2008, the Agency transmitted the assessment to the U.S. Fish and Wildlife Service and initiated formal consultation under section 7(a)(2) of the Endangered Species Act.

**•** The most recent ecological risk assessment for permethrin was completed in September 2010 to evaluate potential direct and indirect effects of permethrin use on the threatened Valley Elderberry Longhorn Beetle (VELB). The assessment resulted in a “May Affect” and “Li kely to Adversely Affect” determination for the VELB from th e labeled uses of permethrin

. Additionally, the Agency determined that there is potential for modification of designated critical habitat of the VELB from the labeled uses of permethrin. In September 2010, the Agency transmitted the assessment to the U.S . Fish and Wildlife Service and initiated formal consultation under section 7(a)(2) of the Endangered Species Act.

Human Health Risk Assessment Status:

The following are key findings of the most recent human health risk assessments for p ermethrin

. For a detailed discussion of the human health risk assessment status, please refer to the16 Permethrin: Registration Review Scoping Document for Human Health Assessments

, June 15

, 2011, located in the registration review docket EPA

- HQ

- OPP

- 2009

- 0039

.

**•** The most rece nt comprehensive human health risk assessment for permethrin w as completed in February 2006 in support of the reregistration of permethrin. The occupational and residential risk assessment for permethrin was updated in April 2009 in support of the Revised Permethrin RED.

Hazard Characterization:

**•** Permethrin is a Type I synthetic pyrethroid. As with the other pyrethroids, permethrin causes 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, potentially resulting in tremors, convulsions, salivation, and other clinical effects.

**•** Permethrin has a low acute toxicity via the oral (Category III), dermal (Category III), and inhalation (C ategory IV) routes of exposure. Permethrin is not an eye or skin irritant and not a skin sensitizer.

**•** The Agency reduced the 10x FQPA safety factor to 1x because the toxicity database was adequate to characterize the potential for pre

- and postnatal risk for infants and children, no reproductive or developmental effects were observed in rats, and there was a lack of evidence of increased susceptibility.

**•** Permethrin is classified as “Likely to be Carcinogenic to Humans” by the oral route based on evidence of two reproducible benign tumor types (lung and liver) in the mouse, equivocal evidence of carcinogenicity in Long

- Evans rats, and supportive structural activity relationships (SAR) information. Mutagenicity studies did not demonstrate any evidence of mu tagenic potential for permethrin.

Dietary :

**•** Acute

, chronic non

- cancer, and cancer dietary (food and water) risk assessments were conducted for the general U.S. population and various population subgroups, with the major emphasis placed on the exposure est imates for infants and children. F or all supported registered commodities, the acute and chronic dietary exposure to permethrin d id not exceed the Agency’s Level of Concern ( LOC ) for the general U.S. population and vulnerable population subgroups.

Resid ential:

**•** In the 2009 risk assessment, non

- cancer (dermal and inhalation) residential handler risk estimates for all residential handler exposure scenarios were below the Agency’s target LOC. For residential handler cancer risks, several exposure scenarios for use on outdoor trees, stored lumber, and wood piles resulted in risk estimates above the Agency’s LOC

.17 However, the Agency does not believe that these exposure scenarios are feasible or likely to occur based on the frequency of application, amount of product handled, and the application met hod paired with the use patterns assessed. Therefore, these scenarios were considered not to be of concern to the Agency.

**•** For residential non

- cancer post

- application exposure scenarios, all risk estimates were bel ow the Agency’s LOC

. The Agency also conducted an adult residential post

application cancer risk assessment as part of the 2009 assessment. Three indoor scenarios resulted in 5 days or less of allowable post

- application exposure. To mitigate the identif ied risk of concern, all permethrin directed broadcast spray and spot treatment sprays on all residential indoor surfaces were voluntarily cancelled and the concentration of all indoor sprays was limited to 0.5% permethrin

.
Aggregate:

**•** Acute, short

- and i ntermediate

- term, chronic non

- cancer, and cancer aggregate risk assessments were conducted as part of the 2009 Revised RED risk assessment. A ggregate risk estimates were below the Agency’s LO C with the exception of some scenarios in the non

- cancer short

- and interme diate

- term aggregate assessment. T he combined residues of permethrin from food, drinking water, and other potential residential ex posures were assessed which resulted in risk estimates above the LOC for the combined turf/indoor carpet broadcast spray exposure to toddlers. To mitigate the identified risk of concern, all permethrin directed broadcast spray and spot treatment sprays on residential indoor surfaces were voluntarily cancelled and the concentration of all indoor sprays was limited to 0.5% permethrin

Occupational :

**•** Due to the scope of the various permethrin occupational uses (there are hundreds of registered permethrin products); the 2009 risk assessment evaluated 39 occupational handler scenarios to represent the major permethrin occ upational handler scenarios based on applic ation equipment and formulation types.

**•** The non

- cancer handler risk estimates presented in the 2009 risk assessment indicate d that all of the occupational handler scenarios resulted in risks that did not exceed th e Agency’s LOC w ith some level of personal protective equipment (PPE) was included

. The level of protective equipment varied based on the occupational handler scenario, from baseline exposure (i.e., long

- sleeve shirt, long pants, shoes and socks) followed by increasing the levels of personal protective equipment (e.g., gloves, double

- layer body protection, and respirators), and then by engineering controls (e.g., enclosed cabs and closed mixing/loading systems).

**•** For all non

- cancer postapplication exposure scenarios assessed

, risks did not exceed the Agency’s LOC.18 **•** O ccupational handler and postapplication cancer risk assessment s w ere also conducted as part of the 2009 risk assessment. The same scenarios, assumptions, and exposure data were used as in t he non

- cancer assessment . Cancer risk estimates for workers handling dusts result ed in exposures above the Agency’s LOC for multiple scenarios. However, the Agency used conservative assumptions that likely overestimate daily usage. Further, additional PP E beyond that already in place could cause additional heat related stress to the worker. Therefore, the Agency concluded that baseline PPE, chemical resistant gloves, and a respirator were protective of cancer risks for all scenarios. For most postapplic ation scenarios, cancer risk estimates did not exceed the Agency’s LOC for cancer risks at baseline exposure. While several scenarios resulted in cancer risk
est imates above the Agency’s LOC, the Agency concluded that it is unlikely that workers would be annually exposed to permethrin residues for 30 days . According to Agency data, permethrin is primarily used during the post

- harvest and dormant seasons, used in lower application rates than those assessed, or on crops with production practices that make c hronic exposure unlikely. Additionally, registrants agreed to reduce maximum application rates and number of applications per year or season to help reduce potential post

- application risks to workers.

Human Studies :

**•** Past permethrin risk assessments r ely 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 expo sure databases such as the Pesticide Handlers Exposure Database (PHED) and the Agricultural Reentry Task Force (ARTF) Database. EPA has reviewed all the studies supporting these multi

- pesticide generic exposure databases, and has found no clear and convin cing 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 o f Human Subjects of Research (40 CPR Part 26) have been satisfied, and there is no regulatory barrier to continued reliance on these studies.

Cumulative:

**•** Permethrin is a member of the pyrethroid class of insecticides. This class also includes cypermethr in, cyfluthrin, tau

- fluvalinate, bifenthrin, fenpropathrin, and lambda

cyhalothrin, among others. EPA developed a draft science policy document on the proposed common mechanism of toxicity for naturally

- occurring pyrethrins and synthetic pyrethroids (Prop osed common mechanism grouping for the pyrethrins and pyrethroids, draft, May 19, 2009; http://www.regulations.gov/search/Regs/home.html#documentDetail?R=090 00064809a6 2df ). This document was supported by the FIFRA Scientific Advisory Panel (SAP) and is available in the docket ( 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 of19 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 a ssessment. EPA ORD is also developing physiologically

- based pharmacokinetic models for several pyrethroids. The status of both of these research modeling efforts was reviewed by the FIFRA SAP in July, 2010 and meeting materials are available in the docke t ( http://www.regulations.gov/search/Regs/home.html#docketDetail?R=EPA

- HQ

- OPP

2010

- 0378 http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids

- pyrethrins.html. ). For information regarding EPA’s efforts to evaluate the risk to pyrethroids,

see

Incidents:

**•** The Office of Pesticide Programs (OPP) Incident Data System (IDS) was consulted for reports of permethrin incidents

. From January 1, 2002 to February 2011, 9

, 992 cases

were reported for permethrin. T here is no unique report that provides details about the incident s and single chemical incidents are not distinguished from multiple chemical incidents; however, a high frequency of incidents indicates there is a high potent ial for exposure and vice versa. For the Main IDS, from January 1, 2002, to February 1, 2011, 2

, 478 cases were reported that involve the active ingredient permethrin. Of these 2

, 478 cases, there are 432 cases reported for single chemical permethrin only in the database and of these there were 5 deaths and 15 human major incidents

. Most of the deaths were due to misuse or unintentional exposure to permethrin. Most of the human major incidents were exposed to the product while using it without protective clothing and were unaware of the adverse effects of permethrin. Based on the number of incidents reported for permethrin and the effects noted in the incidents, permethrin warrants further incident analysis during registration review . This further analy sis will include reviewing permethrin incident data from other sources as well as case studies and a medical literature search on human health effects of permethrin.

**•** A preliminary review was made on January 4, 2011 of the Ecological Incident Information S ystem (EII S), which is maintained by OPP ; and the Avian Monitoring Information System (AIMS), which is maintained by the American Bird Conservancy. No incidents involving permethrin were found in AIMS. EII S indicates a total of 41 reported ecological inci dents associated wi th the use of permethrin from 1994 to January 2011

. The report includes 26 aquatic animal incidents, 8 terrestrial animal incidents and 8 plant incidents (one terrestrial incident involved both plants and animals). The majority of ecol ogical incidents involving permethrin occurred in aquatic environments. Of these incidents, nine are listed as highly probable, ten as probable, and seven as possible. Twenty

- three incidents affected fish species, and the other three reports involved
cray fish. Approximately half (thirteen) of the incidents resulted from registered use of permethrin. Many of these incidents originate d with permethrin application to residences or other buildings, followed by permethrin runoff into nearby water bodies. All ecological incidents considered “minor” only need to be aggregately reported as quarterly counts of incidents by the registrant(s). For permethrin, registrants have reported 1420 minor fish and wildlife incidents, 149 minor plant incidents, and 4 other non

- target incidents.

Tolerances and International Harmonization :

**•** Tolerances are established under 40 CFR §180.378(a) for residues of the insecticide permethrin, including its metabolites and degradates, in or on a variety of food and feed crops. Complia nce with the tolerance levels specified is to be determined by measuring only permethrin [(3

- phenoxyphenyl)methyl 3

- (2,2

- dichloroethenyl)

- 2,2

- dimethylcyclopropane carboxylate], as the sum of its cis

- and trans

- isomers in or on the commodity.

**•** Both Codex and Canada have established M aximum Residue Levels (M RLs ) for permethrin. In most cases, the Codex and Canadian MRLs differ from each other as well as from the U.S. tolerance. Where possible, the Agency will work to harmonize tolerances/MRLs during regi stration review.

Data Call

- In Status :

In May 2009, a generic data call

- in ( GDCI

- 109701

- 26467 ) for permethrin was issued in support of reregistration. Product s pecific data call

- ins (PDCIs) were also issued in May 2009. The following is a summary of the status of data not yet received for GDCI

- 109701

- 26467:

**•** G D LN 875.1200

, Dermal Exposure Outdoors (ULV Cold Fogger) & G D LN 875.1400

, Inhalation Exposure Indoors (ULV Cold Fogger) : The registrant submitted waiver requests for these data requirements and the Agency is in the process of reviewing these requests.

**•** Special Stud ies : Chronic Freshwater Sediment Testing & Special Study: Chronic Estuarine/ Marine Sediment Testing : These studies are past due; f inal Agency review of the protocols was not completed un til January 2011. The registrants have recently provided dates of May 30, 2 012 and June 30, 2012 , respectively, for the anticipated submission of these studies

.

**•** The Agency has yet to receive data to fulfill the following G D LN studies required by the 200 9 GDCI. These studies are past due as of May 28, 2011. The registrants have recently provided the following new anticipated dates for the submission of these studies:

o G D LN 860.1380, Storage Stability

– September 2011

o G D LN 860.1500

, Magnitude of the Resid ue in Crop Plants ( cabbage, grass forage, leaf let tuce, tomato)

– September 2011

o GDLN 860.1500, Magnitude of the Re sidue in Crop Plants (collards)

– January 201221 L abels :

**•** Permethrin Section 3 product labels can be obtained from the Pesticide Product L abel System (PPLS) website: http://oaspub.epa.gov/pestlabl/ppls.hom22 III. SUMMARY OF DATA GAPS

– Permethrin

The table below summarizes all anticipated data needs for permethrin in Section I, of this docum ent (Preliminary Work Plan), the Registration Review

– Preliminary Problem Formulation for the Environmental Fate, Ecological Risk, and Endangered Species and Drinking Water Assessments for Permethrin

, dated June 20 , 2011 and the Permethrin: Registration Re view Scoping Document for Human Health Assessments

, dated June 1 5 , 2011.

Table 1. Anticipated Data Needs for Permethrin Registration Review

Guideline Number Anticipated Data Requirement Test Material Study Duration

835.1230 Adsorption/Desorption TGAI 1 2

835.2240 Photodegradation in Water TGAI 24

835.4100 Aerobic Soil Metabolism TGAI 24

835.4200 Anaerobic Soil Metabolism TGAI 24

835.4300 Aerobic Aquatic Metabolism TGAI 24

835.4400 Anaerobic Aquatic Metabolism TGAI 24

835.6100 Environmental Che mist ry Methods (ECM) and I ndependent Laboratory Validation (I LV ) for Soil 6 TGAI 12

835.6200 Environmental Che mistry Methods (ECM) and I ndependent Laboratory Validation ( ILV ) for Water 6 TGAI 12

850.1010 Acute Toxicity Freshwater Invertebrates TEP 24

850.10 2 0 Acute Toxicity Freshwater Invertebrates ( Hyalella azteca ) 7 ,8 TEP 24

850.1025 Acute Toxicity Estuarine/Marine Organisms ( oyster ) TEP 12

850.1075 Acute Freshwater Fish Toxicit y 7 TEP 12

850.1350 Aquatic Invertebrate Life Cycle (saltwater) TGAI 12

850. 2100 Avian Oral Toxicity (p asserine species) 8 TGAI 12

850.4100 Nontarget Area Phytotoxicity Tier II, Seedling Emergence 9 TEP 12

850.4150 Nontarget Area Phytotoxicity Tier II, Vegetative Vigor 9 TEP 12

850.4400 Nontarget Ar ea Phytotoxicity Tier II, Aquatic Plant Growth (Vascular Plants) 9 TEP 12

850.5400 Nontarget Area Phytotoxicity Tier II, Aquatic Plant Growth (Algal Plants) 9 TGAI 12

870.7800 Immunotoxicity TGAI 12

6 See footnote 7 of 40 CFR 158.1300. EPA anticipates requiring only the environmental chemistry analytical method portion of GDLNs 835.6100

– Terrestrial field dissipation and 835.6200

– Aquatic field dissipation.
7 The anticipat ed DCI will provide that TEP studies on freshwater invertebrates and fr eshwater fish are required on

co

- formulated product s containing the highest ratio of the synergist piperonyl butoxide (PBO) to permethrin and the highest ratio of the synergist MGK

- 264 to permethrin

. 8 The anticipated DCI will require a study protocol to be submitted for review and approval by the Agency prior to this study being initiated.
9 A Tier II study is expected to be required. The DCI expected to be issued will provide that a Tier I plant study may be conducted in lieu of a Tier II study with the understanding that any adverse effects observed by the Tier I study would necessitate conduct and submission of a Tier II study as well.23 Guideline Number Anticipa ted Data Requirement Test Material Study Duration

NON

- GDLN Special Study on Leachability from Treated Wood TEP 12

NON

- GDLN Publically Owned Treatment Works ( POTW ) Treatability Study TGAI 12

NON

- GDLN Test for Measuring the Effects of Sediment Associated Contaminants on Survival, Growth, and Reproduction on Hyalella azteca in USEPA 2000 Methods for Measuring the Toxicity and Bioaccumulation of Sediment

- associated Contaminants with Freshwater Invertebrates. EPA 600/R

- 99/064 TGAI

8 24

NON

- GDLN Life

- cycle Tes t for Measuring the Effects of Sediment

- associated Contaminants on Chironomus dilutus or C. tentans in USEPA 2000 Methods for Measuring the Toxicity and Bioaccumulation of Sediment

- associated Contaminants with Freshwater Invertebrates. EPA 600/R

- 99/064 TG AI

8 24

NON

- GDLN Leptocheirus plumulosus in USEPA 2001 Method for Assessing the Chronic Toxicity of Marine and Estuarine Sediment

associated Contaminants with the Amphipod Leptocheirus plumulosus. EPA 600/R

- 01/020 TGAI

8 24