Docket Number: EPA

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## Permethrin Final Work Plan Registration Review December 20113 PERMETHRIN FINAL WORK PLAN

Introdu ction

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan (FWP) for the registration review of permethrin

. The FWP includes the expected registration review timeline. The FWP also addresses public comments received concerni ng the Preliminary Work Plan (PWP) in the Summary Document

, which was posted i n the permethrin registration review docket ( EPA

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, and any other comments concerning the initial docket postings

. The Summary Document provided information on w hat EPA knows about this pesticide and what additional risk analyses and data or information the Agency believes are needed to make a registration review decision.

The Agency ’s implementation of the r egistration r eview program requires review of each

re gistered pesticide every 15 years to determine whether it continues to meet the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) standard for registration. Changes in science, public policy, and pesticide use practices will occur over time. Th e registration review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet that statutory standard. The public phase of registration review begins whe n the initial docket is opened for each case. Information on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/

.

Permethrin is a broad spectrum, non

- systemic, syn thetic 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 trans portation, 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 dministration (FDA) as a pediculicide for the treatment of head lic e 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 p ublic comments, the 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 aga in 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 permethrin can be found i n docket EPA

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- 0385 at www.regulations.gov4 Updates Since the Preliminary Work Plan was Issued

Changes to Data Requirements

- One study, Guideline 850.1010, acute toxicity freshwater invertebrates, was erroneously listed as a data requirement fo r permethrin in the August 2011 Permethrin Summary Document . This study was not identified as a data gap in the EFED Registration Review Preliminary Problem Formulation for Permethrin

, dated June 20, 2011 and is not required in support of registration rev iew. This change is reflected in this FWP.

Pet Spot

- On Product Label Changes

- On September 30, 2011, EPA sent letters to registrants with pet spot

- on pesticide products, informing them on how to make necessary label changes for their products. In the sp ring of 2009, EPA observed a significant increase in incident reports associated with pet spot

- on products. EPA investigated this increase, received additional information on those incidents from the pet spot

- on pesticide registrants, and conducted an int ensive evaluation of the incidents and the pe t spot

- on products themselves. Examples of label changes EPA believes may be necessary for pet products include: repeating the words “dog” and “cat” throughout the label (as appropriate), including the word “on ly” with size and breed restrictions, adding “do not allow your dog (or cat) to ingest this product,” incorporating a large, clear picture of the appropriate animal in the weight range for the product as packaged on the front panel of the label, and placin g the breed and weight restrictions on the vial itself. EPA expects registrants to submit revised labels addressing all changes described in its letter no later than six months from the receipt of the September 30, 2011 letter. For more information on EP A’s increased restrictions on pet spot

- on products, please visit: http://www.epa.gov/pesticides/health/pets.htm

Impaired Water Bodies

- O n October 11, 2011, EPA issued its final decision regard ing the waters EPA added to Ca lifornia's 2008

- 201 0 list of impaired water bodies that require total maximum daily loads (TMDLs) pursuant to Clean Water Act, section 303(d), and 40 CFR 130.7(d)(2)

. This list includes 1 1 water body impairments due to pyreth roid chemicals (including permethrin), and 3 water body impairments which list the pyrethroids bifenthrin, lambda cyhalothrin, e s fenvaler ate/fen valerate, and permethrin as pollutants

. More information on California’s additional impaired water body listing s can be found at: http://www.epa.gov/region9/water/tmdl/california.html

On October 28, 2011, the California Department of Pesticide Regulation ( DPR ) announced proposed restrictions to 17 pyrethroid pesticides , including permethrin, used by pest control applicators and maintenance gardeners in urban areas to protect water quality in urban areas. Restrictions would include reduced application rates around structures ; and to prohibit appl ications during rain, when puddles are present, and over drains or natural drainage areas. More information about the propo sed regulations are available on DPR’ s website at: h ttp://www.cdpr.ca.gov/docs/legbills/rulepkgs/11

- 004/11

- 004.htm

. National Pollutant Discharge Elimination System (NPDES) Permits

- On October 31, 2011, EPA issued a final NPDES Pesticide General Permit (PGP) for point source discharges from the application of pesticides to waters of the United States. This action was in response to a 20095 decision by the U.S. Sixth Circuit Court of Appeals ( National Cotton Council, et al. v. EPA ) in which the court vacated EPA's 2006 Final Rule on Aquatic Pesticides and fo und that point source discharges of biological pesticides, and chemical pesticides that leave a residue, into waters of the U.S. were pollutants under the Clean Water Act (CWA). The Agency’s final permit covers operators that apply pesticides that result in discharges from the following use patterns: (1) mosquito and other f lying insect pest control; (2) aquatic w eed and algae control; (3) aquatic organism pest control; and (4) forest canopy pest control. The final pesticide general permit requires permit tees to minimize pesticide discharges through the use of pest management measures, and monitor for an d report any adverse incidents. While the permit’s requirements must be met as of October 31 st

, 2011, operators are not required to submit Notices of Inte nt (NOIs) until January 12, 2012. No permit will be required for discharges from agricultural runoff or irrigation return flows, both of which are exempt from permitting under the CWA

. EPA’s pesticide general permit will cover pesticide applications in t he areas where EPA is the permitting authority, which include Massachusetts, New Hampshire, New Mexico, Idaho, Oklahoma, Alaska, Washington, D.C., most U.S. territories and Indian country lands, and many federal facilities. For more information , please vi sit : http://www.epa.gov/npdes/pesticides

. Pyrethrins & Pyrethroids Cumulative Risk Assessment

- The Food Quality Protection Act (FQPA) requires the Agency to consider the cumulative risks of chemicals shari ng a common mechanism of toxicity. Permethrin is a member of the pyrethroid/pyrethrin common mechanism group ( http://www.regulations.gov ; EPA

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- 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 ember 9, 2011 and is available at http://www .regulations.gov ; EPA

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- 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

. Comments Received on the Preliminary Work Plan

The permethrin registration review docket was open fo r a 60

- day comment period beginning on June 29, 2011 . During the public comment period

, t he Agency received eight sets of substantive comments from the California Regional Water Quality Control Board, Centra l Valley Region ; California Regional Water Quali ty Control Board, San Francisco Bay Region ; California Stormwa ter Quality Association (CASQA); Tri

- Technology Advisory Committee (Tri

- TAC ) ; Nat ional Alfalfa & Forage Alliance; Permethrin Data Group II (P DGII); McLaughlin Gormley King Company (MGK); and Bio spotvictims.org. The comments received did not change the planned risk assessment, data needs, or the timeline detailed in the permethrin PWP

. EPA also solicited comments , through the PWP, on three specific topics: environmental justice, water body impai rment, and trade irritants. No comments or information were received on environmental justice or trade irritants. However, the Agency did receive comments on listed and potential impaired water bodies in California attributed to permethrin and pyrethroid s

. This document makes final the work plan for the permethrin registration review process.6 Summary of Comments and Agency Responses

A general summary of substantive comments and the Agency’s response t o comments is provided below. Only comments on d ata requirements, the sc ope of the risk assessments, or not addressed by other response documents included in the permethrin docket, are summarized below along with an Agency response

. Due to the number of similar comments submitted, the comments have bee n combined and summarized, where appropriate.

For a detailed description of the comments received and the Agency’s response to comments please refer to Response to Public Comments on the EFED Registration Review Problem Formulation for Permethrin , dated November 18 , 2011, and Permethrin: Waiver Request for Immunotoxicity Study

, dated October 20, 2011

, which are located in the permethrin docket (EPA

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Comments on the Human Health Data Requirements

Comment 1 [PDGII] : The PDGII requested a waiver for GDLN 870.7800, immunotoxicity, because exposure to permethrin did not result in toxicity to organs involved in the immune system, such as the spleen and thymus, in chronic rat and mouse studies. Additionally, in October 2011, CropLife America (CLA) submitted a retrospective analysis of immunotoxicity studies that indicates that immunotoxicity studies do not provide additional information for risk assessment purposes.

Agency Response 1 : The Agency received CLA’s retrospective analysis of imm unotoxicity studies in October 2011. EPA is currently conducting its own retrospective analysis of the immunotoxicity studies and their impact on risk assessment

. In addition, literature searches on immunotoxicity for permethrin suggested that immune sys tem appears to be a sensitive target organ for permethrin. A guideline immunotoxicity study is needed to better characterize the effect of permethrin on the immune system. Until the Agency has completed its analysis and made its final decision, the immun otoxicity study remains a toxicity data requirement for registration review.

Comments on Ecological Data Requirements and the Scope of the Risk Assessment

Comment 1 [CA Regional Water Board CV Region, CASQA, Tri

- TAC] : Commenters indicated that permethr in pesticides result in adverse impacts to water quality and aquatic life in urban runoff and receiving waters. Regulatory entities must direct considerable resources to address water quality impairments associated with current

- use pesticides that impact water quality, in monitoring and mitigation efforts. Non

- attainment of water quality standards should be considered an unreasonable adverse effect under FIFRA, as non

- compliance with the Clean Water Act (CWA) requirements can be extremely costly for Publi cally Owned Treatment Works ( POTWs ) . Municipalities and POTWs discharging to the water bodies can be impacted through additional requirements established for National Pollutant Discharge Elimination System7 (NPDES) permits and Total Maximum Daily Loads (TM DLs) set for the water bodies by state agencies

, such as the CA State Water Resources Control Board and the associated Regional Water Quality Control Boards. It is essential that the registration review process adequately consider potential water quality impacts that can result in C WA Section 303(d) impaired waters listings and TMDLs

.
Agency Response 1 : The Agency acknowledges the cost of keeping in compliance with the CWA , and will make every effort to ensure that it adequately identifies and mitigates unreasonable adverse effects from permethrin during registration review. Additionally, the Agency determined during reregistration that use of permethrin could result in some risk to aquatic organisms in water bodies, and acknowledges that permethrin use is a contributor to many pyrethroid water body impairments. H owever, the ecological risk assessment for registration review will be nationwide in scope. The consideration of generic exposure scenarios for widespread applicability adds to the difficulty o f estimating the relative contribution of permethrin to pyrethroid impairments in individual watersheds.

Comment 2 [CA Regional Water Quality Control Board CV Region] : The 2 010 C WA §303(d) listings in Central Valley, CA contains 13 stream segments (10 i n urban sites and 3 in agricultural sites) that exceed water quality standards due to pyrethroids in the sediments that are toxic to Hyalella azteca . This list was recently partially approved by the Agency and will be approved “shortly” following the reso lution of unrelated additional listings. Permethrin has been implicated as a contributor to the toxicity observed. While all the pyrethroid

- impaired bodies of water are in Sacramento, open literature articles document the presence of pyrethroids througho ut CA.

Agency Response 2 : As indicated in the “Updates Since the Preliminary Work Plan” section of this document, EPA has confirmed that the §303(d) listings were partial ly agreed upon with the Agency . The Agency’s Region IX sought public comments and a final decision w as issued October 11, 2011. Information on 303(d) listings will be included in the r egistration review ecological risk assessment.

Comment 3 [CA Regional Water Board CV Region, CA Regional Water Board SF Bay Regio n, CASQA, Biospotvictim s.org] : Commenters provided various studies relevant to permethrin and pyrethroids for consideration prior to risk assessment development.

Agency Response 3 : The Agency appreciates the submission of these studies and reports

, and will consider relevant i nformation from these articles and other open literature studies while developing its registration review risk assessments for permethrin.

Comment 4 [CA Regional Water Board CV Region] : The CA Regional Water Board, CV Region, submitted sediment monitoring data tables for urban creek sediment sampled in t he East Bay, CA; Sacremento, CA; and Nashville, TN.8 Agency Response 4 : The Agency appreciates the submission of these data tables. Th is information will be considered at the time of the r egistration r evie w risk assessment for permethrin

.

Comment 5 [CA Regional Water Board SF Bay Region, CASQA] : Commenters encouraged the EPA to develop a set of urban scenarios that better represents realistic urban pesticide use and runoff conditions

. Specific suggestion s included changes to the current urban impervious surface scenario, which uses a 1⁄4

- acre residential lot scenario that does not adequately represent the current urban environment of various lot sizes ; incorporating urban land use applications and applicat ions directly to impervious surfaces into the conceptual model ; and accounting for appropriate wash

- off fractions from impervious surfaces compared to landscaped (pervious) surfaces. The commenters also suggested EPA account for the distinct physical char acteristics of urban storm drainage conveyance systems, which rapidly convey water and pollutants to receiving waters.

Comment 6 [PDGII] : While usage data indicate considerable home and garden use, it should be noted that this use is typically spread out more than in agricultural areas

, because only some homeowners will use a particular product and only on limited parts of their property. Thus

, any off

- site exposure would be much more limited than in agricultural areas. Use on lawns and landscaping plant s would result in permethrin being adsorbed to plant materials, rather than to soils as in cropland areas, and thus less available to runoff on soil particulate matter. Labels limit applications to impervious surfaces to crack and crevice applications, an d prohibit use in sewers or sewer drains.

Agency Response 5 & 6 : The justification for t he use of a 1⁄4

- acre residential lot is based on a past American Housing Survey (AHS), dated 2006 (updated 2009) from the Census Bureau http://www.census.gov/housing/ahs/data/index.html

. Overall, the median lot size was 0.26 acre. The vast majority of the houses were one unit structures, with 95,216,000 units (73%). This analysis suggests that the 1⁄4

- acre l ot is a reasonable approximation of suburban pesticide use. Additionally, as part of the Permethrin RED, various uses of permethrin on impervious surfaces were prohibited or restricted.

The Problem Formulation shows applications over impervious surface s in its conceptual model (not just soil or pervious surfaces). Modeling will include currently published categories of impervious areas in different urban areas of the country (based on National Land Cover Data (NL CD) in order to establish a range of Est imated Environmental Concentrations ( EECs ) from highly dense residential areas with high ratio of impervious to pervious surfaces to low density residential areas with low ratio of impervious to pervious surface). For direct applications over impervious s urfaces, the portion of the pesticide “available for run off” is directly related to wash off factors established for various types of impervious surfaces ( e.g. , asphalt, concrete and others). The fraction of the rate (percent or %) used for impervious su rface modeling will be equal to that expected to be washed off from the type of impervious surfaces. At the present time, the Agency is reviewing a wash

- off study for cypermethrin submitted by the Pyrethroid Working G roup (PWG, MRID 48072902). A nother st udy that included 17 pyrethroid products,9 including permethrin formulations

, will be submitted by the PWG in the near future. Both studies may be used to characterize the wash

- off potential from impervious surfaces.

Comment 7 [CA Regional Water Board, S F Bay Region, CASQA, Tri

- TAC] : Commenters stated that the Office of Pesticide Programs and Office of Water (OPP/OW) common effects assessment methodology will be available in time to use for this risk assessment and requested that the work plan be modified to indicate OPP’s intent to work with OW and to utilize the outcomes of the common effects assessment methodology project in permethrin registration review. Commenters further stated that they support the use of this updated methodology, and that it is i mportant that exposure periods and exposure frequencies used in ecological effects assessments include time periods consistent with those used by OW in addition to the time periods ordinarily used by OPP.

Agency Response 7 : At this time, the OPP/OW common effects methodology framework is under development and a time

- line to include an integrated methodology in OPP's risk assessment process has not been established. The focus of the OPP/OW common effects methodology project has been on characterizing effec ts of s tressors on aquatic organisms. A Scientific Advisory Panel (SAP) on the common effects methodology will be held January 31 , 2012

– February 2, 2012. EPA appreciates comments about the consideration of duration of exposure and will consider this co mment in the continued development of the common effects methodology.

Comment 8 [CASQA] : CASQA encouraged EPA to pursue development of a protocol for quantitative assessment of cumulative impacts of pesticide mixtures, as this appears to be a significant factor contributing to the observed toxicity in urban creeks.

Agency Response 8 : The Agency believes that conducting a prospective ( i.e. , predictive) ecological risk assessment of pesticide mixtures would require a substantial amount of information regard ing the temporal and spatial extent of pesticide usage within a watershed, which is currently lacking. This information is needed to accurately predict (or screen) pesticide concentrations in a water body because different pesticides will be applied at di fferent times and locations within any given watershed. In addition, a watershed

- based model would also need to be developed and reviewed for this particular application in order to capture the temporal and spatial dynamics of multiple pesticide uses and applications. The Agency believes that available monitoring data for pyrethroids do offer some potential to evaluate cumulative ecological risk in a retrospective manner. The Agency will consider monitoring data of pyrethroid mixtures, such
as concentrat ions in sediments, in the context of their potential to provide insight into ecological risks of pyrethroid mixtures

, to the extent that simplified assumptions regarding their combined toxicity (additivity) are scientifically supported.

Comment 9 [Tri

- T AC] : Permethrin from products for pets, for the treatment of fabrics and for head lice treatment can reach POTWs. Based upon these uses, it appears that the fate of permethrin is likely in water and solid emissions ( i.e. , biosolids) from POTWs. Effluent from the POTW will typically be discharged into creeks, rivers, estuaries, or the ocean. The receiving10 bodies of water may have little flow ( i.e. , “effluent dominated” waters). Recycled wastewater has growing use for irrigation, toilet flushing, industri al use, and groundwater recharge. Biosolids may be reused in agriculture or in urban gardens or disposed of in landfills. Roughly fifty percent of the total cost of wastewater treatment is expended on solids handling. Since pyrethroids adsorb strongly t o organic matter, a portion of permethrin entering POTWs will likely partition into biosolids. The analysis of this partitioning has largely been missing from prior studies.

Agency Response 9 : EPA ’s Office of Pesticide Programs is conferring with the O ffice of Pollution Prevention and Toxics, the developer of the E

- FAST “down

- the

- drain” (DTD) model, to depict and select representative EECs more accurately. Regarding the issue of biosolids, as stated in the Problem Formulation, t he Agency is actively ev aluating the extent to which ecological risk from permethrin via land application of biosolids should be addressed in its forthcoming environmental fate and ecological risk assessment and by extension, any additional data that may be required.

Comment 10 [PDGII] : PDGII believes that a new anaerobic soil metabolism study ( G D LN 835.4200 ) , will not give substantial new information because the previous study shows persistence of permethrin under anaerobic conditions. Furthermore, the anaerobic aquatic metabol ism that PDGII will submit should be more relevant to surface water exposure estimates.

Agency Response 10 : Anaerobic soil metabolism data are required for the proper characterization of the environmental fate of permethrin in anaerobic soils. Based on t he characteristics of permethrin (which binds tightly to soils and sediments), it seems unlikely that the chemical would reach subsurfaces to a high degree; however, permethrin has aquatic uses and thus potential to reach anaerobic soils due to adulticide treatment. The single available study lasted only 60 days of anaerobic incubation, a period during which permethrin decreased from 81.7% AR to 68.1% AR (decreasing only 13.6% AR during this period, and making the half

- life highly unreliable) (the required anaerobic period is one year). Also, both trans

- DCVA and m

- PBA increased throughout the study. Additional degradation half

- life information and data are needed.

Comment 11 [PDGII] : PDGII requested clarification regarding the data requirement for 850.10 10

, a cute t oxicity f reshwater i nvertebrates and 850.1020

, a cute t oxicity H. azteca (using highest ratios of PBO and MGK

- 264).

Agency Response 11 : As noted in the “Updates Since the Preliminary Work Plan” section of this Final Work Plan, G D LN 850.1010 was erroneously listed as a data requirement in the Preliminary Work Plan and is not required in support of registration review

. Acute water column toxicity data on permethrin technical and typical end

- use products (TEPs) with PBO and MGK

- 264 are req uired for H. azteca , using G DLN 850.1020 ( Gammarus acute toxicity test guideline) as the basis for conducting the tests. As appropriate modifications to the 850.1020 guideline will be necessary for testing of H. azteca , the registrant is require d to submit a proto col to the Agency prior to conducting the acute test of H. azteca.11 Comment 12 [PDGII] : PDGII requested waivers for G D LN 850.4100 , seedling emergence tier II, G DLN 850.4150, vegetative vig or tier II

, and GDLN 850.4400, aquatic plant g rowth tier II (aqua tic vascular plant toxicity), based on the fact that FMC ( the original registrant for permethrin) generated efficacy data for numerous crops. No phytotoxicity was observed to alfalfa, asparagus, beans, cabbage, sweet and field corn, cucumber, lettuce, pep per, plum, potato, pumpkin and tomato. PDGII does not believe that a new study would generate additional useful data. Additionally, the PDGII stated that G D LN 850.4400 is an unnecessary data requirement

, because only small amounts of permethrin would rea ch adjacent bodies of water because permethrin does not have aquatic uses

, and such amounts would not be bioavailable to macrophytes because permethrin binds to sediments.

Agency Response 12 : T he field trials recently submitted to the Agency are designed for residue chemistry (OCSPP Series 860 Guidelines). Although these data do provide additional lines of evidence regarding the potential phytotoxic effects of permethrin, the studies do not meet the same objectives as a standard seedling emergence and/or vegetative vigor study

, such as germination , growth and phytotoxic damage

. In addition, the 8 major and 149 minor permethrin plant incidents that have been reported indicate that plant damage may occur following use of
t his chemical. Data that will prov ide quantitative information on the potential effects of permethrin exposure to terrestrial plants, including any inhibition of germination, reduction in growth and observed phytotoxicity, are needed for the upcoming ecological risk assessment. Therefore, the request s for waiver s of GDLN 850.410 0, seedling emergence tier II, GDLN 850.4150, vegetative vigor tier II, and GDLN 850.4400, aquatic plant growth tier II (aquatic vascular plant toxicity) are denied.

Comment 13 [PDGII] : Mosquitocide uses are intend ed to remain in the air for a significant period of time and not deposit out; while drift may be enhanced, deposition resulting from that drift will be reduced. Mosquito adulticides may be applied to the air column over a variety of crops, all of which ar e on permethrin agricultural labels, but the rate of 0.007 lb a.i./A is far lower than the maximum crop rates of 0.1 lb a.i./A and higher. Thus, the mosquito use of permethrin will not add, for all practical purposes, to the residues from crop application s of agricultural formulations. This public health use is only allowed under the authority of federal, state, local, or tribal governments and applicators must be certified or under the direct supervision of certified applicators.

Agency Response 13 : Pre vious risk assessments have shown that there may be R isk Q uotients (RQ s ) that exceed one or more of the LOCs for the adulticide uses. Despite that the application rate is low, multiple applications are allowed and the minimum interval between applications is only 1 day (high pest pressure). The seasonal application rate is 0.18 lb a.i./A. Furthermore, in addition to agricultural crop uses, adulticide applications are also allowed over regions that could have extensive impervious surfaces. The Agency ack nowledges the mosquitocide application restrictions ( e.g. , made by certified applicators).

Comment 14 [PDGII] : Based upon the evaluation of available relevant studies , the Permethrin Task Force suggests that the 48

- hour median effect concentration (EC 50 ) of 0. 075 μg/L for the Daphnia magna acute study (MRID 00043736), is more appropriate than the 96

- hour EC 50 of12 0.039 μg/L presented in the Problem Formulation. According to test guideline OPPTS 850.1010, the purpose of the definitive test is to determine the 24

– and 48

– h EC 50 values.

Additionally, an acceptable study for the bluegill ( Lepomis macrochirus ) is available (Bentley 1974; MRID 00110657) and is more suitable for risk assessment than the supplemental study (Hill et al. 1976; MRID 00042128). The Bentl ey (1974) study is preferable since it used statistics to calculate the median lethal concentration (LC 50 ) and reported the control performance (100% survival).

Agency Response 14 : The Agency agrees that the 48

- hour EC 50 value (MRID 00043736) should be us ed for the acute study with Daphnia magna , instead of the 96

- hour EC 50 value

. In this particular study, the test organisms were fed after 48 hours, and the control immobilization was greater than 10% at 96 hours, indicating test organism stress that is no t chemical

- related (13% immobilization was observed in the negative control at 96 hours, compared to 0% immobilization in the negative control at 48 hours).

EPA is aware of both strengths and limitations in the bluegill study referenced in the permethrin probl em formulation (MRID 00042128). However, some of the study limitations include absence of control response reporting, relatively high co

- solvent concentrations and use of graphical methods for LC 50 determination. Some of these limitations can be ad dressed (such as recalculating statistics for LC 50 ), but others do not appear to be repairable, such as use of high

co

- solvent concentration and lack of control data. The bluegill study suggested by the PDGII (MRID 00110657) is not considered useful for r isk assessment purposes and was invalidated because the percent active ingredient of the test substance was not reported and water quality measurements were not taken during the study.

For the final risk assessment of permethrin, the Agency will re

- evalua te its choice of the acute toxicity endpoint for freshwater fish in the context of all available information, including data from the open literature which have yet to be reviewed, and the associated strengths and limitations of the bluegill study (MRID 00 042128) used for risk quotient calculations in previous permethrin ecological assessments

.

Comment 15 [PDGII] : PDGII expressed concern in several comments regarding the uses and labels captured in the partial listing of labels in the permethrin Label Use Information System (LUIS) report and the availability of t he report. PDGII noted that a 180 lb a.i./A (active ingredient/ Acre) use rate for pre

- construction termiticide treatment seemed inaccurate and that the directions for use considerably limited exp osure. PD G II also believed that EPA’s approach of identifying representative agricultural and non

- agricultural label will not be acceptable to the Services if formal endangered species consultation is required. Additionally, PDGII stated that the LUIS Re port is not available in the permethrin registration review docket.

Agency Response 15 : Permethrin has over 700 product labels of which a substantial subset was utilized to prepare the use and usage information in the LUIS report . The LUIS Report is

ava ilable in the permethrin registration review docket without the specific registration numbers13 utilized in compiling the report . It was posted when the docket opened June 29, 2011, as a supporting document, Appendix A: Food/Feed & Non

- Food/Non

- Feed Uses Co nsidered in Registration Review Work Planning , dated September 29, 2010. The labels utilized represent all use patterns, maximum single application rates, and formulation types. This approach was used in the past for endangered species risk assessments ( e .g. , the CA Red Legged Frog/ San Francisco Bay and the Valley Elderberry Longhorn Beetle permethrin assessments). For consistency, the LUIS Report converts all single application rates in t he lb a.i./A measurement, regardless of the labeled unit of measur ement . E PA realizes that the pre

- construction treatment with the mitigation referenced by PDGII is applied to buildings, structures, and their immediate surroundings only, and that the lb a

. i

. / A unit measurement may not be appropriate for this use scenari o. Additionally, E PA will consider the labeled application restrictions when assessing the exposure from this use, which may result in lower exposure scenarios

.

R isk Assessment and Data Needs

The Agency will require data to conduct a comprehensive ecolo gical risk assessment, including an endangered species assessment . The Agency will also require data to conduct a human health exposure risk assessment for all uses of permethrin

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

.

E cological R isk :

**•** The most recent comprehensive national

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

**•** An ecological risk assessment of all registered uses of permethrin will be co nducted during registration review. The new assessment will incorporate the most up

- to

- date modeling methodologies, updated toxicological endpoint s, and data submitted under the registration review data call

- in.

**•** The Agency has not conducted a risk assess ment 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 t hreatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use “may affect” a listed species or its designated critical habitat, the Agency will consult with the U.S. Fish and Wi ldlife Service and/or National Marine Fisheries Service (the Services), as appropriate.14 **•** The Agency will requir e the following data for permethrin in order to conduct the planned ecological risk assessment, including an endangered species assessment :

**•** GDLN 835.1230

– Adsorption/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 Ch emistry Analytical Methods (ECM) and ILV for Water

**•** GDLN 850.1025

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

**•** GDLN 850.1075

– Acute Freshwater Fish Toxicity (TEPs using co

formulated products with the highest ratio of the synergis t 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 (passerine species)

**•** GDLN 850.4100

– Seedling Emergence, Ti er 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) Publically Owned Treatment Works (POTW) Treatability Study

o The Agency is 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 w ould 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

– A cute Toxicity Freshwater Inver tebrates [ 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 ) ]

**•** NON

- GDLN

– ( Special Study) Test Method 100.4: Hyalell a azteca 42

- d Test for Measuring the Effects 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 EP A 600/R

- 99/06415 **•** NON

- GDLN

– (Special Study) Test Method 100.5: Life

- cycle Test for Measuring the Effects of Sediment

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

- associated Contaminants 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 wi th the Amphipod Leptocheirus plumulosus EPA 600/R

- 01/020

**•** Please refer to EFED Registration Review Preliminary Problem Formulation for Permethrin

, dated June 20 , 2011; and the Response to Public Comments on the EFED Registration Review Problem Formulation for Permethrin

, dated November 18 2011

, located in the docket (EPA

- HQ

- OPP

- 201 1

- 0039 ) , for a detailed discussion of t he risk assessment and data needs.

Human Health Risk:

**•** The most recent comprehensive human health risk assessment for permethrin w as comple ted 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 2009 Revised Permethrin RED.

**•** The Agency will require the following data for permethrin in order to re

- evaluate toxicological endpoints and update the human health toxicity profile:

o GDLN 870.7800

– Immunotoxicity

**•** The uncertainty factor (UF) for permethrin is currently 100 X for adults ( 1 X UF

, 10 X for inter

- species, 10 X for intras p ecies variation) and 300X for c hildren <6 years of age ( including a 3X FQPA safety factor ). Under FQPA, the Agency is required to apply a 10X safety factor (SF) to be protective of infants and children unless there is data to support a reduction or remova l. The Agency’s current position is that there is sufficient evidence to reduce the FQPA S F to 1X for adults and 3X for children <6 years of age. The 3X is based on age

- dependent

- pharmacokinetics and is further supported by physiologically

- based pharmaco kinetic (PK) model predictions of a 3

- fold increase of pyrethroid concentration in juvenile target tissue compared to adults. A more complete description of the Agency’s reasoning behind a 3X FQPA SF for children can be found at www.regulations.gov ; EPA

- HQ

- OPP

- 2011

- 0746

- 0011

. These UFs are subject to review and possible revision during the registration review.

**•** During registratio n review, the Agency will update the dietary risk assessment with revised estimated drinking water concentrations and changes in toxicological endpoints, and incorporate any degradates that are determined to be of human toxicological concern.16 Should review of the USDA Pesticide Data Program (PDP) and percent crop treated information show that exposure may be increasing, revised anticipated residues may need to be generated and incorporated into acute and chronic dietary risk assessments.

**•** An updated residential exposure risk assessment will be required under registration review based upon anticipated revisions 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 SF is revised , or revisions to exposure policies and pro cedures are 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.

**•** The Agency will update 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 SF , or if revisions are made to any exposure and/or risk assessment policies and pr ocedures.

**•** The Agency will conduct new occupational handler and post

- application assessments as necessary, based on updated doses, endpoints, and procedures for both dermal and inhalation endpoints.

**•** 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 will update the current tolerance expression to reflect current EPA policies. A lso, permethrin toleran c es will be considered during registration review for pos si ble harmonization with international maximum residue limits (MRLs) should they be established.

**•** For more information

, please refer to Perme thrin : Registration Review Scoping Document for Human Health

, June 15 , 2011, and Permethrin: Waiver Request for Immunotoxicity Study, dated October 20, 2011

, located in the docket (EPA

- HQ

- OPP

201 1

- 0039 )

.

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developm ental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertili ty, 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 Endocrine Disruptor Screening Program17 taxonomic groups. As part of its reregistration decision

, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), permethrin is subject to the endocrine scre ening 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 statu torily required determinations. Tier 1 consists of a battery of 11 screening assays to identi fy the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will pr oceed to the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine

- related effects caused by the substance, and establish a dose

- response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call

- ins for the first group of 67 che micals, which contains 58 pesticide active ingredients 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 assessment 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 battery, please visit our website: http://www.epa.gov/endo/

.18 Timeline

EPA has created the following estimated tim eline for the completion of the permethrin registration review.

Registration Review for Permethrin

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

– June Close Public Comment 2011

– August Case Development Fi nal Work Plan 2011

– December 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 o st

- D ecision F ollow

- up 2017 Total ( years ) 6

Next Steps

The Agency will require multiple ecological effects and human health studies through a data call

- in (DCI), which is expected to be issued in mid

- 2012. This new information will be used to conduct risk assessments for permethrin uses.19 SUMMARY OF DA TA GAPS

– Permethrin

The table below summarizes the data needs for permethrin identified in the “Ecological Risk” and “Human Health Risk” sections of this Final Work Plan document, the Registration Review

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

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

, dated June 15 , 2011.

Table 1. Data Needs for Perme thrin Registration Review

Guideline Number Data Requirement Test Material Study Duration
835.1230 Adsorption/Desorption TGAI 12
835.2240 Photodegradation in Water TGAI 24

835.4100 Aerobic Soil Metabolism PAIRA; TGAI 24

835.4200 Anaerobic Soil Metaboli sm PAIRA; TGAI 24

835.4300 Aerobic Aquatic Metabolism PAIRA; TGAI 24

835.4400 Anaerobic Aquatic Metabolism PAIRA; TGAI 24

835.6100 Environmental Chemistry Methods (ECM) and I ndependent Laboratory Validation (I LV ) for Soil 1 TGAI 24

835.6200 Environmen tal Chemistry Methods (ECM) and I ndependent Laboratory Validation ( ILV ) for Water 1 TGAI 24

850.1025 Acute Toxicity Estuarine/Marine Organisms (oyster) TGAI 12
850.1075 Acute Freshwater Fish Toxicit y 2 ,3 TEP 1 8
850.1350 Aquatic Invertebrate Life Cycle (s altwater) TGAI 12
850.2100 Avian Oral Toxicity (passerine species) 3 TGAI;TEP 12
850.4100 Nontarget Area Phytotoxicity Tier II, Seedling Emergence 4 TEP 12
850.4150 Nontarget Area Phytotoxicity Tier II, Vegetative Vigor 4 TEP 12

850.4400 Nontarget Area P hytotoxicity Tier II, Aquatic Plant Growth (Vascular Plants) 4 TGAI; TEP 12

1 See footnote 7 of 40 CFR 158.1300. Only the environmental chemistry analytical method portion of GDLNs 835.6100

– Terrestrial field dissipation and 835.6200

– Aquatic field dissipation are required.
2 The DCI will indicate that TEP studie s on freshwater invertebrates and freshwater fish are required on co

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

- 264 to permethrin.
3 The DCI will require that a study protocol be submitted for review and approval by the Agency prior to this study being initiated.
4 A Tier II study is required. The DCI 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.20 Guideline Number Data Requirement Test Material Study Duration

850.5400 Nontarget Area Phytotoxicity Tier II, Aquatic Plant Growth (Algal Plants) 4 T EP ; TGAI 12

870.7800 Immunotoxi city TGAI 12
NON

- GDLN Special Study on Leachability from Treated Wood TEP 18
NON

- GDLN Publically Owned Treatment Works ( POTW ) Treatability Study TGAI 24
NON

- GDLN Acute Toxicity Freshwater Invertebrates ( Hyalella azteca ) 2,3 TEP 12

NON

- GDLN Test for Meas uring 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 24

NON

- GDLN Life

- cycle Test 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 Freshw ater Invertebrates. EPA 600/R

- 99/064 TGAI 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 TGA I 24