Docket Number: EPA-HQ-OPP-2011-0039

www.regulations.gov

Permethrin Final Work Plan

Registration Review

December 2011

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PERMETHRIN FINAL WORK PLAN

Introduction

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 concerning the Preliminary Work 

Plan (PWP) in the Summary Document, which was posted in the permethrin registration review

docket (EPA-HQ-OPP-2011-0039), and any other comments concerning the initial docket 

postings. The Summary Document provided information on what 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 registration review program requires review of each

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

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

science, public policy, and pesticide use practices will occur over time. The registration review

program is intended to make sure that, as the ability to assess risk evolves and as policies and

practices change, all registered pesticides continue to meet that statutory standard. The public

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

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

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 

Food and Drug Administration (FDA) as a pediculicide for the treatment of head lice and 

scabies. Permethrin was first registered on February 25, 1979 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, 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 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 permethrin can be found in docket EPA-OPP-HQ2004-0385 at www.regulations.gov
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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 for 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 review. 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 spring 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 

intensive evaluation of the incidents and the pet 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 “only” 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 placing 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 

EPA’s increased restrictions on pet spot-on products, please visit: 

http://www.epa.gov/pesticides/health/pets.htm

Impaired Water Bodies- On October 11, 2011, EPA issued its final decision regarding the waters 

EPA added to California's 2008-2010 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 11 water body impairments due to pyrethroid chemicals (including 

permethrin), and 3 water body impairments which list the pyrethroids bifenthrin, lambda

cyhalothrin, esfenvalerate/fenvalerate, and permethrin as pollutants. More information on 

California’s additional impaired water body listings 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 

applications during rain, when puddles are present, and over drains or natural drainage areas. 

More information about the proposed regulations are available on DPR’s website at:

http://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 2009 
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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 found 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 flying insect pest control; (2) aquatic weed and algae control; 

(3) aquatic organism pest control; and (4) forest canopy pest control. The final pesticide general 

permit requires permittees to minimize pesticide discharges through the use of pest management 

measures, and monitor for and report any adverse incidents. While the permit’s requirements 

must be met as of October 31st

, 2011, operators are not required to submit Notices of Intent 

(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 the 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 visit: 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 sharing a common 

mechanism of toxicity. Permethrin is a member of the pyrethroid/pyrethrin common mechanism 

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

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

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

November 9, 2011 and is available at http://www.regulations.gov; EPA-HQ-OPP-2011-0746. 

No cumulative risks of concern were identified, allowing the Agency to consider new uses for 

pyrethroid actives. For information regarding EPA’s efforts to evaluate the risk of exposure to 

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

Comments Received on the Preliminary Work Plan

The permethrin registration review docket was open for a 60-day comment period beginning on 

June 29, 2011. During the public comment period, the Agency received eight sets of substantive 

comments from the California Regional Water Quality Control Board, Central Valley Region;

California Regional Water Quality Control Board, San Francisco Bay Region; California 

Stormwater Quality Association (CASQA); Tri-Technology Advisory Committee (Tri-TAC);

National Alfalfa & Forage Alliance; Permethrin Data Group II (PDGII); McLaughlin Gormley 

King Company (MGK); and Biospotvictims.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 impairment, 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 pyrethroids. 

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

A general summary of substantive comments and the Agency’s response to comments is 

provided below. Only comments on data requirements, the scope 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 been 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 (EPAHQ-OPP-2011-0039).

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 immunotoxicity 

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 system 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 immunotoxicity 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 permethrin 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 Publically Owned Treatment Works 

(POTWs). Municipalities and POTWs discharging to the water bodies can be impacted through 

additional requirements established for National Pollutant Discharge Elimination System 
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(NPDES) permits and Total Maximum Daily Loads (TMDLs) 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 CWA 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. However, 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 of estimating the relative contribution of 

permethrin to pyrethroid impairments in individual watersheds. 

Comment 2 [CA Regional Water Quality Control Board CV Region]: The 2010 CWA §303(d) 

listings in Central Valley, CA contains 13 stream segments (10 in 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 resolution 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 

throughout 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 partially agreed upon with the 

Agency. The Agency’s Region IX sought public comments and a final decision was issued 

October 11, 2011. Information on 303(d) listings will be included in the registration review 

ecological risk assessment. 

Comment 3 [CA Regional Water Board CV Region, CA Regional Water Board SF Bay Region, 

CASQA, Biospotvictims.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 information 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 the East 

Bay, CA; Sacremento, CA; and Nashville, TN.
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Agency Response 4: The Agency appreciates the submission of these data tables. This

information will be considered at the time of the registration review 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 suggestions 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 

applications 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 characteristics 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 plants 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, and prohibit use in 

sewers or sewer drains.

Agency Response 5 & 6: The justification for the 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 lot 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 surfaces 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 

(NLCD) in order to establish a range of Estimated 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 surfaces, 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 surface 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 Group (PWG, MRID 48072902). Another study that included 17 pyrethroid products, 
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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, SF 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 important 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 effects of stressors 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 comment 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 regarding 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 different 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 concentrations 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-TAC]: 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 receiving 
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bodies of water may have little flow (i.e., “effluent dominated” waters). Recycled wastewater 

has growing use for irrigation, toilet flushing, industrial 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 to 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 Office 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, the Agency is actively evaluating 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 (GDLN 

835.4200), will not give substantial new information because the previous study shows 

persistence of permethrin under anaerobic conditions. Furthermore, the anaerobic aquatic 

metabolism 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 the 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 

850.1010, acute toxicity freshwater invertebrates and 850.1020, acute toxicity 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, GDLN 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 required for H. azteca, using GDLN 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 required to submit a protocol 

to the Agency prior to conducting the acute test of H. azteca.
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Comment 12 [PDGII]: PDGII requested waivers for GDLN 850.4100, seedling emergence tier 

II, GDLN 850.4150, vegetative vigor tier II, and GDLN 850.4400, aquatic plant growth tier II 

(aquatic 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, pepper, plum, potato, 

pumpkin and tomato. PDGII does not believe that a new study would generate additional useful 

data. Additionally, the PDGII stated that GDLN 850.4400 is an unnecessary data requirement,

because only small amounts of permethrin would reach 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: The 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 

this chemical. Data that will provide 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 requests for waivers of GDLN 850.4100, 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 intended 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 are 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 applications 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: Previous risk assessments have shown that there may be Risk Quotients

(RQs) 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 acknowledges 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 (EC50) of 0.075 μg/L for the 

Daphnia magna acute study (MRID 00043736), is more appropriate than the 96-hour EC50 of 
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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 EC50 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 Bentley (1974) study is preferable since it used 

statistics to calculate the median lethal concentration (LC50) and reported the control 

performance (100% survival).

Agency Response 14: The Agency agrees that the 48-hour EC50 value (MRID 00043736) should 

be used for the acute study with Daphnia magna, instead of the 96-hour EC50 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 not 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

problem 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 LC50 determination. Some of these limitations can be addressed (such as 

recalculating statistics for LC50), 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 risk 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-evaluate 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 00042128) 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 the 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 exposure. PDGII 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 Report 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 

available in the permethrin registration review docket without the specific registration numbers 
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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 Considered 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 the lb a.i./A measurement, 

regardless of the labeled unit of measurement. EPA 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 

scenario. Additionally, EPA will consider the labeled application restrictions when assessing the 

exposure from this use, which may result in lower exposure scenarios.

Risk Assessment and Data Needs

The Agency will require data to conduct a comprehensive ecological 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 permethrin.

Ecological Risk:

• 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 conducted 

during registration review. The new assessment will incorporate the most up-to-date 

modeling methodologies, updated toxicological endpoints, and data submitted under the 

registration review data call-in.

• 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 affect” 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.
14

• The Agency will require 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 Chemistry 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 coformulated 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 (passerine 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) 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 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 – Acute Toxicity Freshwater Invertebrates [TEPs using coformulated 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: Hyalella 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 EPA 600/R-99/064 
15

• 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 Bioaccumulation 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 with 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-2011-0039), for a detailed discussion of the risk 

assessment and data needs.

Human Health Risk:

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

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 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 100X for adults (1X UF, 10X for 

inter-species, 10X for intraspecies variation) and 300X for children <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 removal. The Agency’s current position is that there is sufficient 

evidence to reduce the FQPA SF 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 pharmacokinetic (PK) model predictions of a 3-fold increase of 

pyrethroid concentration in juvenile target tissue compared to adults. A more complete 

description of the Agency’s reasoning behind a 3X FQPA SF for children can be found at 

www.regulations.gov; EPA-HQ-OPP-2011-0746-0011. These UFs are subject to review 

and possible revision during the registration review.

• During registration 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 procedures 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 procedures. 

• 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 permethrin, 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. 

Also, permethrin tolerances will be considered during registration review for possible 

harmonization with international maximum residue limits (MRLs) should they be 

established.

• For more information, please refer to Permethrin: 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-OPP2011-0039). 

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, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

Endocrine Disruptor Screening Program
17

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 screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

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

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. 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 timeline 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

Final 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 

Decision

2016 – July – Sept.

Close Public Comment Period 2016 – Oct. – Dec.

Registration Review Decision and Begin Post-Decision Follow-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 DATA 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 Environmental 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 Permethrin 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 Metabolism 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 Independent 

Laboratory Validation (ILV) for Soil1 TGAI 24

835.6200 Environmental Chemistry Methods (ECM) and Independent 

Laboratory Validation (ILV) for Water 1 TGAI 24

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

850.1075 Acute Freshwater Fish Toxicity2,3 TEP 18

850.1350 Aquatic Invertebrate Life Cycle (saltwater) 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 Vigor4 TEP 12

850.4400 Nontarget Area Phytotoxicity 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 studies on freshwater invertebrates and freshwater fish are required on coformulated 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 TEP;TGAI 12

870.7800 Immunotoxicity 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 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 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 Freshwater 

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 Sedimentassociated Contaminants with the Amphipod Leptocheirus 

plumulosus. EPA 600/R-01/020

TGAI 24