Page 2 of 26

and postapplication), and occupational (handler and postapplication) routes for 

permethrin.

The toxicity database for permethrin is complete at the present time with the exception of 

an immunotoxicity study. The Food Quality Protection Act (FQPA) safety factor (SF) 

for permethrin will need to be re-evaluated during registration review following a final 

determination of the potential for increased susceptibility of infants and children to 

pyrethroid pesticides based on the results of all available data. Upon receipt of the 

immunotoxicity study, HED will reevaluate the points of departure and uncertainty 

factors for the dietary and occupational exposure assessments.

Permethrin is among the group of 58 pesticide active ingredients on the initial list to be 

screened under the Endocrine Disruptor Screening Program (EDSP) 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. 

The existing residue chemistry database for permethrin is adequate for risk assessment 

purposes. The qualitative nature of the residue(s) of permethrin in plants and animals has 

been adequately identified/characterized and is understood. The residues of concern in 

plants and animals include cis- and trans-permethrin for purposes of both tolerance 

assessment and risk assessment. The acute, chronic non-cancer, and chronic cancer

dietary analyses from the 2009 permethrin risk assessment are considered highly refined

estimates of dietary exposure. All calculated dietary risk estimates were below the 

Agency’s level of concern. New acute, chronic non-cancer, and chronic cancer dietary 

risk assessments may need to be conducted during registration review. The assessments 

should include updated consumption information, any revised toxicological points of 

departure, and utilize the newest version of Dietary Exposure Evaluation Model software 

with the Food Commodity Intake Database (DEEM-FCID). Additionally, should a 

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 the acute and chronic dietary risk assessments.

The residential exposure database is adequate to support the registration review process 

for permethrin. In the 2009 risk assessment, all of the non-cancer residential handler and 

postapplication risk estimates and almost all of the cancer residential handler and 

postapplication risk estimates were below the Agency’s level of concern. An updated 

residential exposure assessment may be required under registration review based upon 

revisions to HED’s Residential Standard Operating Procedures (SOPs) which was 

reviewed by the Scientific Advisory Panel (SAP) in October 2009. An updated 

assessment may also be required if new data are identified which impact exposure 

estimates, new points of departure, a revised FQPA SF, or revisions to exposure policies 

and procedures are made.

In the 2009 permethrin risk assessment, HED performed acute, short- and intermediateterm, chronic, and cancer aggregate risk assessments. All of the aggregate scenarios that 

were assessed did not result in aggregate risks of concern, with the exception of the 

combined turf/indoor carpet broadcast spray exposure scenario to toddlers in the short-
Page 3 of 26

and intermediate-term aggregate assessment. An updated aggregate exposure and risk 

assessment may be required under registration review if dietary or residential exposure 

estimates are updated or revisions are made to the permethrin points of departure or 

FQPA SF.

The occupational exposure database is adequate to support the registration review process 

for permethrin. In the 2009 risk assessment, all of the non-cancer occupational handler 

risk estimates and almost all of the cancer occupational handler risk estimates were below 

the Agency’s level of concern at some level of risk mitigation. In the 2009 risk 

assessment, all of the non-cancer and cancer occupational postapplication risk estimates 

were below the Agency’s level of concern. An updated occupational exposure 

assessment may be required under registration review if new data are identified which 

impact exposure estimates, new points of departure are selected, or if revisions to 

exposure policies and procedures are made.

Introduction

Permethrin is a broad spectrum synthetic pyrethroid insecticide used to control a variety 

of insects. HED has reviewed the most recent exposure and risk assessments for 

permethrin, as well as toxicity data, exposure and usage databases, and the latest Agency 

science policy and risk assessment methodologies to determine if sufficient data are 

available and if updates are needed to support registration review. Additionally, the team 

conducted a screening-level literature search for any information that would aid in 

assessing human health risks to permethrin.

Chemical Identity

Permethrin [(3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane

carboxylate] is a broad spectrum, non-systemic, synthetic pyrethroid insecticide 

registered for use on numerous food/feed crops, livestock and livestock housing, modes 

of transportation, structures, buildings (including food handling establishments), and for 

residential uses. Permethrin is formulated as an emulsifiable concentrate, a wettable 

powder (including water soluble bags), a granular, a dust, as well as a number of ready to 

use formulations, such as aerosol cans, foggers, trigger pump sprayers, ear tags, etc. 

In addition to the pesticidal uses, there is also a non-Federal Insecticide, Fungicide, and 

Rodenticide Act (FIFRA) pharmaceutical use of permethrin as a pediculicide for the 

treatment of head lice and scabies. The Food and Drug Administration (FDA) approves 

uses of the pesticidal-containing pharmaceutical products under the Federal Food, Drug, 

and Cosmetic Act (FFDCA). 

The chemical structure and nomenclature of permethrin and the physicochemical 

properties of technical grade permethrin are presented in Tables 1 and 2.

Hazard Identification/Toxicology

As with the other pyrethroids, permethrin causes neurotoxicity in insects and mammals 

by the modulation of nerve axon sodium channels. Pyrethroids interfere with the ability 

of the nervous system to relay nerve transmissions, potentially resulting in tremors, 

convulsions, salivation, and other clinical effects. 
Page 4 of 26

The toxicity database for permethrin is complete at the present time with the exception of 

an immunotoxicity study (see Table 4). Permethrin has a low acute toxicity via the oral, 

dermal, or inhalation route of exposure. Permethrin is not an eye or skin irritant and not a 

skin sensitizer.

For a summary of the subchronic and chronic toxicity profile, see Table 3C. The critical 

effect for permethrin (i.e., neurotoxicity) is based on the most sensitive species, rats. The 

effects of permethrin in several species are early in onset and short-term, without 

indications that incidence or severity of effects would increase based on metabolism 

studies that permethrin is rapidly absorbed, metabolized, and almost completely 

eliminated from the body within a short period of time. The oral exposure limits for all 

durations were based on an acute neurotoxicity study in rats. The dermal exposure limits 

for all durations were based on a 21-day rat dermal toxicity study. The inhalation 

exposure limits for all durations were based on a rat 15-day inhalation study.

As part of the 2009 risk assessment, the Agency requested that a DNT study be 

conducted on rats with permethrin. This request was based on evidence of neurotoxicity 

in the acute and subchronic neurotoxicity studies and other subchronic and chronic 

toxicity studies in dogs and rats. Increased incidence of microscopic lesions associated 

with neurotoxic effects at high doses in the subchronic neurotoxicity studies further 

supported this request. However, based on the Agency’s review of existing pyrethroid 

data, EPA has come to the conclusion that the DNT is not a particularly sensitive study 

for comparing the sensitivity of young and adult animals to pyrethroids. The science 

supporting this conclusion can be found in “Pyrethroids: Evaluation of Data from DNTs 

& Consideration of Comparative Sensitivity” (E. Scollon, 1/20/10, D371723), available 

at http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html. In an effort to 

ensure the highest level of protection of infants and children, the Agency plans to 

continue reviewing scientific data regarding the potential increased susceptibility of 

pyrethroid pesticides as it becomes available.

The total uncertainty factor for permethrin is currently 100X (1X FQPA Safety Factor, 

and 10X for inter-species variation, and 10X for intra-species variation). The FQPA 

safety factor was reduced to 1X because: (1) the toxicity database is adequate to 

characterize the potential for pre- and postnatal risk for infants and children; (2) no 

reproductive or developmental effects were observed in rats; and (3) there is no evidence 

(qualitative or quantitative) for increased susceptibility following in utero and/or pre-

/post-natal exposure in the developmental toxicity studies in rats and rabbits and multigeneration reproduction studies in rats. The FQPA factor for permethrin will be reevaluated during registration review following a final determination of the potential for 

increased susceptibility of infants and children to pyrethroid pesticides based on the 

results of all available data. 

 

Permethrin is classified as “Likely to be Carcinogenic to Humans” by the oral route based 

on evidence of two reproducible benign tumor types (lung and liver) in the mouse, 

equivocal evidence of carcinogenicity in Long-Evans rats, and supportive SAR 

information. Mutagenicity studies did not demonstrate any evidence of mutagenic 

potential for permethrin.
Page 5 of 26

For a summary of the relevant toxicological endpoints and points of departure used in 

risk assessment, please see Tables 3D (dietary and residential endpoints) and 3E

(occupational endpoints).

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 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). 

Endocrine Disruption Screening Program

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (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 permethrin 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/. 

Conclusions for Hazard Identification/Toxicology

The toxicity database for permethrin is complete at the present time with the exception of 

an immunotoxicity study (see Table 4). The FQPA SF for permethrin will be reevaluated during registration review following a final determination of the potential for 
Page 6 of 26

increased susceptibility of infants and children to pyrethroid pesticides based on the 

results of all available data. 

Residue Chemistry

Permethrin [(3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane

carboxylate] is a synthetic pyrethroid insecticide. The existing residue chemistry 

database for permethrin is adequate for risk assessment purposes. No additional data are 

required at this time pending receipt and review of residue chemistry data required to 

resolve deficiencies outlined in the most recent residue chemistry chapter for permethrin 

(S. Kinard, D313662, 03/17/2005). These studies were required in the 2009 Permethrin 

DCI (GDCI-109701-26467). HED has received and reviewed a portion of the required 

studies (D. Wilbur, D382837, D382842, D382844, 01/26/2011). The remaining 

outstanding studies include:

• OPPTS 860.1500 (Crop Field Trials) for cabbage; collards; grass, forage; lettuce, 

leaf; soybean, forage; and soybean, seed.

The qualitative nature of the residue(s) of permethrin in plants and animals has been 

adequately identified/characterized and is understood. The residues of concern in plants 

and animals include cis- and trans-permethrin for purposes of both tolerance assessment 

and risk assessment. Adequate methods are available for the enforcement of established 

tolerances, as currently defined. Adequate analytical methods exist for data collection. 

Adequate storage stability, processed food, and magnitude of the residue data exist.

Conclusions for Residue Chemistry

The residue chemistry database for permethrin is complete at the present time with the 

exception of the outstanding data required in the 2009 GDCI.

Dietary Exposure and Risks

Acute, chronic, and cancer dietary (food and water) exposure risk assessments were 

conducted (S. Ary, D325429, 02/01/2006) using the DEEM-FCID, Version 2.03

model, which uses food consumption data from the USDA’s Continuing Surveys of Food 

Intakes by Individuals (CSFII) from 1994-1996 and 1998. The dietary risk assessment 

incorporated all available information, including: usage data (percent crop treated), 

anticipated residues (ARs) based on field trial data, and ARs based on USDA Pesticide 

Data Program (PDP) monitoring data. Estimated drinking water concentrations were 

directly incorporated into the dietary exposure assessments. 

The Environmental Fate and Effects Division used Tier-II modeling to generate estimated 

environmental concentrations (EECs) in surface water (J. Melendez, D324197, 

1/17/2006). Only surface water values (as opposed to groundwater values) were used in 

the acute and chronic assessments as these represent upper bound concentrations that 

would be expected in drinking water. The EDWCs for permethrin were calculated based 

on a maximum application rate of 2.0 lb ai/A. The concentration used in the acute dietary 

assessment was calculated from surface water at 0.00479 ppm. The concentrations used 

in the chronic and cancer dietary assessments were calculated from surface water at 

0.000901 ppm and 0.000751 ppm, respectively, using the Georgia onion scenario. The 

chronic value represents the mean value over a 30-year period and is a high end estimate 

Drinking Water
Page 7 of 26

that is 1.7 times the next lowest scenario, California lettuce at 0.000545 ppm. The cancer 

value also represents the mean value over a 30-year period and is a high end estimate that 

is 1.6 times the next lowest scenario, California lettuce at 0.000475 ppm. Water residues 

were incorporated in the DEEM-FCID into the food categories “water, direct, all 

sources” and “water, indirect, all sources”. Given the conservative nature of the 2006 

EFED drinking water assessment, HED does not anticipate the need for a new drinking 

water estimates during registration review.

A highly refined probabilistic (Monte-Carlo) acute dietary exposure assessment was 

conducted to estimate the dietary risks (S. Ary, D325429, 02/01/2006). Permethrin 

residue estimates used in this assessment included cis- and trans-permethrin, calculated 

as total permethrin, along with the percent crop treated (%CT) estimates reported by the 

Biological and Economic Analysis Division (BEAD). The anticipated residue (AR) 

estimates are based primarily on the USDA PDP monitoring data (PDP data). Tolerance 

values were used for livestock commodities. DEEM 7.81 default processing factors were 

used in this assessment for several commodities along with the available data from the 

processing studies. Acute dietary risk estimates are provided for the general U.S. 

population and various population subgroups, with the major emphasis placed on the 

exposure estimates for infants and children. This assessment concluded that for all 

supported registered commodities, the acute dietary risk estimates did not exceed HED’s 

level of concern (less than 100% of the aPAD) at the 99.9

Acute Dietary Exposure and Risk (Food and Drinking Water) 

th exposure percentile for the 

U.S. population (4% of the aPAD) and all population subgroups, with the highest 

exposed population subgroup being all infants less than 1 year old at 16% of the aPAD.

A highly refined chronic dietary exposure assessment was conducted to estimate the 

dietary risks associated with permethrin (S. Ary, D325429, 02/01/2006). Permethrin 

residue estimates used in this assessment include cis- and trans-permethrin, calculated as 

total permethrin, along with the %CT estimates reported by BEAD. The AR estimates 

are based primarily on the PDP data. Feeding studies along with %CT on feed items and 

dermal studies were used to calculate AR estimates for livestock commodities if PDP 

data were not available. DEEM 7.81 default processing factors were used in this 

assessment for several commodities along with the available data from the processing 

studies. Chronic dietary risk estimates are provided for the general U.S. population and 

various population subgroups, with the major emphasis placed on the exposure estimates 

for infants and children. This assessment concluded that for all supported registered 

commodities, the chronic dietary risk estimates did not exceed HED’s level of concern 

(less than 100% of the cPAD) for the U.S. population and all population subgroups (all 

were less than 1% of the cPAD).

Chronic Non-Cancer

A highly refined cancer dietary exposure assessment was conducted to estimate the 

dietary risks of permethrin. Permethrin residue estimates used in this assessment include 

cis- and trans-permethrin, calculated as total permethrin, along with the %CT estimates 

reported by BEAD. The AR estimates are based primarily on the PDP data. Feeding 

studies along with %CT on feed items and dermal studies were used to calculate AR 

estimates for livestock commodities if PDP data were not available. DEEM 7.81 default 

Chronic Cancer
Page 8 of 26

processing factors were used in this assessment for several commodities along with the 

available data from the processing studies. The estimated exposure of the general U.S. 

population to permethrin is 0.000117 mg/kg/day. Applying the Q1* of 9.567 x 10-3

(mg/kg/day)-1 to the exposure value results in a cancer risk estimate of 1.1 x 10-6.

Conclusions for Dietary Exposure and Risk Assessment

An updated dietary risk assessment may be required during the registration review 

process to further refine residues in drinking water and food, and any revised points of 

departure (PoDs) or uncertainty factors. The revised assessments should include updated 

consumption information and will utilize the newest version of DEEM-FCID. 

Additionally, should a review of the PDP and other relevant information show that 

exposure may be increasing, revised anticipated residues may need to be generated and 

incorporated into the dietary risk assessments.

Residential Exposure and Risks

Permethrin is registered for use in a variety of indoor and outdoor residential 

environments including: lawns, gardens, indoor surfaces and spaces, ornamentals, and on 

pets. Due to this use profile, adult residential homeowners may experience exposure to 

permethrin during application of the chemical (i.e., residential handler exposures). 

Adults and children may experience exposure to permethrin when contacting permethrintreated areas (i.e., residential postapplication exposure).

In addition to homeowner uses in residential settings, permethrin is labeled for mosquito 

adulticide use, which is applied by occupational handlers, but may result in 

postapplication exposures in residential settings. Permethrin is also used in residential 

automatic misting systems for mosquito control, as well as impregnated into clothing 

which also may result in occupational handler exposure and residential postapplication

exposure.

The most recent permethrin risk assessment (C. Smith, D357566, 04/01/2009) addressed 

the potential residential handler exposures to adults and the potential residential 

postapplication exposures to adults and children of varying ages.

There are hundreds of permethrin products currently registered for use by homeowners. 

The 2009 risk assessment assessed 25 residential handler scenarios which reflect the 

major residential uses of permethrin based on types of application equipment. 

Residential handler exposures were estimated using exposure data from a number of data 

sources, including: the Pesticide Handler Exposure Database (PHED), the Outdoor

Residential Task Force (ORETF), the Non-Dietary Exposure Task Force (NDETF), the 

Chemical Manufacturers Association (CMA) Antimicrobial Exposure Assessment Study,

and four proprietary exposure studies.

Residential Handlers

The non-cancer handler risk estimates presented in the 2009 risk assessment indicate that 

all of the residential handler scenarios resulted in risks that did not exceed HED’s level of 

concern (i.e., MOEs > 100). 
Page 9 of 26

A residential handler cancer risk assessment was also conducted as part of the 2009 risk

assessment. The same scenarios, assumptions, and exposure data were used as in the 

non-cancer assessment. HED estimated cancer risks assuming a maximum of 1 day of 

exposure per year which resulted in cancer risk estimates ranging from 1.6 x 10-11 to 7.4 x 

10-7. In addition, HED calculated the maximum number of days of handler exposure per 

year that still would result in cancer risks less than or equal to 1x10-6. Four scenarios 

resulted in 5 days or less of allowable handler exposure. 5 days was used as the target 

based on survey data from the Residential Exposure Joint Venture (REJV) that showed

that homeowners use permethrin products on an average of 5 times a year.

Permethrin can be used in many areas that can be frequented by the general population 

including residential areas. As a result, individuals can be exposed by entering these 

areas if they have been previously treated. Permethrin can also be used on companion 

animals, which can lead to exposures by contact with the treated animals.

Residential Postapplication

In the 2009 risk assessment, a number of postapplication residential exposure scenarios 

were assessed for adults and children. These scenarios included playing on a treated 

lawn (adults and children), playing on a treated indoor surface (adults and children), 

playing with treated companion animals (children only), wearing permethrin impregnated 

clothing (adults and children), working in a treated garden, mowing (adults only), and 

mosquito treatments (adults and children). For adults, dermal exposures were assessed 

for all scenarios except for mosquito treatments where inhalation was the focus. Children 

dermal and non-dietary ingestion exposures were assessed for all scenarios except the 

mosquito treatments where inhalation was the focus. 

Residential postapplication exposures were estimated using exposure data from a number 

of data sources, including: the ORETF, the NDETF, and a number of proprietary 

exposure studies. The non-cancer postapplication risk estimates presented in the 2009 

risk assessment indicate that all of the adult (dermal and inhalation) and children (dermal, 

inhalation, and non-dietary ingestion) residential postapplication scenarios resulted in 

risks that did not exceed HED’s level of concern (i.e., MOEs > 100). HED also 

performed a combined residential postapplication assessment by combining children’s 

dermal and non-dietary ingestion exposures for turf (i.e., dermal, hand-to-mouth, objectto-mouth, and soil ingestion), indoors (i.e., dermal and hand-to-mouth), pets (i.e., dermal 

and hand-to-mouth), and impregnated clothing (i.e., dermal and object-to-mouth). All of 

these combined postapplication residential scenarios resulted in risks that did not exceed 

HED’s level of concern (i.e., MOEs > 100).

An adult residential postapplication cancer risk assessment was also conducted as part of 

the 2009 risk assessment. The same scenarios, assumptions, exposure data were used as 

in the non-cancer postapplication assessment. HED estimated cancer risk assuming 

estimates for an annual a maximum of 1 day of exposure per year. The estimates 

represent one day of postapplication exposure per year and exposure on the day of 

application (i.e., day 0) for each year of a 50-year exposure period. Cancer risk estimates 

ranged from 9.2 x 10-10 to 8.4 x 10-7

. In addition, HED calculated the maximum number 

of days of handler exposure per year that still would result in cancer risks less than or 
Page 10 of 26

equal to 1x10-6. Three indoor scenarios resulted in 5 days or less of allowable 

postapplication exposure. 

Conclusions for Residential Exposure and Risk Assessment

The residential exposure database is adequate to support the registration review process 

for permethrin. An updated residential exposure assessment may be required under 

registration review based upon revisions to HED’s Residential SOPs which was reviewed 

by the Scientific Advisory Panel (SAP) in October 2009. An updated assessment may 

also be required if new data are identified which impact exposure estimates, new points 

of departure, a revised FQPA SF, or revisions to exposure policies and procedures are 

made.

Aggregate Risk Assessment

In the 2009 permethrin risk assessment, HED determined that acute, short- and

intermediate-term, chronic, and cancer aggregate risk assessments were appropriate. The 

acute and chronic aggregate assessments were equivalent to the acute and chronic dietary 

risk assessments. The acute and chronic dietary risk estimates for the general population 

and all population subgroups were not of concern to HED.

For the short- and intermediate-term aggregate assessment, HED examined a number of 

possible residential combined scenarios including turf/indoor surfaces, turf/vegetable 

gardens, and turf/pets to represent a variety of high-end, health protective residential 

adult and toddler exposures. These combined residential exposures were then combined 

with the chronic dietary exposures. HED concluded that, except for the combined 

turf/indoor carpet broadcast spray exposure to toddlers, the combined residues of 

permethrin from food, drinking water, and other potential residential exposures do not 

result in short- and intermediate-term aggregate risks of concern.

For the cancer aggregate assessment, HED examined a number of possible residential 

combined scenarios including turf/indoor surfaces and turf/vegetable gardens to represent 

a variety of high-end, health protective residential adult exposures. These combined 

residential exposures were then combined with the cancer dietary exposures. HED 

concluded that combined residues of permethrin from food, drinking water, and other 

potential residential exposures do not result in cancer aggregate risks of concern.

Conclusions for Aggregate Exposure and Risk Assessment

An updated aggregate exposure and risk assessment may be required under registration 

review if dietary or residential exposure estimates are updated. An updated assessment 

may also be required if new data are identified which impact the permethrin points of 

departure, the FQPA safety factor for permethrin, or if revisions are made to any 

exposure or risk assessment policies and procedures.

Occupational Exposure and Risks

Permethrin is registered for numerous food/feed crops, livestock and livestock housing, 

modes of transportation, structures, and buildings (including food handling 

establishments). Based on these uses, there is a potential for exposure to permethrin in 

occupational scenarios from handling permethrin products during the application process 

(i.e., mixer/loaders, applicators, flaggers, and mixer/loader/applicators) and a potential 
Page 11 of 26

for postapplication worker exposure from entering into areas previously treated with 

permethrin. The most recent permethrin risk assessment (C. Smith, D357566, 

04/01/2009) included risk estimates for both occupational handler and occupational 

postapplication scenarios.

Due to the scope of the various permethrin occupational uses (there are hundreds of 

registered permethrin products); the 2009 risk assessment evaluated 39 occupational 

handler scenarios to represent the major permethrin occupational handler scenarios based 

on application equipment and formulation. Occupational handler exposures were 

estimated using exposure data from a number of data sources, including: PHED, the 

ORETF, the CMA, and two proprietary exposure studies.

Occupational Handlers

The non-cancer handler risk estimates presented in the 2009 risk assessment indicate that 

all of the occupational handler scenarios resulted in risks that did not exceed HED’s level 

of concern (i.e., MOEs > 100) at some level of risk mitigation. 

An occupational handler cancer risk assessment was also conducted as part of the 2009 

risk assessment. The same scenarios, assumptions, and exposure data were used as in the 

non-cancer assessment. HED estimated cancer risks assuming a maximum of 10 days of 

exposure per year based on data from a Biological & Economic Analysis Division 

(BEAD) memo dated March 24, 2004 (D. Brassard, 03/24/04). Cancer risk estimates 

ranged from 5.4 x 10-11 to 1.1 x 10-4 depending on the level of risk mitigation.

The Agency has determined that there is the potential for occupational postapplication 

exposures to individuals entering fields treated with permethrin as well as individuals 

who wear (i.e., military battle dress) or make (i.e., garment workers) permethrin 

impregnated clothing. The 2009 risk assessment assessed all of these occupational 

postapplication scenarios.

Occupational Postapplication

In the 2009 risk assessment, the non-cancer occupational postapplication risk estimates 

for agricultural fields were estimated using permethrin specific dislodgeable foliar 

residue (DFR) data collected on cotton and peaches. This assessment also used surrogate 

transfer coefficient data from the Agricultural Reentry Task Force (ARTF) database. For 

all agricultural postapplication exposure scenarios, non-cancer risks did not exceed 

HED’s level of concern (i.e., MOEs > 100) on the day of application – approximately 12 

hours following application. No chemical specific exposure data was available for 

estimating occupational postapplication risk estimates for individuals who wear or make 

permethrin impregnated clothing. All non-cancer postapplication exposure scenarios for 

permethrin-impregnated clothing did not exceed HED’s level of concern (i.e., MOEs > 

100).

An occupational postapplication cancer risk assessment was also conducted as part of the 

2009 risk assessment. The same scenarios, assumptions, and exposure data were used as 

in the non-cancer assessment. HED estimated agricultural postapplication cancer risks 

assuming individuals employed solely by one establishment (i.e., “hired hands”) are 

exposed 10 days per year and individuals employed by multiple establishments (i.e., 
Page 12 of 26

commercial or migratory farmworkers) are exposed 30 days per year. Occupational 

postapplication cancer risks for “hired hands” ranged from 6.9 x 10-9 to 1.4 x 10-6 and 

those for “commercial/migratory farmworkers” ranged from 9.9 x 10-8 to 1.0 x 10-6

. 

HED estimated postapplication cancer risks from wearing impregnated clothing by 

calculating an average residue assuming that the uniforms are worn 7 days between 

washes with a total of 30 washes. Occupational postapplication cancer risk estimates for 

individuals who wear or make permethrin impregnated clothing ranged from 3.6 x 10-6 to 

1.2 x 10-6

.

Conclusions for Occupational Exposure and Risk Assessment

The occupational exposure database is adequate to support the registration review process 

for permethrin. Updated occupational handler exposure assessments may be required 

under registration review based upon revisions to the Agency’s scenario-specific

surrogate handler exposure data (http://www.epa.gov/pesticides/science/handlerexposure-table.pdf). Updated occupational postapplication exposure assessments may 

also be required under registration review based upon revisions to the dermal transfer 

coefficients from the Science Advisory Council for Exposure Policy Number 3

(http://www.epa.gov/pesticides/science/exposac_policy3.pdf). Revised occupational 

handler and postapplication assessments may also be needed if toxicological endpoints 

change or other new data are received by the Agency which impact exposure estimates.

Human Studies

Permethrin risk assessments rely in part on data from studies in which adult human 

subjects were intentionally exposed to a pesticide or other chemical. Studies such as 

PHED, ORETF, NDETF, and the ARTF have been reviewed by the Agency and found 

on the basis of available evidence to have been neither fundamentally unethical nor 

significantly deficient relative to standards of ethical research conduct prevailing when 

they were conducted. The permethrin risk assessment also utilizes a number of chemical 

specific studies (see Table 6) which were also reviewed by the Agency and found on the 

basis of available evidence to have been neither fundamentally unethical nor significantly 

deficient relative to standards of ethical research conduct prevailing when they were 

conducted. There is no barrier in EPA's "Protection of Human Subjects" regulation to 

reliance on any of these studies. 

Public Health and Pesticide Epidemiology Data

An updated review of permethrin incident reports was recently prepared by HED (K. Oo, 

D386498, 03/01/2011). For this evaluation, the OPP Incident Data System (IDS) was

consulted for pesticide incident data on the active ingredient permethrin. Permethrin data 

from the Agricultural Health Study (AHS) were also considered.

The IDS includes reports of alleged human health incidents from various sources, 

including mandatory Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) 

Section 6 (a) (2) reports from registrants, other federal and state health and environmental 

agencies and individual consumers. IDS contain reports from across the U.S. and most 

incidents have all relevant product information recorded. Reports submitted to the IDS 

represent anecdotal reports or allegations only, unless otherwise stated in the report. IDS 

records incidents resulting in higher severity outcomes in more detail, in a module called 
Page 13 of 26

the Main IDS module. This system stores incident data for death, major and moderate 

incidents, and it includes more details about the location, date and nature of the incident.

For IDS aggregate summaries, from January 1, 2002 to February 2011, there are 9992

cases reported for permethrin. Because it falls within the categories reported as counts

(which includes minor, unknown or no effects), there is no unique report that provides 

details about the incident and single chemical incidents are not distinguished from 

multiple chemical incidents; however, a high frequency of incidents indicates there is a 

high potential for exposure and vice versa. For the Main IDS, from January 1, 2002, to 

February 1, 2011, there are 2478 cases reported that involve the active ingredient 

permethrin. Of these 2478 cases, there are 432 cases reported for single chemical 

permethrin only in the database and of these there were 5 deaths (HA) and 15 human 

majors (HB). These are summarized in more detail in the 2011 HED permethrin incident 

report.

The AHS is an epidemiology investigation (prospective cohort study) of health effects 

experienced by pesticide applicators in the states of Iowa and North Carolina. A main 

strength of the study is the ability to determine exposure to pesticides before cancer cases 

are diagnosed which distinguishes this study from other types of epidemiological 

investigations. Within the last three years, researchers with the AHS have produced 

several investigations of both cancer and non-cancer outcomes associated with use of 

permethrin on both livestock and crops (Rusiecki et al. 2008; Hoppin et al. 2008; Slager 

et al. 2010; and, Koutros 2010). The Agency will consider and review this data further as 

appropriate during registration review.

Based on the number of incidents reported for permethrin, the effects noted in the 

incidents, and the available AHS data; permethrin warrants further incident analysis 

during registration review. This further analysis will include reviewing permethrin 

incident data from other sources (such as, SENSOR and PCC) as well as cases studies 

and a medical literature search on human health effects of permethrin.

Tolerance Assessment and International Harmonization

Tolerances are established under 40 CFR §180.378 for residues of the insecticide 

permethrin, including its metabolites and degradates, in or on a variety of food and feed 

crops. A table with the US tolerances, the Canada MRLs, Mexico MRLs, and Codex 

MRLs for permethrin in registered RACs is provided in Table 5. These tolerances and 

MRLs are based on the residue analysis of permethrin.

Both Codex and Canada have established MRLs for permethrin. In most cases, the 

Codex and Canadian MRLs differ from each other as well as from the U.S. tolerance. 

Where possible, the Agency will work to harmonize tolerances/MRLs during registration 

review.

The current tolerance expression as listed in the 40 CFR §180.378 has not been updated 

to reflect current HED policies. The tolerance expression will need to be revised during 

the registration review process. The revised tolerance expression should be as follows: 
Page 14 of 26

“Tolerances are established under 40 CFR §180.378(a) for residues of the insecticide 

permethrin, including its metabolites and degradates, in or on a variety of food and feed 

crops. Compliance with the tolerance levels specified is to be determined by measuring 

only permethrin [(3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-

dimethylcyclopropane carboxylate], as the sum of its cis- and trans- isomers in or on the 

commodity”. 

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered 

in this human health risk assessment, in accordance with U.S. Executive Order 12898, 

"Federal Actions to Address Environmental Justice in Minority Populations and LowIncome Populations," 

http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf. The Office 

of Pesticide Programs (OPP) typically considers the highest potential exposures from the 

legal use of a pesticide when conducting human health risk assessments, including, but 

not limited to, people who obtain drinking water from sources near agricultural areas, the 

variability of diets within the U.S., and people who may be exposed when harvesting 

crops. Should these high exposures indicate potential risks of concern, OPP will further 

refine the risk assessments to ensure that the risk estimates are based on the best available 

information.

Cumulative Risk Assessment

Permethrin is a member of the pyrethroid class of insecticides. This class also includes 

cyfluthrin, cypermethrin, deltamethrin, fluvalinate, bifenthrin, fenpropathrin, and lambdacyhalothrin, among others. EPA developed a draft science policy document on the 

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

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

draft, May 19, 2009; 

http://www.regulations.gov/search/Regs/home.html#documentDetail?R=09000064809a6

2df ). This document was supported by the FIFRA Scientific Advisory Panel (SAP) and 

EPA will finalize the policy document on the pyrethroid common mechanism of toxicity 

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

are subject to cumulative risk assessment under the FQPA. Research is ongoing by 

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

SHEDS Probabilistic Exposure Model which are important for the cumulative risk 

assessment. EPA ORD is also developing physiologically-based pharmacokinetic models 

for several pyrethroids. The status of both of these research modeling efforts was 

reviewed by the FIFRA SAP in July, 2010 and meeting materials are available in the 

docket at (http://www.regulations.gov/search/Regs/home.html#docketDetail?R=EPAHQ-OPP-2010-0378). For information regarding EPA’s efforts to evaluate the risk of 

exposure to pyrethroids, refer to http://www.epa.gov/pesticides/cumulative/.

Data Requirements

HED does not anticipate that additional residue chemistry, toxicology or 

occupational/residential exposure data will be required for the permethrin registration 

review process, with the exception of the following study listed below:

• Immunotoxicity Study (OPPTS 870.7800) (See Table 4 for more details).
Page 15 of 26

The following data were required as part of the 2009 Permethrin DCI (GDCI-109701-

26467). To date, EPA has not received studies to satisfy the following requirements:

• Magnitude of Residue Crop Field Trial Data (OPPTS 860.1500) for cabbage; 

collards; grass, forage; lettuce, leaf; soybean, forage; and soybean, seed.
Page 16 of 26

Table 1. Permethrin Nomenclature

Chemical structure

Common name Permethrin

Molecular Formula C21H20Cl2O3

Molecular Weight 391.3

IUPAC name 3-phenoxybenzyl (1RS)-cis-trans-3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropanecarboxylate

CAS name (3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylate

CAS # 52645-53-1

PC Code 109701

Current Food/Feed Site 

Registration

Numerous food/feed crops, livestock, livestock housing and premises, and food-handling 

establishments

Table 2. Physicochemical Properties of Permethrin

Parameter Value Reference

Boiling point 220 °C (0.05 mm Hg; decomposes) 2001 Farm Chemicals Handbook

Melting point 31 °C

35 °C

RD D274107, 7/12/01, S. Mathur

2001 Farm Chemicals Handbook

pH 4.44 at 20 °C RD D274107, 7/12/01, S. Mathur

Density, bulk density, or 

specific gravity

1.229 g/cc

1.190-1.272 specific gravity at 20 °C

RD D274107, 7/12/01, S. Mathur

2001 Farm Chemicals Handbook

Water solubility 0.21 mg/L at 20 °C

<1 ppm

RD D274107, 7/12/01, S. Mathur

2001 Farm Chemicals Handbook

Solvent solubility 258 mg/kg in methanol at 25 °C

>1000 g/kg in hexane at 25 °C

Miscible in most organic solvents except ethylene glycol; 

soluble in acetone, ethanol, ether, and xylene

RD D274107, 7/12/01, S. Mathur

2001 Farm Chemicals Handbook

Vapor pressure 0.07 mPa at 20 °C

<10 Torr at 50 °C

RD D274107, 7/12/01, S. Mathur

2001 Farm Chemicals Handbook

Dissociation constant, pKa Not applicable because permethrin is neither an acid nor 

a base.

Octanol/water partition 

coefficient

log POW = 4.19 at 20 °C RD D274107, 7/12/01, S. Mathur

UV/visible absorption 

spectrum λmax 1 = 273 nm, 3.22 log ε

At pH 7

λmax 2 = 207 nm, 4.55 log ε

λmax 1 = 276 nm, 3.24 log ε

At pH <2

λmax 2 = 209 nm, 4.43 log ε

λmax 1 = 272 nm, 3.19 log ε

At pH >10

λmax 2 = 212 nm, 4.99 log ε

RD D274107, 7/12/01, S. Mathur
Page 17 of 26

Table 3A. Toxicology Data Requirements for Permethrin

Test

Technical

Required Satisfied

870.1100 Acute Oral Toxicity ......................................................

870.1200 Acute Dermal Toxicity .................................................

870.1300 Acute Inhalation Toxicity .............................................

870.2400 Primary Eye Irritation ...................................................

870.2500 Primary Dermal Irritation..............................................

870.2600 Dermal Sensitization.....................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent) ..............................................

870.3150 Oral Subchronic (nonrodent) ........................................

870.3200 21-Day Dermal .............................................................

870.3250 90-Day Dermal .............................................................

870.3465 90-Day Inhalation .........................................................

yes

yes

yes

no

no

yes

yes

1

yes

1

N/A

N/A

870.3700a Developmental Toxicity (rodent)..................................

870.3700b Developmental Toxicity (nonrodent)............................

870.3800 Reproduction.................................................................

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent) .............................................

870.4100b Chronic Toxicity (nonrodent) .......................................

870.4200a Oncogenicity (rat).........................................................

870.4200b Oncogenicity (mouse)...................................................

870.4300 Chronic/Oncogenicity ...................................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial ....................

870.5300 Mutagenicity—Gene Mutation - mammalian ...............

870.5375 Mutagenicity—Structural Chromosomal Aberrations ..

870.5xxx Mutagenicity—Other Genotoxic Effects ......................

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotox. (hen) ....................................

870.6100b 90-Day Neurotoxicity (hen)..........................................

870.6200a Acute Neurotox. Screening Battery (rat) ......................

870.6200b 90 Day Neuro. Screening Battery (rat) .........................

870.6300 Develop. Neuro.............................................................

no

no

yes

yes

yes

yes

no

yes

yes

no 2

870.7485 General Metabolism......................................................

870.7600 Dermal Penetration .......................................................

870.7800 Immunotoxicity.............................................................

yes

yes

yes

yes

yes

no

Special Studies for Ocular Effects

Acute Oral (rat)................................................................................

Subchronic Oral (rat).......................................................................

Six-month Oral (dog).......................................................................

no

no

no

no

no

no

1. Requirements are satisfied by chronic oral toxicity studies.

2. Based on the Agency’s review of existing pyrethroid data, EPA has come to the conclusion that the DNT 

is not a particularly sensitive study for comparing the sensitivity of young and adult animals to pyrethroid. 

The science supporting this conclusion can be found in “Pyrethroids: Evaluation of Data from DNTs & 

Consideration of Comparative Sensitivity” (E. Scollon, 1/20/10, D371723), available at

http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html.
Page 18 of 26

Table 3B. Acute Toxicity Profile for Permethrin

OPPTS

Guideline Study Type MRID No. Results Toxicity Category

870.1100 Acute oral toxicity in Rats 242899 LD50

2280 mg/kg (F)

= 3580 mg/kg (M) III

870.1200 Acute dermal toxicity in Rabbits 242899 LD50 >2000 mg/kg III

870.1300 Acute inhalation toxicity in Rats 45804302 LC50 >2.08 mg/L IV

870.2400 Acute eye irritation in Rabbits 242899 Irritation 24-48 hrs.

All cleared by 72 hrs. III

870.2500 Acute dermal irritation in Rabbits 242899 All irritation cleared by 48 hrs IV

870.2600 Skin sensitization in Guinea Pigs EPA Memo * Non-sensitizer** Not Applicable

* EPA Memorandum (June 13, 1995) “Permethrin: Review of a series 81-6 dermal sensitization study 

(guinea pig maximization test) and a series 85-2 dermal penetration study.”

** Based on a weight of evidence evaluation of other sensitization study data do not indicate that 

permethrin should be regulated as a potential sensitizer. 

Table 3C. Subchronic, Chronic and Other Toxicity Profile for Permethrin

Guideline No./ 

StudyType

MRID Nos.

Doses/Classification

Results

870.3200

21-Day dermal toxicity

- Rat

41143801,42653301

Ph III Summ: 92142030

0, 50, 150, 500 mg/kg/day

Acceptable/guideline

The systemic NOAEL was 500 mg/kg/day (the highest dose tested), 

the systemic LOAEL was not established. The dermal LOAEL was 50 

mg/kg/day based on skin irritation. A dermal NOAEL was not 

identified. 

870.3465, 82-4

15-Day inhalation

toxicity

- Rat

00096713

0, 0.0061, 0.042, 0.583 mg/L

Acceptable/non-guideline

The LOAEL is 0.583 mg/L in male and female rats based on body 

tremors and hypersensitivity to noise. The NOAEL is 0.042 mg/L. 

870.3700a

Prenatal developmental 

- Rat 

40943603

0, 15, 50, 150 mg/kg/day

Acceptable/Guideline

The maternal toxicity LOAEL is 150 mg/kg/day based on clinical 

signs of toxicity and decreased body weight gain and food 

consumption. The maternal toxicity NOAEL is 50 mg/kg/day.the 

developmental toxicity LOAEL is 150 mg/kg/day based on decrease in 

fetal body weights and an increase in the incidence rate of short length 

extra ribs. The developmental toxicity NOAEL is 50 mg/kg/day.

870.3700b

Prenatal developmental 

- Rabbit

92142091,40943602, 92142036

0, 600, 1200, 1800 mg/kg/day

Acceptable/guideline

The maternal toxicity LOAEL is estimated to be <600 mg/kg/day 

based on decreased body weight gain. The maternal toxicity NOAEL 

is not identified.

The developmental toxicity LOAEL is 1200 mg/kg/day based on 

increased post-implantation loss, greater numbers of early and late 

resorptions and an equivocal decrease in ossification of the fore- and 

hind-limbs. The developmental toxicity NOAEL is 600 mg/kg/day.

870.3800

Reproduction and 

fertility effects

- Rat

00102108

00120271

92142092

92142037

0, 500,1000,2500 ppm

(0, 25,50,125 mg/kg/day)

Acceptable/guideline

The LOAEL for systemic toxicity is 2500 ppm (125 mg/kg/day) based 

on tremors observed in the F0 females, and the F1 and F2

The reproductive toxicity NOAEL is ≥2500 ppm (125 mg/kg/day) and 

the reproductive toxicity LOAEL is not identified.

males and 

females. The systemic toxicity NOAEL is 1000 ppm (50 mg/kg/day).

The NOAEL for offspring growth and development is ≥2500 ppm 

(125 mg/kg/day) and the offspring LOAEL is not identified.

870.4300

Chronic toxicity 

-Rat

92142123

0, 500, 1000, or 2500 ppm

0, 19.4, 36.9, 91.5 mg/kg/day (M)

0, 19.1, 40.2, 104 mg/kg/day (F)

Acceptable/guideline

The chronic toxicity LOAEL is 2500 ppm (91.5 mg/kg/day for males 

and 104 mg/kg/day for females), based on tremors and 

hypersensitivity. The NOAEL is 500 ppm (36.9 mg/kg/day for males 

and 19.4 mg/kg/day for females). 

No tumor
Page 19 of 26

Table 3C. Subchronic, Chronic and Other Toxicity Profile for Permethrin

Guideline No./ 

StudyType

MRID Nos.

Doses/Classification

Results

870.4100b

Chronic toxicity

- dog

00129600

0,5,100,1000 mg/kg/day

(capsule)

Acceptable/Guideline

The systemic toxicity LOAEL is 1000 mg/kg/day based on clinical 

neurotoxic signs and decreased body weight gain and food 

consumption. The NOAEL is 100 mg/kg/day.

870.4200b

Carcinogenicity 

- mouse

00062806, 92142033

0, 3, 71, 286 mg/kg/day (M)

0, 3, 357, 714 mg/kg/day (F)

Acceptable/guideline

There were statistically significant increases in liver adenoma at all 

doses for males and at mid- and high-doses for females with a 

significant dose-related trend in both sexes. 

870.4200b

Carcinogenicity 

- mouse

00102110, 92142032

0, 26.9, 110.5, 287.2 mg/kg/day (M). 

0, 29.8, 124.2, 316.1 mg/kg/day (F)

Acceptable/guideline

There was no evidence of significant increase in unusual tumor types. 

A non-significant increase in lung adenomas in males and in lung 

adenomas plus carcinomas in females was seen at the highest dose.

870.4200b

Carcinogenicity 

- mouse

45597105

0, 5000 ppm (Females only)

(0, 780-807 mg/kg/day)

Acceptable/non-guideline

There were significant increases in the incidences of lung 

bronchioloalveolar adenomas in mice. The increased incidences of 

basophilic hepatocellular adenoma did not show a relationship to the 

treatment duration. No progression to carcinoma was observed in the 

lung or liver.

870.5100

Gene mutation

Salmonella typhimurium

41031107

Acceptable/guideline

There were no evidence of increased revertant colonies above control 

in 5 Salmonella strains up to 5000 μg/plate (solubility limit).

870.5550

Unscheduled DNA 

40943604

Acceptable/guideline

There was no evidence of unscheduled DNA synthesis above control 

up to 10-4 M and possibly 10-2 M Limits of cytotoxicity).

870.5395

Mouse Bone Marrow 

Micronucleus

42723302

Acceptable/guideline

There was no evidence that permethrin is clastogenic in the bone 

marrow cells of mice.

870.6200

Acute Neurotoxicity

- Rat

43046301

45657401

Acceptable when considered together

NOAEL = 25 mg/kg/day

LOAEL = 75 mg/kg/day based on observations of clinical signs (i.e., 

aggression, abnormal and/or decreased movement) and increased body 

temperature.

870.6200

Subchronic 

neurotoxicity

- Rat 

00071952

2500,3000,3750,4500, 5000, 7500 ppm

Acceptable/nonguideline

The systemic and neuro- toxicity LOAEL is 2500 ppm (125 mg/kg) 

based on clinical signs of toxicity and decreases in body weight gain 

and food consumption. The systemic and neuro- toxicity NOAEL was 

not identified for this preliminary study.

870.6200b

Subchronic 

neurotoxicity 

-Rat 

40766807

0, 100, 200, 400 mg/kg/day

Acceptable/nonguideline

The systemic LOAEL is 200 mg/kg/day based on tremors and 

irritability. The systemic NOAEL is 100 mg/kg/day. The NOAEL is 

> 400 mg/kg/day with respect to morphological and histological 

changes. 

870.6100b

Delayed Neurotox 

- Hen

00112933

approx. 9000 mg/kg (94.9% a.i.)

cis:trans 36:58.9

Acceptable/guideline

Oral administration of permethrin does not produce delayed 

neuropathy in the hen.

870.6100b

Delayed Neurotox 

- Hen

00097426

0, 2000,4000 mg/kg

cis:trans 25:75

Acceptable/guideline

Oral administration of permethrin up to 4000 mg/kg does not produce 

delayed neuropathy in the hen.
Page 20 of 26

Table 3D. Summary of Toxicological Doses and Endpoints for Permethrin for Use in 

Dietary and Residential Human Health Risk Assessments

Exposure Scenario Dose Used in Risk 

Assessment, UF

Special FQPA SF* and 

Level of Concern for 

Risk Assessment

Study and Toxicological Effects

Acute Dietary

(Females 13-50 years 

of age)

Acute RfD = 

No applicable

An appropriate endpoint attributable to a single dose was not identified.

Acute Dietary

(General population 

including infants and 

children

Oral

NOAEL = 25

mg/kg/day

UF = 100

Acute RfD = 

0.25 mg/kg/day

FQPA SF = 1X

aPAD = 

 FQPA SF

acute RfD

= 0.25 mg/kg/day

Acute Neurotoxicity Study in Rats

LOAEL = 75 mg/kg/day based on 

observations of clinical signs (i.e., 

aggression, abnormal and/or decreased 

movement) and increased body 

temperature.

Chronic Dietary

(All populations)

Oral

NOAEL= 25

mg/kg/day

UF = 100

Chronic RfD = 

0.25 mg/kg/day

FQPA SF = 1X

cPAD = 

FQPA SF

chronic RfD

= 0.25 mg/kg/day

Acute Neurotoxicity Study in Rats

LOAEL = 75 mg/kg/day based on 

observations of clinical signs (i.e., 

aggression, abnormal and/or decreased 

movement) and increased body 

temperature.

Short- and Intermediate 

Term Incidental Oral

Oral

NOAEL = 25 

mg/kg/day

Residential LOC for 

MOE = 100

Acute Neurotoxicity Study in Rats

LOAEL = 75 mg/kg/day based on 

observations of clinical signs (i.e., 

aggression, abnormal and/or decreased 

movement) and increased body 

temperature.

Short-, Intermediate-, 

and Long-Term Dermal 

Dermal

NOAEL= 500 

mg/kg/day

Residential LOC for 

MOE = 100

Occupational LOC for 

MOE = 100

21-Day Dermal Toxicity Study in Rats

LOAEL was not established.

Short-, Intermediate-, 

and Long-Term Term 

Inhalation

Inhalation 

NOAEL=

0.042 mg/l

(Converts to oral 

equivalent of

11 mg/kg/day)

Residential LOC for 

MOE = 100

Occupational LOC for 

MOE = 100

15-Day Inhalation Study in Rats

LOAEL = 0.583 mg/l (converts to oral 

equivalent of 154 mg/kg/day) based on 

body tremors and hypersensitivity to noise.

Cancer 

(Oral, dermal, 

inhalation)

Classification: “Likely 

to be Carcinogenic to 

Humans” based on 

female mouse lung 

adenoma and/or 

carcinoma combined 

tumor rates.

Q1* (mg/kg/day)-1 = 

9.567 x 10-3

NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. FQPA SF = 

FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic).
Page 21 of 26

Table 3E. Summary of Toxicological Doses and Endpoints for Permethrin for Use in 

Occupational Human Health Risk Assessments

Exposure Scenario Dose Used in Risk 

Assessment, UF

Level of Concern for 

Risk Assessment

Study and Toxicological Effects

Short-, Intermediate-, 

and Long-Term Dermal 

Dermal

NOAEL= 500 

mg/kg/day

Residential LOC for 

MOE = 100

Occupational LOC for 

MOE = 100

21-Day Dermal Toxicity Study in Rats

LOAEL was not established.

Short-, Intermediate-, 

and Long-Term Term 

Inhalation

Inhalation 

NOAEL=

0.042 mg/l

(Converts to oral 

equivalent of

11 mg/kg/day)

Residential LOC for 

MOE = 100

Occupational LOC for 

MOE = 100

15-Day Inhalation Study in Rats

LOAEL = 0.583 mg/l (converts to oral 

equivalent of 154 mg/kg/day) based on 

body tremors and hypersensitivity to noise.

Cancer 

(Oral, dermal, 

inhalation)

Classification: “Likely to be Carcinogenic to Humans” based on female mouse lung adenoma 

and/or carcinoma combined tumor rates.

Q1* (mg/kg/day)-1 = 9.567 x 10-3

NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. 
Page 22 of 26

DCI Justification for Immunotoxicity Study

Table 4: Guideline Number: 870.7800 

Study Title: Immunotoxicity - Permethrin

Rationale for Requiring the Data

This is a new data requirement under 40 CFR Part 158 as a part of the data requirements 

for registration of a pesticide (food and non-food uses). 

The Immunotoxicity Test Guideline (OPPTS 870.7800) prescribes functional 

immunotoxicity testing and is designed to evaluate the potential of a repeated chemical 

exposure to produce adverse effects (i.e., suppression) on the immune system. 

Immunosuppression is a deficit in the ability of the immune system to respond to a 

challenge of bacterial or viral infections such as tuberculosis (TB), Severe Acquired 

Respiratory Syndrome (SARS), or neoplasia. Because the immune system is highly 

complex, studies not specifically conducted to assess immunotoxic endpoints are 

inadequate to characterize a pesticide’s potential immunotoxicity. While data from 

hematology, lymphoid organ weights, and histopathology in routine chronic or 

subchronic toxicity studies may offer useful information on potential immunotoxic 

effects, these endpoints alone are insufficient to predict immunotoxicity. 

Practical Utility of the Data

How will the data be used?

Immunotoxicity studies provide critical scientific information needed to characterize 

potential hazard to the human population on the immune system from pesticide 

exposure. Since epidemiologic data on the effects of chemical exposures on immune 

parameters are limited and are inadequate to characterize a pesticide’s potential 

immunotoxicity in humans, animal studies are used as the most sensitive endpoint for 

risk assessment. These animal studies can be used to select endpoints and doses for use 

in risk assessment of all exposure scenarios and are considered a primary data source for 

reliable reference dose calculation. For example, animal studies have demonstrated that 

immunotoxicity in rodents is one of the more sensitive manifestations of TCDD 

(2,3,7,8-tetrachlorodibenzo-p-dioxin) among developmental, reproductive, and 

endocrinologic toxicities. Additionally, the EPA has established an oral reference dose 

(RfD) for tributyltin oxide (TBTO) based on observed immunotoxicity in animal studies 

(IRIS, 1997).

How could the data impact the Agency's future decision-making?

If the immunotoxicity study shows that the test material poses either a greater or a 

diminished risk than that given in the interim decision’s conclusion, the risk assessments 

for the test material may need to be revised to reflect the magnitude of potential risk 

derived from the new data. If the Agency does not have this data, a 10X database 

uncertainty factor may be applied for conducting a risk assessment from the available 

studies.
Page 23 of 26

Table 5. Permethrin International Residue Limits 

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico Codex 2 3

40 CFR 180.378:

Plant/Livestock: Combined residues of 

the insecticide cis- and trans-permethrin

isomers [cis-(3-phenoxyphenyl)methyl 

3-(2,2-dichloroethenyl)-2,2-

dimethylcyclopropane carboxylate] and 

[trans-(3-phenoxyphenyl)methyl 3-(2,2-

dichloroethenyl)-2,2-

dimethylcyclopropane carboxylate] 

Plants/Livestock/Dairy 

commodities: (3-

phenoxyphenyl)methyl 3-

(2,2-dichloroethenyl)-2,2-

dimethylcyclopropane 

carboxylate

(For livestock/ dairy 

commodities calculated on 

the fat content)

Permethrin (sum of 

isomers) (fat- soluble)

Commodity1 Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico Codex 2

Alfalfa, forage 20 100 Alfalfa fodder (dry 

wt)

Alfalfa, hay 45

Almond 0.05 0.1

Almond, hulls 20

Artichoke, globe 5.0

Asparagus 2.0 1

Avocado 1.0

Broccoli 2.0 0.5 2

Brussels sprouts 1.0 0.5 1

Cabbage 6.0 0.5 5 Cabbage, Savoy, 

cabbage head, Chinese 

cabbage (type pe-tsai)

Cattle, fat 1.5 0.1

Cattle, meat 0.10 0.1

Cattle, meat byproducts 0.10 0.1 0.1 4 Edible offal 

(mammalian)

Cauliflower 0.5 0.5

Cherry, sweet 4.0

Cherry, tart 4.0

Corn, field, forage 50

Corn, field, grain 0.05 2 Cereal grains (Po)

Corn, field, stover 30 100 Maize fodder (dry) 

dry wt

Corn, pop, grain 0.05 2 Cereal grains (Po)

Corn, pop, stover 30

Corn, sweet, forage 50

Corn, sweet, kernel plus cob with husks 

removed

0.10 0.1 Sweet corn (corn-onthe-cob)

Corn, sweet, stover 30

Egg 0.10 0.1

Eggplant 0.50 1

Fruit, pome, group 11 0.05 1.0 Apples, pears 50 Apple pomace, Dry; 2 

Pome fruits

Garlic, bulb 0.10

Grain, aspirated fractions 0.50

Goat, fat 1.5

Goat, meat 0.10
Page 24 of 26

Table 5. Permethrin International Residue Limits 

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico Codex 2 3

Goat, meat byproducts 0.10 0.1 4 Edible offal 

(mammalian)

Hazelnut 0.05

Hog, fat 0.05

Hog, meat 0.05

Hog, meat byproducts 0.05 0.1 4 Edible offal 

(mammalian)

Horse, fat 1.5

Horse, meat 0.10

Horse, meat byproducts 0.10 0.1 4 Edible offal 

(mammalian)

Horseradish 0.50 0.5

Kiwifruit 2.0 2

Leaf petioles subgroup 4B 5.0 5.0 Celery 2 Celery

Leafy greens subgroup 4A 20 20 Leaf lettuce

Lettuce, head 20 10 2

Milk, fat (reflecting 0.88 ppm in whole 

milk)

0.2 Milk; 0.2 

Other dairy 

products 

3.0 0.1 F

Mushroom 5.0 0.1

Onion, bulb 0.10

Peach 1.0 

Peaches/Nectarin

es

1.0

Pepper, bell 0.50 0.5 Peppers 1 Peppers; 10 Peppers 

Chili, dried

Pistachio 0.10 0.05 Pistachio nuts (*)

Potato 0.05 0.05 (*)

Poultry, fat 0.15 0.1

Poultry, meat 0.05 0.1 0.1

Poultry, meat byproducts 0.05 0.1

Sheep, fat 1.5

Sheep, meat 0.10

Sheep, meat byproducts 0.10 0.1 4 Edible offal 

(mammalian)

Soybean, seed 0.05 0.05 Soya bean (dry) (*); 

50 Soya bean fodder (dry 

wt); 0.1 Soya bean oil, 

Crude

Spinach 20 20 2

Tomato 2.0 0.5 1

Vegetable, cucurbit, group 9 1.5 0.5 Cucumbers 0.5 Cucumber, Gherkin, 

Squash summer, Winter 

squash; 0.1 Melons, 

except watermelon

Walnut 0.05

Watercress 5.0

MRLs with no US equivalent

Beans 0.5 0.1 Beans (dry)

Blackberries 1

Carrot 0.1
Page 25 of 26

Table 5. Permethrin International Residue Limits 

Summary of US and International Tolerances and Maximum Residue Limits 

Residue Definition:

US Canada Mexico Codex 2 3

Citrus fruits 0.5

Coffee beans 0.05 (*)

Common bean (pods and/or immature 

seeds)

1

Cotton seed 0.5

Cotton seed oil, Edible 0.1

Currants, Black, Red, White 2

Dewberries (including boysenberry and 

loganberry)

1

Gooseberry 2

Grapes 2.0 2.0

Hops, Dry 50

Kale (including among others:Collards, 

Curly kale, Scotch kale, thousandheaded kale; not including Marrow-stem

5 (see regional 

registrations below)

Kohlrabi 0.1

Leek 0.5

Meat (from mammals other than marine 

mammals)

1 (fat) 4

Olives 1

Peanut 0.1

Peas, Shelled (succulent seeds) 0.1

Plums 0.5

Radish, Japanese 0.1

Rape seed 0.5 0.05 (*)

Raspberries, Red, Black 1

Sorghum straw and fodder, Dry 20

Spring Onion 0.5

Stone fruits 2

Strawberry 1

Sugar beet 0.05 (*)

Sunflower seed 1

Sunflower seed oil, crude 1

Sunflower seed oil, edible 1

Tea, Green, Black (black, fermented and 

dried)

20

Wasabi 0.5

Wheat bran, Unprocessed 5 (PoP)

Wheat flour 0.5 (PoP)

Wheat germ 2 (PoP)

Wheat wholemeal 2 (PoP)

Completed: M. Negussie; 02/10/2011 1 Includes only commodities of interest for this action. Tolerance values should be the HED 

recommendations and not those proposed by the applicant.

2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP 

= processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be 

measured on the fat portion of the sample. F = measured in the milk fat. MRLs indicated as proposed have 

not been finalized by the CCPR and the CAC.

4 The MRL accommodates external animal treatment.
Page 26 of 26

Table 6: Proprietary Studies Utilized in 2009 Permethrin Risk Assessment

MRID # Title

44518501 Carbaryl Mixer/Loader/Applicator Exposure Study During Application of RP2 Liquid (21%) to Fruit Trees and Ornamental Plants. D. Merricks. (1998).

44459801 Carbaryl Mixer/Loader/Applicator Exposure Study During Application of RP2 Liquid (21%), Sevin Ready to Use Insect Spray or Sevin 10 Dust to Home 

Garden Vegetables. D. Merricks. (1997).

44439901 Carbaryl Applicator Exposure Study During Application of Sevin 5 Dust to 

Dogs by the Non-Professional. D. Merricks. (1997).

41054701 Exposure of Applicators to Propoxur During Trigger Pump Spray Application 

of a Liquid Product: 99100. R. Knarr. (1988).

45250702 Fipronil: Worker Exposure Study During Application of Regent 20GR in 

Banana Plantation. P. Pontal. (1996).

46601001 Human Exposure During and Following Use of a Pyrethrins/Piperonyl 

Butoxide/MGK-264 Shampoo Formulation on Dogs. S. Selim. (2005).

46188618 Measurement of Air Concentration, Dermal Exposure, and Deposition of 

Pyrethrin and Piperonyl Butoxide Following the Use of an Aerosol Spray. S. 

Selim. (2002).

44658401 Dermal Exposure and Inhalation Exposure to Carbaryl by Commercial Pet 

Groomers During Application of Adams Carbaryl Flea and Tick Shampoo: Lab 

Project Number: 97649: 2405Z-60-97-109: 44088. T. Mester. (1998).

N/A Permethrin transfer from treated cloth to the skin surface; potential for 

exposure in humans. Journal of Toxicology and Environmental Health, 35: 91-

105. H. Snodgrass H. (1992).

46594103 Stroking Test in Dogs After Topical Application of Imidacloprid 10% (w/v) + 

Permethrin 50% (w/v) Spot On. T. Bach; R. Krebber. (2002).

Table 7: HED Memoranda Relevant to Registration Review

Author Barcode/TXR # Date Title

S. Kinard D313662 03/17/2005 Permethrin. Revised Residue Chemistry 

Considerations for Reregistration Eligibility 

Decision (RED) Document.

S. Ary D325429 02/01/2006 Permethrin. Second Revised Acute, 

Chronic, and Cancer Dietary Exposure 

Assessments for the Reregistration 

Eligibility Decision (RED) Document.

C. Smith D325428 04/04/2006 Permethrin: Third Revision of the 

Occupational and Residential Exposure 

Assessment for the Reregistration Eligibility 

Decision Document.

C. Smith D357566 04/01/2009 Permethrin: Sixth Revision of the HED 

Chapter of the Reregistration Eligibility 

Decision Document (RED).

K. Oo D386498 03/01/2011 Permethrin: Review of Human Incidents