DEET Human Health Risk Assessment DP No. D413872 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

Date: February 27, 2014 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: DEET {N,N-diethyl-meta-toluamide). Revised Human Health Risk Assessment 

in Support of Registration Review. 

PC Code: 080301 

Decision No.: 481725 

Petition No.: NA 

DP Barcode: D413872 

Registration No.: NA 

Regulatory Action: Registration Review Risk 

Assessment 

Risk Assessment Type: Single Chemical 

TXRNo.: NA 

CaseNo.: NA 

CAS No.: 134-62-3 

MRIDNo.: NA 

FROM: 

THROUGH: 

TO: 

40 CFR: NA 

Ronnie J. Bever Jr., PhD, DABij/J ico gist ~ ~- . Alexandra LaMay, Biologist r jv- ~ 

ldeliz Negron-Encarnacion, Ph. ., Chemist ~ Risk Assessment Branch V Nil / 

Health Effects Division (7509P) Lid/ 

Michael Metzger, Branch Chief 

Wade Britton, Industrial Hygienist ltc. ~~r------.:~ 

Risk Assessment Branch V Nil 

Health Effects Division (7509P) 

Susan Bartow, Risk Manager Reviewer 

Kevin Costello, Branch Chief 

Risk Management and Implementation Branch IV (RMIB IV) 

Pesticide Re-Evaluation Division (7508P) 

Note: This document was revised to indicate that it represents the scoping and preliminary risk 

assessment for DEET. 

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DEET Human Health Risk Assessment DP No. D413872

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1.0 Executive Summary ........................................................................................................... 3

2.0 HED Recommendations .................................................................................................... 3

2.1 Data Deficiencies: . ........................................................................................................ 3

2.2 Tolerance Considerations.............................................................................................. 3

2.3 Label Recommendations................................................................................................ 4

3.0 Introduction........................................................................................................................ 4

3.1 Chemical Identity ........................................................................................................... 4

3.2 Physical/Chemical Characteristics ............................................................................... 5

3.3 Pesticide Use Pattern...................................................................................................... 5

3.4 Anticipated Exposure Pathways................................................................................... 5

3.5 Consideration of Environmental Justice...................................................................... 6

4.0 Hazard Characterization and Dose-Response Assessment............................................ 6

4.1 Toxicology Studies Available for Analysis................................................................... 6

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)............................... 7

4.2.1 Dermal Absorption..................................................................................................... 8

4.3 Toxicological Effects ...................................................................................................... 8

4.4 Safety Factor for Infants and Children (FQPA Safety Factor) ................................. 9

4.4.1 Completeness of the Toxicology Database.............................................................. 10

4.4.2 Evidence of Neurotoxicity ........................................................................................ 10

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal........ 10

4.4.4 Residual Uncertainty in the Exposure Database ................................................... 11

4.5 Toxicity Endpoint and Point of Departure Selections .............................................. 11

5.0 Dietary Exposure and Risk Assessment......................................................................... 11

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ............................. 11

7.0 Aggregate Exposure/Risk Characterization.................................................................. 12

8.0 Cumulative Exposure/Risk Characterization ............................................................... 12

9.0 Occupational Exposure/Risk Characterization ............................................................ 12

10.0.1 Literature References .................................................................................................. 12

10.0.2 Other References.......................................................................................................... 13

Appendix A. Toxicology Profile................................................................................................ 14

A.1 Toxicology Data Requirements................................................................................... 14

A.2 Toxicity Profiles............................................................................................................ 15

A.3 Hazard Identification and Endpoint Selection: ....................................................... 18

A.4 Executive Summaries: ................................................................................................ 18

Appendix B. Metabolism Summary Table: ........................................................................... 18

Appendix C. Physical/Chemical Properties: ......................................................................... 18

Appendix D. Review of Human Research................................................................................ 19

Appendix E. Endocrine Disruptor Screening Program....................................................... 19
DEET Human Health Risk Assessment DP No. D413872

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1.0 Executive Summary

HED has prepared a qualitative human health risk assessment to support registration review for 

the uses of DEET (N,N-diethyl-meta-toluamide). When writing this risk assessment, HED 

primarily considered the following four documents: (i) The HED Chapter of the Reregistration 

Eligibility Document (RED) for N,N-diethyl-meta-toluamide (DEET) (Kathleen Martin, 

4/22/1997, DEETCH.RED.pdf); (ii) EPA. R.E.D. Facts (1998,

http://www.epa.gov/oppsrrd1/REDs/factsheets/0002fact.pdf); and (iii) DEET Summary of 

Toxicology Data and Hazard Characterization, 4/30/1997).

Every year, approximately one-third of the U.S. population is expected to use DEET (Veltri, et

al., 1994), as a residential personal insect repellent. Individuals are exposed to DEET primarily 

via the dermal route; however, inhalation is possible when sprays are used and ingestion is 

possible if hands are not washed after application. Residential exposure is expected to be 

typically of a short- and intermediate-term duration; however, long-term exposures are possible 

for some individuals in some climates. Except for a few veterinary labels, all uses of DEET are 

residential. There are no food uses for DEET; therefore, dietary exposure is not anticipated. 

The toxicity of DEET has been investigated since the 1940's, and the toxicology database is 

extensive. Based on the available toxicological data, the Agency believes that using DEET 

according to the label instructions does not present a health concern to the general U.S. 

population. The empirical toxicity testing does not demonstrate significant human toxicity to 

DEET. 

No data deficiencies were identified for the toxicology or residential exposure databases. 

A quantitative risk assessment is not required for DEET. No dietary or occupational exposures 

are anticipated. Residential and aggregate were not risks of concern for DEET, due to the lack of 

hazard.

2.0 HED Recommendations

HED has no objection for continued registration of the current DEET pesticide products.

2.1 Data Deficiencies: None.

2.2 Tolerance Considerations

DEET is not a food-use chemical. There are no US tolerances established for DEET.
DEET Human Health Risk Assessment DP No. D413872

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2.3 Label Recommendations

On September 3, 1991, EPA issued label improvement statements (i.e., PR 91-4) to decrease the

likelihood of adverse health effects from possible misuse or overuse of DEET products. Among 

the required statements are: "do not spray in enclosed areas;" "do not apply to eyes and mouth 

and do not apply to the hands of young children;" "do not spray directly on face;" and "after 

returning indoors, wash treated skin with soap and water." HED has no further label 

recommendations at this time.

3.0 Introduction

DEET is a widely used personal insect repellant that can be applied directly to the skin of adults 

and children. The structure, chemical names, and other identifiers are found in the chemical 

identity table below.

3.1 Chemical Identity

Table 3.1 Test Compound Nomenclature.

Compound Chemical Structure

Common name DEET

IUPAC name N,N-Diethyl-3-methylbenzamide

CAS name N,N-Diethyl-3-methylbenzamide

CAS # 134-62-3

PC Code 080301

End-use product/(EP) Not applicable
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3.2 Physical/Chemical Characteristics

Table 3.2 Physicochemical Properties of DEET1 

Parameter Value Reference

Boiling point 285 °C

pH 6.7 (in 1% distilled water) 45163501

Density 0.998 g/mL

Water solubility ( 25°C) 9.04 mg/mL 45163503

Solvent solubility (g/100mL at 25°C) Soluble in acetone, ethanol, isopropanol, 

heptanes, toluene, mineral spirits, 

vegetable oil, and triethyl citrate at 

25/75, 50/50/ and 75/25 ratios.

45163501

Octanol/water partition coefficient 

Log(KOW)

2.5 45163503

UV/visible absorption spectrum 200-225 nm (10 ppm DEET in 

methanol)

45163502

1

Product Chemistry Review: TGAI; Paul Homg; D276463, D274018, D270354, and D262310; 07/26/2001.

3.3 Pesticide Use Pattern

DEET is an insect repellent used in households/domestic dwellings, on the human body and 

clothing being worn, on cats, dogs, horses and pet living/sleeping quarters. There are no food 

uses. It is used to repel flies, midges, black flies, chiggers, deer flies, fleas, gnats, horse flies, 

mosquitoes, no-see-ums, sand flies, small flying insects, stable flies, and ticks. In 1998 it was 

estimated that about 30% of the US population uses DEET annually (K. Martin, DEET RED, 

4/22/1997). DEET can be applied on clothing or directly on the skin. 

Currently, there are 123 active registrations for DEET: 15 correspond to co-formulations with 

MGK 326 and MGK 264, 10 formulations with sunscreen and 1 registration for use on horses. 

The products are available as aerosol sprays (44), pump sprays (38), impregnated materials (15), 

and ready to use solutions/emulsifiable concentrates (25) with concentrations of DEET ranging 

from approximately 4% to 100%. The products can be used either by adults or children single or 

multiple times per day. 

3.4 Anticipated Exposure Pathways

DEET is only applied directly to the human body/clothing, cats, dogs, pet quarters and 

household/domestic dwellings. Dermal exposure it is anticipated to be the primary route of 

exposure; however, inhalation is possible when sprays are used and ingestion is possible if hands 

are not washed after application. Because of its use pattern, people are not normally exposed to 

residues of DEET through the diet. Because the majority of DEET products are ready-to-use and 

based on DEET’s residential use pattern, mixers and loaders are not exposed to DEET; only 

applicators are exposed.
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3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, will be considered in 

future human health risk assessments for DEET, 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. As a part of every 

pesticide risk assessment, OPP considers a large variety of consumer subgroups according to 

well-established procedures. In line with OPP policy, HED estimates risks to population 

subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water 

consumption, and activities in and around the home that involve pesticide use in a residential 

setting. Extensive data on food consumption patterns are compiled by the USDA under the 

Continuing Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk 

assessments for all registered food uses of a pesticide. These data are analyzed and categorized 

by subgroups based on age, season of the year, ethnic group, and region of the country. 

Additionally, OPP is able to assess dietary exposure to smaller, specialized subgroups and 

exposure assessments are performed when conditions or circumstances warrant. Whenever 

appropriate, non-dietary exposures based on home use of pesticide products and associated risks 

for adult applicators and for toddlers, youths, and adults entering or playing on treated areas 

post-application are evaluated. Further considerations are currently in development as OPP has 

committed resources and expertise to the development of specialized software and models that 

consider exposure to bystanders and farm workers as well as lifestyle and traditional dietary 

patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

4.1 Toxicology Studies Available for Analysis

The toxicology database on DEET is sufficient for the assessment of toxicity and characterizing 

the hazard of DEET. The toxicology studies for DEET are summarized in Appendix A. 

Several guideline and open literature toxicity studies are available for DEET; however, endpoints 

for risk assessment have not been selected for DEET. This decision was supported by the 

FIFRA Scientific Advisory Panel (June 4, 1997): “The Panel agrees with the Agency’s hazard 

characterization and decision not to establish toxicity endpoints to be used for risk assessment, as 

exposure to DEET does not result in clearly specific toxicological responses; to rationally choose

toxicity endpoints that reflect a consistent response to DEET would be impossible.” 
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Since the last risk assessment was performed in 1997, several acute 6-pack studies have been 

submitted. Additionally, the following studies were submitted: Pharmacokinetics and 

Comparative Dermal Absorption Study of N,N Diethyl-m-Toluamide (DEET) in the Rat (MRID 

44783301), and Blood Level Study in Rats Following Single and Repeated Dermal Applications 

of N,N-Diethyl-m-Toluamide (DEET; MRID 45041603). These studies are not expected to 

change the conclusions of the SAP.

Several studies were found in the open literature suggesting that dermal exposure may result in 

neurotoxicity in rats. These studies are listed in the Reference Section 10.0 below. On June 7, 

2012, HED’s Hazard Science Policy Council (HASPOC) reviewed these published reports (July 

31, 2012, TXR # 0056346) in consultation with the Office of Research and Development (ORD). 

The HASPOC concluded that these studies do not contribute high quality scientific information

useful for human risk assessment and thus do not suggest that the Agency’s current experimental 

toxicology database is insufficient for evaluating potential hazard to humans. 

The database includes the following toxicity studies (some of which were considered 

Unacceptable/Guideline): 

 Subchronic: 90-day dermal toxicity in rats and micropigs, 90-day feeding in rats, mice, 

and hamsters, 8-week feeding in dogs, 8-week capsule in dogs

 Developmental toxicity: developmental toxicity in rats and rabbits

 Reproduction: 2-generation reproduction study in rats 

 Chronic: combined oral chronic toxicity/carcinogenicity in rats, carcinogenicity in mice, 

chronic oral toxicity in dogs

 Neurotoxicity: acute neurotoxicity in rats, neurotoxicity screening with in utero exposure 

until the age of 9 months (in rats)

4.2 Absorption, Distribution, Metabolism, & Elimination (ADME)

The absorption, distribution, metabolism, and elimination (ADME) of DEET have been 

examined in rats following both oral and dermal administration with varying dose levels and 

durations of treatment (MRIDs 41994401 and 41994402). It was demonstrated that DEET is 

rapidly absorbed, metabolized, and excreted in the urine. Peak blood levels were reached within 

0.5 hour in males and 2 hours in females following oral administration, while after dermal dosing 

levels reach a plateau lasting 1.5-24 hours post-dose. Approximately 53-62% of the orally 

administered dose (AD) was absorbed. After 7 days, less than 0.7% AD remained in the body. 

The major route of elimination was the urine. In a human dermal absorption study (MRID 

42578501), essentially all of the absorbed DEET was metabolized prior to elimination and 

excreted in the urine (6-8% AD), while <0.1% AD was isolated in the feces. There were two 

major metabolites found in the urine. One derived from the oxidation of the ring methyl group 

of DEET, while the other was the product of N-dealkylation of an ethyl group of the 

diethylamide moiety and the oxidation of the ring methyl group. Four minor metabolites were 

also noted.
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4.2.1 Dermal Absorption

In a human dermal absorption study (MRID 42578501), the dermal absorption was 

conservatively estimated to be 20% of the administered dose (AD) of a 15% DEET solution and 

12% of the AD for undiluted DEET.

4.3 Toxicological Effects

DEET may bind to olfactory receptors of insects, interfering with their normal feeding response. 

DEET serves as a true repellent in that some insects intensely dislike the smell of the chemical 

repellent (Z. Syed, 2008). 

Reduced body weight was a common finding among species and the various toxicity tests. Liver 

weight increases were noted in some studies, but there were no accompanying microscopic 

lesions. Tremors in dogs and reduced activity in rats were observed. Testis and epididymides 

degeneration was reported in hamsters. DEET induced α2μ-globulin kidney lesions that are 

specific to male rats and are not relevant to human health. There is no mutagenicity concern for 

DEET (TXR No. 011831, report dated January 4, 1996), and it was classified as Category D 

("Not Classifiable as to Human Carcinogenicity") for carcinogenicity. Increased sensitivity was 

not observed in the offspring; and evidence of neurotoxicity was considered to be of negligible 

biological significance. Technical grade DEET is of low acute toxicity: Category III for oral 

and dermal toxicity and eye irritation; Category IV for inhalation toxicity and dermal irritation. 

DEET is not a dermal sensitizer. 

In subchronic oral toxicity studies in rats (MRIDs 42518101 and 40241703), mice (MRID 

40241704), and hamsters (MRID 41344101), notable responses to treatment include decreased 

body weight, body weight gain, and/or food consumption. Other findings in rodents included 

renal lesions in male rats associated with α2μ-globulin, increased incidences of small testes and 

epididymides with degeneration and cellular debris in hamsters, and increased liver weight 

without corroborating histological evidence of an adverse effect in mice and rats. In dogs 

(MRIDs 43514201 and 43514202), there was body weight loss and decreased organ weights, due 

to rejection of the diet in the feeding study. When DEET was administered to dogs in capsules, 

pytalism was observed in both sexes and abnormal head movements in males; and decreased 

body weight in both sexes, cholesterol in males, and food consumption in females. Decreased 

testes and epididymides weights were noted (without corroborating gross or histological 

pathology), but were not observed at the same dose in the chronic study. 

In the combined chronic oral toxicity/carcinogenicity study in rats (MRID 43514203), findings 

included decreased body weight and food consumption and increased cholesterol in females. 

The chronic oral toxicity study in mice (MRID 41351501) demonstrated decreased body weight, 

body weight gain, and food consumption in both sexes. When DEET was administered to dogs

(MRID 43320101) in capsules, the following findings were observed: increased ptyalism, 

tremors, platelets (females only), and hyperplasia of the uterine epithelium; and decreased body 

weight in both sexes, food consumption in both sexes (with associated thin appearance), and 

cholesterol (males only, rather than the increase seen in rats). 
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In a 90-day dermal study in rats (MRID 40241703 and 40241702), systemic effects included 

decreased body weight in males and increased liver weight in both sexes; α2μ-globulin 

nephropathy was noted in male rats. Local site of application effects included acanthosis and 

hyperkeratosis. In a 90-day dermal study in micropigs (MRID 41344101), systemic effects were 

not observed; acanthosis and/or hyperkeratosis were noted at the skin application site.

Limited inhalation toxicity data are available from studies conducted by the US Army. These 

studies do not indicate an inhalation hazard. Further inhalation toxicity information for 

registration review purposes is not needed at this time.

Several studies were found in the open literature suggesting that dermal exposure may result in 

neurotoxicity in rats. These studies are listed in the Reference Section 10.0 below. On June 7, 

2012, HED’s Hazard Science Policy Council (HASPOC) reviewed these published reports (July 

31, 2012, TXR # 0056346) in consultation with the Office of Research and Development (ORD). 

The HASPOC concluded that these studies do not contribute high quality scientific information 

and thus do not suggest that the Agency’s current experimental toxicology database is 

insufficient for evaluating potential hazard to humans.

In Aggregate IDS (S. Recore, D402939), from January 1, 2007 to February 22, 2012, there were 

2769 reported incidents involving DEET resulting in low severity outcomes. For the Main IDS, 

from January 1, 2007 to February 22, 2012, there are 387 exposures reported for single chemical 

only in the database (382 exposure classified as resulting in a moderate severity, 4 classified as 

major severity and 1 classified as an undetermined severity). DEET is not included in the AHS, 

and therefore this study does not provide information for this report. Overall, a high absolute 

number of incidents have been reported involving DEET. Although the vast majority of these 

incidents were of low severity, several high severity outcomes are reported in the IDS database. 

It is important to note, however, that there are a large number of users of DEET (approximately 

104 million, based on the estimated use rate in 1984-1989 provided by Veltri, 1994). One 

possible explanation for the seizures in children is coincidence. Seizure coinciding with DEET is 

not unexpected, given an estimated 15,000-20,000 afebrile seizures in children (ages zero-19 

years) estimated annually and an estimated 17 million children using DEET 10 times a year. 

While incident information can be an important source of feedback to the Agency, reports of 

adverse health effects allegedly due to a specific pesticide exposure (i.e., an “incident”) are 

largely self-reported and therefore, generally speaking, neither exposure to a pesticide or 

reported symptom (or the connection between the two) is validated or otherwise confirmed. 

Typically, causation cannot be determined based on incident data. Since the last incident 

summary was only recently completed, a revised summary is not required at this time. As data 

warrant, preparation of an updated assessment may be considered in the future. 

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)

DEET does not require food tolerances and is considered to be a ‘non-food use’ chemical; 

therefore, it is not subject to the amendments to the Federal Food, Drug, and Cosmetic Act 

(FFDCA) promulgated under the Food Quality Protection Act (FQPA) of 1996.
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4.4.1 Completeness of the Toxicology Database

The toxicological database on DEET is adequate and will support re-registration eligibility. 

Based on a weight-of-evidence (WOE) approach and considering all of the available DEET 

hazard and exposure information, the HASPOC recommended that subchronic dermal toxicity, 

subchronic inhalation toxicity, and immunotoxicity studies are not required (Kristin Rury, 

7/31/2012, 080301.haspoc.docx; Kristin Rury, 9/3/2013, 080301.haspoc.docx). 

4.4.2 Evidence of Neurotoxicity

There are both acute and subchronic neurotoxicity studies in rats. The acute study (MRID 

41368501) demonstrated transient signs (recovery within 24 hours) that included piloerection, 

increased vocalization, decreased horizontal and vertical activity, and increased response to heat. 

The subchronic neurotoxicity study was derived from a rat multi-generation reproduction study 

(MRID 41368401) and had both in utero and post-natal exposure. Transiently increased motor 

activity was observed in this study. 

The Agency's Office of Pesticide Programs (OPP) Health Effects Division Toxicity Endpoint 

Selection (TES) Committee considered subchronic dermal and neurotoxicity data for the short 

and intermediate-term endpoint on October 18, 1995. The TES Committee determined that the 

possible neurotoxic effect in the two neurotoxicity screening studies was not robust enough to 

provide an adequate basis for risk assessment for the following reasons: (1) the increase in 

horizontal activity seen in the 225 mg/kg/day dose of the subchronic toxicity was transient with 

significance only at the first measuring period; (2) the effect was not accompanied by any 

clinical signs or histopathological changes; and (3) the magnitude of the effect was small.

Although abnormal head movements were noted in the 400 mg/kg/day males only from the 

8-week oral (capsule) dog study (MRID 43514201), this is a relatively large, bolus dose that 

does not occur through dermal application. 

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

DEET did not demonstrate increased sensitivity to offspring in the rat and rabbit developmental 

toxicity studies. In the rat developmental toxicity study (MRID 41351401), maternal toxicity 

was noted following gavage doses of 750 mg/kg/day, included clinical signs (hypoactivity, 

ataxia, decreased muscle tone, foot splay, perinasal encrustation, and perioral wetness), 

decreased body weight and food consumption, increased mortality, and increased liver weight. 

On Day 7, 2/25 animals were sacrificed in extremis and gross necropsy revealed stomach 

ulceration (possibly a localized, irritant effect). These sacrifices occurred following an oral 

gavage dose of 750 mg/kg/day, which is a bolus dose that is not comparable to the current 

dermal dose. At this same dose, there was a slight increase in post-implantation loss and 

decrease in fetal body weight. An oral rabbit developmental toxicity study (MRID 42141101) 

did not indicate either definite maternal or fetal effects at the highest dose tested. The rat multigenerational reproduction study (MRID 40979001) demonstrated systemic effects in the pups 

(decreased body weight); a concern for increased susceptibility was not indicated, because 

kidney effects were seen in all treated males. 
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4.4.4 Residual Uncertainty in the Exposure Database

No quantitative risk assessment was performed; therefore, there are no residual uncertainties. 

4.5 Toxicity Endpoint and Point of Departure Selections

Toxicity endpoints and point of departure selections were not selected. A qualitative toxicity 

assessment is appropriate for DEET. This decision was supported by the FIFRA Scientific 

Advisory Panel (June 4, 1997): “The Panel agrees with the Agency’s hazard characterization 

and decision not to establish toxicity endpoints to be used for risk assessment, as exposure to 

DEET does not result in clearly specific toxicological responses; to rationally choose toxicity 

endpoints that reflect a consistent response to DEET would be impossible.” 

Since the last risk assessment was performed in 1997, several acute 6-pack studies have been 

submitted. Additionally, the following studies were submitted: Pharmacokinetics and 

Comparative Dermal Absorption Study of N,N Diethyl-m-Toluamide (DEET) in the Rat (MRID 

44783301), and Blood Level Study in Rats Following Single and Repeated Dermal Applications 

of N,N-Diethyl-m-Toluamide (DEET; MRID 45041603). These studies are not expected to 

change the conclusions of the SAP.

5.0 Dietary Exposure and Risk Assessment 

As an active ingredient, there are no food uses for DEET.

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

DEET is registered for use as an insect repellent, and for use on clothing or directly on the skin. 

There are also registered DEET-impregnated products, such as tablecloths. DEET products are 

available in multiple formulations, including aerosol sprays, creams, lotions, and in multiple 

concentrations. Exposures to DEET may occur from deliberate application to the skin and 

clothing of individuals. Repellent-use can be on the order of days or weeks or longer, depending 

on the activity pattern and geographic area. Exposure is expected to be of short- and 

intermediate- term exposure duration; however, long-term exposures are possible for some 

individuals in some climates. 

Insect repellents are used on people of all ages. Adults are assumed to experience both dermal 

and inhalation handler exposures, as well as post-application dermal and, potentially, inhalation 

exposure. Adults are assumed to apply repellents to themselves or to others. Additionally, for 

aerosol repellents, individuals to whom the products are being applied can experience indirect 

inhalation exposure during the application. For children, post-application exposure consists of 

dermal, (potentially) inhalation, and hand-to-mouth exposure. An exposure assessment was 

previously prepared to support the Registration Eligibility Decision (RED). A new Standard 

Operating Procedure for Residential Pesticide Exposure Assessment (February 2012, 

http://www.epa.gov/pesticides/science/residential-exposure-sop.html) is now available for the 

exposure assessment of insect repellents. However, since no endpoints have been identified for 
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DEET (1997 RED), a quantitative exposure and risk assessment for DEET products is not 

required at this time. 

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

DEET. An updated residential exposure assessment is not required as a quantitative exposure 

and risk assessment is not required.

7.0 Aggregate Exposure/Risk Characterization

As quantitative dietary and residential exposure assessments are not required for DEET, a 

quantitative aggregate assessment is not required either. Based on the low hazard associated 

with DEET, HED concludes that aggregate risks are not of concern.

8.0 Cumulative Exposure/Risk Characterization

The Agency has not determined that DEET shares a common mechanism of toxicity with other 

chemical substances; therefore, a cumulative risk assessment to support registration review is not 

required at this time.

9.0 Occupational Exposure/Risk Characterization

There is no occupational exposure associated with DEET; therefore, a quantitative assessment is 

not required. 

10.0.1 Literature References

Abdel-Rahman, AK Shetty and MB About-Donia (2001) Subchronic dermal application of 

N,N-diethyl m-toluamide (DEET) and permethrin to adult rats, alone or in combination, causes 

diffuse neuronal cell death and cytoskeletal abnormalities in the cerebral cortex and the 

hippocampus, and Purkinje neuron loss in the cerebellum. Experimental Neurology 

172:153-171.

Abdel-Rahman, A, Dechkovskaia AM, Goldstein LB, Bullman SH, Khan W, El-Masry EM, MB 

Abou-Donia (2004) Neurological deficits induced by malathion, DEET, and permethrin, alone 

and in combination in adult rats. J. Toxicology and Environ. Health. Part A. 67:331-356.

Abou-Donia MB, Goldstein LB, Dechovskaia A, Bullman S, Jones KH, Herrick EA, AbdelRahman AA, Khan WA (2001) Effects of daily dermal application of DEET and permethrin, 

alone and in combination, on sensorimotor performance, blood brain barrier, and blood-testis 

barrier in rats. J. Toxicology and Environmental Health, Part AL Current Issues 62(7):523-541.

Abou-Donia, MB, Goldstein LB, Jones KH, Abdel-Rahman AA, Damodaran TV, Dechkovskaia 

AM, Bullman SL, Amir BE, Khan WA (2001) Locomotor and sensorimotor performance deficit 

in rats following exposure to pyridostigime bromide, DEET, and permethrin, alone and in 

combination. Toxicological Sciences 60:305-314.
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Fediuk DJ, Wang T, Raizman, JE, Parkinson FE Gu X (2010) Tissue deposition of the insect 

repleent DEET and the sunscreen oxybenzone from repeated skin applications in rats. Int. J. 

Toxicol 29(6):594-603.

Jortner BS (2006) The return of the dark neuron. A histological artifact complicating 

contemporary neurotoxicological evaluation. NeuroToxicology 27: 628-634. 

Keil DE, McGuinn WD, Dudley AC, EuDaly JG, Gilkeson GS, Peden-Adams MM.

N,N,-diethyl-m-toluamide (DEET) suppresses humoral immunological function in

B6C3F1 mice. Toxicol Sci. 2009 Mar;108(1):110-23. doi: 10.1093/toxsci/kfp001.

Epub 2009 Jan 13. PubMed PMID: 19141786.

Peden-Adam MM, Eudaly J, Eudaly E, Dudley A, Zeigler J, Lee A, Robbs J,

Gilkeson G, Keil DE. Evaluation of immunotoxicity induced by single or concurrent

exposure to N,N-diethyl-m-toluamide (DEET), pyridostigmine bromide (PYR), and

JP-8 jet fuel. Toxicol Ind Health. 2001 Jun;17(5-10):192-209. PubMed PMID:

12539864.

Van Haaren FV, Haworth SC, Bennett SM, Cody BA, Hoy JB, Karlix JL, Tebbett IR (2001). 

The effects of pyridostigmine bromide, permethrin and DEET alone, or in combination, on fixed 

ratio and fixed-interval behavior in male and female rats. Pharmacology, Biochemistry and 

Behavior 69:23-33.

10.0.2 Other References

Kathleen Martin; The HED Chapter for the Reregistration Eligibility Decision Document (RED) 

for N,N-diethyl-meta-toluamide (DEET) (Case 0002; PC Code 080301), 04/22/1997.

Martin, K. 1997. The HED Chapter of the Reregistration Eligibility Document (RED) for N,Ndiethyl-meta-toluamide (DEET) (Case 0002; PC Code 080301)

Shanna Recore; Revised DEET: Review of Human Incidents; D402939 or D401139, 06/19/2012.

Steven M. Knott, OREB Exposure Assessment and Recommendations for the Reregistration 

Eligibility Document (RED) for DEET, 09/22/1995.

Syed Z. and Leal, W.S. 2008. Mosquitoes smell and avoid the insect repellent DEET, 

Proceedings of the National Academy of Sciences of the United States of America, June 12, 

2008.

Veltri, J.C., Osimitz, T.G., Bradford, D.C., and Page, B.C. 1994. Retrospective analysis of calls 

to Poison Control Centers resulting from exposure to the insect repellent N,N-diethyl-mtoluamide (DEET) from 1985-1989. Clinical Toxicology, 32(1):1-16.
DEET Human Health Risk Assessment DP No. D413872

Page 14 of 20

Appendix A. Toxicology Profile

A.1 Toxicology Data Requirements

The requirements (40 CFR 158.340) for non-food use for DEET are in Table 1. Use of the new guideline numbers 

does not imply that the new (1998) guideline protocols were used.

Study 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 (non-rodent).......................................

870.3200 21/28-Day Dermal........................................................

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

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

yes

yes

no

yes

no

yes

no c

N/A

yes a

N/A

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

870.3700b Developmental Toxicity (non-rodent)..........................

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

yes

yes

yes

yes

yes

yes

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

870.4100b Chronic Toxicity (non-rodent) .....................................

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

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

870.4300 Chronic Toxicity/Carcinogenicity ................................

yes

yes

yes

yes

yes

yes

yes

yes

yes

no c

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

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

870.5375 Mutagenicity—Structural Chromosomal Aberrations..

870.5395 Mutagenicity—Other Genotoxic Effects......................

yes

yes

yes

yes

yes

no b

yes

yes

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

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

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

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

870.6300 Developmental Neurotoxicity ......................................

no

no

yes

yes

no

no

no

no c

yes

N/A

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

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

870.7800 Immunotoxicity in Rats.....................................

yes

yes

yes

yes

yes

yes

a

a This requirement was waived by HASPOC.

b There are mutagenicity studies which evaluate both somatic and germinal cells, which is considered sufficient to satisfy 

CFR requirements.

c The 870.3150 study was not submitted. The 870.4300 study was found to be acceptable/guideline in females only, because 

an adverse effect was not noted in males. The 870.6200b study was classified as acceptable/nonguideline. Considering the 

totality of the toxicological database, no additional studies are necessary. HASPOC indicated no further data requirements 

in July 2012.

N/A = Not Applicable

NR = Not Required
DEET Human Health Risk Assessment DP No. D413872

Page 15 of 20

A.2 Toxicity Profiles

Table A.2.1 Acute Toxicity Profile - DEET

Guideline No. Study Type MRID(s) Results Toxicity Category

870.1100 Acute oral [rat] 00134359

43763201

LD50 = 2170 to 

3664 mg/kg

III

870.1200 Acute dermal [rabbit] 00134359 LD50 = 4280

mg/kg

III

870.1300 Acute inhalation [rat] 00134359 LC50 = 5.95 mg/L IV

870.2400 Acute eye irritation [rabbit] 00134359 Eye irritation and 

corneal opacity 

cleared by day

seven and three,

respectively

III

870.2500 Acute dermal irritation [rabbit] 00134359 Minimal irritationcleared by day 

seven.

IV

870.2600 Skin sensitization 00134359 Minimal irritationcleared by day 

seven

---

Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/TXR #/

Classification /Doses Results

870.1500 Subchronic oral –

non- rodent 

(dog/dietary) 

43514202 (1995)

TXR # 0011625

Unacceptable

0, 300, 1000, 3000, or 

6000/4500/3000 ppm 

(equivalent to 0, 8.4, 28.6, 93.3, 

or 19.5 mg/kg/day in males or 

0, 9.7, 30.6, 91.8, or 11.5 

mg/kg/day in females)

No effects at 3000 ppm or less. The 

6000/4500/3000 ppm dose group 

demonstrated food rejection with 

associated body weight and organ 

weight decreases; thin appearance; fat 

depletion; and histological alterations 

in the kidneys (vacuolation of tubules 

in the cortex), bone marrow, and 

thymus. 

Reliability compromised because only 

two dogs/sex. 

870.1500 Subchronic oral –

non- rodent 

(dog/capsule)

43514201 (1995) 

TXR # 0011625

Unacceptable

0, 50, 100, 200, or 400 

mg/kg/day 

NOAEL = 50 mg/kg/day.

LOAEL = 100 mg/kg/day, based on 

ptyalism. At 400 mg/kg/day, 

decreased body weight in both sexes, 

food consumption in females, 

cholesterol in males, and testis/ 

epididymides weight (no associated 

gross or histopathology) and abnormal 

head movements in males. 

870.3100 Subchronic oral –

rodent (rat)

40241703 (1987)

TXR # 0006599

NOAEL = 500 mg/kg/day

LOAEL = 1000 mg/kg/day, based on 
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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/TXR #/

Classification /Doses Results

Acceptable/Non-Guideline

0, 100, 500, 1000, 2000 or 4000 

mg/kg/day

body weight and food consumption 

decreases. 

(Note: kidney effects at all doses and 

mortality at 4000 mg/kg/day). 

870.3100 Subchronic oral –

rodent (rat)

42518101 (1992)

TXR # 0010528 and 0012510

Unacceptable but 

Acceptable/Non-guideline 

0 or 400 mg/kg/day in males of 

three different rat strains

Kidney lesions in the CD and Fischer 

strains. The NBR strains did not 

develop the kidney lesions. 

Note: p. 6 of the DER shows that the 

Fischer and CDR strains have the 

hyaline droplets and the regenerative 

tubules. 

870.3100 Subchronic oral –

rodent (hamsters)

41344101 (1989)

TXR # 0007833

Acceptable/Guideline

0, 61, 305, 624, or 940 

mg/kg/day

NOAEL = 61 mg/kg/day.

LOAEL = 305 mg/kg/day, based on 

decreased food consumption and body 

weight. Gross (small appearance) and 

histological alterations (degeneration 

or cellular debris) in the testis and 

epididymides at higher doses. At 940 

mg/kg/day, there was mortality. No 

indication of renal lesions. 

870.3100 Subchronic oral -

rodent (mouse)

40241704 (1987)

TXR # 0006599

Not classified

0, 300, 1000, 3000, 6000, or 

10,000 mg/kg/day

NOAEL < 300 mg/kg/day, based on 

slight increase in liver weight. At 

higher doses, there was decreased 

body weight and food consumption. 

870. 3200 Subchronic dermal 

(rat)

40241702 (1987)

TXR # 0006599

Unacceptable

0, 100, 300, or 1000 mg/kg/day

Kidney effects at all doses. 

NOAEL = 100 mg/kg/day

LOAEL = 300 mg/kg/day, based on 

increased liver weight. At higher 

doses, decreased body weight.

870. 3200 Subchronic dermal 

(rat, castrated 

males)

41199301 (1989)

TXR # 0007740

Unacceptable

0 or 1000 mg/kg/day

Castration did not prevent the 

formation of renal lesions 

characteristic of the α2μ-globulin 

model. 

870. 3200 Subchronic dermal 

(micropigs)

44100309 (1996)

TXR # 0012685 and

0029294

Acceptable/Guideline

0, 100, 300, or 1000 mg/kg/day

NOAEL > 1000 mg/kg/day

(Lesions at the site of application 

noted.)

870.3465 Subchronic 

inhalation (dog and 

rat)

1979 studies (MRID #s 

00137973 (with dogs) and 

00137975 (with rats) are in the 

bibliography no DERs could be 

found. 

Studies would not meet current 

guidelines. 

Available study reports are not easily 

readable. Reports appear to be for the 

pathology sections only. Only 2 dogs 

or rats per sex assessed. 

870.3700 Developmental 

(rat)

41351401 (1990)

TXR # 0008117

Acceptable

0, 125, 250, or 750 mg/kg/day

Maternal:

NOAEL = 250 mg/kg/day (slight 

increase in liver weight).

LOAEL = 750 mg/kg/day, based on 
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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/TXR #/

Classification /Doses Results

clinical signs (hypoactivity, ataxia, 

foot splay, perinasal encrustation, and 

perioral wetness), reduced body 

weight and food consumption, 

increased mortality, and increased 

liver weight. 

Developmental:

NOAEL = 250 mg/kg/day.

LOAEL = 750 mg/kg/day, based on 

slight increase in percent postimplantation loss and decrease in fetal 

body weight. 

870.3700 Developmental 

(rabbit)

42141101 (1991)

TXR# 0009470 and 0012510

Not classified. 

Upgraded to Acceptable), 30, 

100, or 325 mg/kg/day.

No maternal or developmental effects 

at HDT. 

870.3800 Multi-generation 

reproduction (rat)

40979001 (1989)

44100304 (1996)

TXR # 007645

Acceptable/Guideline

0, 500, 2000, or 5000 ppm. 

Parental systemic:

(Kidney effects at all doses)

Reproductive: 

NOAEL > 5000 ppm

Offspring:

NOAEL = 500 ppm

LOAEL = 2000 ppm, based on 

reduction in body weights for male 

pups starting on Day 7 for males and 

Day 14 for females. 

870.4100 Chronic oral 

(dog/capsule)

43320101 (1994)

TXR # 0011630

Acceptable/Guideline

0, 30, 100, or 400 mg/kg/day

NOAEL = 100 mg/kg/day

LOAEL = 400 mg/kg/day, based on 

ptyalism; tremor; decreased food 

intake, body weight, and cholesterol; 

thin appearance; increase in platelet 

levels (females only); and hyperplasia 

in uterine epithelium. 

870.4200 Carcinogenicity 

(mouse)

41351501 (1990)

TXR # 0008117

Acceptable/Guideline

0, 250, 500, or 1000 mg/kg/day

NOAEL = 500 mg/kg/day

LOAEL = 1000 mg/kg/day, based on 

decreased body weight, body weight 

gains, and food consumption. 

870.4300 Combined chronic 

toxicity/ 

carcinogenicity 

(rat)

43514203 (1995)

TXR # 0011625

Acceptable/Guideline for 

females, but males were dosed 

too low. 

0, 10, 30, or 100 mg/kg/day

NOAEL = 30 mg/kg/day for females, 

> 100 mg/kg/day for males. 

LOAEL = 100 mg/kg/day for females, 

based on decreased body weight and 

food consumption; and increased 

cholesterol levels. Not established for 

males.

No evidence of carcinogenicity. 

870.5100 Mutagenicity –

Ames test. 

41344801 (1989)

TXR # 0008111

Acceptable/Guideline

No evidence of mutagenicity. 

870.5375 Chromosome 41344401 (1989) No evidence of induced chromosome 
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Table A.2.2 Subchronic, Chronic and Other Toxicity Profile

Guideline No. Study Type MRID No. (year)/TXR #/

Classification /Doses Results

 aberration in CHO 

cells 

TXR # 0008111

Acceptable/Guideline

aberrations. 

870.5550 Unscheduled DNA 

synthesis

41344301 (1989)

TXR # 0008111

Acceptable/Guideline

No evidence of unscheduled DNA 

synthesis. 

870.6200a Acute 

neurotoxicity (rat)

41368501 (1990)

TXR # 0009829

Acceptable/Guideline

0, 50, 200, or 500 mg/kg/day.

NOAEL = 50 mg/kg/day.

LOAEL = 200 mg/kg/day, based on 

decreased vertical activity one hour 

after dosing. At 500 mg/kg/day, 

piloerection, increased vocalization, 

decreased horizontal and vertical 

activity, and an increased response 

time to heat. 

870.6200b Subchronic 

neurotoxicity (rat)

44100307 (1996)

TXR # 0009829

Acceptable/Non-Guideline. 

0, 500, 2000, or 5000 ppm.

NOAEL = 2000 ppm.

LOAEL = 5000 ppm, based on 

increased motor activity. 

870.6300 Developmental 

neurotoxicity

No Study [Some aspects of a developmental 

toxicity study were evaluated in the 

neurotoxicity subgroup in the rat 

multi-generation reproduction study, 

but only in adults. The study does not 

have protocol consistent with the DNT 

study protocol.] 

870.7485 General 

metabolism (rat)

41994401 (1990)

41994402 (1991)

41994403 (1991)

TXR # 0009065

Absorption, distribution, elimination, 

and metabolite 

identification/quantification was 

investigated. These studies satisfy the 

requirement for a general metabolism 

study. 

870.7600 Dermal absorption 

(humans)

42578501 (1995)

TXR # 0010587

[Selim, S, et al, FAP 

Toxicology, 25:95-100]

Dermal absorption factors of 20% for 

a fifteen percent formulation and 12% 

for undiluted DEET. 

A.3 Hazard Identification and Endpoint Selection: Only a qualitative assessment was 

performed for DEET.

A.4 Executive Summaries: Please refer to the DEET Summary of Toxicology Data and 

Hazard Characterization (April 30, 1997).

Appendix B. Metabolism Summary Table: This table is not necessary for DEET, considering 

its use profile.

Appendix C. Physical/Chemical Properties: These properties were provided in Section 3.2 

above.
DEET Human Health Risk Assessment DP No. D413872

Page 19 of 20

Appendix D. Review of Human Research

A dermal absorption study with human volunteers (1992, MRID 42578501) involving intentional 

exposure to DEET was relied on in earlier assessments to provide the dermal absorption factor. 

This study was reviewed by the OPP Human Research Ethics Reviewer (report dated July 6, 

2012) and there is "no barrier in law or regulation to its being relied upon in actions under 

FIFRA or §408 of FFDCA". If EPA decides to use any other studies with human volunteers, 

EPA will ensure that all applicable regulatory requirements are met, including, but not limited to, 

the requirements for EPA ethics review and Human Studies Review Board review of certain 

research involving intentional exposure of human subjects.

Appendix E. Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, 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 required by FFDCA section 408(p), DEET 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. A second list of 

chemicals identified for EDSP screening was published on June 14, 20131and includes some 

pesticides scheduled for Registration Review and chemicals found in water. For further 

information on the status of the EDSP, the policies and procedures, the lists of chemicals, future 

lists, the test guidelines and the Tier 1 screening battery, please visit our website.2

 

1

See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.

2

http://www.epa.gov/endo/
DEET Human Health Risk Assessment DP No. D413872

Page 20 of 20

In the interim, EPA is making no human health or environmental safety findings associated with 

the EDSP screening of DEET. Before completing this Registration Review, the Agency will 

make an EDSP FFDCA section 408(p) determination.