Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 134-62-3 Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • N,N-Diethyl-m-toluamide
  • BENZENAMIDE,N,N-DIETHYL-3-METHYL (9CI)
  • DEET
  • CHEMFORM
  • DETA
  • DIELTAMID
  • MGK
  • NAUGATUCK DET
  • AUTAN

Human Toxicity Excerpts

  • UNDILUTED CMPD MAY IRRITATE MUCOUS MEMBRANES BUT REPELLENT CONCENTRATIONS CAN BE APPLIED SAFELY TO SKIN; DAILY APPLICATION TO FACE AND ARMS FOR 5 CONSECUTIVE DAYS GAVE ONLY MILD IRRITATION. [Spencer, E. Y. Guide to the Chemicals Used in Crop Protection. 7th ed. Publication 1093. Research Institute, Agriculture Canada, Ottawa, Canada: Information Canada, 1982., p. 165]**PEER REVIEWED**
  • IT IS: IRRITANT TO EYES, MUCOUS MEMBRANES ... INGESTION CAN CAUSE CNS DISTURBANCES. [The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983., p. 412]**PEER REVIEWED**
  • CHILD EXPOSED TO PRODUCT CONTAINING M-DET EXPERIENCED DISORIENTATION, STAGGERING GAIT, SLURRED SPEECH AND EPISODES CONSISTING OF STIFFENING INTO SITTING POSITION, CRYING OUT, EXTENDING EXTREMITIES, FLEXING FINGERS AND DORSIFLEXING TOES. [Weast, R.C. (ed.). Handbook of Chemistry and Physics. 64th ed. Boca Raton, Florida: CRC Press Inc., 1983-84., p. II-346]**PEER REVIEWED**
  • A five-yr-old girl, sprayed with DEET nightly for three months, developed headaches and slurred speech, progressing to athetosis, shaking, screaming, and convulsions. She died 24 days after hospitalization. At autopsy the brain showed generalized edema with intense congestion of meninges. There was no demyelination and no evidence of meningitis. An 18-mo-old child who ingested an unknown quantity of a liquid prepn of DET exhibited similar signs and symptoms but eventually recovered. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-346]**PEER REVIEWED**
  • Seizures and acute behavior change developed in an 8 yr old girl following exposure to Muskol and Off insect repellents. She recovered within 3 days with supportive treatment; including anticonvulsant (phenytoin) medication. The assumed toxic agent was N,N-diethyltoluamide. [Roland EH et al; Can Med Assoc J 132 (2): 155-56 (1985)]**PEER REVIEWED**
  • One patient who was accidentally sprayed in the eye with OFF had immediate smarting sensation which subsided rapidly when he flushed his eye with water. Two hr later the only abnormality was fine gray stippling of the corneal epithelium with tiny gray dots in the palpebral fissure. Vision at that time was reduced from 20/15 to 20/20. The eye returned rapidly to normal. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 338]**PEER REVIEWED**
  • This is a case report of a 6-yr-old girl who extensively used an insect repellent containing N,N-diethyltoluamide (DET; DEET). The family history and tests performed on the child indicated that the girl was deficient in ornithine carbamoyl transferase (OCT). This deficiency was apparently agitated by the extensive use of DET. Phthalyl alcohol was identified in the child's liver at least 10 days after administration. [Heick HMC et al; J Pediatr 97 (3): 471-3 (1980)]**PEER REVIEWED**
  • BULLOUS ERUPTIONS, SKIN NECROSIS, & PROLONGED DISABILITY WAS REPORTED IN MILITARY PERSONNEL IN SOUTH VIETNAM. ALTHOUGH AN INSECT HAD BEEN PREVIOUSLY THOUGHT WHOLLY THE CULPRIT, DIETHYL TOLUAMIDE, INSECT REPELLENT USED PRODUCES SIMILAR ERUPTIONS. CAUTION ADVISED. [LAMBERG SI, MULRENNAN JA; ARCH DERMATOL 100 (5): 582-6 (1969)]**PEER REVIEWED**
  • A 42 year old woman with no prior atopic history touched a companion who had just sprayed himself with repellent containing 52% deet. Generalized pruritus rapidly developed and progressed to generalized angioedema. The woman became nauseated and unconscious en route to hospital, where her blood pressure was found to be 70/40 mm Hg. She responded to treatment with epinephrine, diphenhydramine, and in corticosteroids. Periorbital edema developed after another exposure to deet I week later. In a controlled setting, a small amount of deet in isopropyl alcohol was applied to the patient's forearm. Pruritus occurred in the treated area within 15 sec and or progressed to localized urticaria despite immediate washing of the arm. The patient was treated with epinephrine and diphenhydramine when she reported pruritis of lips and the contralateral arm. She responded to therapy, but the localized urticaria lasted for over 1 hr. Isopropyl alcohol alone elicited non response. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1503]**PEER REVIEWED**
  • A 35 year old woman presumed allergy reaction to insect when she had used several repellents on frequent camping trips and noticed that a "red, raised lesion" appeared about 30 min after application. Open patch testing on the forearm with "pure" deet revealed, within 20 min, a macular erythema that evolved into a wheal-and-flare response. Similar tests with dimethyl phthalate and butopyronoxyl were negative. The response was passively transferred, suggesting a possible immunologic mechanism. It was indicated that this particular case of contact urticaria was of immediate-type hypersensitivity (stage 1). [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1503]**PEER REVIEWED**
  • Several cases of a deet-associated toxic encephalopathy have been reported in young females. A 3.5 year old girl suffered a bizarre illness after all of a 180 ml aerosol can of deet had been used each evening for 2 weeks to spray her and her night clothes and bedding. Because of this exposure and because careful medical examination failed to suggest any other cause, the possibility was considered that deet was the cause. However, it was pointed out that, even if the child had absorbed all of the deet discharged from the aerosol can, the dosage of active e ingredient would have been only 0.14 ml/kg/day, a level tolerated by animals. The signs were disorientation, staggering gait, slurred speech, and episodes consisting of stiffening into a sitting position, crying out, extending the extremities, flexing the fingers, and dorsiflexing the toes. Therapy, which began 1 day after onset, was symptomatic. Recovery was complete in 4 days. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1503]**PEER REVIEWED**
  • A 30 year old man following self-medication with 75% deet for a papular, truncal, erythematous rash that was later diagnosed as pityriasis rosea. It was his recollection that he had used deet successfully to treat a similar condition 4 years previously. Beginning 2 weeks prior to admission to the hospital, he daily applied deet on one side of his body and entered a homemade sauna for 60-90 min; he emerged from the sauna, treated the other side of his body, and reentered the sauna for another 60-90 min. This procedure was continued for 1 week. He was occasionally lethargic and incoherent following the deet-sauna treatment. Four days prior to admission, he developed marked personality changes that included delusions of grandeur and verbal aggressivity. He became more irritable and belligerent and was admitted to the hospital, where he required seclusion because of his violent behavior. His condition worsened and was diagnosed as acute manic psychosis. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1504]**PEER REVIEWED**
  • Serious adverse effects have occurred when used under tropical condition, when it was applied to areas of skin that were occluded during sleep (mainly the antecubital and popliteal fossae). Under these conditions, the skin became red and tender, then exhibited blistering and erosion, leaving painful weeping denuded areas that were slow to heal. Severe scarring occasionally resulted from some of these severe reactions. [U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 80]**PEER REVIEWED**
  • Toxic encephalopathic reactions have apparently occurred in rare instances following dermal application, mainly in children who were intensively treated. The more frequently cause of systemic toxicity has been ingestion, deliberate in adults, accidental in young children. [U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 80]**PEER REVIEWED**
  • Manifestation of toxic encephalopathy have been behavioral disorders including headache, restlessness, irritability, ataxia, rapid loss of consciousness, hypotension, and seizures. Some cases have shown flaccid paralysis and areflexia. Deaths have occurred following very large doses. Blood levels of DEET found in fatal systemic poisonings have ranged from 168 to 240 mg/l. Interpretation of DEET toxicity in some fatal cases has been complicated by effects of simultaneously ingested ethanol, tranquilizers, and other drugs. One well documented case of anaphylactic reaction to DEET has been reported. One fatal case of encephalopathy in a child heterozygous for ornithine carbamoyl transferase deficiency resembled Reyes syndrome, but the postmortem appearance of the liver was not characteristic of the syndrome. [U.S. Environmental Protection Agency/Office of Prevention, Pesticides, and Toxic Substances. Reigart, J.R., Roberts, J.R. Recognition and Management of Pesticide Poisonings. 5th ed. 1999. EPA Document No. EPA 735-R-98-003, and available in electronic format at: http://www.epa.gov/pesticides/safety/healthcare, p. 81]**PEER REVIEWED**
  • Application of deet to the face and arms of five volunteers daily for 5 consecutive days produced only slight irritation of the face and nose and some desquamation about the nose. Similar changes, plus dryness of the face and slight tingling sensation, occurred among those who received applications for 3 consecutive days/week for 6 weeks, but all symptoms disappeared during each 4-day period of rest. [Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 631]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • IN 200-DAY FEEDING TRIALS RATS RECEIVING 10000 MG/KG DIET EXHIBITED NO ADVERSE EFFECTS. [Worthing, C.R., S.B. Walker (eds.). The Pesticide Manual - A World Compendium. 7th ed. Lavenham, Suffolk, Great Britain: The Lavenham Press Limited, 1983., p. 194]**PEER REVIEWED**
  • ON GASTRIC INTUBATION IN RATS THE ORTHO-ISOMER IS MOST TOXIC AND THE PARA-ISOMER LEAST TOXIC. ... TOXIC DOSES IN RATS AND RABBITS HAVE PRODUCED DEPRESSION, LOSS OF RIGHTING REFLEXES, LABORED RESPIRATION, COMA AND TERMINAL CONVULSIONS. ... IN RABBITS ERYTHEMA AND DESQUAMATION ARE DESCRIBED AS WELL AS PERCUTANEOUS INTOXICATION /AFTER DERMAL APPLICATION OF UNDILUTED MATERIAL AND 50% SOLN/. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-346]**PEER REVIEWED**
  • Application of pure N,N-diethyl-m-toluamide to rabbit eyes has caused edema of the conjunctiva, lacrimation, discharge, and slight transient cloudiness of the corneas. Injury of the epithelium, indicated by staining with fluorescein, persisted for two days, but the eyes returned to normal in five days. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 337]**PEER REVIEWED**
  • 100 & 1000 MG/KG WERE APPLIED ON BARE RAT SKIN DAILY BEFORE & DURING ENTIRE PREGNANCY. CONCEPTION WAS SIMILAR IN TEST GROUP & CONTROLS, WHILE RATE OF IMPLANTATION, SHOWING DECR IN GROUP GIVEN 100 MG/KG, WAS GREATLY DECR BY 1000 MG/KG DUE TO PRE-IMPLANTATION AND POST-IMPLANTATION RESORPTION. [GLEYBERMAN SE ET AL; FARMAKOL TOKSIKOL 2: 202-5 (1975)]**PEER REVIEWED**
  • AEROSOL SPRAY CONTAINING DEET (3.75-75.0%) APPLIED TO HORSE'S SKIN. DEET PRODUCED DERMATOSIS IN ONE OR BOTH OF PAIRED HORSES ADMIN 15% OR GREATER. MOST COMMON SIGN OF TOXICOSIS WAS HYPERSTEATOSIS. RELATIONSHIP BETWEEN APPEARANCE OF HYPERSTEATOSIS & CONCN WAS DIRECT. [PALMER JS; AM J VET RES 30 (11): 1929-32 (1969)]**PEER REVIEWED**
  • SINGLE DOSE OF N,N-DIETHYL-M-TOLUAMIDE IN CORN OIL WAS ADMIN TO MALE MICE BY GAVAGE IN DOMINANT LETHAL ASSAY TO EVALUATE ITS MUTAGENICITY IN MALE GERM CELLS. THE CMPD DID NOT INDUCE A POSITIVE MUTAGENIC RESPONSE. [SWENTZEL, KC; INVESTIGATION OF N,N-DIETHYL-M-TOLUAMIDE(M-DET) FOR DOMINANT LETHAL EFFECTS IN THE MOUSE; REPORT, ISS USAEHA-51-0034-78, ORDER NO AD-A058414; 12 (1977)]**PEER REVIEWED**
  • Rats, both sexes, were exposed for single 4 hr periods to aerosols of M-Det at concn of 4100, 2900 or 2300 mg/cu m. The rats were given a battery of behavioral tests. The results permitted distinctions to be made between performance at all 3 levels for both males and females. Tests incl measures of activity endurance, balance, tactical sensitivity, postexposure learning, and memory of a task learned the day before exposure. Necropsy did not show any gross physical changes. Thus behavioral tests were able to establish changes resulting from acute exposures at concn below those at which toxic signs could be seen. [Sherman RA; Behavorial effects of acute aerosol exposure to N,N-diethyl-m-toluamide (M-Det), January-February 1979; Report, ISS USAEHA-75-51-0034-80, Order No AD-A076939; 28 (1979)]**PEER REVIEWED**
  • IN A 15 DAY SUBCHRONIC STUDY, RABBITS WERE ADMIN 528 MG/KG/DAY ORALLY. BODY WT GAIN WAS DECR THROUGHOUT THE STUDY. SERUM CALCIUM LEVELS DECR & CHOLESTEROL & TRIGLYCERIDE LEVELS INCR SIGNIFICANTLY. NO OTHER TOXIC SIGNS WERE OBSERVED DURING THE 15 DAY TREATMENT PERIOD. [HAIGHT EA ET AL; SUBCHRONIC ORAL TOXICITY OF THE INSECT REPELLENT N,N-DIMETHYL-M-TOLUAMIDE (M-DET), SEPT 1978-MAY 1979; US NTIS AD REP AD-A082,131/4: 27 PP (1980)]**PEER REVIEWED**
  • A comparison of nine commercial repellents was made on human volunteers against Aedes aegypti using dose-response methods. In the first series of tests measuring intrinsic repellency (0 hr), stabilene, and MGK Repellent 326 were significantly inferior to deet, dibutylphthalate, indalone, dimethylphthalate, MGK Repellent II, ethyl hexanediol, and citronyl (ranked by ED50). A second series of tests conducted to measure the persistence of these compounds, showed stabilene, MGK Repellent 326, and dibutylphthalate were ineffective after 4 hr. Efficacy ranking by 4 hr ED50 was indalone, citronyl, dimethylphthalate, ethyl hexanediol, and deet. The relative superiority of deet in comparison to other standard repellents is discussed. [Buescher MD et al; Mosq News 42 (3): 428-433 (1982)]**PEER REVIEWED**
  • Standard and experimental topical repellents were tested against the neotropical sand fly Lutzomyia longipalpis, using dose-response techniques. Deet, indalone, and citronyl were the most effective of the standard repellents tested on humans. ...Comparative sensitivity of this sand fly species to repellents is greater than that of certain mosquito, flea, tick, and reduviid bug species. [Buescher MD et al; J Med Entomol 19 (2): 176-180 (1982)]**PEER REVIEWED**
  • Relative repellency of citronyl, deet, dimethylphthalate, N-benzoyl piperidine (NBP), and N-toluyl piperidine was evaluated against Simulium himalayense. The chemical concentrations of 10, 15, and 20% were used on the skin of human subjects. Citronyl, NBP, and N-toluyl piperidine were better repellents than deet, and dimethyl phthalate 20% citronyl provided 8.5 hr average protection, whereas deet and dimethyl phthalate were effective for 7 and 6 hr, respectively. [Das SC et al; Ind J Med Res 81: 378-381 (1985)]**PEER REVIEWED**
  • Rats killed by dosages in the LD50 range showed lacrimation, chromodacryorrhea, depression, prostration, tremors, and asphyxial convulsions; respiratory failure usually preceded cardiac failure. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1500]**PEER REVIEWED**
  • Five standard topical repellents and a synthetic pyrethroid were evaluated against the tsetse Glossina morsitans using a dose-response testing procedure on white rabbits. The repellents, in decreasing order of effectiveness based on 0 hr ED50 tests, were dimethylphthalate, 2-ethyl-1,3-hexanediol, and indalone were significantly (p<0.05) more potent than citronyl. None of the materials tested were significantly more effective than deet. ... [Wirtz RA et al; J Med Entomol 22 (3): 271-75 (1985)]**PEER REVIEWED**
  • It was: found that single dermal applications to rabbits at rates of about 2000 or 4000 mg/kg produced no systemic effect but did produce mild to moderate erythema. Repeated dermal application of 50% solutions for 13 weeks at the rate of about 200 mg/kg/day produced no evidence of systemic toxicity but did produce desquamation, coriaceousness, dryness, and fissuring in the same species. Except for some scarring, these lesions cleared within 3 weeks. Instillation of deet into the eyes of rabbits produced mild to moderate edema of the nictitating membrane, lacrimation, conjunctivitis, and some corneal injury, as revealed by fluorescein staining. After 5 days all eyes appeared normal. The irritating effects of deet at the dermal application site and to the eye have been corroborated by others. No sensitization was seen in guinea pigs. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1500]**PEER REVIEWED**
  • When rats were fed deet at a dietary level of 10,000 ppm for about 200 days, their growth was decreased without a decrease in food intake. There was a significant increase in the relative weight of the testes and liver in males, of the liver and spleen in females, and of the kidneys in both males and females. Some of these changes were seen in lesser degree at a dietary level of 1000 ppm. No gross or significant histological changes were seen at any dietary level, and no changes of any kind were observed at 100 or 500 ppm (about 25 mg/kg/day). [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1501]**PEER REVIEWED**
  • The cardiovascular effects of deet was examined in in rats and dogs. When anesthetized rats were treated intraperitoneally with 75% deet in ethyl alcohol at dosages of 225, 125, and 63 mg/kg, a dose-related drop in mean blood pressure was observed within 30 min; heart rate also was reduced at 225 mg/kg. Dogs similarly treated at 225 mg/kg had decreased blood pressure, heart rate, and cardiac output, along with minor changes in the electrocardiogram. Deet at 225 mg/kg also reduced the responsiveness of anesthetized rats to exogenous acetylcholine, indicating that the hypotensive effects of the repel lent might be due partly to an interaction with cholinergic systems. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1501]**PEER REVIEWED**
  • Similar results were found in other subacute dermal and feeding studies with deet in rats, rabbits, and dogs. In these oral studies, 2000 ppm proved to be a no-effect level. Oral administration of deet to dogs at rates of 100 and 300 mg/kg/day caused tremor and hyperactivity and occasional vomiting, but no other effects. Blood studies (hemoglobin, hematocrit, sedimentation rate, platelet counts, total and differential white cell counts) on dogs receiving 300 mg/kg orally or dermally or on rabbits receiving 300 mg/kg dermally revealed no effect on the hematopoetic system. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1501]**PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Rat (male) oral 3000 mg/kg [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1500]**PEER REVIEWED**
  • LD50 Rat (female) oral 2000 mg/kg [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1500]**PEER REVIEWED**
  • LD50 Rabbit dermal was about 3180 mg/kg [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1500]**PEER REVIEWED**
  • LC50 Rat inhalation >4100 mg/cu m/4 hr [Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994., p. 327]**PEER REVIEWED**
  • LD50 Rat skin 5000 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1199]**PEER REVIEWED**
  • LD50 Mouse skin 3170 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1199]**PEER REVIEWED**
  • LD50 Rabbit oral 1584 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1199]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • (14)C-DEET IN 0.3% SOLN OF 20% ETHANOL WAS APPLIED TO BACKS OF MICE. HIGH CONCN OF RADIOACTIVITY FOUND IN LACRIMAL GLAND, LIVER, BILE, INTESTINAL CONTENTS, KIDNEY, URINE, & NASAL MUCOSA. RESULTS WERE SIMILAR TO THOSE OBTAINED AFTER IV ADMIN. A 25% SOLN OF (14)C-DEET IN ABSOLUTE ALC WAS APPLIED TO HUMAN VOLUNTEERS, & URINARY EXCRETION WAS MEASURED. URINARY CONCN REACHED A PEAK AFTER SEVERAL HOURS. [BLOMQUIST L, THORSELL W; ACTA PHARMACOL TOXICOL 41 (3): 235-43 (1977)]**PEER REVIEWED**
  • (14)C-DEET WAS RAPIDLY RESORBED IN LARGE AMT BY SKIN OF MICE & PENETRATED INTO BLOOD WITH MAX CONCN IN 1 HR. EXCRETION WAS ALMOST COMPLETE FROM BLOOD WITHIN 1-3 DAYS & MOST WAS EXCRETED IN URINE. RESIDUAL AMT DETECTED FOR 1-3 MO IN SKIN, FATTY TISSUE, & MUSCLES. [LURE AA ET AL; MED PARAZITOL PARAZIT BOLEZNI 47 (1): 72-7 (1978)]**PEER REVIEWED**
  • AT AN APPLICATION DOSE OF 0.25 UG/SQ CM, 9.6% IN VIVO & 9.7% IN VITRO /OF THE ADMINISTERED DOSE/ EVAPORATED FROM THE SKIN OF HUMANS IN THE FIRST HR AFTER APPLICATION. [SPENCER TS ET AL; J INVEST DERMATOL 72 (6): 317-9 (1979)]**PEER REVIEWED**
  • After intravenous injection, DET is rapidly distributed through the body /of mice/ and quickly recovered in urine within the first 8 hr. The cmpd is selectively concentrated within the lacrimal glands, nasal mucosa, and mouse yolk sac. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-346]**PEER REVIEWED**
  • Deet is absorbed and distributed rather rapidly following movement through the skin. ... Topically applied radioactive deet reached a maximum concentration in the blood by 1 hr postapplication; it was almost completely eliminated from the blood within 1-3 days. Deet is rapidly eliminated mainly in the urine and to a lesser extent in the feces. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1500]**PEER REVIEWED**
  • DEET is efficiently absorbed across the skin and by the gut. Blood concentrations of about 3 mg/l have been reported several hours after dermal application in the prescribed fashion. [Morgan DP; Recognition and Management of Pesticide Poisonings. 4th ed, p.50 EPA 540/9-88-001. Washington, DC: U.S. Government Printing Office, March 1989]**PEER REVIEWED**
  • Using radioautography following iv injection of (14)C-deet, high tissue levels were found at first in the liver, kidney, lacrimal gland, and nasal mucosa. Very soon, concentrations higher than that in the blood were found in the thyroid and brown fat. Concentrations were highest and most persistent in the lacrimal gland. Concentrations in the fetus remained lower than those in the mother. Excretion was rapid and mainly by way of the kidney. By 4 hours after injection, very little radioactivity remained in any tissue, except the lacrimal gland ... An essentially similar picture was seen following dermal application. However, low levels of excretion continued during the entire 1 month period of observation. Direct measurement of the skin indicated that persistent excretion depended mainly on continuing absorption from the skin ... . [Hayes, Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and Wilkins, 1982., p. 630]**PEER REVIEWED**
  • ... 7 to 13% of a topical treatment of about 1 mg/sq cm & from 9% of a dose of 1.86 mg/sq cm to 56% of a dose of 0.077 mg/sq cm penetrated the skin of volunteers. ... Only 16% of a topical application to the forearm at 4 micrograms/sq cm penetrated during a 96 hr interval. ... The penetration of deet into & through human abdominal skin was 29.8% (29.6% remained in skin, 0.2% penetrated) at 1 hr after application of the lower concn & 36.3% (29.7% remained in skin, 6.6% penetrated) at 12 hr following application of the higher concn. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1502]**PEER REVIEWED**
  • About 10 to 15% of each dose can be recovered unchanged from the urine. Volume of distribution is 2.1 L/kg. Plasma half-life is 2.5 hr. DEET is eliminated by hepatic oxidative metabolism through the P450 enzyme system. About 10 to 14% is excreted in the urine unchanged. Urinary half-life is 4 hr. DEET and its metabolites can be detected in the urine for 2 weeks and from the skin and adipose tissues for 1 to 3 months after dermal application. It exhibits an enterohepatic recirculation. [Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1655]**PEER REVIEWED**

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Metabolism/Metabolites

  • OXIDATION OF THE BENZYLIC MOIETY AND HYDROXYLATION OF SIDE-CHAIN OF DEET MOLECULES APPEARED TO BE PREDOMINANT ROUTES OF METABOLISM IN MAN. [WU A ET AL; J HIGH RESOLUT CHROMATOGR CHROMATOGR COMMUN 2 (9): 558-62 (1979)]**PEER REVIEWED**
  • Although the metabolites of deet have yet to be completely characterized, found m-toluric, hippuric, and benzoic acids in urine of rats and rabbits exposed to deet in aerosol form; no unchanged deet was detected. By use of autoradiography following intravenous injection of radiocarbon-labeled deet into mice, high tissue levels were found initially in the liver, kidney, lacrimal gland, and nasal mucosa. Very soon, concentrations higher than that in blood were found in the thyroid and brown fat. Concentrations were highest and most persistent in the lacrimal gland. Concentrations in the fetus remained lower than those in the mother. By 4 hr after injection, very little radioactivity remained in any tissue, except the lacrimal gland. Deet does cross the placenta; however, pregnant rabbits receiving repeated dermal applications of deet throughout gestation showed no evidence of bioaccumulation in maternal tissue or individual fetuses. ... [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 1501]**PEER REVIEWED**

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TSCA Test Submissions

  • N,N-diethyl-m-toluamide (CAS # 134-62-3) was evaluated for acute oral toxicity. The test substance was administered to male albino Charles River CD rats. Dosages and mortality data are as follows: 0.4 g/kg (0/3); 0.8 g/kg (0/3); 1.6 g/kg (0/3); 3.2 g/kg (1/3); 5.0 g/kg (3/3). Signs of intoxication included lethargy, ataxia, ptosis, salivation, slow respiration, lacrimation, prostration, and loss of righting reflex. Gross autopsy revealed moderately red and swollen (2x) small intestines with a clear fluid and marked to moderate lung redness. There were no visible lesions in the survivors. The LD50 was roughly estimated to between 3.2 and 5.0 g/kg.[ROHM & HAAS CO; Initial Submission: Acute Toxicity Screen for RH-22,195 (Final Report) with Cover Letter Dated 02/05/92; 06/23/78; EPA Doc No. 88-920000883; Fiche No. OTS0535385]**UNREVIEWED**
  • N,N-diethyl-m-toluamide (CAS # 134-62-3) was evaluated for subchronic toxicity. The test substance was administered by subcutaneous injection to 30-35/group mated female Sprague-Dawley rats (Crl:CD (SD)BR) for 10 days at dosage levels of 0.5, 0.62, 0.78, 0.96, or 1.0 ml/kg/day or 1.0 ml water/kg/day (control). No females survived 10 days of dosing with 1.0 ml/kg/day. Deaths occurred in all groups except the low dose (0.5 ml/kg/day) group. The LD50 was determined to be 0.71 ml/kg/day. There was no significant increase in body weights, but liver and kidney weights were significantly increased. At 0.62 ml/kg/day, fetal weights were significantly reduced. No gross external malformations were noted.[NATL INSTIT OCCUP SAFETY & HLTH; Preliminary Report MDET Reproductive Toxicity and Teratology Study; 08/13/84; EPA Doc No. FYI-OTS-0884-0340; Fiche No. OTS0000340-0]**UNREVIEWED**
  • N,N-diethyl-m-toluamide (CAS # 134-62-3) was evaluated for subchronic toxicity. The test substance was administered by subcutaneous injection to 20/group male Sprague-Dawley rats for 5 days/week for 9 weeks. Dosages and mortality data are as follows: 0.30 ml/kg/day (0/20); 0.47 ml/kg/day (4/19); 0.73 ml/kg/day (1/20); 1.15 ml/kg/day (18/20); or 1.8 ml/kg/day (20/20). One male in the 0.47 ml/kg/day group and another in the 1.80 ml/kg/day group failed to impregnate at least one female in a companion reproductive toxicity and teratology study. Necropsy of the males revealed hemorrhagic lungs in the 5 rats that died in the 0.47 and 0.73 ml/kg/day groups. Several males developed lesions at one or several injection sites. Clinical signs included partial paralysis of the hind limbs, varying degrees of self-mutilation (cannablized the toes from their feet), and a dose-related decline in the rotorod performance test.[NATL INSTIT OCCUP SAFETY & HLTH; Report on Behavioral Testing of N,N-diethyl-3-toluamide (MDET); 08/15/84; EPA Doc No. FYI-OTS-0884-0340; Fiche No. OTS0000340-0]**UNREVIEWED**
  • N,N-diethyl-m-toluamide (CAS # 134-62-3) was evaluated for teratogenicity. The test substance was administered by subcutaneous injection to 30-35/group mated female Sprague-Dawley rats (Crl:CD (SD)BR) on gestation days 6-15 at dosage levels of 0.5, 0.62, 0.78, 0.96, or 1.0 ml/kg/day or 1.0 ml water/kg/day (control). Males selected for breeding received subcutaneous injections of the test substance 5 days/week for 9 weeks at dosage levels of 0.30 or 0.73 ml/kg/day. No mortality occurred in treated females, but maternal toxicity was reflected in reduced body weights, a transient reduction in food consumption, and increased maternal liver weight. Clinical signs included a partial paralysis of the hind limbs in 2 rats. Two grossly malformed fetuses were observed, one control fetus with omphalocele (umbilical hernia) and one treated fetus with craniorachischisis (fissure of skull and spinal column) and an open eye.[NATL INSTIT OCCUP SAFETY & HLTH; Preliminary Report MDET Reproductive Toxicity and Teratology Study; 08/13/84; EPA Doc No. FYI-OTS-0884-0340; Fiche No. OTS0000340-0]**UNREVIEWED**
  • N,N-diethyl-m-toluamide (CAS # 134-62-3) was evaluated for chromosomal effects. No treatment-related induction of mutations was evident in dominant lethal tests using 30-35/group mated female Sprague-Dawley rats (Crl:CD (SD)BR) receiving dosage levels of 0.5, 0.62, 0.78, 0.96, or 1.0 ml/kg/day or 1.0 ml/kg/day (control) by subcutaneous injection for 10 days; mated with 20/group male Sprague-Dawley rats at dosage levels of 0.30, 0.47, 0.73, 1.15, or 1.8 ml/kg/day by subcutaneous injection for 5 days/week for 9 weeks. No further information was provided in regards to the dominant lethal test.[NATL INSTIT OCCUP SAFETY & HLTH; Preliminary Report MDET Reproductive Toxicity and Teratology Study; 08/13/84; EPA Doc No. FYI-OTS-0884-0340; Fiche No. OTS0000340-0]**UNREVIEWED**
  • N,N-diethyl-m-toluamide (CAS # 134-62-3) was evaluated for chromosomal aberrations and sister chromatid exchange (SCE) in Chinese hamster ovary cells. The test substance was tested with and without an Aroclor 1254 induced rat liver S-9 activation system. Aberration induction was evaluated over a range of 0.2 ul/ml to 1.0 ul/ml and SCE induction at 0.2 ul/ml to 0.8 ul/ml. No increase in either aberrations or SCE was seen in the absence of S-9, but in its presence dose related increases to significance levels of p <0.01 for aberrations and p <0.001 for SCE were observed.[ICI AMERS INC; Initial Submission: Mutagenicity Evaluation of N,n-diethyltoluamide with Attachment and Cover Letter Dated 08/28/92; 08/28/92; EPA Doc No. 88-920007628; Fiche No. OTS0545820]**UNREVIEWED**
  • N,N-diethyl-m-toluamide (CAS # 134-62-3) was evaluated for forward mutation in L5178Y TK+/- mouse lymphoma cells with and without the presence of S-9 metabolizing system prepared from the livers of Aroclor 1254 induced rats. The test substance was negative over the dose range of 0.01 to 0.9 ul/ml without S-9, but was positive (increased mutant frequency by twice the background) at a dose of 0.15 ul/ml with activation. The test substance was determined to have a weak mutagenic potential.[ICI AMERS INC; Initial Submission: Mutagenicity Evaluation of N,n-diethyltoluamide with Attachment and Cover Letter Dated 082892; 08/28/9284; EPA Doc No. 88-920007628; Fiche No. OTS0545820]**UNREVIEWED**

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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Web page last updated on May 14, 2008