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DIETHYLTOLUAMIDE-DEET

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) DEET prevents contact with a variety of insects thereby protecting against various communicable diseases transmitted by insect vectors.

Specific Substances

    1) BENZAMIDE, N,N-DIETHYL-3-METHYL-
    2) DIETHYL-m-TOLUAMIDE
    3) DIETHYLTOLUAMIDE
    4) m-DELPHENE
    5) M-DET
    6) M-DETA
    7) m-TOLUAMIDE, N,N-DIETHYL-
    8) m-TOLUIC ACID DIETHYLAMIDE
    9) METADELPHENE
    10) MGK DIETHYLTOLUAMIDE
    11) N,N-DIETHYL-m-TOLUAMIDE
    12) 3-METHYL-N,N-DIETHYLBENZAMIDE
    13) REPEFTAL
    14) REPELLENT, INSECT
    15) CAS 134-62-3
    1.2.1) MOLECULAR FORMULA
    1) C12-H17-N-O

Available Forms Sources

    A) FORMS
    1) DEET is available in various formulations, including aerosol sprays, non-aerosol sprays, lotions, creams, sticks, foams, and towelettes (U.S. Environmental Protection Agency (EPA), 1998).
    2) According to the US Environmental Protection Agency, commercially available products can contain DEET in concentrations ranging from 4% to 100% (U.S. Environmental Protection Agency (EPA), 2012).
    a) Formulation types registered as end-use products with their respective concentrations are as follows (U.S. Environmental Protection Agency (EPA), 1998):
    1) Impregnated material (eg, towelettes): 7.15% to 82%
    2) Liquid (ready to use): 7% to 100%
    3) Pressurized liquid: 3.99% to 80%
    4) Sunscreen/DEET: 7.13% to 20%
    B) USES
    1) Diethyltoluamide (DEET) is a common active ingredient in topical insect repellents, and is most effective against biting insects (eg, chiggers, biting flies), mosquitoes, and ticks (Osimitz et al, 2010; U.S. Environmental Protection Agency (EPA), 1998).
    2) MILITARY USE: An Extended Duration Topical Insect and Arthropod Repellent (EDITAR) consisting of 33% DEET in a polymer formulation is available. It was formulated to provide about 9 hours or more of protection from biting arthropods (Debboun et al, 2001).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Diethyltoluamide (DEET) is the most common active ingredient in topical insect repellants. DEET is a nearly colorless liquid at room temperature with a faint, characteristic odor. Commercially available products in the US contain DEET concentrations in the range of 4% to 100%. High concentration products may be available in industrial settings.
    B) TOXICOLOGY: DEET is primarily toxic to the central nervous system, although the mechanism is unknown. Some in vitro studies show that DEET may have a weak and reversible cholinesterase inhibitory effect.
    C) EPIDEMIOLOGY: Exposure is common; serious toxicity is unusual. The risk of serious adverse effects after using DEET products, according to the manufacturer's recommendations, appear to be very low. Children occasionally develop adverse events, and the American Academy of Pediatrics has recommended using formulations that contain less than 10% DEET in children.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: DEET ingestion may cause nausea, vomiting, and abdominal pain. Contact urticaria may develop after dermal exposure to DEET. Abdominal pain, nausea, and vomiting, may also develop after excessive dermal exposure to DEET. Eye exposure to DEET may result in a burning sensation.
    2) SEVERE TOXICITY: In severe cases, neurologic toxicities (ie, encephalopathy, seizures, movement disorders, coma) may occur after oral or dermal exposure, most commonly in children. Other manifestations include: hypotension, bradycardia, and toxic hepatitis. Anaphylaxis and severe urticaria have been described after DEET use. Fatalities from ingestion and chronic dermal application of DEET-containing products are rare, but have been described. Rarely, acute paranoid psychosis from repeated dermal application of DEET has been reported.
    0.2.3) VITAL SIGNS
    A) Hypotension after ingestion of DEET may occur.
    0.2.20) REPRODUCTIVE
    A) In one study, daily DEET use in pregnant women during their second and third trimester was not associated with any increase in adverse effects among their offspring.
    B) DEET was not teratogenic in rats and rabbits.

Laboratory Monitoring

    A) Monitor serum electrolytes and blood glucose in patients with CNS toxicity.
    B) Monitor liver enzymes in symptomatic patients.
    C) In cases where the diagnosis is unclear, consider CT and lumbar puncture to rule out other causes of neurologic effects.
    D) Plasma concentrations of DEET are not rapidly available or useful to guide treatment, but can confirm exposure.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment for mild and moderate symptoms consists of predominantly symptomatic and supportive care.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treat seizures with IV benzodiazepines (eg, diazepam, lorazepam). Add phenobarbital or propofol if seizures persist. Treat hypotension with IV fluids; add vasopressors if needed.
    C) DECONTAMINATION
    1) Gastrointestinal decontamination is generally not recommended. Toxicity is most common from chronic exposures. Most cases of acute ingestion are low risk, and patients with large acute ingestions are at risk for seizures, coma, and subsequent aspiration. Remove contaminated clothing wash exposed skin with soapy and water. remove contact lens and irrigate exposed eyes.
    D) AIRWAY MANAGEMENT
    1) Patients who cannot protect their own airway or have signs and symptoms of respiratory failure may need intubation for respiratory support, but this rare.
    E) ANTIDOTE
    1) There is no specific antidote for the treatment of DEET toxicity.
    F) ENHANCED ELIMINATION
    1) It is unknown if hemodialysis would remove DEET. Dialysis is not routinely recommended.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: Asymptomatic patients with an inadvertent "taste" ingestion of low concentration products (10%) can be monitored at home.
    2) OBSERVATION CRITERIA: Symptomatic patients, and those with large or deliberate ingestions, or ingestions of high concentration products should be referred to a healthcare facility and observed for 6 hours or until signs of toxicity are clearly improving.
    3) ADMISSION CRITERIA: Patients with significant signs or symptoms should be admitted for treatment and monitoring. Patients with hypotension, coma, seizures, or respiratory failure should be admitted to an ICU setting.
    4) CONSULT CRITERIA: Contact a medical toxicologist or poison center for any patient with severe toxicity or in whom the diagnosis is unclear.
    H) PITFALLS
    1) Failure to monitor for neurotoxicity with known exposure and initially asymptomatic.
    I) PHARMACOKINETICS
    1) Dermal absorption: approximately 50% within 6 hours; peak plasma concentration is reached in one hour. Ingestion: may result in severe symptoms within 30 minutes, implying very rapid absorption. DEET is metabolized by oxidative enzymes in the liver.
    J) DIFFERENTIAL DIAGNOSIS
    1) Caustic or irritant exposure, organophosphate or carbamate poisoning, grayanotoxin toxicity, and other causes of seizure, electrolyte abnormalities, or hypoglycemia.
    0.4.4) EYE EXPOSURE
    A) Remove contact lenses and irrigate exposed eyes.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Remove contaminated clothing and wash affected areas twice with copious amounts of soap and water. Alcohol-detergent solutions such as "green soap" are most efficient for this purpose. A physician may need to examine the exposed area if irritation or pain persist after the area is washed.

Range Of Toxicity

    A) TOXICITY: A specific human toxic dose has not been established. Ingestion of 25 mL of 50% DEET in a 1-year-old child caused severe toxicity. Ingestion of 50 mL of 100% DEET by adolescents or adults has resulted in severe toxicity and death. Extensive daily dermal application of 10% or 15% DEET for 2 days to 3 months has resulted in encephalopathy in children. Sudden onset of a generalized seizure, associated with a diffuse encephalopathic EEG pattern, was reported in a 5-year-old boy who received 2 total-body applications of a DEET-containing insect repellent.

Clinical Effects

Summary Of Exposure

    A) USES: Diethyltoluamide (DEET) is the most common active ingredient in topical insect repellants. DEET is a nearly colorless liquid at room temperature with a faint, characteristic odor. Commercially available products in the US contain DEET concentrations in the range of 4% to 100%. High concentration products may be available in industrial settings.
    B) TOXICOLOGY: DEET is primarily toxic to the central nervous system, although the mechanism is unknown. Some in vitro studies show that DEET may have a weak and reversible cholinesterase inhibitory effect.
    C) EPIDEMIOLOGY: Exposure is common; serious toxicity is unusual. The risk of serious adverse effects after using DEET products, according to the manufacturer's recommendations, appear to be very low. Children occasionally develop adverse events, and the American Academy of Pediatrics has recommended using formulations that contain less than 10% DEET in children.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: DEET ingestion may cause nausea, vomiting, and abdominal pain. Contact urticaria may develop after dermal exposure to DEET. Abdominal pain, nausea, and vomiting, may also develop after excessive dermal exposure to DEET. Eye exposure to DEET may result in a burning sensation.
    2) SEVERE TOXICITY: In severe cases, neurologic toxicities (ie, encephalopathy, seizures, movement disorders, coma) may occur after oral or dermal exposure, most commonly in children. Other manifestations include: hypotension, bradycardia, and toxic hepatitis. Anaphylaxis and severe urticaria have been described after DEET use. Fatalities from ingestion and chronic dermal application of DEET-containing products are rare, but have been described. Rarely, acute paranoid psychosis from repeated dermal application of DEET has been reported.

Vital Signs

    3.3.1) SUMMARY
    A) Hypotension after ingestion of DEET may occur.
    3.3.4) BLOOD PRESSURE
    A) HYPOTENSION has been reported following large oral ingestions of DEET (Wiles et al, 2014; Tenenbein, 1987; Fraser et al, 1995).

Heent

    3.4.3) EYES
    A) IRRITATION: Moderate eye irritation can occur after ocular exposure (Ambrose, 1959).
    B) ANIMAL STUDIES
    1) RABBITS: Topical application of 100% DEET to rabbit eyes resulted in corneal cloudiness, lacrimation, and conjunctivitis, which was reversible within 10 days (MacRae et al, 1984).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypotension has been reported after large ingestions of DEET (Wiles et al, 2014; Tenenbein, 1987; Fraser et al, 1995).
    b) Several cases of hypotension have also been related to dermal exposure of DEET (Qiu et al, 1998).
    B) BRADYCARDIA
    1) WITH POISONING/EXPOSURE
    a) Bradycardia is rare but has been reported after dermal exposure to DEET (Clem et al, 1993).
    C) CARDIAC ARREST
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 33-year-old man developed cardiorespiratory arrest after ingesting 8 ounces of DEET (unknown concentration) (Veltri et al, 1994).
    b) CASE REPORT: A 37-year-old man experienced a cardiac arrest after ingesting up to 6 ounces of a 40% DEET solution (equivalent to 68.04 g [748 mg/kg]). He was successfully resuscitated, but subsequently was unresponsive and areflexic, with development of acidosis, hypothermia, hypotension, and tachycardia. Despite supportive care, he was declared brain-dead approximately 3 days post-ingestion, with tests indicating no cerebral blood blow and no brain activity (Wiles et al, 2014).
    D) ELECTROCARDIOGRAM ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: After ingestion of 19 to 25 mL of a 95% DEET solution, a 19-year-old woman developed hypotension (90/60 mmHg) and CNS depression with ECG revealing right and left atrial enlargement and diffuse ST-T abnormalities with a normal QT interval (Fraser et al, 1995). ECG changes resolved within 12 hours.
    b) CASE REPORT: Tachycardia with QT prolongation (537 msec) occurred in a 37-year-old man following ingestion of up to 6 ounces of 40% DEET solution (equivalent to 68.04 g [748 mg/kg]) (Wiles et al, 2014).
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HYPOTENSION
    a) Animal experiments suggest that DEET-induced hypotension is dose-related, and that it is due to myocardial depression (Leach et al, 1988).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) TOXIC ENCEPHALOPATHY
    1) WITH POISONING/EXPOSURE
    a) Encephalopathy has been reported after ingestion or excessive dermal application of DEET. Signs and symptoms include restlessness, drowsiness, irritability, weakness, ataxia, tremors, confusion, agitation, slurred speech, headaches, athetosis and in severe cases coma (Qiu et al, 1998; Zadikoff, 1979; Edwards & Johnson, 1987; Roland et al, 1985; Tenenbein, 1987; Briassoulis et al, 2001).
    b) CASE SERIES: In a review of 10 published cases of DEET-induced toxic encephalopathy, 9 were children 8 years of age or younger. Seizures/convulsions were among the most common effects observed. Other effects included headache, lethargy, ataxia, agitation, athetosis, disorientation, involuntary movements, tremors, weakness, incoherent speech, and stiffness of the extremities (Qiu et al, 1998).
    c) CASE REPORT: After topical application of 20% DEET consistent with the manufacturer's recommendations, a 27-year-old man developed encephalopathy with paresthesias, auditory hallucinations, tremor, confusion, and severe agitation. The patient required deep sedation and mechanical ventilation; he was discharged 3 days later without further events. Systemic absorption of DEET may have been increased due to high heat and humid weather conditions (Hampers et al, 1999).
    d) Neurologic symptoms may develop within 30 minutes of ingestion (Tenenbein, 1987).
    B) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) Generalized tonic clonic seizures may develop after excessive dermal use or ingestion of DEET (Wiles et al, 2014; Zadikoff, 1979; Tenenbein, 1987; Roland et al, 1985; CDC, 1989; Lipscomb et al, 1992). Symptoms may occur within 30 minutes after an acute ingestion (Tenenbein, 1987).
    b) Most case reports have described a prodrome of ataxia, irritability, confusion, and/or disorientation prior to the onset of seizures; rarely seizures have occurred without warning (Lipscomb et al, 1992).
    c) INCIDENCE: According to an evaluation of cases included in the DEET Registry (a reporting tool of adverse events following DEET exposure), from 1995 to 2001, seizures were reported in 24% (n=59) of patients (n=242), and occurred more frequently in children (n=42, 71%), age 19-years-old or younger, than adults (Osimitz et al, 2010).
    d) PEDIATRIC: A 3-year-old girl ingested approximately 800 mg of insect repellent (4 mL of a 20% DEET solution) and was comatose (Glasgow Coma Score 6) when admitted to the emergency department. Shortly after arrival, she developed brief, generalized, seizures with clonic movements of the facial muscles that were successfully treated with diazepam. Mentation improved over the next 4 hours, and the child was alert and oriented 10 hours later. The patient was discharged to home at 24 hours with no permanent sequelae reported (Petrucci & Sardini, 2000).
    C) MYOCLONUS
    1) WITH POISONING/EXPOSURE
    a) Tremors, ataxia, opisthotonos, athetosis and myoclonic jerking may develop with DEET-induced encephalopathy (Zadikoff, 1979; Tenenbein, 1987; Edwards & Johnson, 1987).
    b) CASE REPORT: Ongoing subchronic exposure to high concentrations of DEET resulted in a movement disorder (asymmetric bilateral action tremor) in a 30 year-old man exposed to 672 g of DEET in 3.5 months or 47 g per week (exposure of greater than 4 g per week can result in neurotoxic effects) (Ratner et al, 2001).
    D) CSF CELL CONTENT: RAISED
    1) WITH POISONING/EXPOSURE
    a) Lumbar puncture in cases of DEET-induced encephalopathy may be normal or may reveal sterile pleocytosis, usually with a lymphocytic predominance (Zadikoff, 1979; Edwards & Johnson, 1987; Heick et al, 1980; Roland et al, 1985).
    E) COMA
    1) WITH POISONING/EXPOSURE
    a) Coma may develop after ingestion or excessive dermal application of DEET in severe cases (Petrucci & Sardini, 2000; Zadikoff, 1979; Heick et al, 1980; Tenenbein, 1987).
    F) CEREBRAL EDEMA
    1) WITH POISONING/EXPOSURE
    a) Cerebral edema has been found on autopsy in fatal cases of DEET exposure (Zadikoff, 1979; Heick et al, 1980).
    b) CASE REPORT: Cerebral edema was noted on a non-contrast brain MRI after a 37-year-old man was declared brain dead 3 days following ingestion of up to 6 ounces 40% DEET solution (equivalent to 68.04 g [748 mg/kg]) (Wiles et al, 2014).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea and vomiting may develop after ingestion of or dermal exposure to DEET (Heick et al, 1980; Pronczuk de Garbino & Laborde, 1983; Roland et al, 1985).
    B) ABDOMINAL PAIN
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Abdominal pain developed in a 6-year-old girl with suspected ornithine carbamoyl transferase deficiency after copious use of a DEET containing insect repellent (Heick et al, 1980).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) TOXIC HEPATITIS
    1) WITH POISONING/EXPOSURE
    a) Toxic hepatitis has been reported in patients developing severe neurologic toxicity after topical exposure or ingestion of DEET (Konovalov & Romanov, 1980; Heick et al, 1980).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) HYPERSENSITIVITY REACTION
    1) WITH POISONING/EXPOSURE
    a) In a sensitization experiment, 4 of 203 subjects showed an initial erythematous response, and 3 of these 4 also had erythema on rechallenge demonstrating either an absent or weak sensitization potential (Ballantyne et al, 1987).
    B) URTICARIA
    1) WITH POISONING/EXPOSURE
    a) Contact urticaria is the major local adverse effect associated with topical application of DEET (Qiu et al, 1998; Wantke et al, 1996; Maibach & Johnson, 1975; Von Mayenburg & Rakoski, 1983).
    1) CASE SERIES: Soldiers exposed to an insect repellent containing 50% DEET developed burning, erythema and blisters during the onset of symptoms, followed by ulceration and scarring in some cases. Erythema progressed to hemorrhagic blisters over several days (Qiu et al, 1998).
    2) CASE REPORT: A 4-year-old boy developed generalized itch and urticaria minutes after application of an insect repellent containing 25% DEET. The authors conducted patch testing which revealed a non-immunologic chemically-induced generalized urticaria, but no type-1 allergy was elicited (Wantke et al, 1996).
    C) BULLOUS ERUPTION
    1) WITH POISONING/EXPOSURE
    a) A bullous eruption in the antecubital and popliteal fossae that may progress to painful skin necrosis and permanent scarring has been described after topical use of 50% to 75% DEET preparations (Lamberg & Mulrennan, 1969; Reuveni & Yagupsky, 1982). In another study, a vesiculobullous eruption on the left antecubital fossa occurred 10 hours after topical application of 33% DEET in a 19-year-old (McKinlay et al, 1998).
    D) CONTACT DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) Contact dermatitis has been described after topical application of DEET (Amichal et al, 1994).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ANAPHYLACTOID REACTION
    1) WITH POISONING/EXPOSURE
    a) Anaphylaxis has been reported after topical DEET application (Miller, 1982).

Reproductive

    3.20.1) SUMMARY
    A) In one study, daily DEET use in pregnant women during their second and third trimester was not associated with any increase in adverse effects among their offspring.
    B) DEET was not teratogenic in rats and rabbits.
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) DEET was not teratogenic at oral doses up to 725 mg/kg/day in rats on days 6 to 15 of gestation, and up to 325 mg/kg/day in rabbits on days 6 to 18 (Schoenig et al, 1994).
    2) DEET was not teratogenic when administered to rats from gestational day 6 to 15 at a dose of 0.30 milliliters/kilogram/day subcutaneously (Wright et al, 1992).
    3) Offspring of male rats that received DEET 0.30 or 0.73 milliliters/kilogram/day subcutaneously 5 days/week for 9 weeks did not show evidence of teratogenic effects (Wright et al, 1992).
    3.20.3) EFFECTS IN PREGNANCY
    A) CHRONIC EXPOSURE
    1) CASE REPORT - A term infant was noted to have an craniofacial morphology at birth with increasing statomotor retardation, muscular hypotonia, central hearing loss, and strabismus noted during the first few months of life. Intrauterine exposure included prophylactic chloroquine and daily use of a lotion containing 25% DEET by the mother. A screening for inborn errors of metabolism and a review of family history for genetic disorders were both negative. Although a causal relationship could not be determined in this case, the authors suggested cautious use of DEET in pregnancy (Schaefer & Peters, 1992).
    B) LACK OF EFFECT
    1) SAFETY OF DEET DURING PREGNANCY
    a) During a one year period, 897 pregnant women were enrolled in a study to determine the safety of daily application of DEET during the second and third trimester of pregnancy. 449 women were enrolled in the DEET only group, and the control group consisted of 448 pregnant women who applied "thanka paste" daily (derived from the crushed branches of the Limonia acidissima tree). The median amount of DEET applied per woman during pregnancy was 214.2 (0 to 345.1) grams. Of the 741 single births reported, 597 were followed for the first year. Comparisons of the two groups indicated that there were no significant differences in development, growth, adverse effects, mortality or lost to follow-up in either group. One year survival for both groups were similar, as well as overall growth parameters (McGready et al, 2001).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor serum electrolytes and blood glucose in patients with CNS toxicity.
    B) Monitor liver enzymes in symptomatic patients.
    C) In cases where the diagnosis is unclear, consider CT and lumbar puncture to rule out other causes of neurologic effects.
    D) Plasma concentrations of DEET are not rapidly available or useful to guide treatment, but can confirm exposure.

Methods

    A) HIGH PERFORMANCE LIQUID CHROMATOGRAPHY
    1) High-performance liquid chromatography was found to be a simple and reliable method for the determination of N,N-diethyl-m-toluamide (DEET) in cosmetic products (Markovic et al, 1999).
    B) GAS-LIQUID CHROMATOGRAPHY
    1) Methods of analysis of body fluids for these compounds by gas-liquid chromatography and HPLC may help confirm the diagnosis, but are not routinely available (Smallwood et al, 1992).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with significant signs or symptoms should be admitted for treatment and monitoring. Patients with hypotension, coma, seizures, or respiratory failure should be admitted to an ICU setting.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Asymptomatic patients with an inadvertent "taste" ingestion of low concentration products (10%) can be monitored at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Contact a medical toxicologist or poison center for any patient with severe toxicity or in whom the diagnosis is unclear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Symptomatic patients, and those with large or deliberate ingestions, or ingestions of high concentration products should be referred to a healthcare facility and observed for 6 hours or until signs of toxicity are clearly improving.

Monitoring

    A) Monitor serum electrolytes and blood glucose in patients with CNS toxicity.
    B) Monitor liver enzymes in symptomatic patients.
    C) In cases where the diagnosis is unclear, consider CT and lumbar puncture to rule out other causes of neurologic effects.
    D) Plasma concentrations of DEET are not rapidly available or useful to guide treatment, but can confirm exposure.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Gastrointestinal decontamination is generally not recommended. Toxicity is most common from chronic exposures. Most cases of acute ingestion are low risk, and patients with large acute ingestions are at risk of seizures, coma, and subsequent aspiration. Remove contaminated clothing and wash exposed skin with soap and water. Remove contact lenses and irrigate exposed eyes.
    6.5.2) PREVENTION OF ABSORPTION
    A) Gastrointestinal decontamination is generally not recommended. Toxicity is most common from chronic exposures. Most cases of acute ingestion are low risk, and patient with large acute ingestions are at risk of seizures, coma, and subsequent aspiration.
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) Treatment for mild and moderate symptoms consists of predominantly symptomatic and supportive care.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Treat seizures with IV benzodiazepines (eg, diazepam, lorazepam). Add phenobarbital or propofol, if seizures persist. Treat hypotension with IV fluids; add vasopressors if needed
    B) MONITORING OF PATIENT
    1) Monitor serum electrolytes and blood glucose in patients with CNS toxicity.
    2) Monitor liver enzymes in symptomatic patients.
    3) In cases where the diagnosis is unclear, consider CT and lumbar puncture to rule out other causes of neurologic effects.
    4) Plasma concentrations of DEET are not rapidly available or useful to guide treatment, but can confirm exposure.
    C) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    D) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) RECOMMENDATION TO STOP TREATMENT
    1) Discourage subsequent use if signs of irritation or sensitization appear.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) HEMODIALYSIS
    1) It is unknown if hemodialysis would remove DEET. Dialysis is not routinely recommended.

Abstracts

Case Reports

    A) PEDIATRIC
    1) A 5-year-old boy with no prior history of preexisting medical conditions received a total body application of a 95% DEET formulation in the morning, followed later by an application of another DEET-containing repellent (concentration unknown). During an afternoon nap that same day, he experienced a prolonged major motor seizure, which was controlled with a single dose of IV diazepam. Sporadic epileptiform discharges and evidence of diffuse encephalopathy were observed on the EEG on the third day of hospitalization, but no further seizures occurred. Follow-up examination 3 weeks later was normal (Lipscomb et al, 1992).

Range Of Toxicity

Summary

    A) TOXICITY: A specific human toxic dose has not been established. Ingestion of 25 mL of 50% DEET in a 1-year-old child caused severe toxicity. Ingestion of 50 mL of 100% DEET by adolescents or adults has resulted in severe toxicity and death. Extensive daily dermal application of 10% or 15% DEET for 2 days to 3 months has resulted in encephalopathy in children. Sudden onset of a generalized seizure, associated with a diffuse encephalopathic EEG pattern, was reported in a 5-year-old boy who received 2 total-body applications of a DEET-containing insect repellent.

Minimum Lethal Exposure

    A) CASE REPORTS
    1) ADULT: Ingestion of 50 mL of 100% DEET by a 33-year-old woman resulted in coma, hypotension, generalized seizures, and death due to massive bowel infarction (Tenenbein, 1987).
    2) ADULT: A 33-year-old man died 9 days after ingestion of 8 ounces of an unknown concentration of an insect repellent containing DEET. The patient experienced cardiorespiratory arrest, was resuscitated, and later died after developing hyperglycemia, status epilepticus, disseminated intravascular coagulopathy, and cerebral edema (Veltri et al, 1994).
    3) ADULT: A 37-year-old man, with severe developmental delays, developed a seizure and experienced cardiac arrest after ingesting up to 6 ounces of a 40% DEET solution (equivalent to 68.04 g [748 mg/kg]). He was successfully resuscitated, but subsequently developed acidosis, hypothermia, hypotension, and tachycardia. The patient was also unresponsive and areflexic. Despite improvement of his hypothermia, hypotension, and tachycardia following supportive care, the patient continued to remain unresponsive. Approximately 3 days post-ingestion, the patient was declared brain dead following tests that indicated no cerebral blood flow or brain activity (Wiles et al, 2014).

Maximum Tolerated Exposure

    A) ROUTE OF EXPOSURE
    1) SUMMARY
    a) CASE SERIES: In a review of 9,086 calls to poison centers for human exposures to DEET from 1985 to 1989, approximately 54% of the patients had no symptoms. Only 4 of 10 patients had symptoms that were thought to be directly related to DEET exposure. Symptoms were more frequent in those patients who had sprayed DEET-containing products into their eyes or inhaled the product and less frequent in those patients who had ingested the product. Most cases (88.2%) did not result in symptoms that necessitated referral to a healthcare facility. Of those, only 4.9% were admitted for medical care (Veltri et al, 1994).
    2) ORAL INGESTION
    a) TODDLER: Ingestion of approximately 25 mL of a 50% DEET product by a 1-year-old child resulted in unresponsiveness, brief seizures, CNS depression, and opisthotonus, followed by recovery (Tenenbein, 1987).
    b) ADOLESCENT: Ingestion of 50 mL of a 100% DEET product by a 14-year-old girl resulted in hypotension and a generalized seizure, followed by full recovery (Tenenbein, 1987).
    c) ADOLESCENT: Ingestion of 50 mL of a 100% DEET product, along with alcohol, by a 16-year-old girl resulted in coma, with recovery (Tenenbein, 1987).
    d) ADULT: A 19-year-old woman ingested 15 to 25 mL of 95% DEET (Muscol) and developed CNS depression and hypotension, with ECG showing atrial enlargement and diffuse ST-T abnormalities, followed by recovery. Serum concentrations of DEET were 63 mg/L, 17.2 mg/L, 1.9 mg/L and less than 0.2 mg/L at 2, 5, 24, and 48 hours after ingestion, respectively (Fraser et al, 1995).
    3) DERMAL EXPOSURE
    a) In several reviews of DEET toxicity, the risk of serious adverse effects after using DEET products according to the manufacturer's recommendations appeared to be low. Adverse events have been reported more frequently in children following DEET exposure. Some authors caution that the data regarding DEET toxicity in children is incomplete, and that the potential for DEET accumulation with multiple applications may occur. The American Academy of Pediatrics has recommended using only low level DEET formulas in concentrations of less than 10% in children (Osimitz & Murphy, 1997; Osimitz & Grothaus, 1995; Garrettson, 1997).
    b) PEDIATRIC EXPOSURE
    1) Application of 15% DEET solution on 10 daily occasions was associated with development of a fatal Reyes-like syndrome in a 6-year-old child (Heick et al, 1980).
    2) Copious application of a 15% DEET solution for 2 days resulted in contact dermatitis, altered behavior, and restlessness in an 8-year-old child. Seizures occurred the following evening after switching to a 100% DEET product (Roland et al, 1985).
    3) Daily dermal application of a 15% solution to a 3-year-old child for 2 weeks resulted in encephalopathy (Gryboski et al, 1961).
    4) Sudden onset of a generalized seizure, associated with a diffuse encephalopathic EEG pattern, was reported in a 5-year-old boy who received two total-body applications of a DEET-containing insect repellent (Lipscomb et al, 1992).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) ROUTE OF EXPOSURE
    a) DERMAL
    1) DEET concentration in blood 8 hours after routine cutaneous application in a 30-year-old man was 0.3 milligrams/deciliter (0.016 millimoles/Liter) (Wu et al, 1979). This patient was not exhibiting unusual behavior.
    b) ORAL
    1) A 33-year-old woman who expired after ingestion of chlorpromazine, hydralazine, ethanol, and a 95% DEET solution had the following levels of DEET (Tenenbein, 1987):
    Gastric lavage fluid10.4 mg/dL (0.54 mmol/L)
    Premortem blood16.8 mg/dL (0.88 mmol/L)
    Postmortem blood11.2 mg/dL (0.58 mmol/L)
    Liver17.7 mg/dL (0.92 mmol/kg)

    2) A 26-year-old man who expired after drinking a 95% DEET solution had the following postmortem DEET levels (Tenenbein, 1987):
    Blood24 mg/dL (1.25 mmol/L)
    Vitreous15 mg/dL (0.78 mmol/L)
    Urine10 mg/dL (0.52 mmol/L)

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (ORAL)RAT:
    1) 1892 mg/kg (RTECS, 2006)
    B) LD50- (SKIN)RAT:
    1) 5 gm/kg (RTECS, 2006)
    C) LD50- (ORAL)MOUSE:
    1) 1170 mg/kg (RTECS, 2006)
    D) LD50- (SKIN)MOUSE:
    1) 3170 uL/kg (RTECS, 2006)

Pharmacology Toxicology

Toxicologic Mechanism

    A) DEET: N,N-Diethyl-M-toluamide is primarily toxic to the central nervous system, although a specific mechanism is unknown (Wille et al, 2011).
    B) Some in vitro studies show that DEET may have a weak and reversible cholinesterase inhibitory effect (Wille et al, 2011; Corbel et al, 2009), suggesting the possibility of strengthening the toxicity of carbamate insecticides if used in combination (Corbel et al, 2009).

Physicochemical

Physical Characteristics

    A) Liquid which appears clear (like water) to amber (HSDB, 2006)

Molecular Weight

    A) 191.27 (HSDB, 2006)

Other

    A) ODOR THRESHOLD
    1) Faint, characteristic odor (HSDB, 2006)

Animal Toxicology

Clinical Effects

    11.1.3) CANINE/DOG
    A) Following exposure to a veterinary product containing both DEET and fenvalerate, dogs exhibited hypersalivation, abnormal chewing motions, vomiting, ataxia, and depression. After showing these signs, clinical improvement occurred within 4 to 24 hours (Mount et al, 1991).
    11.1.6) FELINE/CAT
    A) The most frequently reported clinical signs of suspected FENDEET (fenvalerate 0.09%/N,N-diethyl-m-toluamide 9%) poisoning in 266 cats are listed below (Dorman et al, 1990).
    CLINICAL EFFECTINCIDENCE (%)
    Anorexia12.0
    Ataxia/ incoordination28.2
    Death7.5
    Depression22.9
    Disorientation7.9
    Dyspnea7.1
    Hyperactivity/ hyperexcitability16.2
    Hypersalivation39.8
    Hypothermia9.0
    Mydriasis7.9
    Seizures16.9
    Tremors39.8
    Vocalization7.1
    Vomiting27.1
    1) ONSET: Of clinical signs of toxicosis commonly developed within hours of topical exposure (Dorman et al, 1990).
    2) In one study of 266 cats with suspected FENDEET poisoning, 42% of calls involved female cats, 28% involved male cats, and in 30% sex was not specified (Dorman et al, 1990).
    3) Suspected FENDEET poisoning occurred more frequently (50.4%) in cats up to 9 months of age (Dorman et al, 1990).

Treatment

    11.2.2) LIFE SUPPORT
    A) GENERAL
    1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.
    11.2.4) DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) DOGS/CATS
    a) Exposure is usually related to topical application and secondary oral ingestion from grooming. Bathing with a mild detergent (animal shampoo or Ivory liquid) may be helpful in limiting progression and/or duration of signs. Wear heavy rubber gloves to avoid human dermal exposure.
    b) If oral exposure is suspected, gastric lavage and/or administration of activated charcoal with an osmotic cathartic (magnesium or sodium sulfate) may be used.
    c) Emetics must be used with caution because of the prevalent signs and the presence of petroleum distillate solvents. If within 2 hours of exposure, may induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac orally. Do not use an emetic if the animal is hypoxic. In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage. Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times (Kirk, 1986).
    d) Activated charcoal dose is 2 grams/kilogram orally or via a gastrointestinal tube.
    11.2.5) TREATMENT
    A) DOGS/CATS
    1) Maintain vital functions: Insure a patent airway, correct electrolyte/fluid imbalances and keep the animal warm and quiet.
    2) Severe central nervous system signs may necessitate the use of sedatives. Diazepam, dosed at 1 milligram/kilogram intravenously, may be the best agent. Alternatively methocarbamol, 50 to 150 milligrams/kilogram intravenously, or barbiturates may be used. Do not use phenothiazine tranquilizers.

Range Of Toxicity

    11.3.2) MINIMAL TOXIC DOSE
    A) GENERAL
    1) A study of one veterinary product containing both DEET (9%) and fenvalerate (0.09%) found that 10% or more of a 7 ounce can/kilogram body weight sprayed on cats caused fatalities. Dogs tolerated being sprayed with 40% of a can/kilogram body weight and developed only mild clinical signs. Spraying into the subject's mouth or self-grooming after dermal exposure was 50 to 150 times more likely to cause toxic effects. The study was not able to prove whether DEET or fenvalerate caused these effects (Mount et al, 1991).

Continuing Care

    11.4.2) DECONTAMINATION
    11.4.2.2) GASTRIC DECONTAMINATION
    A) GASTRIC DECONTAMINATION
    1) DOGS/CATS
    a) Exposure is usually related to topical application and secondary oral ingestion from grooming. Bathing with a mild detergent (animal shampoo or Ivory liquid) may be helpful in limiting progression and/or duration of signs. Wear heavy rubber gloves to avoid human dermal exposure.
    b) If oral exposure is suspected, gastric lavage and/or administration of activated charcoal with an osmotic cathartic (magnesium or sodium sulfate) may be used.
    c) Emetics must be used with caution because of the prevalent signs and the presence of petroleum distillate solvents. If within 2 hours of exposure, may induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac orally. Do not use an emetic if the animal is hypoxic. In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage. Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times (Kirk, 1986).
    d) Activated charcoal dose is 2 grams/kilogram orally or via a gastrointestinal tube.

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