DEET Toxicity

8 Interesting Facts of DEET Toxicity 

  1. N,N-diethyl-3-methylbenzamide (DEET) is a common insect repellent; potential toxicity may manifest with:
    • Dermal reactions from topical application usually occur in association with products containing high DEET concentrations (greater than 50%) 
    • Neurotoxicity (eg, lethargy, seizures, toxic encephalopathy) with significant systemic absorption; most cases of serious systemic toxicity result from ingestion, particularly intentional ingestion, and improper dermal use (eg, frequent application of high-concentration product, especially in children)
  2. Most DEET exposures result in minimal to no toxicity and toxicity is generally considered rare; DEET is safe and effective when used as recommended in adults, children older than 2 months, and pregnant and lactating women 
  3. Diagnosis is largely clinical and based on history and physical examination
  4. Treatment rests on removing source of exposure, decontamination measures, and supportive care; no antidote is available for the treatment of toxicity
  5. Admit patient with progressive or severe symptoms for monitoring and supportive care (admission criteria are not rigorously defined) in consultation with poison control center
  6. Monitor exposures in consultation with poison control center or medical toxicologist
  7. Recovery within 36 hours is expected in patients surviving systemic manifestations of toxicity, given appropriate supportive care 
  8. Prevention is one of the most important aspects of care; avoid use of DEET in children younger than 2 months, limit concentration of DEET-containing product to 30% or less in infants and children, and avoid overapplication and chronic application of DEET-containing products 

Pitfalls

  • Achieving a balance in preventing both insect and excessive DEET exposure may be challenging in areas of high tick and mosquito endemicity
    • Counsel caregivers of young children and patients living in tick- and mosquito-endemic areas about DEET toxicity prevention measures and alternate measures to prevent exposure to insects (eg, avoidance of dawn and dusk, long-sleeved clothing)
  • DEET (N,N-diethyl-3-methylbenzamide; diethyltoluamide) is a common insect repellent; potential toxicity may manifest with:
    • Dermal reactions from topical use; reactions usually occur in association with products containing high DEET concentrations (greater than 50%) 
    • Neurotoxicity (eg, lethargy, seizures, toxic encephalopathy) with significant systemic absorption; most cases of serious systemic toxicity result from ingestion, particularly intentional ingestion, and improper dermal use (eg, frequent application of high-concentration product, especially in children) 
  • Most DEET exposures result in minimal to no toxicity and serious toxicity is considered rare; DEET is safe and effective when used as recommended in adults, children older than 2 months, and pregnant and lactating women 

Classification

  • Exposure is classified by the US Department of Health and Human Services as either acute (14 days or less), intermediate (15-364 days), or chronic (365 days or longer) 

Clinical Presentation

History

  • Symptoms usually occur within an hour of toxic exposure and vary somewhat by route of exposure
    • Inhalation
      • Oral irritation, choking, coughing, and dyspnea may develop soon after exposure
      • Gastrointestinal symptoms (eg, nausea, vomiting) may develop
    • Dermal
      • Generalized hives within 10 to 30 minutes of application 
      • Acute onset of tingling and erythema
      • Severe hemorrhagic vesiculobullous eruptions
        • May occur after application to areas occluded during sleep (primarily antecubital fossa and popliteal fossa) and use of products containing high DEET concentration (greater than 50%) 
        • Skin necrosis and desquamation may be associated with severe reactions 
      • Exacerbation of existing skin conditions (eg, psoriasis, atopic dermatitis)
    • Ocular
      • Acute onset of eye irritation and conjunctivitis 
    • Oral ingestion
      • Acute onset of epigastric pain, nausea, and vomiting
      • Numbness and tingling of mucous membranes
    • Systemic effects as a result of excessive absorption
      • Gastrointestinal effects
        • Abdominal pain, nausea, and vomiting
      • Neurologic symptoms
        • Headache 
        • Drowsiness or lethargy
        • Restlessness, irritability, agitation, aggression, and combativeness
        • Seizures 
        • Impaired cognitive function and disorientation
        • Ataxia and slurred speech
        • Tremors and uncontrolled limb movement
        • Muscular cramping, weakness, and rigidity

Physical examination

  • Dermal exposure findings
    • Urticarial lesions
    • Localized reaction with erythema and tenderness
    • Hemorrhagic vesiculobullous eruption followed by skin erosion and desquamation
  • Ocular exposure findings
    • Conjunctival injection without ulceration
  • Inhalational exposure findings
    • Bronchospasm with wheezing or crackles
  • Signs of systemic toxicity
    • Cardiovascular effects
      • Tachycardia, bradycardia, hypertension, or hypotension 
    • Neurologic manifestations
      • Encephalopathic signs such as mental status changes, coma, seizures, opisthotonos, flaccid paralysis, and areflexia
      • Signs consistent with peripheral neuropathy (eg, diminished sensation)
      • Signs of increased intracranial pressure and cerebral edema with herniation may develop with extreme toxicity

Causes

  • Significant DEET toxicity typically occurs from either:
    • Excessive use or repeated cutaneous exposure to high concentrations of DEET-containing product, or
    • Intentional ingestion
  • DEET formulations and general information
    • DEET is effective against mosquitoes, chiggers, biting flies, fleas, and ticks; mechanism of action is largely unknown
    • Available commercial product formulations include aerosol and nonaerosol sprays, lotion, cream, gel, foam, sticks, and wipes 
    • Most commercially available products contain concentrations of less than 30% to 40% DEET (range 4%-100% by weight) 
    • Insect repellent effects plateau at a concentration of about 50% DEET after topical application 
    • Higher DEET concentrations have longer lasting effects than products containing lower concentrations; therefore, products containing higher DEET concentrations require less frequent reapplication
      • Efficacy times are approximate: 10% DEET lasts about 2 hours, 30% lasts about 5 hours, and 100% lasts about 10 hours 
  • Routes of exposure may include:
    • Dermal toxicity
      • Exposure resulting in toxicity may occur after multiple applications to the skin, particularly with preparation with high concentration of DEET 
    • Oral ingestion
      • Exposure resulting in toxicity may be accidental (eg, exploratory ingestion in young children) or intentional (eg, suicide attempt in adult) 
    • Inhalation exposure
      • Exposure resulting in toxicity may occur when aerosol formulations are used, particularly in confined spaces and when sprayed near the face 
  • Pharmacokinetics
    • Absorption
      • Efficient absorption occurs across skin and gastrointestinal tract 
      • Dermal exposure: peak plasma concentration is reached 1 hour after application 
    • Metabolism
      • Occurs via oxidative enzymes in the liver 
  • Toxic dose
    • Specific toxic dose is not definitively known
    • Ingestion of DEET may result in rapid and severe toxicity 

Risk factors and/or associations

Age
  • Infants and children may be at increased risk for DEET toxicity owing to a greater dermal absorption secondary to increased surface area to body weight ratio 
Other risk factors/associations
  • Risk factors for severe toxicity include:
    • Improper use (overly frequent application, chronic use) 
    • Ingestion 
    • Use of high concentration, particularly in children 
  • Absorption of DEET from the skin may be enhanced by other topical compounds, such as sunscreen, ethanol, and certain retinoids 
  • Very limited data suggest that impaired ability to metabolize ammonia (eg, inborn errors of metabolism involving the urea cycle) may increase the risk for DEET toxicity 

Diagnostic Procedures

Primary diagnostic tools

  • Diagnosis is largely clinical and based on history and physical examination
    • Consider in patients with a history of DEET-containing product use and consistent cutaneous or neurologic manifestations
    • Consider lumbar puncture and neuroimaging to aid in differential diagnosis for patients with serious neurologic manifestations and unclear diagnosis 
    • Plasma concentrations of DEET can confirm exposure but are not readily available or useful to guide treatment 
  • No laboratory testing is indicated for most exposures
    • Consider the following routine laboratory analyses for patients with evidence of significant systemic toxicity (eg, central nervous system manifestations, cardiovascular findings): 
      • Serum glucose level, electrolyte levels, and renal function
      • Blood gas and lactic acid level
      • CBC, prothrombin time, and partial thromboplastin time
      • Hepatic function and blood ammonia level
  • Consider routine studies indicated for patients with intentional ingestion
    • Acetaminophen concentration
    • Urine pregnancy test in women of child-bearing age
    • ECG to assess for conduction abnormalities requiring intervention

Laboratory

  • Cerebrospinal fluid analysis
    • Obtain neuroimaging before cerebrospinal fluid analysis in patients with signs of increased intracranial pressure
    • Consider to aid in exclusion of infectious or inflammatory central nervous system process in patients with neurologic manifestations
    • Lymphocytic pleocytosis with normal glucose levels and normal or elevated protein levels may be noted in patients with DEET toxicity

Imaging

  • Neuroimaging
    • Consider to aid differential diagnosis in patients with significant neurologic manifestations 

Differential Diagnosis

Most common

  • Acute encephalitis
    • Inflammation of the brain parenchyma resulting from infectious or autoimmune causes 
    • Characterized by symptoms of encephalopathy (eg, alterations in consciousness, personality changes), which may be similar to those seen in DEET toxicity 
    • Unlike DEET toxicity, acute encephalitis is also characterized by fever, cerebrospinal fluid pleocytosis, or characteristic changes on MRI or electroencephalography 
    • Differentiate by establishing evidence of cerebrospinal fluid inflammation through lumbar puncture 
    • Diagnosis is based on clinical presentation, neuroimaging, lumbar puncture, and subsequent laboratory analyses to help identify the cause
  • Organophosphate or carbamate poisoning
    • Acetylcholinesterase-inhibiting insecticides can have a wide variety of effects depending on the agent, route, and duration of exposure 
    • Central nervous system effects (eg, headache, dizziness, restlessness, ataxia, seizures) and some nicotinic effects (eg, paralysis, weakness, cramping) may resemble those of DEET toxicity 
    • Unlike DEET toxicity, acetylcholinesterase-inhibitor poisoning is typically characterized by concomitant muscarinic effects (eg, pupil constriction, sweating, lacrimation, salivation, wheezing, diarrhea, bradycardia, incontinence) and cardiac conduction interval prolongation (eg, atrioventricular block, QT prolongation) 
    • Diagnosis is based on clinical presentation; presence of muscarinic effects raises strong suspicion for organophosphate poisoning 
  • Pyrethrin and pyrethroid toxicity
    • Pyrethrins and pyrethroids are insecticides included in many commercial products (eg, pet products, products for application on clothing) 
    • Toxic exposure is rare and systemic toxicity usually only occurs after ingestion owing to very slow dermal absorption; however, skin exposure can result in local irritation and paresthesia 
    • May present similarly to DEET toxicity with history of insect control product use, vomiting, ataxia, altered mental status, seizures, and coma 
    • Patients with pyrethroid toxicity typically manifest with signs that may help distinguish from DEET toxicity, such as salivation, hyperexcitability, and sympathomimetic hyperactivity 
    • Duration of toxicity from poisoning is significantly longer than duration typically associated with DEET poisoning 
    • Diagnosis is based on clinical presentation and treatment mirrors that of DEET toxicity (eg, symptomatic care)

Treatment Goals

  • Remove source of exposure and initiate decontamination measures
  • Provide symptomatic and supportive care

Disposition

Admission criteria

Admit patient with progressive or severe symptoms for monitoring and supportive care (admission criteria are not rigorously defined) in consultation with poison control center and medical toxicologist

Maintain a low threshold for admission of patients at high risk for potential toxicity such as those with:

  • Underlying metabolic disorder, hepatic disease, or severe comorbidity 
  • Exposure to excessively high amounts and concentrations of DEET
  • Significant enteral ingestion
Criteria for ICU admission
  • Admit patients with serious manifestations (eg, hypotension, coma, seizures) to the ICU for supportive care

Recommendations for specialist referral

  • Consult local poison control center and medical toxicologist for patients with any exposure to assist with treatment recommendations and monitoring parameters

Treatment Options

Remove source of exposure and initiate decontamination measures

  • For patients with dermal exposure
    • Remove contaminated clothing, irrigate skin with copious amounts of water, and wash skin with soap and water
    • Maintain care to wash behind ears, under nails, and in skin folds
  • For patients with ocular exposure
    • Remove contact lenses when present
    • Irrigate eyes with copious amounts of sterile water or saline 
    • Perform ocular fluorescein evaluation as is indicated after any chemical exposure
    • Pursue further assessment in consultation with ophthalmologist if irritation persists despite prolonged irrigation
  • For patients with oral exposure
    • Do not use ipecac to induce emesis 
    • The effectiveness of activated charcoal in DEET ingestions is uncertain; cautious use of multiple dose activated charcoal can be considered in patients with significant ingestion exposure 
    • May consider charcoal in patients with intentional ingestion less than 2 hours before presentation involving multiple substances, given absence of contraindications 

No specific antidote exists for DEET toxicity

First line therapy is symptomatic treatment and supportive care

  • Manage seizures in standard fashion as indicated for toxin-induced seizures
    • Benzodiazepines are first line treatment 
    • Treat refractory seizures with barbiturates (eg, phenobarbital) 
  • Manage hypotension in standard fashion
  • Management for dermal toxicity
    • Topical steroids and oral antihistamines may be required for significant skin reactions after decontamination process
  • Management for toxic encephalopathy
    • Mirrors standard treatment for noninfectious encephalopathy with supportive care and standard management for increased intracranial pressure when indicated

Nondrug and supportive care

  • Remove source of exposure
  • Initiate decontamination measures (dermal, ocular, and gastric)
  • Intentional ingestions require psychiatric evaluation before considering final disposition

Monitoring

  • Monitor exposures in consultation with poison control center or medical toxicologist

Complications

  • Death
    • Death from DEET toxicity may occur after excessive dermal and oral exposures 
    • Cause of death is usually secondary to cerebral edema with herniation 
    • Cases resulting in death involve either intentional ingestion or repeated excessive dermal use (including a child who had underlying metabolic disease) 
  • Toxic encephalopathy and hepatitis
    • Has been reported in a child with inborn error of ammonia metabolism 

Prognosis

  • Ocular exposure
    • Ocular irritation without significant long-term adverse effects
  • Dermal reactions
    • Urticaria typically resolve spontaneously
    • Minor localized reactions and skin irritation usually resolve with local care
    • Hemorrhagic vesiculobullous eruptions resulting in skin necrosis may heal with scarring
  • Systemic toxicity
    • Recovery within 1 to 2 days is expected in patients surviving systemic manifestations of toxicity given appropriate supportive care 
    • Patients with acute toxic encephalopathy after short-term exposure often recover fairly rapidly without significant sequelae 

Prevention

  • Avoid use of DEET in infants younger than 2 months 
  • Avoid use of more than 30% DEET for infants and children 
  • The species of Aedes mosquitos that carry dengue fever, Zika virus, yellow fever, and some other diseases are most active during the day, so combination products of sunscreen and DEET may be used judiciously in these settings
    • However, sunscreen applied with DEET results in increased systemic absorption of DEET and may diminish the effect of sunscreen products 
  • Avoid use of DEET with topical retinoids
    • Concomitant use of certain topical retinoids (eg, bexarotene, alitretinoin) and DEET may potentiate DEET toxicity 
  • Avoid excessive exposure to DEET-containing products
    • Do not reapply more frequently than recommended reapplication time
    • Use a product with appropriate DEET concentration geared toward anticipated outdoor exposure time; use the lowest concentration of DEET that is effective 
      • 10% DEET provides protection for about 2 hours 
      • 30% DEET provides protection for about 5 hours 
    • Limit application to exposed areas of skin and apply sparingly; avoid use under clothing 
    • Avoid application to areas with cuts, wounds, or irritated skin 
    • Wash off products with soap and water after returning indoors 
    • Wash clothing treated with DEET before next wear 
  • Avoid exposure to mucous membranes, inhalation exposure, and potential for accidental ingestion
    • Avoid direct application to mucous membranes such as mouth and eyes 
    • Do not apply directly to hands in young children owing to risk of inadvertent oral or ocular exposure 
    • Use aerosols and sprays in open area as opposed to confined spaces 
    • Avoid direct aerosolization to facial area; rather, spray hands first then apply 
    • Keep products containing DEET in original marked container
  • Discontinue DEET-containing product immediately if symptoms such as rash, headache, or behavioral changes occur 
  • Counsel about alternate methods to avoid mosquito and arthropod exposure, including the following: 
    • Avoid going outside during times of high mosquito activity (ie, dusk and dawn)
    • Avoid use of strong fragrances, perfumes, scented soaps, or hairspray
    • Wear pants, a long-sleeved shirt, and socks
    • Wear light colors rather than bright colors
    • Avoid areas with damp or rotting vegetation (including seaweed on beaches)
    • Remove large areas of debris that could harbor arthropods (eg, tires, excessive yard vegetation)
    • Use insect nets when necessary
    • Use intact screens for doors and windows (or air conditioning)
    • Consider supplying water reserves (eg, lakes, ponds) with fish and nonpathogenic bacterial species that consume mosquito larvae
    • Eliminate standing water in any container where insects can breed
    • Replace outdoor lighting with lights that tend to attract fewer bugs (eg, yellow bug lights)
    • Use permethrin-impregnated clothing
  • Use DEET only with extreme caution in children with known seizure disorders, multiple allergies, severe atopic dermatitis, underlying hepatic disease, or metabolic disorder 

References

Diaz JH: Chemical and plant-based insect repellents: efficacy, safety, and toxicity. Wilderness Environ Med. 27(1):153-63, 2016

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