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DEET

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Brand names, Trade names
   1.6 Manufacturers, Importers
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First-aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
   3.4 Other characteristics
4. USES/CIRCUMSTANCES OF POISONING
   4.1 Uses
   4.2 High risk circumstance of poisoning
   4.3 Occupationally exposed populations
5. ROUTES OF ENTRY
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Others
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination by route of exposure
7. TOXICOLOGY
   7.1 Mode of Action
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
      7.2.4 Workplace standards
      7.2.5 Acceptable daily intake (ADI) and other guideline levels
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple Qualitative Test(s)
         8.2.1.2 Advanced Qualitative Confirmation Test(s)
         8.2.1.3 Simple Quantitative Method(s)
         8.2.1.4 Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple Qualitative Test(s)
         8.2.2.2 Advanced Qualitative Confirmation Test(s)
         8.2.2.3 Simple Quantitative Method(s)
         8.2.2.4 Advanced Quantitative Method(s)
         8.2.2.5 Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall Interpretation of all toxicological analyses and toxicological investigations
   8.6 References
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 CNS
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Others
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ears, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Others
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Relevant laboratory analyses and other investigations
      10.2.1 Sample collection
      10.2.2 Biomedical analysis
      10.2.3 Toxicological analysis
      10.2.4 Other investigations
   10.3 Life supportive procedures and symptomatic treatment
   10.4 Decontamination
   10.5 Elimination
   10.6 Antidote treatment
      10.6.1 Adults
      10.6.2 Children
   10.7 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from literature
   11.2 Internally extracted data on cases
   11.3 Internal cases
12. ADDITIONAL INFORMATION
   12.1 Availability of antidotes
   12.2 Specific preventive measures
   12.3 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESSES
    1. NAME
     1.1 Substance
       N,N-Diethyltoluamide
     1.2 Group
       Aromatic ester
     1.3 Synonyms
       DEET
       Detamid
       Dieltamid
       diethyltoluamide
       M-Det
       m-DETA
       N,N - Diethyl-3-methylbenzamide
       N,N - Diethyl-m-toluamide
     1.4 Identification numbers
       1.4.1 CAS number
             134-62-3
       1.4.2 Other numbers
             RTECS: XS 3675000
     1.5 Brand names, Trade names
       Metadelphene  (UK, lab. Hercules)
       Autan  (Bayer)
       
       To be completed by PCs
     1.6 Manufacturers, Importers
       To be completed by PCs
    2. SUMMARY
     2.1 Main risks and target organs
       Systemic poisoning is not frequent due to the relatively low 
       toxicity of DEET, but may occur shortly after ingestion of 
       highly concentrated formulations.
       
       Main risks are: CNS depression, generalized seizures, 
       hypertonia with opisthotonic spells and hypotension.  Symptoms 
       are more severe if ingestion is associated with alcohol or 
       sedative drugs.  Toxic hepatitis has been described.  Systemic 
       toxic reactions and encephalopathy have been associated with 
       repetitive cutaneous application and spraying in children.  
       Local adverse reactions have been described after cutaneous 
       exposure. Eye irritation may occur.  Anaphylactic reactions 
       have been described after brief contact with DEET. 
     2.2 Summary of clinical effects
       If small amounts or a low concentration formulation is 
       ingested, only gastrointestinal symptoms such as nausea, 
       vomiting, diarrhoea and abdominal pain may occur.
       
       Ingestion of large amounts of DEET (concentrations of 40 to 
       95%) provoke coma, hypotension, abnormal hypertonic movements, 
       tremors and convulsions within 0.5 to 6 h.
       
       Toxic encephalitis is rarely seen but extremely severe.  It 
       results from repetitive or single exposures to DEET and is 
       characterized by: irritation, altered behaviour, restlessness, 
       convulsions, clonic movements, CNS depression, abnormal CSF 
       (lymphocytic pleocytosis) and altered EEG.  A Reye-like 

       syndrome with severe hyperammonaemia has been described.  It 
       is thought to be associated with ornithyl-carbarmoyl 
       transferase deficiency.
       
       Eye contact causes irritative conjunctivitis. 
       
       Dermatitis with erythema and bulluous reaction or urticaria 
       may occur after prolonged or repeated exposure to highly 
       concentrated formulations.
     2.3 Diagnosis
       The diagnosis is based on the history of ingestion or exposure 
       and the clinical features of hypersensitivity, 
       gastrointestinal symptoms or toxic encephalitis according to 
       the amount absorbed or type of poisoning.
       
       The suspected product should be kept for identification of 
       DEET and its concentration.  Determination of DEET or 
       metabolites in biological fluids is possible but not usual.
       
       Blood alcohol levels and psychoactive drugs should be 
       investigated in biological samples of severe cases.
       
       EEG and CSF analysis should be requested in cases of CNS 
       symptomatology.
     2.4 First-aid measures and management principles
       In cases of minor ingestion, do not induce vomiting. Perform 
       gastric aspiration and/or lavage only in cases of ingestion of 
       large amounts of concentrated product, after airway 
       protection.
       
       In case of recent excessive cutaneous exposure, wash the skin 
       with non-irritant soap and water.
       
       Standard supportive care is recommended in severe cases.
    3. PHYSICO-CHEMICAL PROPERTIES
     3.1 Origin of the substance
       Prepared from m-toluoyl chloride and diethylamine in benzene 
       or ether.
     3.2 Chemical structure
       C12 H17 N O
       
       Molecular weight : 191.26
       
       C = 75.35%          H = 8.96%      N = 7.32%      O = 8.37%
       
       Formula: 
       
       
       
       
       
       Although the commercially available preparations contain a 
       mixture of isomers, the meta form is the more active.

     3.3 Physical properties
       Pure diethyltoluamide is a colourless to amber liquid, 
       slightly aromatic, sparingly soluble in petroleum ether, 
       insoluble in water, freely soluble in alcohol, ether and 
       benzene, and not very volatile.  The volatization for 13 
       days at 24 C is less than 1%.  
       
       Boiling point:   288-292 C.
       
       Density:   0.997-1.000 g/ml
       
       
       Refractive index:   (n25D) = 1.5206
                                     
       
       The technical grade (85-95% m - isomer) has a density of 
       0.996-0.998 g/ml at 24C and a viscosity of 13.3 mPa.s 
       at 30C.
       
       (Aldrich, 1988-1989; British Crop Protection Council, 
       1987;  Merck Index, 1987)
     3.4 Other characteristics
       The commercially available presentations as: lotions, cream 
       sticks, aerosols, towelettes and sprays.  The concentration of 
       DEET may vary according to the country: 10% to 20% in Uruguay, 
       47.5% to 95% in Canada, 5.6 to 75% in USA. Some branded 
       products (for example, 'Muskol') are 95% DEET, whereas 'Off' 
       contains 15% DEET and 'Black-flag' only 7.8%.  In the UK, the 
       gel preparation contains 15%, the spray 28.3% and the stick 
       33%.
       
       Ethyl alcohol, used as a solvent for DEET in some  
       formulations, may contribute to the oserved toxic effects. 
    4. USES/CIRCUMSTANCES OF POISONING
     4.1 Uses
       DEET is an insect repellent which is especially 
       effective against mosquitoes, ticks, fleas, leeches, 
       black flies, harvest bugs, midges, chiggers and biting 
       flies.  It is not effective against stinging insects.  
       It is recognized as the most effective repellent against 
       Aedes aegypti and Aedes taeniorhynchus.
       
       It is usually effective for several hours, but is 
       removed from the skin by rain, sweating, swimming, and 
       must be reapplied to maintain effectiveness. Vanillin 
       significantly prolonged the protection time of DEET 
       (Martindale, 1982).
       
       DEET has been in use since 1957.
     4.2 High risk circumstance of poisoning
       -  Excessive and repetitive skin application and spraying, 
       especially in children's bedding (occurs mainly in the 
       summer). 
       
       -  The risk of systemic poisoning and encephalopathy is higher 
       in small girls, especially if they have enzymatic (for example,
        ornithyl-carbamoyl transferase) deficiency. Since small 
       children have a larger surface area to mass ratio than adults, 
       the percutaneous absorption is relatively higher.
       
       -  Accidental ingestion of lotions or sticks (in children).
       
       -  Suicidal attempt by ingestion of the product.
     4.3 Occupationally exposed populations
       -  Military use is frequent as in the case of soldiers serving 
       in the jungle (tropical areas).
       
       -  Workers of woods in tropical forests and explorers or 
       travellers.
       
       -  Workers manufacturing DEET may present skin effects 
       (Prischepov et al, 1981).
    5. ROUTES OF ENTRY
     5.1 Oral
       DEET is rapidly absorbed after ingestion.
     5.2 Inhalation
       No data available.
     5.3 Dermal
       DEET is absorbed quickly through intact skin; 48% of the 
       applied dose is totally absorbed within 6 hours.  This is the 
       usual route of entry as DEET is normally applied to the skin 
       as a mosquito repellent.  Accumulation in the dermis has been 
       demonstrated (Robins and Cherniak, 1986).
     5.4 Eye
       Instillation of DEET in the eyes of rabbits produced local 
       reversible irritation, but no systemic effect (Zadicoff, 
       1979).
     5.5 Parenteral
       In animal experiments, single intravenous doses of 75 mg/kg 
       are rapidly fatal.  However, five daily injections of 25 mg 
       produce no observable damage (Zadicoff, 1979).
     5.6 Others
       Animal experiments indicate that DEET crosses the placenta 
       (Gleiberman et al, 1975).
    6. KINETICS
     6.1 Absorption by route of exposure
       Between 9% and 56% of dermally applied DEET is absorbed 
       through the skin (Robins & Cherniak, 1986).
       
       Peak blood levels are attained within 1 h.
       
       Absorption through the skin varies according to the site 
       exposed. In the monkey, 68% is absorbed from the ventral 
       forepaw, a surface which corresponds with the human palmar 
       surface, an area heavily exposed during the application of 
       liquid DEET (Moody et al, 1986).
       
       Small children are at increased risk because of their 
       relatively higher surface to volume ratio than adults (Davies 
       et al, 1988).
     6.2 Distribution by route of exposure
       After dermal application, approximately 17% of the absorbed 
       dose enters the bloodstream.  DEET accumulates in the skin, 
       contributing to the local irritation and bullous dermatitis 
       (Robins & Cherniak, 1986). Accumulation within the body has 
       not been reported (Heick et al, 1980), and experimentally 
       there have been no cumulative effects of subtoxic doses of 
       DEET; but case reports toxicity in man suggest that 
       accumulation of the repellent may occur, with deleterious 
       effects (Zadicoff, 1979). 
     6.3 Biological half-life by route of exposure
       No data available.
     6.4 Metabolism
       The metabolism of DEET has not been well studied (Heick et al, 
       1980). It appears to undergo hepatic oxidation and residual 
       metabolites may persist for up to 3 months in the skin, 
       adipose tissue, muscle and other tissues adjacent to the site 
       of application (Lurie et al, 1978).
     6.5 Elimination by route of exposure
       DEET is excreted via the kidneys; the initial phase is 
       initially rapid but not more than 50% of the absorbed dose is 
       excreted during the first 5 days (Robins & Cherniak, 1986).  
       
       In the study performed by Moody (1989), a human volunteer 
       weighing 65.8 kg was treated with 15 g of Muskol (95% DEET). 
       Urinary levels of DEET and a metabolite were measurable 4 h 
       after exposure and persisted 48 h later. Maximum urinary 
       levels of DEET and ethyltoluamide were 207 mg/l at 8 h.
    7. TOXICOLOGY
     7.1 Mode of Action
       The mechanism of toxicity is poorly understood. 
       
       Its local action may be irritant (as a chemical) or 
       immunologically mediated (immediate sensitization).
       
       The systemic effects may be due to the toxicity of metabolites,
       and could be exacerbated in children by some enzymatic 
       deficiencies (such as ornithyl-carbamoyl-transferase (OCT) 
       deficiency) (Lurie et al, 1978), since a low hepatic OCT may 
       increase susceptibility to DEET (Anon, 1981). Neurologic 
       symptoms may represent a hypersensitivity reaction (Roland et 
       al, 1985).
     7.2 Toxicity
       7.2.1 Human data
             7.2.1.1 Adults
                     Dermal application of a 50% solution of DEET 
                     produces a sensation of tingling and mild 
                     desquamation around the nose in volunteers after 
                     5 days of application (1 ml to the face and 2 ml 
                     to the arms).  They did not suffer systemic 
                     toxicity, and the desquamation cleared after two 
                     days (Ambrose, 1959).  A study performed by 

                     Moody et al (1989) in a human volunteer treated 
                     with 15 g of a 95% DEET formulation (yielding a 
                     dose of 227 mg/kg) presented dizziness and an 
                     intolerable dermal burning sensation. About 4 h 
                     later, urinary levels of DEET and ethyltoluamide 
                     were detectable peaking at 207 mg/l after 8 h 
                     and still detectable 48 h after treatment.
                     
                     Workers using DEET as an insect repellent may be 
                     exposed after 6 months to a cumulative dose of 
                     more than 442 g. Neurotoxic effects have been 
                     demonstrated in workers exposed to 4 g or more 
                     weekly (Robins & Cherniak, 1986).
             7.2.1.2 Children
                     Most cases of severe poisoning have been 
                     registered in children, (usually in girls).  A 
                     girl exposed to an estimated dose of 0.14   
                     ml/kg/day of a formulation containing 15% DEET 
                     (corresponding to approximately 21 mg/kg/day), 
                     developed toxic encephalopathy; this dose was 
                     small by compariosn with those used 
                     experimentally (Gryboski et al, 1961) (see also 
                     section 9.4.15).
                     
                     If the median lethal dose in rats (2 g/kg) is 
                     applicable to humans, 50 ml of 100% DEET may is 
                     potentially lethal for an 8-year-old child 
                     (Tenenbein, 1987).
       7.2.2 Relevant animal data
             The systemic signs of toxicity in rats and rabbits given 
             the LD50 dose are: hyperaemia of ears, lacrimation, 
             laboured respiration, tremors and convulsions.  Recovery 
             is complete among the survivors (Zadicoff, 1979).
             
             LD50 oral (rats)   1 to 2 ml/kg (Gryboski et al, 1961)
             LD50 oral (rats)   2 g/kg (Gosselin et al, 1979)
             LD50 dermal (rabbit) 10 ml/kg (Ambrose, 1959).
             
             The main effects described in the rat exposed to toxic 
             amounts are: CNS depression, hyporreflexia, respiratory 
             insufficiency, coma and seizures (Gleason et al, 1979).  
             Signs of toxicity are similar in the rabbit.  Signs at 
             autopsy include lung hyperaemia, intestinal irritation 
             and congestion of the kidneys (Ambrose, 1959).
             
             Regular skin application of DEET to female and male rats,
              as well as pregnant female white rats has a gonadotoxic 
             and embryotoxic effect (Gleiberman et al, 1976).
             
             Skin application of DEET to albino female rats during 
             pregnancy increases embryonal and post-natal death rate 
             and decreases birth weight. DEET is found in the 
             placenta and fetus and in rats 3 months after birth 
             (Gleiberman et al, 1975).

       7.2.3 Relevant in vitro data
             No data available.
       7.2.4 Workplace standards
             Data not found.
       7.2.5 Acceptable daily intake (ADI) and other guideline levels
             No data available.
     7.3 Carcinogenicity
       Few studies have been done in animals: no carcinogenic effect 
       has been demonstrated (Robins & Cherniak, 1986).
     7.4 Teratogenicity
       No embryotoxic effects were demonstrated in animals by Robins 
       and Cherniak (1986) but earlier studies performed by 
       Gleiberman et al (1975, 1976) demonstrated gonadotoxic and 
       embryotoxic effects in the rat.
     7.5 Mutagenicity
       Although studies performed have not been extensive, no 
       mutagenic effects have been found in the animal (Robins & 
       Cherniak, 1986).  According to Gleiberman et al (1975), the 
       application of 100 and 1,000 mg/kg to the skin of albino 
       female rats during the whole period of pregnancy increased 
       embryonal fatality and reduced the size and weight of the new 
       born rats.
     7.6 Interactions
       Two lethal cases of DEET poisoning were associated with 
       ingestion of alcohol and of CNS depressants.  DEET-induced CNS 
       depression may be potentiated by ethyl alcohol or psychotropic 
       drugs (Tenenbein, 1987).
    8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
     8.1 Material sampling plan
       8.1.1 Sampling and specimen collection
             8.1.1.1 Toxicological analyses
             8.1.1.2 Biomedical analyses
             8.1.1.3 Arterial blood gas analysis
             8.1.1.4 Haematological analyses
             8.1.1.5 Other (unspecified) analyses
       8.1.2 Storage of laboratory samples and specimens
             8.1.2.1 Toxicological analyses
             8.1.2.2 Biomedical analyses
             8.1.2.3 Arterial blood gas analysis
             8.1.2.4 Haematological analyses
             8.1.2.5 Other (unspecified) analyses
       8.1.3 Transport of laboratory samples and specimens
             8.1.3.1 Toxicological analyses
             8.1.3.2 Biomedical analyses
             8.1.3.3 Arterial blood gas analysis
             8.1.3.4 Haematological analyses
             8.1.3.5 Other (unspecified) analyses
     8.2 Toxicological Analyses and Their Interpretation
       8.2.1 Tests on toxic ingredient(s) of material
             8.2.1.1 Simple Qualitative Test(s)
             8.2.1.2 Advanced Qualitative Confirmation Test(s)
             8.2.1.3 Simple Quantitative Method(s)
             8.2.1.4 Advanced Quantitative Method(s)
       8.2.2 Tests for biological specimens
             8.2.2.1 Simple Qualitative Test(s)

             8.2.2.2 Advanced Qualitative Confirmation Test(s)
             8.2.2.3 Simple Quantitative Method(s)
             8.2.2.4 Advanced Quantitative Method(s)
             8.2.2.5 Other Dedicated Method(s)
       8.2.3 Interpretation of toxicological analyses
     8.3 Biomedical investigations and their interpretation
       8.3.1 Biochemical analysis
             8.3.1.1 Blood, plasma or serum
                     "Basic analyses"
                     "Dedicated analyses"
                     "Optional analyses"
             8.3.1.2 Urine
                     "Basic analyses"
                     "Dedicated analyses"
                     "Optional analyses"
             8.3.1.3 Other fluids
       8.3.2 Arterial blood gas analyses
       8.3.3 Haematological analyses
             "Basic analyses"
             "Dedicated analyses"
             "Optional analyses"
       8.3.4 Interpretation of biomedical investigations
     8.4 Other biomedical (diagnostic) investigations and their 
       interpretation
     8.5 Overall Interpretation of all toxicological analyses 
       and toxicological investigations
     8.6 References
    9. CLINICAL EFFECTS
     9.1 Acute poisoning
       9.1.1 Ingestion
             Ingestion causes gastrointestinal effects such as nausea,
              vomiting, diarrhoea and malaise which may be followed 
             by systemic effects if the dose is sufficiently large. 
             Within 0.5 to 6 h, the patient develops a decreased 
             level of consciousness, hypotension, tachycardia, 
             convulsions and respiratory depression.
             
             In children, ingestion may also result from heavily 
             sprayed bedding and toys in contact with the mouth 
             (Gryboski et al, 1961).
       9.1.2 Inhalation
             No data available.
       9.1.3 Skin exposure
             Produces local erythema, irritation and even bulluous 
             dermatitis.  An erythematous, coalescent maculopapular 
             rash over face and extremities has been described in 
             association with toxic encephalopathy (Roland et al, 
             1985).  Systemic poisoning may result, especially in 
             children when heavily exposed.
             
             Contact urticaria due to DEET has been reported as due 
             to an immunological response (immediate 
             hypersensitivity) (Maiback & Johnson, 1975).

       9.1.4 Eye contact
             Undiluted material is a moderate to severe irritant in 
             the eye (Gosselin et al, 1979).
       9.1.5 Parenteral exposure
             No data available.
       9.1.6 Other
             No data available.
     9.2 Chronic poisoning
       9.2.1 Ingestion
             No data available.
       9.2.2 Inhalation
             No data available.
       9.2.3 Skin exposure
             Absorption via the skin has been reported after 
             prolonged or repetitive application, especially in 
             children.
       9.2.4 Eye contact
             No data available.
       9.2.5 Parenteral exposure
             No data available.
       9.2.6 Other
             No data available.
     9.3 Course, prognosis, cause of death
       Contact dermatitis, urticaria and gastrointestinal symptoms 
       are usually rapidly reversible after ingestion.
       
       The toxic encephalopathy that may develop in susceptible 
       individuals (for example, those with ornithyl-carbamoyl 
       transferase deficiency) has a very poor prognosis and has 
       proved to be highly lethal in affected children.
       
       The course may be mild or severe depending on the amount 
       ingested.  After large doses, the outcome may be fatal, 
       especially if ingestion was associated with other CNS 
       depressants such as ethyl alcohol or sedative drugs.
     9.4 Systematic description of clinical effects
       9.4.1 Cardiovascular
             In the reported clinical cases, no specific cardiotoxic 
             effect has been described, except tachycardia and 
             hypotension in severe poisonings (Tenenbein, 1987).
       9.4.2 Respiratory
             Respiratory depression has been reported in cases of 
             severe poisoning (Tenenbein, 1987).
       9.4.3 Neurological
             9.4.3.1 CNS
                     Toxic encephalopathy may follow heavy or 
                     repetitive exposure to DEET in children or even 
                     a single ingestion (Zadicoff, 1979; Gryboski et 
                     al, 1961). This has been related in some cases 
                     to ornithyl carbamoyl transferase deficiency 
                     (which is fatal in males but has a variable 
                     severity in girls which allows their survival) 
                     (Heick et al, 1980).  All the reported cases of 
                     toxic encephalopathy occurred in girls.
                     
                     Lethargy, mood changes, headaches, ataxia, 
                     dysarthria and disorientation precede CNS 
                     depression, convulsions, opisthotonus and coma.
                     
                     Initial signs may be: disorientation, staggering 
                     gait, slurred speech, stiffening into sitting 
                     position, crying out, extension of extremities, 
                     flexing the fingers and dorsiflexing the toes 
                     (Gryboski et al, 1961).
                     
                     In some cases, adults who ingest large amounts 
                     of DEET develop a decreased level of 
                     consciousness, persistent coma and convulsions 
                     (Konovalov and Romanov, 1980; Tenenbein, 1987).
                     
                     Tremors have been described in severe cases of 
                     systemic poisoning and during recovery. 
             9.4.3.2 Peripheral nervous system
                     No data available.
             9.4.3.3 Autonomic nervous system
                     No data available.
             9.4.3.4 Skeletal and smooth muscle
                     No data available.
       9.4.4 Gastrointestinal
             Gastrointestinal symptoms are usually observed after 
             ingestion of DEET and are rapidly reversible. They 
             include nausea, vomiting, abdominal pain and diarrhoea. 
             These symptoms may be more severe in cases with toxic 
             encephalopathy.
       9.4.5 Hepatic
             Toxic hepatitis has been described in five patients who 
             purposefully ingested between 50 and 100 ml of DEET, but 
             the outcome was ultimately good (Konovalov & Romanov, 
             1980).
       9.4.6 Urinary
             9.4.6.1 Renal
                     No data available.
             9.4.6.2 Others
                     No data available.
       9.4.7 Endocrine and reproductive systems
             No data available.
       9.4.8 Dermatological
             Contact urticaria may occur in children and adults.  
             With 50% DEET, burning erythema, blisters and ulceration 
             may occur. Rashes are described after skin application 
             of concentrations as low as 10 to 15% DEET.
       9.4.9 Eye, ears, nose, throat: local effects
             DEET can cause severe irritation of the eyes.
       9.4.10 Haematological
              No data available.
       9.4.11 Immunological
              An immunologic response (contact urticaria due to 
              immediate hypersensitivity) has been described and 
              reproduced experimentally (Maiback and Johnson, 1975).

       9.4.12 Metabolic
              9.4.12.1 Acid-base disturbances
                       May be observed in cases of toxic 
                       encephalopathy,  Reye-like syndrome and severe 
                       systemic toxicity.
              9.4.12.2 Fluid and electrolyte disturbances
                       May be observed in cases of toxic 
                       encephalopathy,  Reye-like syndrome and severe 
                       systemic toxicity.
              9.4.12.3 Others
                       No data available.
       9.4.13 Allergic reactions
              One case of an anaphylactic reaction was described in a 
              woman after contact with a person who had been using 
              DEET (Miller et al, 1982).
       9.4.14 Other clinical effects
              No data available.
       9.4.15 Special risks
              A Reye-like syndrome has been reported in association 
              with continued use of DEET and associated with a 
              deficiency of ornithyl-carbamoyl-transferase in a girl 
              (Heick et al, 1980); toxic encephalopathy has also been 
              reported in girls.
              
              DEET crosses the placenta and occurs in the placenta, 
              the fetus and the newborn.
     9.5 Others
       No data available.
     9.6 Summary
    10. MANAGEMENT
      10.1 General principles
         In all cases of ingestion or skin contact, clinical 
         observation, decontamination and symptomatic treatment is 
         usually sufficient.
      10.2 Relevant laboratory analyses and other investigations
         10.2.1 Sample collection
                To be added.
         10.2.2 Biomedical analysis
                Routine biomedical analysis should be requested in 
                cases of severe poisoning, in order to maintain 
                appropriate control of the clinical condition and to 
                uncover any other etiology for the case.
         10.2.3 Toxicological analysis
                To be added.
         10.2.4 Other investigations
                Ornithine carbamoyl transferase activity should be 
                measured in cases of severe poisoning in children, in 
                order to determine whether there is a deficiency of 
                this enzyme and therefore a genetic susceptibility to 
                DEET toxicity.
      10.3 Life supportive procedures and symptomatic treatment
         In case of toxic encephalopathy or severe systemic poisoning,
          supportive therapy is required.

      10.4 Decontamination
         Ingestion of small quantities of DEET does not require 
         decontamination, unless the exposed patient belongs to the 
         group at risk (small girl, enzymatic deficiency).
         
         If large amounts of a highly concentrated DEET formulation 
         have been ingested, the stomach should be aspirated, and a 
         slurry of activated charcoal should be administered, 
         followed by sorbitol or saline cathartics.
         
         Gastric lavage may be performed only after intubation in the 
         comatose patient.
         
         Decontamination measures are not applicable if poisoning 
         occurred after long-term skin application of DEET.
      10.5 Elimination
         Haemodialysis and charcoal haemoperfusion have been reported 
         in a severely poisoned woman who had also ingested CNS 
         depressants (Tenenbein, 1987).
      10.6 Antidote treatment
         10.6.1 Adults
                There is no antidote.
         10.6.2 Children
                There is no antidote.
      10.7 Management discussion
         Investigation is needed on the toxicity of DEET in man, 
         especially on its long-term effects (Vashkov et al, 1976).
         
         The effects of DEET toxicity in individuals with enzyme 
         deficiencies should be investigated.
         
         Scientific publications on the effects of DEET in man should 
         be encouraged in view of the low number of cases reported in 
         the literature, despite the heavy worldwide use of insect 
         repellents.  Severe cases may be misdiagnosed, and labelled 
         as encephalitis, probably attributed to a viral origin, or 
         to meningitis if clinicians are unaware of the effects of 
         DEET (need to alert the pediatrician is especial). 
    11. ILLUSTRATIVE CASES
      11.1 Case reports from literature
         Tenenbein (1987) described five cases of toxic reactions 
         after ingestion of highly concentrated DEET preparations 
         (47.5% to 95%).  The common signs and symptoms were: coma, 
         convulsions and hypotension within 2 h of ingestion.  Two 
         patients died and three survived without sequelae. 
         Conclusion: ingestion of DEET can produce severe toxic 
         reactions or rapid onset that may become fatal.
         
         A Russian report (Konovalov & Romanov, 1980) describes 5 
         cases of systemic toxic reactions following acute ingestion 
         of DEET. Three men and two women, between 15 and 66 years 
         old, who purposefully drank 50 to 100 ml of DEET were 
         critically ill when seen within 0.5 and 6 h after ingestion. 
         They developed CNS depression, hypotension, tachycardia and 
         respiratory depression. Subsequently, they also developed a 

         toxic hepatitis.  Treatment was symptomatic and they all 
         underwent haemodialysis.  The outcome was favourable in 3 
         weeks.
         
         Heick et al (1980) reported the case of a 6-year-old girl 
         heavily exposed to DEET who presented with a Reye-like 
         syndrome.  She was found to be deficient in ornithine 
         carbamoyl transferase.  The report makes reference to 3 
         previously published cases of DEET encephalophy in which a 
         similar enzyme deficiency. 
           
         Roland et al (1985) reported a case of recurrent seizures 
         and abnormal behaviour in an 8-year-old girl after 4 days of 
         copious application of a 15% DEET formulation followed by 
         the use of a 100% DEET repellent. The child developed an 
         erythematous pruritic rash on the face and extremities and 
         altered behaviour and restlessness on the second day of use. 
          On the third day, she had a dermal application of 100% DEET 
         and presented during the night a generalized convulsion with 
         clonic movements of all limb, repeated on two occasions. 
         Blood and urine analysis yielded no abnormality.  The EEG 
         demonstrated a poorly organized, slow background activity 
         (frequency 5 to 7 Hz) and frequent delta, theta and 
         bifrontal sharp waves.  The child recovered fully after two 
         days.  Treatment was symptomatic, with maintenance phenytoin 
         therapy.
         
         Reuveini and Yagupsky (1982) reported skin erythema, 
         blisters and even ulceration and scarring in 10 soldiers, 18 
         to 24 h after skin application of 52% DEET.
      11.2 Internally extracted data on cases
         Most of the consultations received at the CIAT are due to 
         accidental ingestion of DEET repellents (lotions or sticks) 
         by children.  Exposures occur mostly in the summer months.  
         No severe poisonings have been registered, except for a case 
         of encephalopathy in a 17-month-old girl who was heavily 
         sprayed with DEET (20%) during the 15 days previous to 
         hospital admission.  She was found by the mother with a 
         generalized hypertonia.  In the Emergency Room she had 
         convulsions, followed by coma and cardio-respiratory arrest. 
          The provisional diagnoses included Reye's syndrome, 
         meningitis, metabolic illness and epilepsy, but were all 
         excluded by clinical studies. The child died in spite of 
         intensive therapy (Pronczuk & Laborde, 1987).
      11.3 Internal cases
         To be added by user PCC.
    12. ADDITIONAL INFORMATION
      12.1 Availability of antidotes
         No antidotes are available.
      12.2 Specific preventive measures
         Extreme caution is recommended when exposing children, 
         especially to the more concentrated DEET.  Advice should be 
         given against extended, excessive use of the repellent.
         
         It is recommended that DEET containers should carry a 
         warning against use by people with metabolic defects (Anon. 
         1981).
         
         A safer method of using of DEET would be via impregnation 
         into cotton jackets or anklets from which the vapour is 
         slowly released with slow skin contact.  This method remains 
         effective for weeks clothes are stored in a nylon bag 
         (Curtis, 1988).
         
         Withdrawal of preparations containing more than 75% of DEET 
         would reduce the risk of adverse effects or poisoning (but 
         it should be stressed that people using lower concentrations 
         tend to apply larger amounts to obtain the same effect) 
         (Curtis, 1988).
         
         DEET should not be sprayed on the face or lips, on sensitive,
          sunburned or damaged skin or mucous membranes.
         
         Increased awareness of the risk of toxic encephalopathy may 
         prevent an inaccurate diagnosis of epilepsy in some children 
         (Roland et al, 1985).
      12.3 Other
         None.
    13. REFERENCES
    Aldrich 1988-1989. Catalog Handbook of Fine Chemicals. Aldrich 
    Chemical Co. Inc. 
    
    Ambrose AN (1959).  Pharmacologic and toxicologic studies on N,N-
    diethyltoluamide.  Toxicol Appl Pharmacol 1: 97.
    
    Anonymous (1981).  Individual susceptibility.  Lancet 2 (8216): 
    368.
    
    British Crop Protection Council (1987).  The Pesticide Manual, a 
    World Compendium, 8th edition.
    
    Curtis CF (1988).  Making insect repellents safe (letter).  
    Lancet ii: 1021. 
    
    Davies MN, Soto RJ, Stewart RD, Tenenbein H (1988).  Toxicity of 
    diethyltoluamide-containing insect repellents.  J Am Med Assoc 
    350: 2289-2240.
    
    Gleiberman SE, Volkova AP, Nikolaiev GM, Zhukova EV (1975).  
    Study of the embryotoxic properties of the repellent 
    diethyltoluamide.  Farmakol Toksicol 38(2): 202-5. 
    
    Gosselin RE, Hodge HC, Smith RP, Gleason MN (1979).  Clinical 
    Toxicology of Commercial Products. p. 212.  The Williams and 
    Wilkins Co., Baltimore, 4th ed.
    
    Gryboski J, Weinstein D, Ordway NK (1961).  Toxic encepholopathy 

    apparently related to the use of an insect repellent. New Engl J 
    Med 264: 289-291.
    
    Heick HMC, Shipman RI, Norman MG et al (1980).  Reye syndrome 
    associated with use of insect repellent in a presumed 
    heterozygote for ornithine-carbamoyl-transferase deficiency.  J 
    Pediatr 97: 471-473.
    
    Konovalov GA, Romanov AN (1980).  Early hemodialysis in the 
    treatment of severe poisonings with repellents - ETA, benphtalate 
    and dimethylphtalate.  Anesteziol Reanimatol 2: 54-55.
     
    Lurie AA, Gleiberman WE, Tsizin YS (1978).  Pharmacokinetics of 
    insect repellent N,N-diethyltoluamide.  Med Parazitol (Moscow) 
    47(1): 72-77.
    
    Maiback HI, Johnson HL (1975).  Contact urticaria syndrome: 
    contact urticaria to DEET (immediate-type hypersensitivity).  
    Arch Dermatol 111(6): 726-730. 
    
    Martindale (1982)  The Extra Pharmacopeia. Ed. J.E.F. Reynolds.  
    The Pharmaceutical Press, London.
    
    Merck Index (1989). 11th edition. 
    
    Miller JD (1982).  New Engl J Med 307: 1341.
    
    Moody RP, Benoit FM, Riedel R, Ritter L (1989).  Dermal 
    absorption of the insect repellent DEET (n,N-diethyltoluamide) in 
    rats and monkeys: effect of anatomical site and multiple 
    exposure.  J Toxicol Environ Health 26: 137-147.
    
    Moody RP (1989).  The safety of Diethyltoluamide insect 
    repellents (letter).  J Am Med Assoc 262(1): 28-29.
    
    Prischepov VF, Mikhailuts AP, Cstapenko IT, Urbanski AS, Gubin VI 
    (1981).  Cig Tra Prof Zabol 10: 50-51.
    
    Pronczuk de Garbino J, Laborde A (1983).  Toxicity of an insect 
    repellent: N, N-diethyltoluamide.  Vet Hum Toxicol 25: 422-423.
    
    Reuveini & Yagupsky (1982).
    
    Robins PJ & Cherniak MG (1986).  Review of the distribution and 
    toxicity of the inset repellent N,N-diethyl-m-toluamide (DEET).  
    J Tox Env Health 18(4): 503-525.
    
    Roland EH, Jan JE, Rigg JM (1988).  Toxic encephalopathy in a 
    child after brief exposure to insect repellents.  Can Med Assoc J 
    (132): 155-156.
    
    Skinner WA, Tong HC, Johnson H et al (1977).  Influence of human 
    skin surface lipids on protection time of topical insect 
    repellents.  J Pharm Sci 56(12):.
    
    Tenenbein M (1987).  Severe toxic reactions and death following 
    the ingestion of Diethyltoluamide-containing insect repellents.  
    J Am Med Assoc 258(11): 1509-1511. 
    
    Vashkov VI, Gleiberman SE, Volkova AP (1976).  Study on remote 
    after-effects of repellents.  Part 2.  Regulations of use of the 
    repellent di-ethyl toluamide.  Med Parazitol Bolezni 45(6).
    
    Zadikoff CM (1975).  Toxic encephalopathy associated with use of 
    insect repellent. Pediatrica 95(1): 140-2. 
    14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE 
    ADDRESSES
    Author:   J. Pronczuk, MD
              CIAT, piso 7
              Av. Italia s/n
              Montevideo
              Uruguay
    
    Tel: 598-2-804000
    Fax: 598-2-470300
    
    Date:     January 1990
    
    Reviewer:
    
    Date:
    
    Peer Review: London, United Kingdom, March 1990




    See Also:
       Toxicological Abbreviations