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 24°C and a viscosity of 13.3 mPa.s
at 30°C.
(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