FIGURE 3.5 Structure of DEET.

There are reports that military personnel are issued formulations containing up to 75% DEET.

Toxicokinetics

Topical application of DEET formulations results in accumulation of the repellent in skin layers. Penetration of the skin varies with the formulation, but studies in human volunteers suggest that less than 10% of an applied dose is absorbed. A much wider range of absorption rates has been reported in experimental animals than humans (Qiu et al., 1998). As with most organic compounds, percutaneous absorption would be expected to be greater in areas of skin damage.

DEET is detectable in human blood within 2 h of application to the adult forearm and was found to persist in the blood for at least 4 h (Selim et al., 1995). In rats, peak blood concentrations were achieved 1 h after skin application, and elimination was complete in 2–3 days (Schoenig et al., 1996). The compound and its metabolites are widely distributed in the body. Metabolites include carboxylic acids and hydroxymethyl compounds resulting from oxidation of the methyl group and loss of ethyl groups from the amide side chain (Qiu et al., 1998).

Genetic Polymorphisms and Susceptibility

No information specific to DEET is available on genetic polymorphisms.

Mechanism of Action

Little is known about the toxic mechanism of action of DEET.

Acute Human Exposures

DEET’s overall safety record is good when it is used as directed in the labeling, but three deaths and 10 cases of encephalopathy (all cases except one were in children 8 years old and younger) have been reported to be associated with heavy, and sometimes even short-term, use of DEET formulations (Qiu et al., 1998). There have also been reports of seizures, mostly in children, from exposure to DEET. The national DEET registry (from 1960 to 1997) contains 14 cases of seizures potentially related to DEET for which other more likely causes have not been identified and another 32 cases under review to determine whether there are other more likely causes. In a summary prepared for the reregistration of DEET, US EPA (1998) estimated, on the basis of those data, an incidence of seizures of about one per 100 million users. Reports of acute manic psychosis, cardiovascular toxicity, and anaphylaxis are limited to single, isolated cases, but dermatitis, urticaria, and other skin effects have been more commonly reported (Qiu et al., 1998). Veltri and colleagues (1994) summarized 9086 cases of human exposures to DEET products that had been reported to poison control centers in 1985–1989. The largest fraction (32%) of the cases were related to ocular symptoms, including corneal abrasion, resulting from accidental spraying of products into the eyes. It was possible to follow the course of injury in 24.8% of cases; in 98% of the cases that were followed, there were no long-term sequelae (Veltri et al., 1994).



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