No other important adverse effects resulting from DEET have been reported in humans. One study of 249 US Gulf War veterans, however, provides evidence of an association between the frequency and amount of skin application of a repellent containing 75% DEET and the risk of a set of symptoms characterized as “arthro-myo-neuropathy” (Haley and Kurt, 1997). Contact dermatitis and urticaria were also reported in some people who used that formulation (Haley and Kurt, 1997).
A single dose of DEET at 1 or 3 g/kg produced neurotoxicity and neuropathy in rats. Many animals recovered fully, a few remained ataxic, others failed to recover muscle tone or righting reflex over 24 h, and some died. Some animals were killed between 2 h and 8 days after treatment for pathologic assessment. Intramyelinic edema, evident from the earliest time, evolved into a patchy and reversible spongiform myelinopathy largely in the cerebellar roof nuclei. Animals that had long-lasting prostration and partially controlled motor seizures displayed scattered neurons with edematous clefts of uncertain origin and significance (Verschoyle et al., 1992). Those findings provide insight into the possible target or mechanism underlying acute DEET-associated encephalopathy.
In subchronic and chronic repeat-dose studies involving dietary administration of DEET to mice, rats, and rabbits, the only consistent effects observed were decreased body weight gain; increased relative weights of testes, liver, and spleen; and increased serum cholesterol (Schoenig et al., 1999). No evidence of an effect on animal survival or abnormal findings of hematology, urinalysis, or gross or microscopic pathology were reported in any dose group. In dogs, tremor, hyperactivity, emesis, excessive salivation, and slightly reduced hemoglobin and hematocrit were reported at oral doses of 400 mg/kg per day given for 1 year; no effects were seen at 100 mg/kg per day (Schoenig et al., 1999).
Schoenig and colleagues (1993) investigated the neurotoxicity of DEET in rats following acute gavage exposure and following multigenerational dietary exposure. Effects on a functional observational battery (FOB) and motor activity measurements were studied following the acute exposure. In addition to the FOB and motor activity tests, an M-maze, passive avoidance acquisition and retention tests, acoustic-startle habituation, and histologic outcomes were also assessed in the multigenerational study. Other than a slight decrease in motor activity at 5000 ppm in the feeding study (rats taken from the second generation of a two-generation study), no evidence of adverse effects was seen.
An early study (Gleiberman et al., 1975) reported increased prenatal mortality and some effects on reproductive measures in rats at a maternal dose of 1000 mg/kg per day (dermal). Little evidence of effects on reproduction or development, however, was seen in studies in rats (two studies by the dermal route, one by gavage) and in rabbits (one study by the dermal route, one by gavage) (Schoenig et al., 1994). Another more recent study also did not confirm the findings of Gleiberman and co-workers (1975).