Review of the biodistribution and toxicity of the insect repellentN,N‐diethyl‐m‐toluamide (DEET)

Abstract

A review of the biodistribution and toxicity of the insect repellent N,N-diethyl-m-toluamide (DEET) is presented. Workers using repellent containing this compound may be exposed to greater than 442 g in 6 mo. In human studies, variable penetration into the skin of from 9 to 56% of a topically applied dose and absorption into the circulatory system of approximately 17% have been reported. Excretion of DEET by humans was initially rapid but not as complete as in animal models. Only about one-half of the absorbed DEET was excreted by humans over 5 d. Depot storage of DEET in the skin was also documented. Skin irritant effects, including scarring bullous dermatitis in humans, were reported. One animal study that reported embryotoxicity could not be confirmed by other investigators. The limited testing for mutagenicity and carcinogenicity provided negative results. Neurotoxic effects were observed in workers exposed to 4 g or more per week. Six young girls developed encephalopathies after exposure to unspecified amounts of DEET ranging from small to massive doses. Three of these girls later died. The cause of their death has not been resolved. Because of the lack of information, further research into the absorption, carcinogenicity, and neurotoxic effects is needed.

Recent density functional theory model calculations of drug metabolism by cytochrome P450

“…Amide compounds exist in insect repellents, industrial solvents and drugs, possessing important biological activities [104][105][106]. Many of these compounds undergo oxidative N-dealkylation mainly by P450 [107][108][109][110][111][112].…”

Development and evaluation of LIPODEET, a new long-acting formulation of N, N-diethyl-m-toluamide (DEET) for the prevention of schistosomiasis.

“…[21][22][23] Currently available preparations of DEET are contained in vehicles that inevitably increase the absorption of DEET through the skin. 24 This potentially could increase the risk of DEET-induced toxicity.…”

Risk assessments for the insect repellents DEET and picaridin

“…These reports are associated with seizures and encephalopathy in children (Moody, 1989;Osimitz and Grothaus, 1995;Osimitz and Murphy, 1997;Sudakin and Trevathan, 2003) and extensive skin absorption that leads to entrance of large amounts of DEET into systemic circulation (Robbins and Cherniack, 1986). This suggests that exposures with frequent or prolonged topical applications of DEET may result in central nervous system toxicity in some individuals.…”

“…Despite the extensive use and efficacy of DEET and its history of seemingly safe use, there have been a few observations of high exposures leading to potentially unacceptable health risks (Robbins and Cherniack, 1986;Veltri et al, 1994;Qiu et al, 1998). These reports are associated with seizures and encephalopathy in children (Moody, 1989;Osimitz and Grothaus, 1995;Osimitz and Murphy, 1997;Sudakin and Trevathan, 2003) and extensive skin absorption that leads to entrance of large amounts of DEET into systemic circulation (Robbins and Cherniack, 1986).…”