title: The influence of diethyl-m-toluamide (DEET) on the percutaneous absorption of permethrin and carbaryl.
abstract: Simultaneous exposure to DEET and permethrin was recently proposed to be associated with the "Gulf War Syndrome." However, no studies have reported the percutaneous absorption of DEET and permethrin when applied simultaneously to the skin as a mixture, the relevant route of exposure in the Persian Gulf. The present study quantitates percutaneous absorption of DEET and permethrin after coadministration to rodent and pig skin in vitro. Dosing solutions were also prepared with either acetone, dimethyl sulfoxide (DMSO), or ethanol to compare vehicle effects on percutaneous absorption of permethrin and DEET. The influence of DEET on carbaryl absorption and dermal disposition was also assessed in pig studies to statistically demonstrate DEET effects in acetone or DMSO and different solvent concentrations. Topical application of permethrin + DEET resulted in absorption of DEET (1-20% dose), but no permethrin. Permethrin (1.2-1.7% dose) was detected only when mouse skin was dosed solely with permethrin, a finding suggesting that DEET decreased permethrin absorption. DEET also inhibited carbaryl absorption in acetone mixtures, but had no effect on DMSO mixtures. Irrespective of solvent, DEET did not enhance carbaryl penetration into skin. For DEET, absorption was greater in mouse skin (10.7-20.6% dose) than in rat skin (1.1-5.2% dose) and pig skin (2.8% dose). The extent of DEET absorption was greater with DMSO and acetone than with ethanol in rat and mouse skin. These studies support DEET, but not permethrin or carbaryl, as having sufficient systemic exposure to potentially cause signs of toxicity when simultaneously applied with pesticides. Furthermore, these studies demonstrated that DEET does not necessarily enhance dermal absorption of all toxicants as was originally hypothesized.
authors.affiliation: Cutaneous Pharmacology and Toxicology Center, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Baynes
authors.forename: K B
authors.initials: KB
authors.lastname: Halling
authors.forename: J E
authors.initials: JE
authors.lastname: Riviere
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D012721:Carbaryl / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003671:DEET / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D007306:Insecticides / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D026023:Permethrin; D011722:Pyrethrins / Q000493:pharmacokinetics*; D051381:Rats; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013552:Swine
chemical_list: D007306:Insecticides; D011722:Pyrethrins; D003671:DEET; D026023:Permethrin; D012721:Carbaryl