ABSORPTION, METABOLISM, AND EXCRETION OF N,N-DIETHYL-M-TOLUAMIDE FOLLOWING DERMAL APPLICATION TO HUMAN VOLUNTEERS

The absorption, metabolism, and excretion of N,N-diethyl-m-toluamide (DEFT) in male human volunteers following dermal application of [C-14]DEET was studied. DEFT was applied to two groups of six volunteers either as the undiluted technical grade material or as a 15% solution in ethanol, The material was applied over a 4 X 6-cm area on the volar surface of the forearm and was left in contact with the skin for 8 hr, then rinsed off the skin, Application sites also were tape stripped at 1, 23, and 45 hr after rinsing. Serial blood samples and all urine and feces were collected for 5 days after application. Aliquots of these materials were analyzed for total radioactivity in order to define absorption and excretion patterns. Urine samples also were analyzed by HPLC to characterize the metabolic profile and/or to identify metabolites, Absorption of DEET as evidenced by plasma radioactivity occurred within 2 hr after dose application. Elimination of radioactivity from plasma was rapid and quantifiable levels of radioactivity were observed in plasma for only 4 hr after the end of the 8-hr exposure period. Urine was the principal route of excretion of radioactivity and accounted for an average of 5.61 and 8.33% of the applied dose in the undiluted DEET and 15% DEET in ethanol groups, respectively. Excretion of radioactivity in the feces was less than 0.08% of the applied dose in both groups, DEFT did not accumulate in the superficial layers of the skin as evidenced by low amounts of radioactivity in the tape strippings. The major fraction of the applied radioactivity was recovered in the skin rinses. Absorbed DEET was completely metabolized and six major metabolites were observed in urine, Two major urinary metabolites tentatively were identified. Based upon the percentage of applied dose recovered in the excreta, dermal absorption of DEET ranged from 3 to 8% with a mean of 5.6% in the volunteers applied undiluted technical grade DEET. The corresponding values for the volunteers applied 15% DEET in ethanol were 4 to 14% and 8.4%, respectively. (C) 1995 Society of Toxicology.