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]D EET was studied. DEFT was applied to two groups of six volunteers eith er as the undiluted technical grade material or as a 15% solution in e thanol, The material was applied over a 4 X 6-cm area on the volar sur face of the forearm and was left in contact with the skin for 8 hr, th en 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 m aterials were analyzed for total radioactivity in order to define abso rption and excretion patterns. Urine samples also were analyzed by HPL C to characterize the metabolic profile and/or to identify metabolites , Absorption of DEET as evidenced by plasma radioactivity occurred wit hin 2 hr after dose application. Elimination of radioactivity from pla sma was rapid and quantifiable levels of radioactivity were observed i n plasma for only 4 hr after the end of the 8-hr exposure period. Urin e 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 radioa ctivity in the feces was less than 0.08% of the applied dose in both g roups, DEFT did not accumulate in the superficial layers of the skin a s evidenced by low amounts of radioactivity in the tape strippings. Th e major fraction of the applied radioactivity was recovered in the ski n rinses. Absorbed DEET was completely metabolized and six major metab olites were observed in urine, Two major urinary metabolites tentative ly were identified. Based upon the percentage of applied dose recovere d 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 etha nol were 4 to 14% and 8.4%, respectively. (C) 1995 Society of Toxicolo gy.