Reduction in skin permeation of N,N-diethyl-m-toluamide (DEET) by alteringthe skin/vehicle partition coefficient

Reported adverse side effects after using N,N-diethyl-m-toluamide (DEET)-co ntaining mosquito repellent products appear to be the result of significant absorption of DEET through human skin. The overall objective was to develo p formulations of DEET with significantly reduced permeation using the basi c principles and model of skin permeation based on Fick's laws of diffusion at steady state. Ternary phase diagrams of DEFT with water and semipolar s olvents, ethanol, PG and PEG 400, showed an increase in the aqueous solubil ity of DEET. This resulted in a linear decline in octanol/water PC with an increase in the concentration of the solvent. Permeation of DEET across hum an skin was studied from vehicles containing various amounts of PG and PEG 400 using an infinite dose technique and Franz diffusion cell. DEET's flux reduced with increasing PG concentration and the flux from 90% PG was 9.9+/ -2.1 mu g/cm(2) h, 6-fold lower than flux of pure DEET control, 63.2+/-24.5 mu g/cm(2) h. Flux was reduced 6-fold from 60% PEG 400 solution, and perme ation of DEFT was totally prevented from 90% PEG 400 which was Very viscous . However, a combination of 60% PEG 400 with 30% PG not only reduced permea tion 9-fold but was suitable as a vehicle for formulation. The decrease in flux and permeability of DEET with increasing concentration of solvent appe ared to be a direct result of decrease in skin/vehicle PC and octanol/water PC. This study clearly demonstrates that alternative formulations can be d eveloped for DEET aimed at reduced permeation and toxicity unlike the curre nt formulations some of which contain ethanol which has been shown to enhan ce permeation of DEET. A similar approach can be used for developing formul ations of other industrial and occupational agents to prevent their skin pe rmeation when a user may be exposed to them. (C) 2000 Elsevier Science B.V. All rights reserved.