Krishman, K. and P. Poulin. Prediction of Skin Permeability Coefficients of Volatile Organic Chemicals From Information on Their Molecular Structure. The Toxicologist 1999. 48(1S): 71. Abstract #335.

Skin permeability coefficients (Kp) are required for estimating the dermal absorption of volatile organic chemicals (VOCs) using a pharmacokinetic model. At the present time, Kp of VOCs are empirically predicted by fitting molecular structure information of VOCs to experimental data on Kp. Considering the number of VOCs present in our environment and that the resources are limited, these empirical equations have a limited use in risk assessment because in vivo and/or in vitro data on skin absorption are required to derive such empirical equations. Alternatively, mechanistic/molecular structure-based equations need to be developed for predicting Kp of VOCs. The objective of the present study was to develop a mechanistic approach for predicting the human abdominal Kp of 35 VOCs only from information on their molecular structure. The approach consisted of estimating the stratum corneum:water (s:w) partition coefficients (PCs), the diffusion coefficients (D), and the path length of diffusion (I) for eventually calculating Kp [=P(s:w) x D/I]. P(s:w) of VOCs were predicted only from molecular structure information based on a recently validated equation used for predicting the tissue: water PCs of organic chemicals from data on oil:water PCs and lipid and water contents in tissue. Whereas, D were predicted according to the conventional Einstein-Stoke equation using molecular structure information (i.e. molecular radius) of VOCs and data on skin viscosity as the only input parameters. Finally, I was estimated in accordance with the characteristics of the diffusion pathway in the stratum corneum (i.e. transcellular and intercellular pathways). The predicted human abdominal Kp value of several VOCs (alcohols, haloalkanes, aromatics) differed to the experimentally determined ones with an average ratio of 1.04 (S.C.=0.898, 4=0.85, n=35). Incorporating the mechanistic/structure-based equation validated in this study in a pharmacokinetic model should facilitate the risk assessment for a skin exposure to the several VOCs present in our environment.