ATLA::Alternatives to Laboratory Animals

Volume 25, Number 3

The prediction of skin permeability by using physicochemical data.

ATLA 25, 359-370, May/June 1997

Lisa A. Kirchner, Richard P. Moody, Edward Doyle, Ranjan Bose, Jamie Jeffery and Ih Chu

Bureau of Chemical Hazards, Environmental Health Centre M/A #0802C1, de la Colombine Boulevard, Tunney's Pasture, Ottawa, Ontario K1A 0L2, Canada

SUMMARY

A database on physicochemical properties and skin permeation compiled by Health Canada was analysed by using linear regression analysis. The correlation between permeability coefficient (Kp) and the octanol-water partition coefficient (Kow) has been improved by grouping the compounds according to their respective molar volumes. Linear regression analysis of the individual groups has demonstrated a positive correlation for the majority of the groups, with the compounds in the lowest molar volume range (≤ 75Å3) having the best correlation (r2 = 0.86), and the compounds in the highest molar volume range (≤ 301Å3) being the least well-correlated (r2 = 0.55). Due to the diversity of the chemicals used in this analysis, and the statistically significant correlations obtained, this model could permit the prediction of skin permeation of a wide variety of chemical compounds. Although of a simplistic nature, and not yet experimentally validated, this quantitative structure-activity relationship may be useful for predicting human skin permeability coefficients for compounds that fall within the constraints of this data set.

Keywords: QSAR, skin permeability, partition coefficient, molar volume