ABSTRACT
Development of quantitative structure-activity relationships (QSAR) as a predictive tool is one avenue, gaining in importance as an alternative to experimentation in the emerging field of computational chemistry and toxicology. The objective of applying QSAR to skin penetration is the prediction of permeability coefficients of compounds solely from the molecular structure of the penetrant, attempting to develop a universal formula applicable to a wide variety, if not to all classes of chemicals. Percutaneous absorption in vitro is measured under idealized laboratory conditions, and the values are expressed in terms of the permeability constant Kp. Mechanisms invoked in the development of structure-activity relationships predictive of barrier diffusion are operative within a number of limit situations beyond which the predictive equations fail. Determining the rate at which chemicals penetrate the skin remains important both from the standpoint of estimating clinical effectiveness as well as toxicological risk of designed or accidental xenobiotics.
