Modeling skin permeability in risk assessment

The ability of molecules to pass through human skin is an established and wellstudied process in the cosmetic industry and has become increasingly more important to the pharmaceutical industry as it seeks to add to the number of therapeutic agents that can be advantageously administered transdermally. But the most widespread and urgent need to assess dermal penetration will arise in the context of exposures, either occupational or leisure, to chemical substances. The new European Union (EU) REACH legislation (Registration, Evaluation, and Authorization of Chemicals)a is effective from June 2007 and requires that such risk assessment be made for a very much greater number of chemical substances than that for which experimental measurements could reasonably be made. The legislation is one of the largest EU texts ever drafted. It runs to more than a thousand pages and its influence will eventually be felt far beyond Europe. The U.S. chemical industry has taken an interest in the progress of the REACH legislation as it may influence federal policy. This legislation together with the desire to limit, or if feasible to eliminate altogether, particularly in vivo experimental measurements has dramatically increased the need to find reliable and widely applicable modeling techniques that can predict the skin penetration properties of molecules for which no relevant experimental measurements have been made. The existence of validated and accepted models for making predictions of toxicity following dermal exposure will allow for the prioritization of chemicals already designated for further investigation or, if confidence in the model is sufficient, for filtering compounds as part of a multi-tiered risk assessment program.