ABSTRACT
The ability of molecules to pass through human skin is an established and well-
studied 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)
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 vali-
dated 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.
