In Vitro Skin Penetration Characteristics of Ethanol in the Rabbit, Mouse, Rat, and Human

Abstract

The cutaneous penetration of chemicals can be measured by in vitro techniques using a wide variety of animal and human skin samples. In contrast to dermal penetration studies using whole animals, in vitro techniques allow the direct measurement of chemical penetration, which can be used to help predict the absorbed dose and rate of absorption in whole animals and across species. Thus, in vitro methods may provide results that allow better extrapolations of in vivo animal studies to human exposure scenarios, and more accurate assessments of the potential human health risk following dermal exposure to chemicals. When conducting in vitro skin penetration studies, it is critical to know the condition and integrity of skin samples being used. Skin samples that have been improperly handled and/or stored can yield results that either underestimate or overestimate true penetration characteristics. To avoid this, ethanol was used as a model compound to assess the quality of skin samples used for skin penetration studies. During each experimental session, the penetration characteristics of a 25% aqueous solution of [¹⁴C]ethanol were measured and the results compared with values obtained from similar control experiments conducted previously. This paper describes the compilation of ethanol penetration data collected over 6 years using full-thickness rat, mouse, rabbit, and human skin samples from over 175 experiments. In general, the results showed that the order of skin permeability for this model compound was rabbit > mouse > rat ± human. More important, however, is that this unique data base has allowed the statistical description of the distribution of such data and, from this, has established skin penetration criteria of ethanol as a reference chemical that can be used to assess the condition and integrity of skin samples used for in vitro skin penetration studies.