Capacity of an in vitro rat skin model to predict human dermal absorption: Influences of aging and anatomical site

Abstract

In addition to inhalation, dermal absorption is a route of exposure to be considered when assessing occupational risks. To investigate dermal penetration of chemicals, human skin samples are regarded as the gold standard. As human samples can be difficult to obtain, many experiments are performed with rat skins, and the results extrapolated to describe human percutaneous absorption. Here, we examined the characteristics of rat skin samples and compared absorption to that measured with in vitro human skin. The thickness of the stratum corneum layer in rat skin samples was found to be uniform when samples were excised from the animals' backs once they were at least 7-weeks-old. Overall, dorsal skin samples from mature rats could be reliably used to measure the flux of hydrophilic liquid molecules, such as N-methyl-2-pyrrolidone, and N,N-dimethylformamide. In contrast, with a solid lipophilic substance, bisphenol A, dissolved in acetone, the flux obtained with rat skin samples was 3-fold higher than that measured with human skin. Consequently, it does not appear relevant to use rat skin in place of human skin to measure absorption of solid lipophilic substances.