Methods for in vitro percutaneous absorption studies II. Animal models for human skin

The percutaneous absorption of compounds through the skin of selected animal species was compared to that occurring with human skin, using in vitro diffusion cell techniques. The permeability of back skin of the following animals was examined: Hormel miniature pigs, Osborne-Mendel rats, NIH hairless mice, and Swiss mice. Benzoic acid, acetylsalicylic acid, and urea, dissolved in a petrolatum vehicle, were applied and permeability constants were determined. With the faster penetrating compounds, benzoic acid and acetylsalicylic acid, mouse skin and hairless mouse skin were similar and were the most permeable. Little difference was observed in acetylsalicylic acid absorption of human, pig, and rat skin. Pig skin and hairless mouse skin were the best animal models for the slower penetrating urea. The thicknesses of the stratum corneum, epidermis, and whole skin were determined from microtome sections prepared from frozen skin. In addition, the density of hair follicles in each type of skin was determined. In general terms, thickness of the stratum corneum was found to be important: the thickest stratum corneum was that of pig skin and the thinnest was that of the mouse. Often however, differences in permeability and stratum corneum thickness did not correlate on a 1:1 basis, which can be indicative of differences in structure of the different types of skin. The animal model of choice is dependent on the compound. For benzoic acid and acetylsalicylic acid, the pig and rat are good models for human skin. In the case of slow absorbing compounds, such as urea, diffusion through appendages in the skin may make undesirable the use of skin of densely haired animals.