Influence of skin source, penetration cell fluid, and partition coefficient on in vitro skin penetration

Using split-thickness pig skin mounted on in vitro skin penetration-evaporation cells, standard conditions were developed to preserve the viability of the skin as judged by its ability to successfully graft to nude mice. The effects of variations from these conditions on the disposition of radioactivity of radiolabeled compounds were determined. No differences in percutaneous penetration were found for N,N-diethyl-m-toluamide, parathion, and progesterone when Tyrode's solution was used in place of tissue culture media. The percutaneous penetration of benzo(a)pyrene on human and pig skin was unaffected by the presence of sodium azide in the tissue culture media; however, with mouse skin, penetration was lower when sodium azide was present. The disposition of radioactivity following topical application of five radiolabeled compounds was similar on fresh skin compared with skin that had been frozen and exposed to ethylene oxide, although variability of the values was greater with the treated skin. The percutaneous penetration of several compounds was determined on skin with and without the epidermis. The penetration of compounds with a lower log P (log octanol-water partition coefficient) increased to a greater extent (e.g., benzoic acid, log P = 2, sixfold increase) than compounds with a higher log P (e.g., DDT, log P = 5, twofold increase). To further validate the use of pig skin, the percutaneous penetration of 11 compounds on pig skin were correlated (r = 0.79) with the values obtained for human skin under standardized in vitro conditions.(ABSTRACT TRUNCATED AT 250 WORDS)