Percutaneous Absorption of Benzo[a]Pyrene in the Rat: Comparison of in Vivo and in Vitro Results

Abstract

Percutaneous absorption of 14C-labeled benzo[a]pyrene (BaP) was studied in five-day in vivo and in vitro experiments with female Sprague-Dawley rats following single topical doses of 9-10 micrograms/cm2. The in vivo percutaneous absorption was measured by the presence of 14C radioactivity in urine, feces and tissues. In vitro percutaneous absorption was measured with excised (non-viable) skin in Franz-type diffusion cells. Several modifications of standard diffusion cell techniques which are known to enhance the transport of lipophilic compounds were evaluated. In vitro penetration was determined by directly measuring the level of 14C radioactivity in the receptor fluid. BaP was observed to readily penetrate in vivo with a total of 46.2% (n = 4, SD = 3.4%) of the applied dose being absorbed over five days. In in vitro experiments using an approximately 350 micronthick skin section and normal saline receptor solution, only 2.1% of the applied BaP diffused into the receptor fluid over five days. In in vitro experiments using full-thickness skin and a 6% solution of nonionic surfactant receptor fluid, 28.0% of the applied BaP diffused into the receptor fluid over five days. When both an approximately 350 microns-thick skin section and a 6% surfactant receptor solution were used in vitro, 49.9% (n = 4, SD = 3.1%) of the BaP dose was found in the receptor fluid after five days. The results show that the modified in vitro method is suitable for studying percutaneous absorption of lipophilic compounds such as BaP.