Percutaneous absorption/metabolism of phenanthrene in the hairless guinea pig: Comparison of in vitro and in vivo results

Abstract

The in vitro and in vivo percutaneous absorption/metabolism of phenanthrene was investigated in hairless guinea pigs. Flowthrough diffusion cells and Hepes-buffered Hanks' balanced salt solution (HHBSS) as receptor fluid were used in the in vitro system. When phenanthrene was applied to excised guinea pig skin mounted on the cells at dose levels of 6.6 and 15.2 μg/cm 2, 89.7 and 79.1% of the administered doses were respectively absorbed into the skin and receptor fluids during a 24-hr perfusion period. These results are consistent with the in vivo data which showed approximately 80% absorption over the same period of time. Phenanthrene was metabolized in vitro into phenanthrene 9,10-dihydrodiol, 3,4-dihydrodiol, 1,2-dihydrodiol, and traces of hydroxy phenanthrenes. Of the materials absorbed in vitro, 92% was the parent compound and 7% the dihydrodiol metabolites. When a nonviable in vitro system was used 68% of the applied 15.2 μg/cm 2 dose was absorbed. Data from the present study demonstrate that the in vitro system is a good model for predicting in vivo percutaneous absorption of phenanthrene, and that penetration of phenanthrene through the skin is controlled more by the passive rate of diffusion than by metabolism.