PERCUTANEOUS UPTAKE, DISTRIBUTION, AND EXCRETION OF PYRENE IN RATS

Groups of 12 male Wistar rats, of about 400 g body weight, were dosed with 2, 6, or 15 mg/kg of C-14-labeled pyrene, dissolved in acetone, a pplied to 4 cm(2) of a shaved area of the mid back. Three animals in e ach dose group were killed at 1, 2, 4, and 6 d postdosing, and their p rincipal organs were removed and analyzed for pyrene and [C-14]pyrene equivalents. Urine and feces, as well as the area of skin to which the dose was applied, were also analyzed for [C-14]pyrene equivalents. Th e rate of uptake from the skin was rapid (t(1/2), 0.5-0.8 d) relative to rate processes for the other organs, and about 50% of the applied d ose was excreted over the 6 d of the study. The significant decrease i n the fraction of the dose excreted and in the normalized amounts dist ributed to the various organs and tissues, as the dose increased for a ll chemical species measured, was strongly suggestive of nonlinear kin etics, as has been observed in previous studies. Levels of pyrene were highest in the liver, kidneys, and fat. Levels of metabolites were al so high in the lung. It was evident that the dermal route of uptake wa s not insignificant for this model polycyclic aromatic hydrocarbon and may represent a significant exposure route for exposed humans.