Pharmacokinetic studies were conducted to evaluate and compare the uptake and metabolism of styrene in B6C3F1 mice and F344 rats during nose-only inhalation exposure. Blood, liver, and fat samples were collected from rats and mice during and after exposure to 125, 250, or 500 ppm styrene. Samples are being analyzed for styrene and styrene oxide content. In addition, hepatic glutathione levels are being determined in rats and mice at the different time points. A subsequent study was conducted to investigate the effects hepatic P450 induction and inhibition on the in vivo metabolism and pharmacokinetics of styrene and styrene oxide in mice. These data will be used in a physiologically-based pharmacokinetic model to evaluate species and mouse strain differences in styrene toxicity. Clastogenicity and sister chromatid exchange (SCE) were evaluated in female mice and rats exposed to 125, 250, or 500 ppm styrene 6h/day for 14 days. In mice, there was a significant dose related elevation of SCE frequency in lymphocytes from the spleen, and the peripheral blood as well as in cells from the lung. No changes were detected in the frequency of chromosome aberrations in cultured splenocytes or lung cells. Rat samples are still being evaluated. Studies were conducted to evaluate the effects of styrene inhalation on cell proliferation in the liver, and to investigate the role of cell proliferation in the progression of hepatoxicity in the mouse. Evaluations of BrdU-labeled cells are in progress.
