5-day styrene inhalation dose response in CD-1 mice (lung)

Styrene causes increased lung tumors in mice, but not in rats. Mouse lung tumors were found mostly at the conclusion of a life-time (104 weeks for males) exposure study and most were benign. Styrene is largely negative in genotoxicity assays. Styrene metabolism by CYP2F2 produced a different metabolite pattern in mouse lung than in liver or in rats or humans. The purpose of this study was to use genomic analyses to further investigate potential modes of action (MoA) of styrene in mice. Lungs were analyzed by whole genome microarrays for each strain at each dose. Male CD-1 mice were exposed to 6 inhalation concentrations of styrene: 0, 1, 5, 10, 20, 40, and 120 ppm for a single 6 hour exposure. This was intended to gain dose-response data at low-observed-adverse-effect-levels (LOAELs) of styrene (≥ 20 ppm) and at no-observed-adverse-effect-levels (NOAELs) of styrene (< 20 ppm) for comparison with gene expression from similar Styrene inhalation exposures in a second strain of mice (C57Bl/6). Affymetrix control probes (AFFX-prefix, 104 probes) have been excluded from the data matrix. Lung gene expression was evaluated in male CD-1 mice following a single 6-hr inhalation exposure of styrene at 0, 1, 5, 10, 20, 40, and 120ppm