Subchronic hepatotoxicity evaluation of bromobenzene in Fischer 344 rats.

Male Fischer 344 (F344) rats were exposed to bromobenzene (BB) for 5days and 2, 4 and 13weeks. BB was administered by gavage (corn oil vehicle) at doses of 0, 25, 100, 200, 300 and 400mgkg1 per day. Endpoints evaluated included clinical observations, body weights, liver weights, serum chemistry, blood BB, gross pathology and liver histopathology. There were no BB exposure-related clinical signs of toxicity. Mean body weight decreased by 510% compared with control in the 400mgkg1 per day group. Liver weight increases were dose- and exposure time-related and statistically significant at 25mgkg1 per day. Incidence and severity of centrilobular cytoplasmic alteration and hepatocyte hypertrophy were related to dose and exposure time. At early time points (5days and 2weeks), centrilobular inflammation, including granulomatous areas, and necrotic and anisokaryocytic hepatocytes were observed in rats of the two highest BB dose groups. Blood BB concentrations increased linearly with dose and at 13weeks ranged from 8 to 136 mu gml1 (25400mgkg1 per day). In conclusion, rats administered BB doses up to 400mgkg1 per day for up to 13weeks had mild liver effects. A NOAEL of 200mgkg1 per day was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses400mgkg1 per day. Copyright (c) 2012 John Wiley & Sons, Ltd.