Subchronic hepatotoxicity evaluation of 2,3,4,6-tetrachlorophenol in Sprague Dawley rats

Male sprague dawley rats were exposed to 2,3,4,6-tetrachlorophenol (tcp) for 5 days,2 weeks,4 weeks,or 13 weeks. tcp was administered by gavage at doses of 0,10,25,50,100,or 200mg/kg/day. endpoints evaluated included clinical observations,body weights,liver weights,serum chemistry,blood tcp,gross pathology,and liver histopathology. there were no tcp exposure-related clinical signs of toxicity. mean body weight decreased 1222 compared to control in the 100 and 200mg/kg/day groups. serum alt concentrations were increased in rats of the 200mg/k/day. liver weight increases were both dose- and exposure time-related and statistically significant at ≥25mg/kg/day. incidence and severity of centrilobular hepatocytic vacuolation,hepatocyte hypertrophy,and single cell hepatocytic necrosis were related to dose and exposure time. following 13 weeks of exposure,bile duct hyperplasia and centrilobular and/or periportal fibrosis were observed in rats primarily of the highest tcp dose group. blood tcp concentrations increased with dose and at 13 weeks ranged from 1.3 to 8.5g/ml (10 to 200mg/kg/day). a noael of 10mg/kg/day was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥25mg/kg/day. copyright © 2012 darol e. dodd et al.