Formation and Removal of Pentachlorophenol-Derived Protein Adducts in Rodent Liver under Acute, Multiple, and Chronic Dosing Regimens

We investigated the kinetics of production and elimination of chlorinated quinone adducts of liver cytosolic proteins derived from pentachlorophenol (PCP), following oral administration un-der acute dosing (0–40 mg/kg body weight [bw] in Sprague-Dawley rats, 0–120 mg/kg bw in F344 rats, and 0–60 mg/kg bw in B6C3F1 mice), multiple dosing (0–60 mg/kg bw/day for 5 days in F344 rats and B6C3F1 mice), and chronic feeding (60 mg/kg bw/day for 6 months in F344 rats). We measured adducts of both tetrachloro-1,2-benzoquinone (Cl4-1,2-BQ) and tetrachloro-1,4-benzoquinone (Cl4-1,4-BQ) following reduction of cysteinyl ad-ducts by Raney nickel and gas chromatography-mass spectrome-try. Ratios of Cl4-1,2-BQ to Cl4-1,4-BQ adducts were much greater in mice (0.8–2) than in F344 rats (0.04–0.07), indicating that Cl4-1,2-BQ is an important PCP-binding species in mice but not rats. Following acute administration of 20 mg PCP/kg bw t