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

D ow nloaded from 2ABSTRACT We investigated the kinetics of production and elimination of chlorinated quinone adducts of liver cytosolic proteins derived from pentachlorophenol (PCP) following oral administration under acute dosing (0 – 40 mg/kg body wt in Sprague-Dawley rats, 0 – 120 mg/kg body wt in F344 rats, and 0 – 60 mg/kg body wt in B6C3F1 mice), multiple dosing (0 – 60 mg/kg body wt/day for 5 days in F344 rats and B6C3F1 mice), and chronic feeding (60 mg/kg body wt/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 adducts by Raney nickel and gas chromatography-mass spectrometry. 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 body wt to Sprague-Dawley rats and B6C3F