Pretreatment with drinking water solutions containing trichloroethylene or chloroform enhances the hepatotoxicity of carbon tetrachloride in Fischer 344 rats*1, *2

摘要: Previous studies have demonstrated that various compounds, including the common groundwater contaminants trichloroethylene (TCE) and chloroform (CHCl3), can produce a synergistic toxic response when coadministered with model hepatotoxicant carbon tetrachloride (CCl4). This phenomenon has not, however, been following administration of these compounds in drinking water. Initial experiments indicated Fischer 344 (F-344) rats were significantly more sensitive to effects than commonly utilized Sprague-Dawley strain. To establish suitability this strain as model, variety indicators hepatotoxicity was evaluated compared histological evidence injury 24 hr after dosing CCl4 or combination + TCE. Plasma alanine aminotransferase (ALT) activity most reliable indicator hepatic well-correlated histologic data. Dose-response utilizing simultaneous ip confirm sensitivity F-344 rat, demonstrating toxicity at doses low 0.165 mmol/kg 0.6 Synergism also detected 1 0.5 CHCl3. evaluate water exposure, pretreated for 3 days solutions containing TCE (0-40 mM) CHCl3 (0-8 stabilized 1% Emulphor (EL-620P) their only source fluids. A single, dose (1 mmol/kg) then administered later animals killed examination liver histology determination ALT activity. Although none pretreatments detectably hepatoxic, which drank 15 40 mM 8 exhibited an enhanced CCl4.