© 1988 Oxford University Press
research-article |
Assessment of the Minima Effective Dose of Acetone for Potentiation of the Hepatotoxicity Induced by Trichloroethylene–Carbon Tetrachloride Mixtures1
*Department de Pharmacologie et d'Hygiène du Milieu, Faculté de Médecine, Université de Montréal Montréal, Québec, Canada H3C 3J7
Department de Meèdecine du Travail et d' Hygieène du Milieu, Faculté de Médecine, Universiteè de Montreèal Montreèal Queèbec, Canada H3C 3J7
Received May 5, 1987; accepted November 16, 1987
Assessment of the Minimal Effective Dose of Acetone for Potentiation of the Hepatotoxicity Induced by Trichloroethylene-Carbon Tetrachloride Mixtures. CHARBONNEAU, M., PERREAULT, F., GRESELIN, E., BRODEUR, J., AND PLAA, G. L. (1988). Fundam Appl. Toxicol 10, 431–438. Administration of acetone to rats in amounts larger than or equal to a minimal effective dosage (MED) is known to potentiate the severity of the liver damage produced by CC14 alone. It has been reported that CCl4-induced hepatotoxicity is also enhanced by the previous administration of trichloroethylene (TCE). In addition, TCE-CCl4 mixture-induced liver injury is potentiated by acetone. The present study was undertaken to determine if the acetone MED is decreased when the haloalkane challenge is a mixture of TCE-CCl4 instead of CCl4 alone. The effect of varying mixture compositions was also evaluated. In a first series of experiments, male Sprague-Dawley rats received corn oil or acetone (0.05–0.25 ml/kg, po); 18 hr later, they received an lp injection of either CC14 (0.1 ml/kg) or [TCE (0.25 ml/kg)–CCl4 (0.1 ml/kg)]. In a second series, rats received corn oil or acetone (0.75 ml/kg), and were challenged with TCE (1.5 ml/kg), CCl4 (0.25 ml/kg), or a mixture of TCE-CCl4, where TCE and CC4 dosages were equal to 25–757percnt;, 50–50%, and 75–25%, respectively, of those used for the administration of the solvents alone. In both series, rats were killed 24 hr after the haloalkane challenge. Liver injury was assessed biochemically (plasma ALT activities and bilirubin concentrations) and morphologically. When TCE was added to a solution of CCl4, smaller doses of CCl4 were required to produce equally severe liver injury. The MED of acetone required to potentiate CCl4-induced liver injury was at least five times smaller when TCE (0.25 ml/kg) was added to the challenge solution of CCl4- The severity of the injury produced by TCE-CCU mixtures administered in different proportions was constant, and potentiated to the same extent by a given dose of acetone. These observations suggest that the presence of haloalkane mixtures can result in severe liver injury with lower doses of hepatotoxicants. They further illustrate that prior exposure to acetone may markedly affect the response elicited by the haloalkane mixture.