Influence of acetone on the severity of the liver injury induced by haloalkane mixtures.
Acetone potentiation of haloalkane-induced liver injury is a well-known phenomenon. Acetone-treated rats challenged with a trichloroethylene-CCl4 mixture exhibit a more sever liver injury than that predicted by the addition of the single potentiating effects of each. The purpose of the present study was to determine if acetone exerted similar interactions with other haloalkane mixtures. The testing protocol used was designed and performed to allow categorization of interactions occurring among two or three agents. Rats were treated (p.o.) with corn oil or acetone (10.2 mmol/kg) and were administered (i.p.) 18 h later 1,1-dichloroethylene (0.6 mmol/kg), trichloroethylene (5.6 mmol/kg), tetrachloroethylene (19.6 mmol/kg), 1,1,1-trichloroethane (10.0 mmol/kg), 1,1,2-trichloroethane (1.1 mmol/kg), 1,1,2,2-tetrachloroethane (1.0 mmol/kg), CHCl3 (6.2 mmol/kg), CCl4 (1.0 mmol/kg), or a mixture of two haloalkanes (all 28 combinations were tested). Liver injury was assessed 24 h later using plasma alanine aminotransferase activity and a quantitative histological evaluation. In corn oil pretreated rats, the hepatotoxic responses observed for the 28 mixtures were additive for 26 of 28 mixtures and supra-additive for 2 of 28, whereas in acetone-pretreated rats the responses observed were additive for 17 of 28, infra-additive for 10 of 28, and supra-additive for 1 of 28. Mixtures containing 1,1,1-trichloroethane or tetrachloroethylene resulted only in no change in toxicity or infra-additivity. Increased toxic responses (additivity and supra-additivity) were observed with certain binary mixtures containing CCl4, CHCl3, 1,1,2-trichloroethane, or 1,1-dichloroethylene.(ABSTRACT TRUNCATED AT 250 WORDS)
Charbonneau
M
M
Département de médecine du travail et d'hygiène du milieu, Faculté de médecine, Université de Montréal, Québec, Canada.
Greselin
E
E
Brodeur
J
J
Plaa
G L
GL
D000096:Acetone / Q000008:administration & dosage / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000633:toxicity; D004357:Drug Synergism; D006843:Hydrocarbons, Chlorinated / Q000008:administration & dosage / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000293:injuries*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D006843:Hydrocarbons, Chlorinated; D000096:Acetone; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase