Hepatotoxic interactions of ethanol with allyl alcohol or carbon tetrachloride in rats.
To assess whether potential toxic interactions occur between ethanol and allyl alcohol or carbon tetrachloride following subacute, concurrent chemical exposure, male Fischer 344 rats, approximately 70 d of age, were given ethanol at 0, 0.05, 0.1, 0.2, or 0.5 ml/kg in corn oil daily by gavage for 14 d (ETOH group), or the same levels of ethanol with 21 mg allyl alcohol/kg (ALAC group), or the same levels of ethanol with 20 mg carbon tetrachloride/kg (CCL4 group). Hepatic response was assessed 24 h after the last dose. Interactions were evaluated by comparing the ETOH group with either the ALAC group or the CCL4 group using multivariate analysis of variance procedures. No statistically significant interaction was seen between the ETOH group and the ALAC group at the dosages used. Although an interaction between ethanol and carbon tetrachloride given simultaneously was not statistically significant, a small interactive effect on weight gain from d 0 to termination was apparent (p = .057). Exposure to ethanol alone resulted in a concentration-dependent decrease in absolute and relative liver weight, with a threshold between 0.05 and 0.1 ml/kg. There was no histopathological evidence of hepatic damage with ethanol alone, and no effect on hepatic cytochrome P-450 and glutathione levels or on serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALK). Exposure to allyl alcohol alone resulted in significant increases in absolute and relative liver weights, liver glutathione, and periportal hepatocellular vacuolar degeneration. Exposure to carbon tetrachloride alone resulted in significant increases in absolute and relative liver weight, serum levels of ALT, AST, and ALK, and centrilobular hepatocellular vacuolar degeneration and necrosis. These observations indicate that subacute, concurrent exposure of ethanol with carbon tetrachloride or allyl alcohol at ethanol levels comparable to those reported in gavage vehicles did not result in interactive toxicity.
Berman
E
E
Developmental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
House
D E
DE
Allis
J W
JW
Simmons
J E
JE
D000433:1-Propanol / Q000633:toxicity; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002251:Carbon Tetrachloride / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004347:Drug Interactions; D000431:Ethanol / Q000633:toxicity*; D005978:Glutathione / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects*; D008297:Male; D015999:Multivariate Analysis; D009929:Organ Size / Q000187:drug effects; D020005:Propanols; D051381:Rats; D011916:Rats, Inbred F344
D020005:Propanols; D000431:Ethanol; C006463:allyl alcohol; D003577:Cytochrome P-450 Enzyme System; D000433:1-Propanol; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D005978:Glutathione