Publications : 1993

Steup DR, Hall P, McMillan DA, Sipes IG. 1993. Time course of hepatic injury and recovery following coadministration of carbon tetrachloride and trichloroethylene in Fischer-344 rats. Toxicol Pathol 21:327–334.


Simultaneous administration of trichloroethylene (TCE), at an oral dose of 0.5 mVkg, resulted in a marked potentiation of liver injury caused by an oral dose of carbon tetrachloride (CCl,, 0.05 mVkg). Hepatic glutathione levels were depressed at 24 hr only in the rats given TCE and CCl,. Using serum enzyme (ALT and SDH) as indicators of hepatotoxicity, potentiation of CCl,-injury was most apparent at 24 hr. Upon histological examination of H&E stained liver sections, the differences between livers obtained from TCE and CC1,-treated rats versus CC1,-treated rats were most apparent at later time points (48 and 72 hr). At 48 hr after CCl,, livers showed a distinctive and uniform pattern of injury with regeneration features predominating over necrosis. At this time, livers from TCE and CC1,-treated rats were characterized by extensive zone 3 coagulative necrosis. Inflammatory infiltrations were less prominent. At 72 hr, morphological features of livers from TCE and CCl, rats were similar to those from ralSgven CCl, alone at 48 hr. From the results obtained, it appears that the regenerative activity of the liver may be delayed in rats simultaneously administered TCE and CCI, as compared to rats administered only CCI.  Interactive hepatotoxicity; glutathione; synergism; alanine amhotransferase; sorbitol dehydrogenase; halogenated hydrocarbons; regeneration