Correlation of human hepatotoxicants with hepatic damage in animals

Substances that cause liver damage in humans were identified through a literature search conducted on Toxline and Medline. Using the same search strategy, species other than man were selected, in whom hepatic injury could be attributed to exposure to the identified substances. A total of 38 substances were identified as producing liver damage, manifested by either clinical chemistry or histopathology. The substances included 24 drugs, 9 industrial chemicals, 3 environmental agents, 1 pesticide, and ethanol. Twelve of the 36 compounds have been toxicologically evaluated in man, rodent, and non-rodent. Histopathologic liver damage was reported in all three species for 11 of these compounds. Only carbencillin produced histopathologic damage in man but not in either the rodent or non-rodent. Where clinical chemistry changes were reported for all three species categories, only eight substances induced similar reactions in all three species. Only with two substances did man and rodent react similarly (both positive), while the non-rodent was negative. The two substances were polychlorinated biphenyl (PCB) and tetrachlorethane. In the majority of the cases in which either or both histopathologic or clinical chemistry changes were reported for man or for the rodent or non-rodent, the changes that occurred were qualitatively similar. The rodent was as sensitive a predictor for hepatic effects as the non-rodent. Although it is impossible to predict how liver damage observed in a laboratory animal is correlated with human liver damage, hepatotoxicity in the rodent must be considered as indicative of potential hepatic damage in man.