The liver slice system: A rapid in vitro acute toxicity test for primary screening of hepatotoxic agents

A simple method for the rapid screening of hepatotoxic agents is described. Liver slice systems were prepared from rats and mice, and incubated in Krebs-Ringer-Hepes medium with different concentrations of the test compounds. Hepatotoxicity was monitored by determination of liver enzymes in the slice medium. Enzyme leakage was dose- and time-dependent. Histopathological changes in the hepatotoxin-treated slices were well correlated with the extent of enzyme leakage. Species differences in susceptibility to various hepatotoxins could be easily detected by this in vitro system: the dose-toxicity curves revealed that the mouse is more vulnerable than the rat to acetaminophen and furosemide. These findings are well correlated with those of in vivo experiments. A preliminary study showed that, in the same species, the relative toxicities of various chemicals in the liver slice system were similar to those reported in vivo. In summary, these results on the tissue slice system are encouraging. However, much more work will have to be done before the system can be considered sufficiently well validated for routine use.