COMPARISON OF THE TOXICITY OF ALLYL ALCOHOL, COUMARIN AND MENADIONE IN PRECISION CUT RAT, GUINEA-PIG, CYNOMOLGUS MONKEY AND HUMAN LIVER SLICES

The toxicity of allyl alcohol, coumarin and menadione has been studied in precision-cut liver slice cultures. Liver slices were prepared fro m male Sprague-Dawley rats, male Dunkin-Hartley guinea-pigs and from s amples of Cynomolgus monkey and human liver using a Krumdieck tissue s licer. The liver slices were cultured with the test compounds for 24 h in a dynamic organ culture system. Toxicity was assessed by measureme nt of protein synthesis, potassium content and the MTT assay. At the c oncentrations examined, menadione produced marked toxicity in liver sl ices from all four species, whereas rat liver slices were less suscept ible to allyl alcohol toxicity. Coumarin produced concentration-depend ent toxic effects in rat and guinea-pig liver slices, whereas Cynomolg us monkey and human liver slices were relatively resistant, especially at low coumarin concentrations. At some concentrations of the test co mpounds examined, the MTT assay appeared to be a less sensitive indica tor of toxicity than either protein synthesis or potassium content. Th ese results demonstrate the usefulness of precision-cut liver slices f or assessing species differences in xenobiotic-induced toxicity.