EVALUATION OF THE CYTOTOXICITY OF 10 CHEMICALS ON HUMAN CULTURED-HEPATOCYTES - PREDICTABILITY OF HUMAN TOXICITY AND COMPARISON WITH RODENT CELL-CULTURE SYSTEMS

The cytotoxic effect of the first 10 chemicals on the MEIC list (evaluated in the Multicentre Evaluation of In Vitro Cytotoxicity organized by the Scandinavian Society of Cell Toxicology) was evaluated on human and rat cultured hepatocytes and in the non-hepatic murine 3T3 cell line. The MTT test was used as an endpoint to evaluate cytotoxicity after 24 hr of exposure to the chemicals. The predictability of human toxicity using human hepatocytes was analysed and compared with the results using rodent cell culture systems and rat and mouse LD50 tests. Ferrous sulphate, diazepam and isopropyl alcohol produced about the same toxicity in all three cell culture models; paracetamol and acetylsalicylic acid were more toxic to human and rat hepatocytes than to mouse 3T3 cells; amitriptyline, ethylene glycol, methanol and ethanol were more toxic to human hepatocytes than to rodent cells. Digoxin was the most cytotoxic chemical to human hepatocytes (IC50, 4.9 nM), the alcoholic compounds (isopropanol, ethylene glycol, ethanol and methanol) were the least toxic (IC50, 125-819 mM) and paracetamol, acetylsalicylic acid, ferrous sulphate, diazepam and amitriptyline showed intermediate cytotoxicities (IC50, 0.05-6 mM). The data suggest that for these 10 chemicals, acute toxicity in humans was more accurately predicted using human hepatocytes than using rat hepatocytes or mouse non-hepatic 3T3 cells.