EVALUATION OF THE CYTOTOXICITY OF 10 CHEMICALS IN HUMAN AND RAT HEPATOCYTES AND IN CELL-LINES - CORRELATION BETWEEN IN-VITRO DATA AND HUMANLETHAL CONCENTRATION

The cytotoxicity of 10 chemicals from the Multicentre Evaluation of In vitro Cytotoxicity (MEIC) list (nos 21-30) was evaluated in human and rat cultured hepatocytes and in two established cell lines (HepG2 and 3T3) according to the MEIC programme organized by the Scandinavian So ciety of Cell Toxicology. The MTT test was used as the endpoint of cyt otoxicity after 24 hr of exposure to the chemicals. Theophylline, phen obarbital and paraquat were the least cytotoxic compounds in the cellu lar systems (IC50 = 450-17,000 mu M) except for the 3T3 cells. The sev en remaining chemicals (dextropropoxyphene, propranolol, arsenic triox ide, cupric sulfate, mercuric chloride, thioridazine and thallium sulf ate) showed a similar relative cytotoxic ranking in the four in vitro systems in the lower range of concentrations (IC50 = 2-350 mu M). The data suggest that these 10 chemicals have a basal cytotoxic effect com mon to the four in vitro systems, and probably none of these compounds could be considered either hepatotoxic or species specific. The corre lation between in vitro data and human lethal blood concentrations sho wed that the predictability of the in vitro systems was similar to tha t of in vivo rodent tests (LD(50)) only when low cytotoxic concentrati ons (IC10) were used for correlation.