ACUTE CYTOTOXICITY OF 10 CHEMICALS IN HUMAN AND RAT CULTURED-HEPATOCYTES AND IN CELL-LINES - CORRELATION BETWEEN IN-VITRO DATA AND HUMAN LETHAL CONCENTRATIONS

The cytotoxicity of ten chemicals from the MEIC list (nos 11-20) was e valuated in human and rat cultured hepatocytes and in two established cell lines (HepG2 and 3T3) according to the Multicentre Evaluation of In Vitro Cytotoxicity programme organized by the Scandinavian Society of Cell Toxicology. The lactate dehydrogenase intracellular activity a nd the MTT test were used as endpoints of cytotoxicity after 24 hr of exposure to the chemicals. Sodium chloride and lithium sulphate were t he least cytotoxic compounds in all of the cellular systems (IC50, 25- 150 mM). The eight remaining chemicals (1,1,1-trichloroethane, phenol, sodium fluoride, malathion, 2,4-dichlorophenoxyacetic acid, xylene, n icotine and potassium cyanide) showed a similar cytotoxic potential in the four in vitro systems in a narrow range of concentrations (IC50 1 -30 mM). The data suggest that these ten chemicals have a basal cytoto xic effect common to the four in vitro systems, and probably none of t hese compounds could be considered either hepatotoxic or to exert spec ies-specific toxicity. The correlation between in vitro data and human lethal blood concentrations showed a relatively low predictability fo r the toxicity of six compounds with important lethal effects on the C NS. The predictability of the in vitro systems was similar to that of in vivo rodent tests (LD(50)) only when low cytotoxic concentrations ( IC10) were used for the correlation.