Cytotoxicity of 28 MEIC chemicals to rat hepatocytes using two viability endpoints: correlation with acute toxicity data in rat and man

By Roguet, R. - Cotovio, J. - Gaetani, Q. - Dossou, K.G. - Rougier, A.

28 of the chemicals on the MEIC list were tested on rat hepatocytes in culture. Firstly, the metabolic capacities of the cell model were characterised, i.e. cytochrome P450 content and conjugation activities. Two independent endpoints, MTT (tetrazolium salt) reduction (for mitochondrial integrity) and neutral red uptake (NRU, for lysosomal integrity), were then used to measure the cytotoxicities of the test compounds after incubation with the cells for 24 hours. The relative toxicities of the test chemicals were measured by the determination of IC50 values for each parameter. Statistical analysis revealed a correlation between the results obtained in the two assays. The NRU assay, however, proved to be more sensitive than the MTT reduction assay. When the in vitro results were compared with those obtained from an in vivo data bank, good agreement was found with the acute toxicities of the test products in rats, with the exception of thioridazine, malathion, copper sulphate (all overestimated) and potassium cyanide (underestimated). In addition, a good correlation between basal cytotoxicity values for rat hepatocytes and LD50 for rats or lethal doses for humans was observed. These results suggest that the MTT reduction and/or NRU assays could be useful indicators of the cytotoxic potential of chemicals in rat hepatocyte cultures and thus provide information on the intrinsic lethal toxicity of compounds and their metabolites to rats and humans.