EVALUATION OF THE CYTOTOXIC EFFECTS OF MEIC CHEMICALS 31-50 ON PRIMARY CULTURE OF RAT HEPATOCYTES AND HEPATIC AND NONHEPATIC CELL-LINES

The cytotoxicities of 20 chemicals (numbers 31-50) from the Multicente r Evaluation of In Vitro Cytotoxicity (MEIC) programme were assessed w ith a primary culture of rat hepatocytes and with two hepatic cell lin es (Hep G2 and FaO) and one non-hepatic cell line (3T3). The cytotoxic ities of the chemicals were evaluated by using the MTT test after the cells had been exposed to the chemicals for 24 hours. For a better eva luation of results, dose-response curves were mathematically linearise d and cytotoxicity was expressed as IC50 values and IC10 values (the c oncentration causing 50% and 10% loss of cell viability, respectively) . We found that ail the compounds showed similar acute basal cytotoxic ity in all four cellular systems (regardless of whether the cells were , or were not, metabolically competent or were or were not of human or igin). When these results were used to predicit human toxicity in term s of a mathematical parameter (prediction error [PE]), we found that a ll four systems gave similar predictions of human toxicity. The best c ytotoxicity parameter included in the PE calculation was the IC50/10, because of an underestimation of human toxicity by in vitro systems. H owever, when PEs were calculated for rodent toxicity, better results w ere obtained. Data from the literature obtained by using other experim ental models for predicting human toxicity were analysed according to the same criteria. We conclude that cellular systems are better predic tive tools for human toxicity than are prokaryotic cells or whole-orga nism models.