Assessment of the toxicity of chemical mixtures with isolated rat hepatocytes: cadmium and chloroform.
The suitability of isolated rat hepatocytes for the investigation of the toxicity of chemical mixtures has been studied. Cadmium chloride and chloroform were used because both had been previously investigated in hepatocytes and both produce hepatotoxicity after in vivo administration. The addition of the two chemicals caused an increase in cytotoxicity as assessed by loss of intracellular potassium ion and aspartate aminotransferase. There was even a toxic response form the mixture at concentrations where the chemicals alone yielded no such response. The metabolic parameter, lactate to pyruvate ratio, was less consistently affected. The nature of the interaction could, under the varying conditions employed, be described as one of synergism, potentiation, or addition. The data support the proposed role of isolated hepatocytes in screening chemical mixtures for toxic effects.