Toxicity of combinations of chlorinated aliphatic hydrocarbons in vitro and in vivo.
Hepatocyte suspensions were exposed to carbon tetrachloride (CT), chloroform (CF) or 1,1,1-trichloroethane (TE) or the various combinations of these three chemicals over a 3-hr incubation period. Enhanced toxicity, as determined by loss of intracellular potassium ion and cytoplasmic enzyme leakage, was demonstrated for each combination in hepatocyte suspensions. Other rats were exposed to these chlorinated hydrocarbons by ip injection and blood samples were taken 24 hr later to determine plasma enzyme levels as indicators of hepatotoxicity. Exposure in vivo resulted in a positive interaction of CT + CF and CF + TE but not for CT + TE or CT + CF + TE. The data indicate that, while there is some correlation of response between results in vitro and in vivo, there is not complete agreement. This indicates that care is necessary in extrapolating results obtained in vitro to predict responses in vivo for toxicity of chemical combinations. Nevertheless, the positive correlation demonstrated for some of the combinations supports further investigations of the use of toxicity testing in vitro for the prediction of enhanced toxicity on exposure to chemical mixtures.
Stacey
N H
NH
National Institute of Occupational Health and Safety, The University of Sydney, NSW 2006, Australia.