A chemical mixture of 25 groundwater contaminants, including heavy metals, aromatic hydrocarbons, and halogenated solvents is being studied by the National Toxicology Program for potential toxicologic effects in rats and mice by the dosed water route of exposure. Studies were initiated to examine the effect of this chemical mixture on oxidative phosphorylation in isolated rat liver mitochondria. The total chemical mixture inhibited state-r (oxidation) and state-3 (phosphorylation) respiration rates at 1/500 the concentration used in the dosed water study. Cadmium was by far the most potent inhibitor of mitochondrial oxidative phosphorylation of any component in the mixture. Neither a mixture of the organic components nor the individual heavy metals inhibited the mitochondrial state-3 or state-4 respiration rates at the effective concentration of the total mixture. Thus, the inhibition of mitochondrial respiration by the chemical mixture is probably due to a synergistic effect of some of its components. the chemical mixture was also toxic to isolated rat hepatocytes, causing extensive leakage of lactate dehydrogenase after 4 hours of incubation.
