A mixture of 25 groundwater contaminants identified in and around hazardous waste sites was formulated in water at various multiples of the average concentrations found in analytical surveys of ground water for water soluble compounds or at various dilutions of the 90% saturation level of the poorly soluble compounds. This mixture which contained heavy metals, aromatic hydrocarbons, and halogenated solvents was administered in drinking water or by gavage to Fischer 344 rats for 14 days. Evaluations were made of the effect of this mixture on hepatic biochemical parameters including mitochondrial respiration, lipid peroxidation, and levels of cytochrome P-450, aryl hydrocarbon hydroxylase, and glutathione- S transferase. A decrease in mitochondrial state-3 respiration (phosphorylation of ADP) was the most notable effect of administration of this chemical mixture. In vitro studies are in progress to identify the specific affects of the components of this mixture on mitochondrial respiration. Preliminary data indicate that cadmium was the most potent inhibitor of ADP phosphorylation in the mixture; however, inhibition occurred at lower concentrations by the mixture than that caused by cadmium. An additive or possibly a synergistic effect of components of this mixture on mitochondrial oxidative phosphorylation is suggested.
