Enhancement of the metabolism and hepatotoxicity of trichloroethylene and perchloroethylene.

Trichloroethylene anesthesia (1% for 2 hr) caused acute hepatic injury in rats pretreated with five different inducers of the hepatic mixed function oxidase system, phenobarbital, Aroclor 1254, hexachlorobenzene, 3-methylcholanthrene and pregnenolone-16-α-carbonitrile. Injury did not occur after trichloroethylene in rats pretreated with spironalactone or controls given vehicle alone. Morphologic liver injury was most severe in the phenobarbital- and Aroclor 1254-pretreated animals and was accompanied by marked perturbations in liver electrolyte content and more than 20-fold elevations in serum transaminase. Extent of serum transaminase elevation appears to relate directly to prolongation of anesthesia recovery time and the enhanced urinary excretion of trichlorinated metabolites. Metabolism of perchloroethylene (7.5 m-moles/kg, p.o.) was increased 5- and 7-fold, respectively, in phenobarbital- and Aroclor 1254-pretreated animals, but liver injury after perchloroethylene appeared only in Aroclor 1254 animals. Differential induction of various components of the microsomal mixed function oxidase system was quantified in parallel experiments using animals similarly pretreated with isomolar doses of the six inducers and the vehicle control and sacrificed at times corresponding to onset of chloroethylene exposure. Magnitude of induction of cytochrome P-450 among these seven groups of animals correlates with the mean extent of trichloroethylene-induced liver injury as quantitated by serum transaminases level (r = 0.95), with prolongation of anesthesia recovery time (r = 0.95Z) and with enhanced urinary excretion of trichlorinated metabolites (r = 0.88).