Metabolic Interactions between Organic Solvents — with Highly and Poorly Metabolized Compounds

Metabolic interactions between organic solvents were clarified with highly and poorly metabolized compounds. m-Xylene (m-X) and trichloroethylene (TRI) were used as examples of highly metabolized compounds. 1,1,1-Trichloroethane (1,1,1) was used as an example of a poorly metabolized compound. Adult male Wistar rats were exposed to various concentrations of m-X, TRI or 1,1,1 for 6 hours singly or as a combination of 2 compounds (m-X and TRI; m-X and 1,1,1). The blood concentrations of parent compounds (m-X, TRI or 1,1,1) at the end of the exposure and the urinary cumulative excretion of their metabolites (m-methylhippuric acid and/or trichloroethanol & trichloroacetic acid) during and after exposure were determined. In vitro metabolic interactions between m-X and TRI and those between m-X and 1,1,1 were also determined with microsomes from rat livers. The in vivo experiment showed that the metabolic interactions occur only when the exposure concentration of a coexistent solvent is higher than the metabolic saturation point. The in vitro experiment demonstrated that the patterns of metabolic interactions between the solvents used in this experiment approximated those of noncompetitive inhibition.