A DESCRIPTIVE AND MECHANISTIC STUDY OF THE INTERACTION BETWEEN TOLUENE AND XYLENE IN HUMANS

This study was undertaken to characterize the mechanism of toxicokinet ic interaction between toluene (TOL) and m-xylene (XYL) in the rat usi ng physiologically-based toxicokinetic (PBTK) modeling approach. First , the metabolic rate constants were determined by conducting closed-ch amber inhalation exposures with individual solvents (Vmax: TOL=4.8, XY L= 8.4 mg/hr/kg; Km: TOL= 0.55, XYL= 0.2 mg/l). Then, using the same e xperimental set-up, rats were exposed to different binary mixtures of TOL and XYL. PBTK analysis of the data showed competitive inhibition a s the plausible mechanism of TOL/XYL interaction. This mechanistic mod eling study suggests that the interaction between TOL and XYL is likel y to be observed when the exposure concentration exceeds 50 ppm of eac h solvent.