A descriptive and mechanistic study of the interaction between toluene and xylene in humans

This study was undertaken to characterize the mechanism of toxicokinetic interaction between toluene (TOL) and m-xylene (XYL) in the rat using physiologically-based toxicokinetic (PBTK) modeling approach. First, the metabolic rate constants were determined by conducting closed-chamber inhalation exposures with individual solvents (Vmax: TOL = 4.8, XYL = 8.4 mg/hr/kg; Km: TOL = 0.55, XYL = 0.2 mg/l). Then, using the same experimental set-up, rats were exposed to different binary mixtures of TOL and XYL. PBTK analysis of the data showed competitive inhibition as the plausible mechanism of TOL/XYL interaction. This mechanistic modeling study suggests that the interaction between TOL and XYL is likely to be observed when the exposure concentration exceeds 50 ppm of each solvent.