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.
Tardif
R
R
Départment de Médecine du travail et hygiène du milieu, Faculté de Médecine, Université de Montréal, Québec, Canada.
Laparé
S
S
Krishnan
K
K
Brodeur
J
J
D000818:Animals; D001273:Atmosphere Exposure Chambers; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004781:Environmental Exposure; D006801:Humans; D008297:Male; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D014050:Toluene / Q000493:pharmacokinetics* / Q000633:toxicity; D014992:Xylenes / Q000493:pharmacokinetics* / Q000633:toxicity
D014992:Xylenes; D014050:Toluene; C031285:3-xylene