Hepatic metabolism of toluene after gastrointestinal uptake in humans.
The metabolism of toluene and the influence of small doses of ethanol were measured in eight male volunteers after gastrointestinal uptake, the toluene concentration in alveolar air and the urinary excretion of hippuric acid and ortho-cresol being used as the measures of metabolism. During toluene exposure to 2 mg.min-1 for 3 h the alveolar toluene concentration was 0.07 (range 0-0.11) mg.m-3; exposure to 6 mg.min-1 for 30 min increased the alveolar concentration to 0.9 (range 0.03-2.6) mg.m-3. Ingestion of 0.08, 0.16, and 0.32 g of ethanol per kilogram of body weight during toluene exposure of 2 mg.min-1 increased the alveolar concentration within 10 min, and maximal alveolar concentrations of 5 (SD 3), 24 (SD 11), and 39 (SD 28) mg.m-3 were reached after 30, 60, and 90 min for the three doses, respectively. Hippuric acid excretion was only decreased by an ethanol dose of 0.32 g.kg-1. Very low doses of ethanol inhibit toluene metabolism, and the procedure is sensitive enough to measure metabolic interactions between solvents and other xenobiotics in humans.
Baelum
J
J
Institute of Environmental and Occupational Medicine, University of Aarhus, Denmark.
Mølhave
L
L
Honoré Hansen
S
S
Døssing
M
M
D000284:Administration, Oral; D000328:Adult; D000395:Air Pollutants, Occupational / Q000493:pharmacokinetics*; D003408:Cresols / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000493:pharmacokinetics; D006626:Hippurates / Q000493:pharmacokinetics; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D014050:Toluene / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000395:Air Pollutants, Occupational; D003408:Cresols; D006626:Hippurates; D014050:Toluene; D000431:Ethanol; C077977:cresol; C030514:hippuric acid