Relationship between uptake and elimination of toluene and debrisoquin hydroxylation polymorphism.
The toxicokinetics of toluene were studied in six healthy subjects. Three of the subjects were phenotyped as rapid hydroxylators of debrisoquin and three subjects were phenotyped as slow hydroxylators of debrisoquin. The subjects were exposed in an exposure chamber to toluene vapor (3.25 mmol/m3) for 4 hours. Solvent concentrations in blood and the metabolites, hippuric acid and o-cresol, in urine were measured during the exposure period and 3 hours after exposure. The capacity to metabolize debrisoquin was determined in three volunteers who had earlier experimentally been exposed to toluene. The uptake of toluene was about 3 mmol, or 50% of the inhaled dose in both rapid and slow hydroxylators. There were no significant differences between the two phenotypic groups with regard to concentrations of toluene in blood, apparent blood clearance of toluene, or excretion of hippuric acid and o-cresol.
Löf
A
A
National Institute of Occupational Health, Solna, Sweden.
Hansen
S H
SH
Näslund
P
P
Steiner
E
E
Wallén
M
M
Hjelm
E W
EW
D001273:Atmosphere Exposure Chambers; D001711:Biotransformation; D003408:Cresols / Q000652:urine; D003647:Debrisoquin / Q000378:metabolism*; D006207:Half-Life; D006626:Hippurates / Q000652:urine; D006801:Humans; D006900:Hydroxylation; D007546:Isoquinolines / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D010641:Phenotype; D011110:Polymorphism, Genetic; D012119:Respiration; D014050:Toluene / Q000097:blood / Q000493:pharmacokinetics*
D003408:Cresols; D006626:Hippurates; D007546:Isoquinolines; D014050:Toluene; C030514:hippuric acid; D003647:Debrisoquin; C034047:2-cresol