Intra and interindividual variability in the kinetics of a poorly and highly metabolising solvent.
Human subjects were experimentally exposed three times simultaneously to tetrachloroethene (PER) and trichloroethene (TRI) under conditions of rest and exercise. In each subject the individual kinetics for both PER and TRI were determined three times by means of frequent sampling of alveolar air up to 70-500 and 20-310 hours respectively. For PER the following parameters were found: the weighted pulmonary clearance (Clpul) = 0.27-0.64 l/min, terminal half time (t1/2(z] = 54-250 hours, mean residence time (MRT) = 35-155 hours, and volume of distribution (Vdss) = 1100-3570 1. For TRI the apparent hepatic clearance (CLhep) = 0.5-1.7 l/min, weighted Clpul = 0.41-1.48 l/min, t1/2(z) = 13-55 hours, MRT = 2.3-22 hours, and the Vdss = 420-3100 1. The intra and intersubject variation in the kinetics were reflected in the predictions of the individual time course of the solvent in the blood at repeated exposure up to five weeks (eight hours a day, five days a week). For PER the intrasubject variation in the predicted concentrations on the Monday mornings was within 5-15% whereas the intersubject variation was about twofold. For TRI the intrasubject variation in the predicted morning concentrations was substantial (two to threefold), whereas the intersubject variation was about 10-fold. The intrasubject variation was probably caused mainly by the level of exercise during exposure. The Clhep was not greatly influenced by the level of exercise, whereas exercise during exposure increased the MRT. Exercise during exposure probably speeds up the process of distribution and, therefore, there is a lower concentration in the blood relative to the increased respiratory intake. As a consequence, despite the increased Clpul and the rather unchanged Clhep, pulmonary and metabolic excretion will be delayed and the MRT increased. The MRT is more suited to predict the individual cumulation of both PER and TRI than the terminal t1/2(z).
Opdam
J J
JJ
Coronel Laboratory, Faculty of Medicine, University of Amsterdam, The Netherlands.
D000328:Adult; D001711:Biotransformation; D005260:Female; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D005082:Physical Exertion; D012997:Solvents / Q000493:pharmacokinetics*; D013750:Tetrachloroethylene / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors; D014018:Tissue Distribution; D014241:Trichloroethylene / Q000097:blood / Q000493:pharmacokinetics*
D012997:Solvents; D014241:Trichloroethylene; D013750:Tetrachloroethylene