Development of a physiologically based pharmacokinetic model of organic solvent in rats.
A physiologically based pharmacokinetic model of the transfer of organic solvents in rat bodies was developed. The model has six compartments, i.e. lungs, vessel-rich tissue, muscles, fat tissue, tail, and liver, each being interconnected by the blood flow system. The transfer of organic solvents was expressed by simultaneous differential equations, which were then solved numerically by a personal computer using a simple spreadsheet program. m -xylene was used to represent organic solvents. The physiological parameters for rats (alveolar ventilation, cardiac output, tissue volume, tissue blood flow, etc.) and physicochemical or biochemical properties (blood/air partition coefficient, tissue/blood partition coefficients, metabolic constants, etc.) of m -xylene were based on the data obtained from the literature and our experiments. The partition coefficient of m -xylene for the tail and the blood flow and the volume of the rat tail were experimentally determined with adult rats. The results of simulation of rat exposure to m -xylene (50 and 500 ppm for 6 h) were essentially in good agreement with the experimental data on rats, i.e. the parent compound (m -xylene) concentration in the tail blood and the cumulative excretion of the metabolites in the urine were consistent.
Kaneko
T
T
Department of Environmental Health, Medical University of Yamanashi, Tamaho, Yamanashi, Japan. tkaneko@res.yamanashi-med.ac.jp
Horiuchi
J
J
Sato
A
A
D000280:Administration, Inhalation; D000818:Animals; D003198:Computer Simulation; D006626:Hippurates / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000493:pharmacokinetics; D014992:Xylenes / Q000493:pharmacokinetics*
D006626:Hippurates; D012997:Solvents; D014992:Xylenes; C031421:3-methylhippuric acid; C031285:3-xylene