Development of a physiologically based pharmacokinetic model of organic solvent in rats

A physiologically based pharmacokinetic model of the transfer of organic so lvents in rat bodies was developed. The model has six compartments, i.e. lu ngs, vessel-rich tissue, muscles, fat tissue, tail, and liver, each being i nterconnected by the blood flow system. The transfer of organic solvents wa s expressed by simultaneous differential equations, which were then solved numerically by a personal computer using a simple spreadsheet program. rn-x ylene 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 parti tion 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 w ith adult rats. The results of simulation of rat exposure to m-xylene (50 a nd 500 ppm for 6 h) were essentially in good agreement with the experimenta l data on rats, i.e. the parent compound (in-xylene) concentration in the t ail blood and the cumulative excretion of the metabolites in the urine were consistent. (C) 2000 Academic Press.