Biological Monitoring of Exposure to Organic Solvent Vapors I. A Physiological Simulation Model of m-Xylene Pharmacokinetics in Man

A physiological pharmacokinetic model of the transfer of organic solvents in the human body was developed. The model was comprised of seven compartments, i.e., lungs, vessel-rich tissues, vessel-poor tissues, muscles, fat tissues, gastrointestinal tissues, and liver, each being connected to the others by blood fiow. 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 as the repi'esentative organic solvent. ・ .Partition coefficients of m-xylene betweeii blood and air and between body tissue and blood were experimentally determined with blood and tissues of rats. The metabelic constants (Vmax and Km) of m-xylene metabolism and the excretion rate constant of m-methyl hippuric acid (m-MHA) were also determined using rats. These animal data "rere scaled up and used as the simulation parameters for humans. The results of the simulation of human exposure to m-xylene were '. essentially in agreement with human experimental data.