Abstract
A seven-compartment physiologically based pharmacokinetic (PBPK) model was developed to predict biological levels of tetrahydrofuran under various exposure scenarios. Affinities for the tissues were estimated from measurements of liquid-gas partition coefficients for water, olive oil, and blood. Metabolism was assumed to follow a rapid first order reaction. Urinary excretion was simulated considering passive reabsorption of tetrahydrofuran in the tubules. The validity of the model was tested by comparison with available experimental and field data. Agreement was satisfactory with all studies available except one, which showed much higher results than expected. The source of this difference could not be identified, but cannot be explained by different exposure conditions, such as duration, concentration, or physical work load. However, it is recommended that this particular study not be used in the establishment of a biological exposure index. Simulation of repeated occupational exposure with the PBPK model allowed the prediction of biological levels that would be reached after repeated exposure at the American Conference of Governmental Industrial Hygienists' threshold limit value, time-weighted average of 200 ppm. For samples taken at the end of the shift, the PBPK model predicts 5.1 ppm for breath, 57 µmol/L (4.1 mg/L) for venous blood, and 100 µmol/L (7.2 mg/L) for urine.