Biological monitoring of tetrahydrofuran: Contribution of a physiologically based pharmacokinetic model

A seven-compartment physiologically based pharmacokinetic (PBPK) model was developed to predict biological levels of tetrahydrofuran under various exp osure scenarios. Affinities for the tissues were estimated from measurement s of liquid-gas partition coefficients for water, olive oil, and blood. Met abolism was assumed to follow a rapid first order reaction. Urinary excreti on 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 a vailable except one, which showed much higher results than expected. The so urce of this difference could not be identified, but cannot be explained by different exposure conditions, such as duration, concentration, or physica l work load. However, it is recommended that this particular study not be u sed in the establishment of a biological exposure index. Simulation of repe ated occupational exposure with the PBPK model allowed the prediction of bi ological levels that would be reached after repeated exposure at the Americ an Conference of Governmental Industrial Hygienists' threshold limit value, time-weighted average of 200 ppm. For samples taken at the end of the shif t, the PBPK model predicts 5.1 ppm for breath, 57 mu mol/L (4.1 mg/L) for v enous blood, and 100 mu mol/L (7.2 mg/L) for urine.