Reconstruction of exposure to volatile organic compounds from venous blood concentration and an uncertain physiologically-based pharmacokinetic model

Abstract

Physiologically-based pharmacokinetic modeling was applied to determine exposures to volatile organic compounds, specifically focusing on m-xylene. Passive diffusion was used to describe permeation through the skin. The proposed model agreed with the experimental data and allowed researchers to monitor the concentration profiles in different compartments. The study also focused on the impact of parameter uncertainty on the model predictions. Local and global sensitivity analyses evaluated the influence of partition parameters, diffusion coefficients in the skin, and metabolic parameters on the blood concentration. Both methods show that the Michaelis-Menten kinetics and the lean tissue:blood partition coefficients contributed the most to the total variability. A reverse dosimetry approach used the measured biomarker level to estimate the exposure dose in four hours. The results aligned with experimental data when simulations were conducted using random parameters selected within twenty-five percent of the mean.