Use of physiologically based pharmacokinetic models to establish biological exposure indexes

This paper presents a simulation modeling approach to establish biological exposure indexes (BEIs) from ambient occupational exposure limits (OELs). A physiologically based pharmacokinetic (PB-PK) model was used to describe the disposition of volatile organic chemicals in the human. The model was used to simulate an exposure regimen similar to a typical work schedule. Exposure concentrations were set to equal the ambient OELs of the corresponding chemicals. Chemical concentrations in the expired air and blood and concentrations of metabolites in the urine were estimated with the PB-PK model for this exposure condition. Because the OELs establish the criteria for ambient exposure to chemicals, the concentrations of chemicals or their metabolites in biological media resulting from exposure to the OELs would likewise define acceptable exposure standards. On the basis of this rationale and method, BEIs were developed for 13 common industrial organic chemicals.