Objective

To understand whether previous styrene exposure increases the human liver's ability to convert styrene into styrene oxide.

Methods-The hypothesis was tested that the average linear metabolic rate constant kappa was the same in both exposed and unexposed groups, when the exposed group comprised people with a history of styrene exposure and the unexposed group had no exposure.

In an experimental chamber, these two groups of subjects were exposed to a concentration of 80 ppm styrene for two hours.

A three compartment pharmacokinetic model was used to define kappa.

Based on large sample theory, the comparison of estimated mean values of kappa in the exposed and unexposed groups was shown to be equivalent to a comparison of the estimated mean values of the hepatic clearance X in the two groups.

A method was developed to estimate X for each subject in both groups from the subject's height, weight, and estimated asymptotic styrene decay constant alpha.

Here, alpha was estimated individually from observed blood concentrations over time when sufficient time had elapsed after the controlled exposure.

Results

The proposed methodology of comparing the estimated mean values of K in exposed and unexposed groups reduced the number of specific physiological variables involved to three, all of which were estimable from data based on simple direct measurements. (...)