A Bayesian compartmental model for the evaluation of 1, 3-butadiene metabolism

Abstract : We propose a Bayesian model for physiologically based pharmacokinetics of 1,3-butadiene (BD). BD is classified as a suspected human carcinogen and exposure to it is common, especially through cigarette smoke as well as in urban settings. The main aim of the methodology and analysis that are presented here is to quantify variability in the rates of BD metabolism by human subjects. A three-compartmental model is described, together with informative prior distributions for the population parameters, all of which represent real physiological variables. The model is described in detail along with the meanings and interpretations of the associated parameters. A four-compartment model is also given for comparison. Markov chain Monte Carlo methods are described for fitting the model proposed. The model is fitted to toxicokinetic data obtained from 133 healthy subjects (males and females) from the four major racial groups in the USA, with ages ranging from 19 to 62 years. Subjects were exposed to 2 parts per million of BD for 20 min through a face mask by using a computer-controlled exposure and respiratory monitoring system. Stratification by ethnic group results in major changes in the physiological parameters. Sex and age were also tested but not found to have a significant effect.