Exposure estimation using repeated blood concentration measurements

Physiologically based toxicokinetic (PBTK) modeling has been well established to study the distributions of chemicals in target tissues. In addition, the hierarchical Bayesian statistical approach using Markov Chain Monte Carlo (MCMC) simulations has been applied successfully for parameter estimation. The aim was to estimate the constant inhalation exposure concentration (assumed) using a PBTK model based on repeated measurements in venous blood, so that exposures could be estimated. By treating the constant exterior exposure as an unknown parameter of a four-compartment PBTK model, we applied MCMC simulations to estimate the exposure based on a hierarchical Bayesian approach. The dataset on 16 volunteers exposed to 100 ppm (a parts per thousand...0.538 mg/L) trichloroethylene vapors for 4 h was reanalyzed as an illustration. Cases of time-dependent exposures with a constant mean were also studied via 100 simulated datasets. The posterior geometric mean of 0.571, with narrow 95% posterior confidence interval (CI) (0.506, 0.645), estimated the true trichloroethylene inhalation concentration (0.538 mg/L) with very high precision. Also, the proposed method estimated the overall constant mean of the simulated time-dependent exposure scenarios well with slightly wider 95% CIs. The proposed method justifies the accuracy of exposure estimation from biomonitoring data using PBTK model and MCMC simulations from a real dataset and simulation studies numerically, which provides a starting point for future applications in occupational exposure assessment.