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Exposure estimation using repeated blood concentration measurements

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Abstract

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 (≅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.

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Acknowledgments

The authors are most grateful to Dr. F.Y. Bois and Prof. R.S.H. Yang for giving invaluable comments on an earlier manuscript, and Dr. Bois for providing the human trichloroethylene (TCE) dataset (through personal communication). This work was supported by grants from the National Science Council (NSC 96-2118-M-400-001) and the National Health Research Institutes of Taiwan (BS-096-PP-11). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Health Research Institutes of Taiwan.

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Authors and Affiliations

  1. Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan

    Chu-Chih Chen

  2. Department of Mathematics, Tamkang University, Taipei, Taiwan

    Meng-Chiuan Shih

  3. Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University, Taipei, Taiwan

    Kuen-Yuh Wu

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  1. Chu-Chih Chen
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  2. Meng-Chiuan Shih
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  3. Kuen-Yuh Wu
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Correspondence to Chu-Chih Chen.

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Chen, CC., Shih, MC. & Wu, KY. Exposure estimation using repeated blood concentration measurements. Stoch Environ Res Risk Assess 24, 445–454 (2010). https://doi.org/10.1007/s00477-009-0332-0

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