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Journal of Toxicology
Volume 2012 (2012), Article ID 760281, 18 pages
http://dx.doi.org/10.1155/2012/760281
Research Article

Reconstruction of Exposure to m-Xylene from Human Biomonitoring Data Using PBPK Modelling, Bayesian Inference, and Markov Chain Monte Carlo Simulation

1Health and Safety Laboratory, Harpur Hill, Buxton, Derbyshire SK17 9JN, UK
2Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI 48674, USA
3Mathematical Sciences Unit, Health and Safety Laboratory, Harpur Hill, Buxton, Derbyshire SK17 9JN, UK

Received 22 September 2011; Revised 8 December 2011; Accepted 14 December 2011

Academic Editor: Kannan Krishnan

Copyright © 2012 Kevin McNally et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

There are numerous biomonitoring programs, both recent and ongoing, to evaluate environmental exposure of humans to chemicals. Due to the lack of exposure and kinetic data, the correlation of biomarker levels with exposure concentrations leads to difficulty in utilizing biomonitoring data for biological guidance values. Exposure reconstruction or reverse dosimetry is the retrospective interpretation of external exposure consistent with biomonitoring data. We investigated the integration of physiologically based pharmacokinetic modelling, global sensitivity analysis, Bayesian inference, and Markov chain Monte Carlo simulation to obtain a population estimate of inhalation exposure to m-xylene. We used exhaled breath and venous blood m-xylene and urinary 3-methylhippuric acid measurements from a controlled human volunteer study in order to evaluate the ability of our computational framework to predict known inhalation exposures. We also investigated the importance of model structure and dimensionality with respect to its ability to reconstruct exposure.