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

McNally K, Cotton R, Cocker J, Jones K, Bartels M, Rick D, Price P, Loizou G - J Toxicol (2012)

Bottom Line: There are numerous biomonitoring programs, both recent and ongoing, to evaluate environmental exposure of humans to chemicals.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.

View Article: PubMed Central - PubMed

Affiliation: Health and Safety Laboratory, Harpur Hill, Buxton, Derbyshire SK17 9JN, UK.

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.

No MeSH data available.


Related in: MedlinePlus

(a) Venous blood concentrations of m-xylene. Data from three volunteers were prepared and measured on a different day than other four. This set of data has the expected appearance and was considered acceptable for use in reverse dosimetry. (b) Venous blood concentrations of m-xylene. Data from four volunteers were prepared and measured on a different day than other three. This set of data does not have the expected appearance and was considered unacceptable for use in reverse dosimetry.
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fig1: (a) Venous blood concentrations of m-xylene. Data from three volunteers were prepared and measured on a different day than other four. This set of data has the expected appearance and was considered acceptable for use in reverse dosimetry. (b) Venous blood concentrations of m-xylene. Data from four volunteers were prepared and measured on a different day than other three. This set of data does not have the expected appearance and was considered unacceptable for use in reverse dosimetry.

Mentions: Venous blood samples were taken at 0, 1, 2, 3, 4, 4.33, 4.67, 5, 6, 7, 8, and 23 hours. The blood data were separated into two sets corresponding to measurements made on different occasions to investigate the importance of data quality in reverse dosimetry (Figures 1(a) and 1(b)). The analysts explain that blood data deemed unreliable may be due to imperfect sealing of sample vials leading to losses. This explanation is plausible when compared to the appearance of the exhaled breath and urine data for all volunteers, which are qualitatively similar. Also, the peak CV concentrations of the reliable data are quantitatively and qualitatively comparable with data from similar human volunteer studies [28, 29].


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

McNally K, Cotton R, Cocker J, Jones K, Bartels M, Rick D, Price P, Loizou G - J Toxicol (2012)

(a) Venous blood concentrations of m-xylene. Data from three volunteers were prepared and measured on a different day than other four. This set of data has the expected appearance and was considered acceptable for use in reverse dosimetry. (b) Venous blood concentrations of m-xylene. Data from four volunteers were prepared and measured on a different day than other three. This set of data does not have the expected appearance and was considered unacceptable for use in reverse dosimetry.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3376947&req=5

fig1: (a) Venous blood concentrations of m-xylene. Data from three volunteers were prepared and measured on a different day than other four. This set of data has the expected appearance and was considered acceptable for use in reverse dosimetry. (b) Venous blood concentrations of m-xylene. Data from four volunteers were prepared and measured on a different day than other three. This set of data does not have the expected appearance and was considered unacceptable for use in reverse dosimetry.
Mentions: Venous blood samples were taken at 0, 1, 2, 3, 4, 4.33, 4.67, 5, 6, 7, 8, and 23 hours. The blood data were separated into two sets corresponding to measurements made on different occasions to investigate the importance of data quality in reverse dosimetry (Figures 1(a) and 1(b)). The analysts explain that blood data deemed unreliable may be due to imperfect sealing of sample vials leading to losses. This explanation is plausible when compared to the appearance of the exhaled breath and urine data for all volunteers, which are qualitatively similar. Also, the peak CV concentrations of the reliable data are quantitatively and qualitatively comparable with data from similar human volunteer studies [28, 29].

Bottom Line: There are numerous biomonitoring programs, both recent and ongoing, to evaluate environmental exposure of humans to chemicals.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.

View Article: PubMed Central - PubMed

Affiliation: Health and Safety Laboratory, Harpur Hill, Buxton, Derbyshire SK17 9JN, UK.

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.

No MeSH data available.


Related in: MedlinePlus