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

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.

Analytical challenges in breath analysis and its application to exposure monitoring

“…One option comprises an insulated aluminum tube that holds a collapsible Tedlar sampling bag (85 mL). After collecting end-tidal breath in the bag, an adsorption tube is attached to the sampling tube to adsorb the volatiles in breath [81][82][83]. A recent modification comprises an insulated aluminum tube maintained at 40-45ºC to prevent condensation of the water vapor [84].…”

“…Pre-concentration on solid sorbents followed by thermal desorption (TD) is the most frequent method for the analysis of VOCs in breath samples [9][10][11][12][13]16,[19][20][21][22][23][24][25][26][27][28][43][44][45]47,55,62,75,[81][82][83][84][85]95,96]. Sorbent traps present the advantages that they can be prepared on a micro-scale and coupled on-line with a GC system to allow near real-time measurements [97][98][99][100][101], and the sorbent configuration can be easily changed to adapt to different compounds.…”

“…Five categories of study can be found in the literature: (1) simulations in controlled chambers [21,77,82,83]; (2) swimming and domestic water activities [12,24,68,78,84,119]; (3) services related to mechanical vehicles [22,23,28,69,120,121]; (4) solvents and volatile compounds in the workplace [15,19,79,[122][123][124]; and, (5) active and passive smoking [16,20,25,27,29,51,86,125].…”

“…Breath analysis and physiologically-based pharmacokinetic (PBPK) modeling were used to estimate exposure to m-xylene at 50 ppmv [82] and 40 ppmv [83] in laboratory controlled-atmosphere facilities for 4-h and 12-h periods. In both cases, a modified Haldane-Priestly tube coupled to an adsorption trap was used to collect end-tidal samples, and analyses were performed with a TD-GC-MS system.…”

The role of human biological monitoring in health risk assessment

“…The detailed methodology involved in the probabilistic approaches are beyond the scope of this review article and the readers are directed to related publications in this area (Clewell et al, 2008;Tan and Clewell, 2010;Tan et al, 2012;Grulke et al, 2013;Côté et al, 2014). This approach has been used to derive exposure distributions to several VOCs such as chloroform bromodichloromethane, dibromochloromethane, and bromoform using NHANES III dataset (Tan et al, 2007;Lyons et al, 2008;McNally et al, 2012).…”