Using population physiologically based pharmacokinetic modeling to determine optimal sampling times and to interpret biological exposure markers: The example of occupational exposure to styrene.
BACKGROUND
Biomonitoring of chemicals in the workplace provides an integrated characterization of exposure that accounts for uptake through multiple pathways and physiological parameters influencing the toxicokinetics.


OBJECTIVE
We used the case of styrene to (i) determine the best times to sample venous blood and end-exhaled air, (ii) characterize the inter-individual variability in biological levels following occupational exposure and (iii) propose biological limit values using a population physiologically based pharmacokinetic (PBPK) model.


METHODS
We performed Monte Carlo simulations with various physiological, exposure and workload scenarios. Optimal sampling times were identified through regression analyses between levels in biological samples and 24-h area under the arterial blood concentration vs. time curve. We characterized the variability in levels of styrene in biological samples for exposures to a time weighted average (TWA) of 20ppm.


RESULTS
Simulations suggest that the best times to sample venous blood are at the end of shift in poorly ventilated workplaces and 15min after the shift in highly ventilated workplaces. Exhaled air samples are most informative 15min after the shift. For a light workload, simulated styrene levels have a median (5th-95th percentiles) of 0.4mg/l (0.2-0.6) in venous blood at the end of shift and 0.5ppm (0.3-0.8) in exhaled air 15min after the end of shift.


CONCLUSIONS
This study supports the current BEI(®) of the ACGIH of 0.2mg/l of styrene in venous blood at the end of shift and indicates a biological limit value of 0.3ppm in end-exhaled air 15min after the end of shift.
Institute of Environmental Medicine, Karolinska Institute, Solna 171 77, Sweden. Karol.thompson@fda.hhs.gov
Marc-André
MA
Verner
Robin
R
McDougall
Gunnar
G
Johanson
D000395:Air Pollutants, Occupational / Q000097:blood / Q000493:pharmacokinetics*; D001944:Breath Tests / Q000379:methods; D003198:Computer Simulation; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009010:Monte Carlo Method; D016273:Occupational Exposure / Q000032:analysis*; D020058:Styrene / Q000097:blood / Q000493:pharmacokinetics*
D000395:Air Pollutants, Occupational; D020058:Styrene