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Variability in biological exposure indices using physiologically based pharmacokinetic modeling and Monte Carlo
R S Thomas1, P L Bigelow, T J Keefe
1Department of Environmental Health, Colorado State University, Fort Collins 80523, USA.
American Industrial Hygiene Association Journal
|January 1, 1996
Summary
Physiologically based pharmacokinetic (PBPK) modeling reveals current biological exposure indices (BEIs) may not adequately protect all workers from industrial solvent exposure. This study suggests a new approach for establishing BEIs to ensure consistent worker protection.
Area of Science:
- Occupational Health and Safety
- Toxicology
- Pharmacokinetics
Background:
- Biological Exposure Indices (BEIs) are used to assess worker exposure to chemicals.
- Existing BEIs are based on limited data regarding interindividual variability.
- Threshold Limit Values (TLVs) are established for occupational exposure to various industrial solvents.
Purpose of the Study:
- To estimate interindividual variability in chemical concentrations in workers' exhaled breath and urine using physiologically based pharmacokinetic (PBPK) modeling.
- To compare model-derived protection levels with existing BEIs for six industrial solvents.
- To evaluate the adequacy of current BEIs in protecting the worker population.
Main Methods:
- Physiologically based pharmacokinetic (PBPK) modeling coupled with Monte Carlo simulation.
- Simulation of a typical workday exposure regimen for six industrial solvents (benzene, chloroform, carbon tetrachloride, methylene chloride, methyl chloroform, trichloroethylene).
- Exposure concentrations set at ambient Threshold Limit Values (TLVs).
Main Results:
- Current BEIs may not protect the majority or all workers, with significant variability in population protection.
- End-expired air indices for benzene and methyl chloroform protected 95% and <10% of workers, respectively.
- Urinary metabolite indices showed variable protection: phenol (68%), trichloroacetic acid (TCAA) for methyl chloroform (54%), trichloroethanol (TCOH) for methyl chloroform (97%), and TCAA for trichloroethylene (84%).
Conclusions:
- Existing BEIs offer inconsistent protection levels across the worker population.
- PBPK modeling provides a robust method for assessing and improving BEI recommendations.
- This approach can inform administrative decisions for establishing more uniform and effective biological monitoring strategies.