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Biomarker variance component estimation for exposure surrogate selection and toxicokinetic inference
Jon R Sobus1, Joachim D Pleil, Michael D McClean
1Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, 109 T.W. Alexander Drive, Research Triangle Park, NC 27711, USA. sobus.jon@epa.gov
Toxicology Letters
|September 21, 2010
Summary
Urinary biomarkers like 1-hydroxypyrene are effective surrogates for asphalt exposure, but hydration and time of day significantly impact results. Toxicokinetics play a minor role in biomarker variance.
Area of Science:
- Occupational Health
- Environmental Epidemiology
- Biomarker Research
Background:
- Biomarkers offer integrated exposure assessment and account for individual toxicokinetic differences.
- Urinary polycyclic aromatic hydrocarbon (PAH) biomarkers are potential surrogates for occupational exposures.
- Hot asphalt emissions pose significant health risks to road-paving workers.
Purpose of the Study:
- To evaluate specific urinary PAH biomarkers as surrogates for exposure to hot asphalt emissions.
- To assess the biasing effects of different urinary biomarkers on exposure-response relationships.
- To determine the influence of toxicokinetics versus covariates on biomarker variance.
Main Methods:
- Utilized linear mixed-effects models to analyze data from 20 road-paving workers.
- Estimated within- and between-person variance components for urinary biomarkers.
- Assessed variation in phenanthrene (Phe) metabolism to hydroxylated isomers (OH-Phe) and related covariates.
Main Results:
- 1-hydroxyphenanthrene (1-OH-Phe), (2+3)-OH-Phe, and 1-hydroxypyrene (1-OH-Pyr) were the least-biasing surrogates.
- Hydration level and sample collection time significantly increased bias estimates for urinary biomarkers.
- Phe exposure, time, hydration, smoking, BMI, and age explained 63-82% of biomarker variance; toxicokinetics explained only 6-23%.
Conclusions:
- Selected urinary PAH biomarkers are suitable surrogates for asphalt exposure, with 1-OH-Phe and 1-OH-Pyr showing promise.
- Observable factors like hydration and time are more influential on biomarker variance than unobserved toxicokinetic processes.
- The described methods are valuable for selecting and interpreting biomarkers in future exposure studies.
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