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Use of Markov Chain Monte Carlo Analysis with a Physiologically‐Based Pharmacokinetic Model of Methylmercury to Estimate Exposures in U.S. Women of Childbearing Age

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  • Bruce C. Allen
  • C. Eric Hack
  • Harvey J. Clewell

Abstract

A Bayesian approach, implemented using Markov Chain Monte Carlo (MCMC) analysis, was applied with a physiologically‐based pharmacokinetic (PBPK) model of methylmercury (MeHg) to evaluate the variability of MeHg exposure in women of childbearing age in the U.S. population. The analysis made use of the newly available National Health and Nutrition Survey (NHANES) blood and hair mercury concentration data for women of age 16–49 years (sample size, 1,582). Bayesian analysis was performed to estimate the population variability in MeHg exposure (daily ingestion rate) implied by the variation in blood and hair concentrations of mercury in the NHANES database. The measured variability in the NHANES blood and hair data represents the result of a process that includes interindividual variation in exposure to MeHg and interindividual variation in the pharmacokinetics (distribution, clearance) of MeHg. The PBPK model includes a number of pharmacokinetic parameters (e.g., tissue volumes, partition coefficients, rate constants for metabolism and elimination) that can vary from individual to individual within the subpopulation of interest. Using MCMC analysis, it was possible to combine prior distributions of the PBPK model parameters with the NHANES blood and hair data, as well as with kinetic data from controlled human exposures to MeHg, to derive posterior distributions that refine the estimates of both the population exposure distribution and the pharmacokinetic parameters. In general, based on the populations surveyed by NHANES, the results of the MCMC analysis indicate that a small fraction, less than 1%, of the U.S. population of women of childbearing age may have mercury exposures greater than the EPA RfD for MeHg of 0.1 μg/kgg/day, and that there are few, if any, exposures greater than the ATSDR MRL of 0.3 μgg/kgg/day. The analysis also indicates that typical exposures may be greater than previously estimated from food consumption surveys, but that the variability in exposure within the population of U.S. women of childbearing age may be less than previously assumed.

Suggested Citation

  • Bruce C. Allen & C. Eric Hack & Harvey J. Clewell, 2007. "Use of Markov Chain Monte Carlo Analysis with a Physiologically‐Based Pharmacokinetic Model of Methylmercury to Estimate Exposures in U.S. Women of Childbearing Age," Risk Analysis, John Wiley & Sons, vol. 27(4), pages 947-959, August.
    • Handle: RePEc:wly:riskan:v:27:y:2007:i:4:p:947-959
    DOI: 10.1111/j.1539-6924.2007.00934.x
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    References listed on IDEAS

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    1. Clark D. Carrington & Michael P. Bolger, 2002. "An Exposure Assessment for Methylmercury from Seafood for Consumers in the United States," Risk Analysis, John Wiley & Sons, vol. 22(4), pages 689-699, August.
    2. Harvey J. Clewell & Jeffery M. Gearhart & P. Robinan Gentry & Tammie R. Covington & Cynthia B. VanLandingham & Kenny S. Crump & Annette M. Shipp, 1999. "Evaluation of the Uncertainty in an Oral Reference Dose for Methylmercury Due to Interindividual Variability in Pharmacokinetics," Risk Analysis, John Wiley & Sons, vol. 19(4), pages 547-558, August.
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    Cited by:

    1. Clark D Carrington & Michael Bolger, 2008. "Letter to the Editor," Risk Analysis, John Wiley & Sons, vol. 28(5), pages 1137-1140, October.
    2. Jeong-wook Seo & Byoung-gwon Kim & Young-seoub Hong, 2020. "The Relationship between Mercury Exposure Indices and Dietary Intake of Fish and Shellfish in Women of Childbearing Age," IJERPH, MDPI, vol. 17(13), pages 1-16, July.

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