Computational toxicology of chloroform: reverse dosimetry using Bayesian inference, Markov chain Monte Carlo simulation, and human biomonitoring data.

BACKGROUND: One problem of interpreting population-based biomonitoring data is the reconstruction of corresponding external exposure in cases where no such data are available. OBJECTIVES: We demonstrate the use of a computational framework that integrates physiologically based pharmacokinetic (PBPK)...

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Published in:Environmental Health Perspectives Vol. 116; no. 8; pp. 1040 - 1047
Main Authors: Lyons MA, Yang RSH, Mayeno AN, Reisfeld B
Format: research Journal Article
Published: National Institute of Environmental Health Sciences Aug2008
Online Access:View this record in EBSCOhost
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      jtl: Environmental Health Perspectives
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      dt: Aug2008
      vid: 116
      iid: 8
      pid: 56539
      pub: National Institute of Environmental Health Sciences
      place: Research Triangle Park, North Carolina
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        10.1289/ehp.11079
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        atl: Computational toxicology of chloroform: reverse dosimetry using Bayesian inference, Markov chain Monte Carlo simulation, and human biomonitoring data.
      aug:
        au:
          Lyons MA
          Yang RSH
          Mayeno AN
          Reisfeld B
        affil: Quantitative and Computational Toxicology Group, Colorado State University, Fort Collins, Colorado, USA
      sug:
        subj:
          Air Pollutants
          Computer Simulation
          Environmental Monitoring Methods
          Environmental Pollutants
          Probability
          Solvents
          Systems Analysis
          Air Pollutants Analysis
          Air Pollutants Blood
          Bioinformatics
          Environmental Pollutants Analysis
          Environmental Pollutants Blood
          Funding Source
          Human
      ab: BACKGROUND: One problem of interpreting population-based biomonitoring data is the reconstruction of corresponding external exposure in cases where no such data are available. OBJECTIVES: We demonstrate the use of a computational framework that integrates physiologically based pharmacokinetic (PBPK) modeling, Bayesian inference, and Markov chain Monte Carlo simulation to obtain a population estimate of environmental chloroform source concentrations consistent with human biomonitoring data. The biomonitoring data consist of chloroform blood concentrations measured as part of the Third National Health and Nutrition Examination Survey (NHANES III), and for which no corresponding exposure data were collected. METHODS: We used a combined PBPK and shower exposure model to consider several routes and sources of exposure: ingestion of tap water, inhalation of ambient household air, and inhalation and dermal absorption while showering. We determined posterior distributions for chloroform concentration in tap water and ambient household air using U.S. Environmental Protection Agency Total Exposure Assessment Methodology (TEAM) data as prior distributions for the Bayesian analysis. RESULTS: Posterior distributions for exposure indicate that 95% of the population represented by the NHANES III data had likely chloroform exposures < or = 67 microg/L [corrected] in tap water and < or = 0.02 microg/L in ambient household air. CONCLUSIONS: Our results demonstrate the application of computer simulation to aid in the interpretation of human biomonitoring data in the context of the exposure-health evaluation-risk assessment continuum. These results should be considered as a demonstration of the method and can be improved with the addition of more detailed data.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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